Screening Guidelines for Primary Care

 All rights reserved. This material material may be freely reproduced reproduced for educational and not for profit profit  purposes. No reproduction by or for commercial organizations is permitted without the express written permission from the Family Medicine Specialists Association Association of Malaysia.

First Edition 2015

Published by: Family Medicine Specialists Association of Malaysia Room14, Level 5, Malaysian Medical Association Building 124, Jalan Pahang, 53000 Kuala Lumpur [email protected] http://fms-malaysia.org

ISBN 978-967-11389-2-2

 All rights reserved. This material material may be freely reproduced reproduced for educational and not for profit profit  purposes. No reproduction by or for commercial organizations is permitted without the express written permission from the Family Medicine Specialists Association Association of Malaysia.

First Edition 2015

Published by: Family Medicine Specialists Association of Malaysia Room14, Level 5, Malaysian Medical Association Building 124, Jalan Pahang, 53000 Kuala Lumpur [email protected] http://fms-malaysia.org

ISBN 978-967-11389-2-2

FOREWORD Congratulations to the Family Medicine Specialists Association (FMSA) of Malaysia on publishing this Consensus Guide on Adult Health Screening in Primary Care. In particular, the chairperson, committee members, authors, reviewers and editors deserve mention for their enormous efforts in providing guidance to practitioners on appropriate, beneficial and cost-effective tools in primary care.  The decision to screen for diseases must be made on a sound basis and take into consideration elements of treatability and progression. As the pillar of health services in a country, country, primary care plays a very important role in identifying diseases early. early. Focussing on screening and early intervention for selected medical conditions has much lower costs than treating after late detection. The saying ‘prevention is better than cure’ is very true. Therefore, a good screening tool based on sound evidence is very essential.  The review review on screening screening for each disease disease condition condition in this Consensus Guide was was done quite extensively. extensively. I am proud that this is the first evidence-based guide in Malaysia. It is my hope that these screening guidelines will be used by all primary care providers in both government and private sectors and become a useful tool at point of first contact with healthcare services in this country.

DATUK DR NOOR HISHAM BIN ABDULLAH

Director General of Health Ministry of Health Malaysia

Foreword

iii

FOREWORD Screening is a process of identifying apparently healthy people who may be at increased risk of a disease or condition. They can be offered information, further tests and appropriate treatment to reduce their risk and/or any complications arising from the disease or condition. Screening for diseases, and their risk factors, has been implemented in many countries. Via screening, early intervention can be done. Moreover, the treatment outcome may differ compared to late detection. Screening is generally done, and is worth doing, if early intervention proves to be beneficial in terms of outcome and cost-effectiveness. Primary care is a suitable place to conduct medical screening due its role as the point of first contact to health services in a country, and the point to incorporate the wellness element in patient care apart from the disease-oriented approach. Primary care providers also manage patients with various risk factors and medical conditions. There is a need, therefore, to guide primary care providers on medical screening.  To meet this need, the Family Medicine Specialists Association (FMSA) of Malaysia took the initiative to produce evidence-based guidelines on screening at primary care level to facilitate primary care providers in their day-to-day practice. The screening guidelines herein provides information on the epidemiology and magnitude of each medical problem, the benefits of screening and treatment, specific recommended screening tests as well as any harm from screening. Due to the challenge of having a wide variety of medical conditions seen at primary care level, the committee decided to prioritize certain conditions that can be intervened early in this country. FMSA hopes that this Guide will assist primary care providers to optimize their roles and functions based on evidence, locally available resources and cost effectiveness.

DR NORSIAH ALI

President  Family Medicine Specialists Association

iv

Foreword

PREFACE  This is a consensus guide on recommendations for health screening in primary care clinic settings. The recommendations are based on the best available evidence tailored to local context. In a broader sense, health screening is one of the components of preventive health care. Other components of preventive health care include promoting a healthy life-style, immunisation and chemoprevention. Although health screening is relevant to all stakeholders in the health sector, primary care is directly responsible for it because it is the first point of contact for people seeking healthcare and, thereafter, provides continued care to individual patients.  There are credible screening guidelines, such as, the Canadian Taskforce for Preventive Services, the United States Preventive Service Task Force and the Royal Australian College of General Practice. However, the local context has to be considered when recommending screening due to differences in morbidity and mortality patterns which affects the predictive ability and, thus, cost-effectiveness of screening tests. At face value, health screening appears compelling as it may be seen as a one-stop health assessment to ensure one is free of specific diseases. However, there are shortcomings in some health screening tests.  The benefits of health screening can also be misunderstood by health care providers and the public. Although many screening tests are beneficial, there are also tests that may cause more harm than good. These recommendations aim to provide a summary of evidence for or against screening in order to guide decisions when offering health screening to patients at primary care settings.

PROFESSOR DR TONG SENG FAH

Chair Consensus working group Screening Guidelines 2015

Preface

v

CONSENSUS WORKING GROUP Chair Dr Tong Seng Fah Professor, Department of Family Medicine Faculty of Medicine, Universiti Kebangsaan Malaysia

Contributors (in alphabetical order) Cardiovascular risk assessment

Dr Ambigga Devi A/P S. Krishnapillai

Associate Professor, Discipline of Primary Care Medicine Faculty of Medicine and Defence Health, National Defence University of Malaysia Dr Maizatullifah Miskan

Senior Lecturer, Discipline of Primary Care Medicine Faculty of Medicine and Defence Health, National Defence University of Malaysia Dr Mazapuspavina Md. Yasin

Senior Lecturer, Discipline of Primary Care Medicine, Faculty of Medicine, Universiti Teknologi MARA Dr Ng Kien Keat

Senior Lecturer, Discipline of Primary Care Medicine Faculty of Medicine and Defence Health, National Defence University of Malaysia Osteoporosis and Thyroid dysfunction

Dr Adibah Hanim Ismail

Associate Professor, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Dr Cheong Ai Theng

Associate Professor, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Dr Tong Seng Fah

Professor, Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Dr Zuhra Hamzah

Senior Lecturer, Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Chronic obstructive pulmonary disease

vi

Consensus Working Group

Dr Ching Siew Mooi

Senior Lecturer, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia

Chronic obstructive pulmonary disease

Dr Verna Lee Kar Mun

Cervical cancer Breast cancer Colorectal cancer Prostate cancer

Dr Fuziah Paimin

Associate Professor, Department of Family Medicine, International Medical University Consultant Family Medicine Specialist Klinik Kesihatan Kajang Dr Hasliza Hassan

Family Medicine Specialist Klinik Kesihatan Sungai Pelek Dr Harmy bin Mohamed Yusoff

Professor, Department of Family Medicine, Faculty of Medicine, Universiti Sultan Zainal Abidin Dr Irmi Zarina Ismail

Senior Lecturer, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Dr Norhayati Mohd Noor

Associate Professor, Department of Family Medicine School of Health Science, Universiti Sains Malaysia Depression Nicotine addiction Alcohol addiction Illicit substance addiction

Dr Baizury Bashah

Consultant Family Medicine Specialist Klinik Kesihatan Putrajaya Precint 18 Dr Faezah Hassan

Senior Lecturer, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Dr Norizzati Bukhari

Family Medicine Specialist Klinik Kesihatan Bangi Dr Norsiah Ali

Consultant Family Medicine Specialist Klinik Kesihatan Masjid Tanah Dr Sherina Mohd Sidik 

Professor, Department of Psychiatry Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Human immuno deficiency virus Infection

Dr Vickneswari A/P Ayadurai

Consultant Family Medicine Specialist Klinik Kesihatan Taman Medan

Consensus Working Group

vii

CONSENSUS WORKING GROUP Domestic violence

Dr Inderjit Singh Ludher

Family Physician Academy of Family Physicians of Malaysia Dr Sajaratulnisah Binti Othman,

Associate Professor, Department of Primary Care Medicine Faculty of Medicine, University of Malaya Scoliosis in adolescent

Dr Sri Wahyu Taher

Older age group: Hearing loss  Visual impairment  Fall risk Dementia Urinary incontinence 

Dr Ambigga Devi A/P S. Krishnapillai

Consultant Family Medicine Specialist Klinik Kesihatan Simpang Kuala Associate Professor, Discipline of Primary Care Medicine Faculty of Medicine and Defence Health,  National Defence University of Malaysia Dr Ho Bee Kiau

Consultant Family Medicine Specialist Klinik KesihatanBotanik  Dr Lee Ping Yein

Associate Professor, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Dr Noorlaili Mohd Tohit @ Mohd Tauhid

Senior Lecturer, Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Dr Ruziaton Hasim

Consultant Family Medicine Specialist Klinik Kesihatan Pandamaran Dr Sazlina Shariff Ghazali

Associate Professor, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia Dr Zaiton Ahmad (Late)

Senior Lecturer, Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia

viii

Consensus Working Group

REVIEWERS (in alphabetical order) Internal reviewers

Dr Harmy bin Mohamed Yusoff

Professor, Department of Family Medicine, Faculty of Medicine, Universiti Sultan Zainal Abidin Dr Khoo Ee Ming

Professor, Department of Primary Care Medicine Faculty of Medicine, University of Malaya Dr Mastura Ismail

Family Medicine Specialist Klinik Kesihatan Seremban 2 Dr Norsiah Ali

Family Medicine Specialist Klinik Kesihatan Tampin Dr Teng Cheong Lieng

Professor, Department of Family Medicine, International Medical University Dr Tong Seng Fah

Professor, Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia External Reviewers (international)

Professor James Dickinson

Family Medicine and Community Health Science University of Calgary Professor Mark Harris,

Centre for Primary Health Care and Equity, University of New South Wales External Reviewers (national)

Dr Asma Abdullah

Professor, Department of Otorhinolaryngology Faculty of Medicine, Universiti Kebangsaan Malaysia Dr Feisul Idzwan Mustapha

Public Health Physician, Non-Communicable Disease Section Disease Control Division, Ministry of Health Dr Lee Fatt Soon

Geriatrician, Department of Medicine Hospital Kuala Lumpur Dr Lee Tong Weng

Family Physician Klinik T W Lee Sdn Bhd Reviewers

ix

REVIEWERS External Reviewers (national)

Dr Lee Wai Khew

Family Medicine Specialist Klinik Kesihatan Luyang Dr. Marhani Midin

Professor, Department of Psychiatry Faculty of Medicine, Universiti Kebangsaan Malaysia Dr. Mohamad Aziz Salowi

Public Health Ophthalmologist, Department of Ophthalmology Hospital Selayang Dr Nor Azmi Kamarudin

Professor, Department of Medicine Faculty of Medicine, Universiti Kebangsaan Malaysia Dr Ong Teng Aik 

Associate Professor, Department of Surgery Faculty of Medicine, University of Malaya Dr Pang Yong Kek 

Professor, Department of Medicine Faculty of Medicine, University of Malaya Dr Sabarul Afian Mokhtar

Professor, Department of Orthopaedic Faculty of Medicine, Universiti Kebangsaan Malaysia Dr Salmiah Sharif

Family Medicine Specialist, Klinik Kesihatan Batu 9 Cheras Dr Shaiful Bahari Ismail

Professor, Department of Family Medicine School of Health Science, Universiti Sains Malaysia Dr Sheila A/P Marimuthu

Paediatrician, Department of Paediatric Hospital Kuala Lumpur Dr Suresh Kumar A/L Chidambaram

Infectious Disease Physician, Department of Medicine Hospital Sungai Buluh Dr Tan Chow Wei

Family Physicians The People’s Dispensary

x

Reviewers

 ACKNOWLEDGMENTS Since health screening covers a wide range of illnesses across various systems, age groups and gender, a large team of experts was involved in drawing up these guidelines. I wish to thank all the editors, contributors and reviewers for contributing to the content of this guide. On behalf of the guideline development team, we wish to acknowledge the support of the Division of Family Health Development of the Ministry of Health, Family Medicine Specialists Association, the Department of Family Medicine of Universiti Putra Malaysia and other contributors for either funding or providing the infrastructural support for the group. We would like to also thank the following colleagues who provided input during the development of the guides: Dr. Feisul Idzwan Mustapha

Public Health Physician, Non-Communicable Disease Section Disease Control Division, Ministry of Health Dr Mohd Aminuddin Mohd Yusof

Public Health Physician, Health Technology Assessment Ministry of Health Dr. Noridah bt. Mohd Saleh

Public Health Physician, Primary Health Division,

 Acknowledgments

xi

Defining Health Screening Conventional health screening and health checks are different although they have similar underlying concepts. Health screening aims to identify asymptomatic populations who are at higher risk of a disease. At primary care settings, however, health screening should go beyond identifying the at-risk asymptomatic population for a particular disease – as in the definition of screening. It should also identify risk behaviours, such as smoking, and unreported symptomatic illnesses, such as domestic violence and depression. These are not necessarily asymptomatic. Thus, for these guidelines, it is more appropriate to expand the above definition of health screening, which is essentially the same concept as health checks, to include the following: 1.

Screening for asymptomatic conditions such as hypertension, diabetes, hypercholesterolaemia and colon cancer.

2.

Screening for symptomatic conditions that are under-reported by patients such as depression.

3.

Assessing health risk behaviours such as smoking and nutritional status.

Determining the evidence for health screening By evidence-based practice, health screening should only be recommended if its benefit is proven to outweigh harm. However, proving that health screening is beneficial can be challenging. Most people presenting or being offered health screening are in good health to begin with. Therefore, subjecting them to any harm arising from health screening is unjustified. Furthermore, evidence of any benefit from health screening is difficult to establish. Proving that an illness is prevented - the main benefit resulting from health screening – is more difficult than proving that its symptoms have improved and the illness has been cured. In addition, the benefit is often delayed. Although randomized controlled trials (RCTs) are the highest level of evidence to inform practice, RCTs evaluating the benefit of health screening take years to complete. In contrast, the harmful effects of screening often emerge earlier. Hence, many recommendations put forward for health screening may not be supported by robust evidence. Instead, many inferences are made to justify the recommendations. These may have contributed to the inconsistencies in screening guidelines over the years and from different expert committees.

xii

Define Health Screening

Given the limited resources, we proposed our recommendations based on evidence from the following: 1.

Review of primary literature from MEDLINE and Cochrane database

2.

Review of screening guidelines from the United States Preventive Service  Task Force (USPSTF), Canadian Task Force for Preventive Care (CTFPC) and Guidelines for preventive activities in general practice 8th edition

For each condition, the evidence was appraised by the authors before making their recommendation on screening. The reviews and recommendations were subjected to internal and external reviewers.

Determining the benefits of health screening  The final aim of health screening is to reduce morbidity and mortality associated with the disease screened. Achieving the final benefits requires a series of actions from initiating screening to management of the disease detected. Potential harms associated with the series of actions and factors diluting the benefits of screening have to be considered before the final benefits are ascertained. (Figure 1)

Fig 1: Process of screening and factors diluting the benefit of screening Patients

Screenin

Risk of disease

Referral for diagnosis

False negative test  Adverse effect of procedure

False sense of security

Long term impact of missed diagnosis

Referral for treatment

1. Non adherence to follow up tests 2. Psychosocial impact of false positive test 3. Adverse effects of   procedure

Morbidity and Mortality benefits

Non adherence to treatment

 Adver se effect of treatment on patient’s quality of life (patient started off as healthy

Many factors can dilute the net benefits of screening. A lower risk of disease will result in a higher chance of obtaining a false positive results, and adverse effects associated with it. False positive results may lead to an adverse impact on the psychological and

Determining the benefits of health screening

xiii

social wellbeing of patients. On the other hand, a false negative result due to poor test sensitivity is a concern as well because disease diagnosis will be missed, and a false sense of security will be created. Adverse effects can occur from the screening test, diagnostic test and treatment. Documenting and quantifying some of these factors, such as a false sense of security, can be challenging. Since many studies do not formally assess these factors, many recommendations are based on consensus expert opinion.

Objectives and scope of the recommendations Objectives  The aim of these recommendations is to assist clinicians in making evidence-based decisions on health screening. There are many possible areas for screening ranging from cardiovascular risk factors to cancers and mental health. In each of these areas, we asked the following questions to justify our recommendations: a. How common is the condition? b. What is the disease burden? c. What are the benefits of screening and treating the condition? d. What are the optimal screening tools available? e. What are the harm of screening? Target user  The recommendations are intended for use by doctors and allied health care workers who offer health screening to their patients. They would include: a.

Primary care physicians (at various levels: medical officers running primary care clinics, general practitioners, family physicians or family medicine specialists)

b.

Allied health professionals who are given the responsibility to provide health screening

Scope and limitations of the recommendations  The recommendations do not include all preventive activities and are limited to only health screening in primary care settings. Hence, counselling, health promotion, health education, immunisation, life-style advice and management of health risk factors are not included in these recommendations. For patients attending outpatient clinics, the recommendations include the assessment of risk factors and screening tests, which may consist of questionnaires, laboratory or radiological tests. The recommendations are not applicable to pre-employment health checks which serve different objectives.  These recommendations also do not cover management strategies for detected xiv

Objectives and scope of the recommendations

diseases (e.g., treatment for diabetes or cervical cancer). Screening for disease complications is not considered as health screening because patients diagnosed with a medical condition represent different risks and should be considered under disease surveillance (e.g., screening for diabetic retinopathy).  These recommendations are based on evidence up to the date of publishing. They are generally valid for up to three years unless new evidence becomes available. Statement of Intent   These recommendations are meant to guide clinical practice. Adherence to these recommendations should take into consideration the strength of the recommendations, individual patient’s risk profile, patient’s values and the setting of the health services. Every healthcare provider is responsible for the management of his or her unique patient population. These recommendations also consider local data and options of tests available, or potentially available, locally.

Consensus Development Methods  The development of consensus involved a central committee and the contributors of specific chapters. The central committee members are appointed by the Family Medicine Specialists Association, whereas the contributors of specific chapters are primary care providers with special interest in the respective chapter topic. The central committee was responsible for deciding on the topics/chapters to be included, reviewing the content of each chapter and making suggestions to improve the drafts submitted. The committee also standardized the approach to writing each chapter. Guide for contributors 1. Perform a literature review using primary literature and reviewing established screening guidelines on the following key clinical questions: a.

c. d.

What is the magnitude of the problem (e.g., the prevalence and burden of breast cancer, and its mortality and morbidity)? What are the benefits of treatment if disease or risk factors are detected early? Does screening improve disease mortality and morbidity? What is the validity of screening tools or tests?

e.

What are the harms associated with screening?

b.

2. Search the literature to include major electronic data of PubMed, and Cochrane Systematic Reviews.

Consensus Development Methods

xv

3. Use major preventive guidelines as reference points as these guidelines have undergone rigorous development protocols. 4. Appraise, summarise and synthesise information adopting the classification of strength of evidence developed by the United States Preventive Service Task Force. 5. Summarise the evidence and make recommendations based on the following criteria: • The condition has significant disease burden, i.e., the condition is prevalent and associated with high mortality and morbidity • Effective management of the condition or risk factors is available, which leads to significant morbidity and mortality benefit • Screening of the condition leads to improvement in disease mortality and morbidity • Valid and acceptable screening tests are available for early detection of the condition • Harm from screening is justifiable

 

Grading of evidence Level I

Evidence obtained from at least one properly randomized controlled trial

II - 1

Evidence obtained from well-designed controlled trials without randomisation

II - 2

Evidence obtained from well-design cohort or case-control analytic studies, preferably from more than one centre or research group

II - 3

Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence

III

Opinions of respected authorities based on clinical experience; descriptive studies and case reports; or reports of expert committees

Source: U.S. / Canadian preventive services task force (adopted by Health Technology Assessment of Malaysia)

Grading of recommendation  The grades range from A, B, C, D and I (see the table below). Grade D is unique grade of recommendation. It denotes good certainty that the test has no benefit.

xvi

Grading

Hence, we recommend against offering such tests. The grading of recommendations is not necessarily consistent with the level of evidence, however. Some recommended screening, such as asking about smoking, may not have direct level I evidence of benefit i.e., that asking about smoking results in reduced risk of mortality or morbidity. However, supporting evidence is sufficiently strong to warrant a grade A recommendation. Key to Grade of recommendation (adopted from the USPSTF 2012) Grade

Definition

Offer or provide this service.

A

The USPSTF recommends the service. There is high certainty that the net benefit is substantial.

Offer or provide this service.

B

The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.

Only offer or provide this service for selected patients depending on individual circumstances.

The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.

Discourage the use of this service.

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

C

D

I Statement

Suggestions for Practice

Source: U.S. preventive services task force

Process of reviewing  The draft of the guidelines was sent to reviewers for appraisal. Feedback from the reviewers was discussed in the group meeting before finalizing the guidelines.

Grading

xvii

Implementing health screening Proactive and Opportunistic health screening In order to be effective, discussions about health screening tests that have proven to be beneficial should be initiated proactively or opportunistically. The public may not be aware of the recommended health screening or have inaccurate or false beliefs about health screening. Primary care settings offer great opportunities for personal contact between the community and health care. These contacts are potential encounters where such discussions can be initiated. Universal health screening Screening with level A or B recommendations has clear benefits outweighing harm. Universal health screening is recommended where patients are routinely screened according to the criteria stated. However, the benefits of screening should be discussed. A system needs to be created to record the screening test, follow through with the results, remind patients for screening or repeat screening, manage patients with positive results and counsel patients with negative results at appropriate screening intervals. Shared decision approach in selecting tests for health screening Screening with level C or I recommendation requires careful discussion with patients.  This should involve informing on direct medical benefit, harms of screening, cost incurred, and patients’ values and beliefs. In most instances, because of the difficulty in getting good evidence to support the recommendations, a discussion is needed to avoid undue anxiety and unnecessary tests. Health care providers need to inform patients on: 1. 2. 3. 4. 5.

The test procedures The aim of the test, i.e., benefit of screening and treatment following screening The screening process including the steps after the test results Harms from the screening and diagnostic procedures, and from treatment resulting from positive diagnosis upon confirmation of screening tests. Patient’s personal goals for undertaking the screening

Patients should then participate in the decision-making of undertaking the tests.  This shared decision approach aims to provide sufficient information to patients, and allows them to examine their own values and perspective in undertaking such tests.  This may be done with decision aids (if available), printed information or counselling by allied health care workers or doctors. Patients should be aware of the conditions they are being assessed or tested on, the implications of a positive or negative test, the need fora confirmatory test, and the harm and benefit of the diagnostic test xviii Implementing health screening

and the treatment resulting from a positive diagnosis. Doctors also need to actively participate in recommending tests after a thorough assessment of the patients’ risks.  This balanced approach will minimise negative experiences and regret over an initial health screening decision.

Using this consensus recommendations  These recommendations were drafted with the intention of ease of use at the point of care during clinic consultation. This booklet is also meant to provide a summary of information concerning screening to help counsel patients while discussing health screening. We aimed to include sufficient details to justify the recommendations made.  This booklet is presented in two sections: 1. 2.

Summary of recommendations of health screening according to gender and age Description of each condition to (or not to) justify screening

 The summary charts, 1, 2 and 3, provide a list of recommendations according to grade level for screening for different age groups. The charts should provide a quick reference at the point of care, and practitioners can use the chart to track the recommended screening as patients are being followed up. Some tests, requiring initial risk assessment, should only be offered to specific risk groups while other tests can be offered routinely. The tests that are offered to specific risk groups are shaded yellow while the checks offered routinely are shaded red. The alphabets within the box represent the grade of the recommendation. The grade of recommendations are A, B or C (see previous section for their definitions). Chart 1 is for male patients and chart 2 for female. Grades D and I are not included in charts 1 and 2 because those tests are not recommended or there is insufficient evidence to support undertaking the tests.  These are summarized in Chart 3. Practitioners may want to read further on the justification for the screening in Section 2. In this section, the description of screening for each condition starts with a summary Box in yellow with the recommendation for it in blue. This is followed by narrative reviews of the information and evidence for the screening. Where appropriate, the steps needed before offering the test are provided. Where appropriate, assessment of risk factors should be undertaken and patients assigned to different risk categories (e.g., high risk for colon cancer). The recommendations should then be provided accordingly.  An Appendix at the end of each chapter in Section 2 provides a description of relevant screening tools (e.g., for cardiovascular risk calculator and for illicit drug use). Using this consensus recommendations

xix

TABLE OF CONTENTS Foreword Foreword Preface Consensus Working Group Reviewers  Acknowledgments Defining Health Screening Determining the Evidence for Health Screening Determining the Benefits of Health Screening Objectives and Scope of the Recommendations Consensus Development Methods Implementing Health Screening Using this Consensus Recommendations  Table of Contents Health Screening Schedule for Adult Male Health Screening Schedule for Adult Female Conditions Not Recommended for Health Screening 1.

Cardiovascular Disease (CVD) Risk Factors: Screening for Adults

1.1 1.2 1.3 1.4 2.

Thyroid Dysfunction

2.1 2.2 2.3 2.4 3.

4.

Introduction Benefit of screening and treating subclinical thyroid dysfunction Screening test Harm of screening

Osteoporosis

xviii xix xx xxv xxvi xxvii 1 2 3 4 10 21 22 23 23 23

3.1 Introduction 3.2 Benefit of screening and treating osteoporosis

26 26 27

3.3 Screening tests 3.4 Harm of screening

28 29

Chronic Obstructive Pulmonary Disease (COPD)

32 32 33 33 33

4.1 4.2 4.3 4.4

xx

Introduction Benefits of screening and treating CVD risk factors Screening Tools & Tests Harm of CVRFs assessment

iii iv v vi ix xi xii xii xiii xiv xv

Contents

Introduction Benefit of treatment or early intervention Screening tests Harm of screening

5.

Cervical Cancer

5.1 5.2 5.3 5.4 6.

Breast Cancer

6.1 6.2 6.3 6.4 7.

8.

Introduction Benefit of screening and treating breast cancer Screening tests Harm of screening

Colorectal Cancer

7.1 Introduction 7.2 Benefit of screening and treating colorectal cancer 7.3 Screening Tests 7.4 Harm of Screening

52 53

Prostate Cancer

58 58 59 60 61

Introduction The benefit of screening and treating prostate cancer Screening tests Harm of screening

Tobacco

9.1 9.2 9.3 9.4

Introduction Benefit of screening and treating tobacco addiction Screening tests Harm of screening

10. Alcohol

 

42 42 43 44 47 49 49 51

8.1 8.2 8.3 8.4 9.

Introduction Benefit of screening and treating cervical abnormalities Screening tests Harm of screening

35 35 36 37 38

63 63 63 64 64

10.1 Introduction 10.2 Benefit of screening and treating alcohol use

66 66 67

10.3 Screening tests 10.4 Harm of screening

67 67

11. Illicit Drugs

11.1 Introduction 11.2 Benefit of screening and treating illicit drug use 11.3 Harm of screening

70 70 70 70

Contents

xxi

TABLE OF CONTENTS 12. Human Immunodeficiency Virus Infection

12.1 12.2 12.3 12.4

Introduction Benefit of screening and treating HIV infection Screening tests Harm of screening

13. Domestic Violence

13.1 13.2 13.3 13.4

Introduction Benefit of screening and managing domestic violence Screening tests Harm of screening

14. Depression

1.1 Introduction 14.1 Benefit of screening and treating depression 14.2 Screening tests 14.3 Harm of screening 15. Scoliosis in Adolescents

15.1 15.2 15.3 15.4

Introduction Benefit of screening and treating adolescent idiopathic scoliosis Screening tests Harm of screening

16. Hearing Loss in Older Older People

16.1 16.2 16.3 16.4

Introduction Benefit of screening and treating hearing impairment Screening tests Harm of screening

17. Visual Impairment in Older Persons

17.1 Introduction 17.2 Benefit of screening visual impairment and treating common causes of visual impairment 17.3 Screening tests 17.4 Harm of screening 18. Risk of Fall in Older People People

xxii

72 72 73 73 74 78 78 79 80 81 83 83 84 85 85 91 91 92 92 93 95 96 96 97 97 99 99 100 100 100

18.1 Introduction 18.2 Benefit of screening and intervention for fall prevention 18.3 Screening tests

103 103 104 105

18.4 Harm of screening

105

Contents

19. Dementia in Older People

19.1 19.2 19.3 19.4

Introduction Benefit of screening and treating dementia Screening tests Harm of screening

20. Urinary Incontinence in Older People

20.1 Introduction 20.2 Benefit of screening urinary incontinence and treating urinary incontinence 20.3 Screening tests 20.4 Harm of screening

107 107 108 108 109 111 112 112 112 112

Contents

xxiii

SECTION 1

Health Screening Schedule for Adult Male Tests recommended for male

Global CV risk assessment

Cardiovascular (CV) risk

Fr equency low risk 

2- 5

intermediate

6/12 -1year

high

Individualised

Notes

Reference page

Age 18

20

25

30

40

50

60

65

70

75

80

B

B

B

B

B

B

B

years

Smoking or nicotine addiction

Opportunistic

Should be done as part of clinic vital sign recording

 A

A

A

A

A

A

A

A

A

A

A

Hypertension

 Yearly

More frequent for individual with higher CV risk 

 A

A

A

A

A

A

A

A

A

A

A

Diabetes Mellitus

 Yearly

Earlier for individual with DM risk 

 A

A

A

A

A

A

A

A

A

A

A

Dyslipidaemia

 Yearly

 At any age for individual with CV risk 

 A

A

A

A

A

A

A

A

A

A

A

Family history of premature CVD

Once at first presentation

Obesity

2-yearly

B

B

B

B

B

B

B

B

B

B

B

Unhealthy diet

2-yearly

B

B

B

B

B

B

B

B

B

B

B

Physical inactivity

2-yearly

B

B

B

B

B

B

B

B

B

B

B

 A

A

A

A

A

A

 A

A

A

A

A

A

A

average

 Yearly (FOBT)

high

5-yearly (colonoscopy)

Colon cancer

HIV infection  Alcohol misuse Depression

Fall risk assessment

2

B More frequent for individual with higher CV risk  More frequent for individual with higher CV risk  More frequent for individual with higher CV risk 

10 years earlier than the age of first diagnosis of CRC in the family  At any age for high risk individuals

47

70

A

A

A

A

A

A

A

A

A

A

A

Opportunistic

 Among at risk individual

65

B

B

B

B

B

B

B

B

B

B

B

Opportunistic

Screening is appropriate in setting with support for treatment

83

C

C

C

C

C

C

C

C

C

C

C

 Yearly

Among at risk individual

C

C

C

C

C

Opportunistic

104

The alphabet in each cell denotes the grade of recommendation. Colour coding:

Offer to all patients Offer to patients with risk factors

Health screening schedule for adult female

xxv

Health Screening Schedule for Adult Female Tests recommended for female

S co li os is

Global CV risk assessment

Cardiovascular (CV) risk 

Frequency

Notes

Once

Screening is through school based p rog ramm e

l ow r isk

2 -5 y ear s

intermediate

6/12 -1year

high

Individualised

Smoking or nicotine a dd ic ti on

Opportunistic

Hypertensio n

Yearly

Diabetes Mellitus

 Yearly

Earlier for individual w ith DM r isk

Dyslipidaemia

Yearly

 At any age for individual with CV risk

Family history of premature CVD

Once at first presentation

Obesity

2-yearly

Unhealthy diet

2-yearly

Physical inactiv ity

2-yearly

Age

Reference page

12

88

B

Should be done as part of clinic vital signs r eco rd in g More frequent for individual with higher CV risk

18

20

25

30

40

50

60

65

70

75

80

B

B

B

B

B

B

B

 A

A

A

A

A

A

A

A

A

A

A

 A

A

A

 A

A

A

A

A

A

A

A

 A

A

A

A

A

A

A

A

A

A

A

 A

A

A

A

A

A

A

A

A

A

A

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

B

2

Every 3 years (5 -yearly interval for co-testing of cy tol ogy )

Cervical Cancer

Breast cancer

2-yearly

average

 Yearly (FOBT)

high

5-yearly (colonoscopy)

C olon cancer

Osteoporosis (BMD) H IV infection

2-yearly

Opportunistic

Domestic Violence  Alcohol misuse D epression

Fall risk assessment

Opportunistic

Opportunistic

Yearly

B More frequent for individual with higher CV risk More frequent for individual with higher CV risk More frequent for individual with higher CV risk Start screening 3 years after sexually active. Screening can be done up to 70 years old if no prior pap-smear Discuss earlier screening for high-risk group.

10 years earlier than the age of first diagnosis of CRC in the f am il y

A

A

B

B

 A

A

A

A

A

A

A

A

A

A

A

A

C

C

C

C

C

C

A

A

A

A

A

A

47  A

 At any age for high risk i nd iv id ual s

70

A

For pregnant women

77

B

B

B

B

B

B

For at risk individuals

65

B

B

B

B

B

B

83

C

C

C

C

C

C

Offer to patients with risk factors

C

B

21

Screening is appropriate in setting with support for t re at me nt  Among at risk i nd iv id ual s

A

B

Start screening for individual with higher of fragility fracture

Offer to all patients

xxvi Health screening schedule for adult female

A

39

104

The alphabet in each cell denotes the grade of recommendation. Colour coding:

 A

32

A

A

A

A

B

B

B

B

B

B

B

B

B

B

C

C

C

C

C

C

C

C

C

C

Conditions Not Recommended for Health Screening Universal health screening is not recommended for the following conditions – the conditions that do not have sufficient evidence to support screening (Grade I recommendation) or have evidence of harm from screening (Grade D recommendation):

Conditions

Reference page

Grade of recommendation

Thyroid dysfunction

16

I

Osteoporosis in male

21

I

Chronic obstructive pulmonary disease

28

D

Prostate cancer

55

D

Illicit substances

67

I

Hearing loss in older age group

92

I

Visual impairment in older age group

96

I

Dementia in older age group

104

I

Urinary incontinence in older age group

108

I

Note: Older age group is individual ≥ 65 years old The alphabet in each cell denotes the grade of recommendation.

Conditions Not Recommended for Health Screening xxvii

SECTION 2

xxviii

01

Cardiovascular Disease (CVD) Risk Factors: Screening for Adults SUMMARY

CVD is a leading cause of morbidity and mortality in Malaysia and globally. Major modifiable risk factors for CVD include smoking, hypertension, dyslipidaemia, diabetes, obesity and physical inactivity. Treatment of major cardiovascular risk factors reduces CVD mortality. Given the high prevalence of various CVD risk factors in Malaysia, a targetedindividual risk factor screening approach is likely justifiable for adults above 18 years of age. Global CVD risk scoring may be beneficial for individuals aged 40 years and above without prior known CVD risk factors. For individuals aged above 30 years with identified CVD risk factors, a global CVD risk estimation may be helpful in deciding on management strategies and treatment target.

RECOMMENDATIONS

Screening for hypertension, smoking, is indicated for all adults (18 years and above) at all appropriate primary care visits.

Grade A

Screening for overweight and obesity, unhealthy diet and physical inactivity and family history of premature CVD is indicated for all adults (18 years and above) at all appropriate primary care visits.

Grade B

Early screening (18 years and above) for diabetes mellitus and dyslipidaemia is indicated for high risk individuals.

Grade A

Framingham Risk Score (10-Year General Cardiovascular Risk Model) is indicated for all adults above 40 years old or with prior known CVD risk as a guide to identify high-risk individuals for more comprehensive measures.

Grade B

Regular assessment of cardiovascular risk factors is required for asymptomatic adults based on their initial risk classification.

Grade C

Generally, cardiovascular risk screening using new biomarkers is not indicated.

Grade D

CVD risk factors: Screening for adults

1

1.1

Introduction

Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels (1). In the context of this consensus guide, CVD refers to coronary heart disease, cerebrovascular disease and peripheral artery disease where atherosclerosis is the main underlying pathological process (2). CVD is a leading cause of morbidity and mortality worldwide (2-4). In Malaysia, 24.4% of deaths in government hospitals were attributed to CVD (5). In terms of the number of years of life lost due to premature death in Malaysia, coronary heart disease and cerebrovascular disease were the highest in the ranking of causes in 2010. Moreover, both disease burdens, as measured by disability-adjusted life years (DALYs), have increased by 85% and 39%, respectively, compared to 1990 statistics (6). Cardiovascular risk factors (CVRFs) are biomedical, behavioural and genetic conditions that promote the process of atherosclerosis and lead to a greater risk of CVD. The likelihood of CVD developing and manifesting over a certain period will be based on the presence, intensity and interplay among the multiple risk factors (7, 8).  The recognized CVD risk factors are listed in Table 1 (2, 9-13)

Level II-2, III:

Table 1: Recognized CVD Risk Factors Modifiable risk factors

• • • • • • • • •

Smoking (tobacco use) a Physical inactivity a Raised blood pressure (hypertension) a Raised blood glucose (diabetes) a Raised blood lipids (dyslipidaemia) a Overweight and obesity (central obesity and high body mass index) a Unhealthy diet (high salt, fat and calorie intake; low fibre intake) Harmful use of alcohol Psychosocial factors (stress, depression, poverty and low educational status)

Non-modifiable risk factors

• • •

Advancing age a,b Male gender Inherited (genetic) predisposition (ethnicity, family history of premature CVD c and familial hypercholesterolaemia) a

a  Considered as major CVD risk factors; play a key role in the aetiology of atherosclerosis  b  >55 years for men, >65 years for women  c  < 55 years for men, <65 years for women 

 According to the annual report of the Acute Coronary Syndrome (ACS) Registry 2010, a fiveyear national cardiovascular database (2006-2010), 90% of patients with ACS had at least 2

Introduction

one established CVRF. BMI > 23 kg/m2 (overweight and obesity) was the most prevalent modifiable CVRF (75%), followed by hypertension (61%), diabetes (43%), smoking (33%) and hypercholesterolaemia (33%) (14). In the National Health and Morbidity Survey 2011 report, the most prevalent modifiable CVRF among adults of 18 years and above in Malaysia is unhealthy diet (inadequate fibre intake, 92.5%), followed by overweight and obesity (60.5%), physical inactivity (35.7%), hypercholesterolaemia (35.1%), hypertension (32.7%), smoking (25%) and diabetes (15.2%).  The survey also highlighted the high proportion of adults with undiagnosed CVRFs, namely, hypercholesterolaemia (26.6%), hypertension (19.8%) and diabetes (8%) (15). Given the high proportion of undiagnosed CVRFs, screening and management of these risk factors potentially can reduce cardiovascular morbidity and mortality in Malaysia.

1.2

Benefits of screening and treating cvd risk factors

 Treating major CVD risk factors has been proven to reduce cardiovascular mortality (1618). Interventions, such as blood pressure lowering, glucose lowering, lipid lowering, weight reduction, smoking cessation, dietary modification, and increasing physical activities, are effective measures to treat individuals diagnosed with known CVRFs (9-11, 19-29). On the other hand, evidence showing the benefits of screening is less established. A Cochrane Review by Krogsbøll LT et al. (2012) did not find a beneficial effect of CVD risk factor screening on CVD mortality (RR 1.03, 95% CI 0.91-1.17)(30) level I. However, the trials included in the review were old with different treatment strategies recommended compared to the present. A large good quality retrospective cohort study from Korea using national representative samples demonstrated the benefit of cardiovascular screening in reducing cardiovascular mortality and overall mortality (RR 0.58, 95% CI 0.53-0.63, RR 0.63, 95% CI 0.60-0.64 respectively) (31) Level II. In a local study modelling Malaysian NHMS 2006 data, which used the Framingham Risk Score (FRS) in its analysis, targeted screening at older ages was shown to be more cost effective than universal screening. Coverage for the highrisk population was estimated to be higher than 99%, even if screening started at 40 years of age compared to universal screening of all age groups (32) Level III. Since there is a multiplicative effect of CVD risk when clustering various CVRFs on CVD mortality and morbidity, a standardized tool to assess global CVD risk is advocated to help clinicians to individualise CVRF management (33-35). However, evidence of its benefit in screening is weak because the advantage of this total CVD risk approach compared to an ad hoc single risk factor approach has not been assessed by a randomized controlled trial (36).

Benefits of screening and treating CVD risk factors

3

 Although several risk prediction algorithms have been developed and validated for clinical use, FRS is the most widely used assessment tool for the purpose of total CVD risk estimation (37) Level II-2. In fact, it has been incorporated into local clinical practice guidelines to manage hypertension and hypercholesterolaemia (9, 10). However, the FRS-prediction model was not validated nor recalibrated for the local population prior to its adoption into clinical practice (38, 39). In individuals with certain clustering of CVRFs (e.g., age, ethnicity, gender, family history of premature CVD, familial hypercholesterolemia, etc.), FRS often over- or underestimates the global cardiovascular risk of different risk groups from various origins and regions (40-44) Level II-2 . For this reason, FRS should be applied as a guide tool to identify those adults who are asymptomatic but at high risk for CVD and require a more comprehensive intervention (45). Global risk scoring per se does not translate to better clinical outcomes unless it is used appropriately by health care providers with effective communication so that individuals fully understand the global CVD risks and are able to make sustainable lifestyle changes (46, 47). Given the high prevalence of various CVRFs in Malaysia, a targeted-individual based screening approach is likely justifiable. Global CVD risk scoring may be beneficial for individuals 40 years old and above without prior known CVRFs. However, individual CVRF screening is recommended as the benefits of identifying risk factors at a younger age have been shown in many major reviews. Once a CVRF is detected in the individual, a global CVD risk estimation may be helpful for adults over 30 years old* for decisions on management strategies and treatment target. * In the Framingham Heart Study, the studied population of interest was adults aged 30 -74  years old without CVD at baseline enrolment (48-50). Therefore, FRS is not applicable for those under 30 years old in terms of global CVD risk assessment.

1.3

Screening Tools & Tests

 According to the Framingham Study Group, the FRS has been recalibrated and validated for use as a general CVD risk assessment tool (37) rather than coronary heart disease (CHD) risk. This FRS risk prediction function is recommended as the basis for FRS because it performed better than the previously used Framingham CHD risk prediction in predicting CVD risk. Based on the FRS assessment, each individual’s total CVD risk is stratified as low (< 10%), intermediate (10 - 20%), or high (> 20%) for a CVD event over a 10-year period. To encourage the use of FRS in primary care practice, the main prediction model has been simplified by using only clinic-based predictors that do not require laboratory testing. These variables include age, gender, body mass index (replacing lipids), systolic blood pressure, anti-hypertensive medication use, current smoking and diabetes status (50).  The recommendations for global CVD risk assessment and individual CVRF screening are summarized in Table 2 and Table 3.

4

Screening Tools & Tests

In addition to conventional risk factors, the use of newer blood and urine biomarkers (high-sensitivity C-reactive protein, apolipoprotein B, fibrinogen, homocysteine, estimated glomerular filtration rate, uric acid, microalbuminuria, and genetic biomarkers) has shown only marginal benefit in predicting cardiovascular outcomes. None of these markers has been evaluated as a screening test in randomized controlled trials with clinical events as outcomes (51-55). Thus, the following screening assessments are not recommended for re-stratification of general CVD risk: i. ii. iii.

Uric acid (56) Level III, Grade D Genomic Testing (35, 53) Level III, Grade D Lipoprotein Apo B (35, 54) Level III, Grade D

Whereas, the following screening assessments are not recommended for re-stratification of general CVD risk for low or high-risk sub-groups. But, there is insufficient evidence for or against the use of these screening tests for the intermediate risk sub-group. They might be useful for revision or re-classification of CVD risk for therapeutic intervention: i. ii.

HS-C-Reactive Protein (35, 51, 54) Homocysteine (54) Level II-2, Grade I

iii.

Haemoglobin A1C (35)

Level II-2, Grade I

Level II-2, Grade I

Microalbuminuria (urine albumin excretion of 30 - 300 mg/24 hour or urine protein: creatinine ratio of 15-44 mg/mmol/L) might be useful in further risk-stratifying individuals with intermediate risk or there is a coexistence of CVRFs of hypertension, diabetes mellitus or hypercholesterolaemia (35, 54) Level II-2. Generally, these new biomarkers are not necessary in the initial assessment of CVD risk.

Screening Tools & Tests

5

  :    )    d    l   o   s   r   a   e   y    8    1    ≥    d   e   g    A    (   s    t    l   u    d    A   c    i    t   a   m   o    t   p   m   y   s    A    f   o    t   n   e   m   s   s   e   s   s    A   s    F    R    V    C   r   o    f   n   o    i    t   a    d   n   e   m   m   o   c   e    R

   n    o     i    t    c    n    u     f    n    o     i    t    c     i    d    e    r    p    k    s     i    r    h    t     i    w    t    n    e    m    s    s    e    s    s    a    k    s     i    r    D    V     C    l    a    b    o    l     G    :    2    e    l    b    a    T

   e    c    n    e    r    e     f    e    R

   )    7    5  ,    9    2  ,    2    1    (

   e    n    c    o     i    n    e    f    t    d    o    a    d     i    v    e    n    E    d    e     f    a    m    o    r    l     G    m    e    o    v    c    e    e    r    L

   I    I    I    l    e    v    e    L

   l    a    v    r    e    t    n    I

   e    c    n    e    r    e     f    e    R    n    o     i    t    e     f     f    c    o    a    d    o    n    l    e    e    n    e    d    d    e    v    i    a    m    e    v    r    L    E    G    m    o    c    e    r

   s    l    o    o    T

   e    g    A    )    s    g    r    n    a     i    e    n    Y    e    (    e    r    c     S

   l    d    e    e    d    d    o    n    M    e    n    m    o     i    m   t    c    o    i    c    d    e    e    R    r    P

   o    N

6 6  Table 2

    C    e    d    a    r     G

   5      2    :    k    s    i    r    D    V     C    s    r    w   a    o    e    L    y

   1    D    o    V    t     C    s    t    e    h    t    a    n    o    i    d    m    e    6    m    r    :    r    e    a    t    k    s    e    n    I    i    r    y

   l    a    c    i    n    i    l    :    k    d    c    s    e    o    i    t    r    z    i    l    D    a    g    i    t    V    u    n    d    x     C    d    i    r    e    v    o    t    h    i    n    g    d    c    i    c    o    H    n    I    a    c

   )    8    3  ,    7    3    (

   2      I    I    l    e    v    e L

   B    e    d    a    r     G

   r    o    I    d    i    p    i    M    l    B    g    g    n    i    n    i    s    s    u    u     S    S    R    R    F    F    n    w    o    n    k    r    o    i    r    p    h    t    i    w   s  ,    0    F    3    R    V    ≥    C

   )    1    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R (

   r    o    i    r    p    t    s    u    F    o    R    h    V    t    i     C    w  ,    n    0    w    4    o    n    ≥    k

   l    d    )    a    l    e    g    r    t    s    e    e    n    a    d    d    i    i    r    n    e    p    o    l    l    i    r    o    e    t    l    m    o    c    G    n    r    o    r    g    d     S    r    e    u   d    t    e    n    o    i    e    k    a    s    t    d    e    o    s    c    fi    s    l    e    i    Y    n    l    e    l    a    i    l    a    B    R      o    e   h   o    l    g   s    p    p    r    r    n    c    e    d    h    e    i    t    e   l    u   c   c    r    m    m   0    i    e   i    (    s    e   t    o    s    l    a    1    d   k    s    a   L    I    a    o    b   a   t    h    r    :    n    e    t    s    k    e    a   r    e   y    r    o   D   M    g    o    s    g   e   m   i    i    n    i     f     S   D   T    S   P   T   H   B    n    i    )    r    A    G     S    D  .  .  .    m  .  .  .  .    i  .    i    a    i    R    i    i    i    i    i    i    i    v    v    r    F    V    i    v    i    v    i    F    (     C    v

 .    1

  g   n    i   n   e   e   r   c   s    F    R    V    C    l   a   u    d    i   v    i    d   n    I   :    3   e    l    b   a    T

   e    c    n    e    r    e     f    e    R

   )    0    6  ,    7    5  ,    9    (

   )    7    5  ,    4    3    (

   e    n    c    o    n    f     i    t    e    o    a    d    d     i    n    v    e    e    E    d    a     f    r    m    o    G    m    l    o    e    c    v    e    e    r    L

   I    I    I    l    e    v    e    L

    C    e    d    a    r     G

   I    I    I    l    e    v    e    L

    f    i    D    V    D    s    V    &    r     C    y     C    a     C    i    d    e    n    r     f    y    a    o    W    y    e    t    l    l    l    s    2    t    u    c    a    a    a    a    y     f    o    u    r    e    r    h    m    r    k    n    k    e    t    s    n    c    s    o    v    i    i    n    i    n    :    E    w    r    A    i    r    I    r    M    o    F    B    •    •

   l    a    v    r    e    t    n    I

   e    c    n    e    r    e     f    e    R

   )    9    5      7    5  ,    4    3    (

   y    t    i    s    e    s    i    b    e    o    r    r    e    o    h    t     f    i    t    y    l    h    g    h    t    i    n    e    o    w    r    m   e    v    6    o

   D    V     C    h    g    i    h     f    e    r    i    o    y    l    m   t    n    k    e    c    u    e    q    k    e    s    h    r C    f    i    r

   B    e    d    a    r     G

   P    P    B    B    c    l    c    i    i    l    o    t    o    t    s    a    s    i    y    d    s    g     f    H    i    d    n    y    a    m    l    l    a    0    m    u    3    5    n    1    8    n    A    <   <

    f    i    9      s    3    5    h    t    1      n    0    8    P    o    B    m   3    1    c    i    6    l    o    g   -    P    B    t    H    3    c    s    a    m    i    i    l    n    i    o    d    m    h    t    t    s    d    i    y    n    9    W   s    a    8

   D    V     C    h    g    i    h     f    e    r    i    o    y    l    m   t    n    k    e    c    u    e    q    k    h    r    e    i    s     C    f    r

   )    0    6  ,    7    5  ,    9    (

  n

   o     i    t     f    e    f    a    o    c    o    d    l    n    e    n    e    e    d    e    v    i    d    e    v    a    r    m    L    E    G    m    o    c    e    r

   s    d    o    h    t    e    m     /    s    l    o    o    T

   )    r    a    e    Y    (    e    g    A    g    n     i    n    e    e    r    c     S

   2      I    I    l    e    v    e    L

   B    e    d    a    r     G

   I    I    I    l    e    v    e    L

   d    )    e    s     C   s    e    W    (    s    s    e    a    c    e    n    b    e    r    d    e    l     f    u    m   o    u    h    s    c    r    i    I    c    M    t    B    s    i    d    a    n    W   a

   8    1    ≥    s    t    l    u    d    a    l    l    A

   A    e    d    a    r     G

   s    e    c    i    v    e    d    g    n    i    w    o    l    :    l    o    d     f    e    e    s    h    t    u     f    e    o    b    y    n    n    a    A    c

   )    e    t    s    t    a    i    i    i    r    s    p    v    o    e    r    r    p    a    p    c    a    y    l    l    r    a    a    m    t    i    a    r    (    p

   8    1    ≥    s    t    l    u    d    a    l    l    A

   s    P    e    c    i    B    v    y    r    r    r    e    d    o    e    e    t    t    c    t    l    e    e    i    a    u    n   m   )    m   n    b    o    r    o    o    d    m   n   r    t    m    n    u   a    a    c    l    a    e    a    o   m   d    m   l    c   o    n    e    d    e    a    y    t    d   o    d    t    r    a   s    m    m    s    i    e    u   g    g    fi    o    m   e    c    c    d    i    r    y    y    l    r    h   o    e   h    r    t    t    o   i    v    e   p    n   p    e    u   e     G    m   s    (    a   s    c    a   d    •

   •

   •   •

   )    s    t    e    t    i    a    s    i    i    r    v    p    e    o    r    r    p    a    p    c    a    y    r    l    l    a    a    m    t    i    r    a (    p

   2

   k    s     i    r    r    a    l    s    u   r    c   o    s    t    a   c    a    v    f    o     i    d    r    a     C

   o    N

   s    e    l    s    2    a    e    m   l    a    m     /    n   m    g    i    e    k     f    m   n    5  .    c    i    7   0    2   9   m    c    ≥    :    I    ≥   0    y     C   8    t    i    M    s    B   W   &    e    b     O    •   •  .    1

   m     /    g    k    5  .    7    2    <    o    t    :    t    3    h    2    g    I    i    e    M    w    r    B    e    v     O    •

   n    o    i    s    n    e    t    r    e    p    y    H

   g    H    m    m    0    9     /    0    4    1    ≥    P    B

 .    2

 Table 3

7 7

   e    c    n    e    r    e     f    e    R

   )    0    1    (

   e    n    c    o     i    n    e    f    t    d    o    a    d     i    v    e    n    E    d    e     f    a    m    o    r    l     G   m    e    o    v    c    e    e    r    L

   I    I    I    l    e    v    e    L

   B    e    d    a    r     G

   I    I    I    l    e    v    e    L

   e    c    n    e    r    e     f    e    R

   B    e    d    a    r     G

   s    r    o    o    t    n    c    a     f     f    i    k    s    r    s    i    a    r    e    s    y    e    t    3    e   -    b    a    1    i    d

   d    i    p    l    i    l    a    e    m    h    t    r    o     f    i    n    y    l    s    i    l    a    l    e    u    fi    n    o    n    r    A    p

   l    a    v    r    e    t    n    I

   )    2    6  ,    1    6  ,    7    5    (

 ,    4    3  ,    )    2    7    2    5  ,    1    1    (

   )    4    3  ,    0    1    (

   I    I    I    l    e    v    e    L

   s    r    h    o    t    t    i    w   c    a    t     f    n    k    e    s    u    i    q    r    e    r    s    e     f    t    e    e    r    b    o    a    i    M   d

   B    e    d    a    r     G

   n    o    i    t    a    t    n    e    s    e    r    p    t    s    r     fi    t    A

   )    3    6      1    6  ,    7    5    (

   )    2    2  ,    1    1    (

  n

   o     i    t    e     f     f    c    o    a    d    o    n    l    e    e    n    e    d    d    e    v    i    a    m    e    v    r    L    E    G    m    o    c    e    r

   s    d    o    h    t    e    m     /    s    l    o    o    T

   )    r    a    e    Y    (    e    g    A    g    n     i    n    e    e    r    c     S

   k    s     i    r    r    a    l    s    u   r    c   o    s    t    a   c    a    v    f    o     i    d    r    a     C

   o    N

8 8  Table 3

   I    I    I    l    e    v    e    L

   A    e    d    a    r     G

   e    l    )     fi    G    o    r    T    p    d    n    d    i    a    p    i    l     C      g    L    n    i    D    t    s    H    a  ,     f     C      e    t    L    e    l    D    p    L  ,    m    C    o    T     C    (

   I    I    I    l    e    v    e    L

   g    n    i    t    s    e    a    s     f    o  ,    c    e    u    s    l    o    g    c    l    u    a    r    l    g    o  ,    d    e    o    s    o    o    l    b    c    u    l    m   g    o    d    d    n    o    o    a    l    R    b

   )    3    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R    (

   n    w    o    n  ,    )    k    T    t    y    r    P    i    o    i    H    s    e    r    p  ,  .    b    o    g    h  .  ,    t    i    e    (    s    w   s    e    t  ,    e    8    F    b    R    1    V    i    a    ≥    C    D

   r    o    n    t    w   c    a    o    f    n    k    k    s    r    h    i    t    i    s    w   t    e  ,    8    e    b    1    i    a    ≥    d

   r    o    i    r    p    t    s    u    F    o    R    h    V    t    i     C    w  ,    n    0    w    4    o    n    ≥    k

   s    u    t    i    l    l    e    M    s    e    t    e    b    a    i    D

   a    i    m    e    a    d    i    p    i    l    s    y    D

 .    7

   A    e    d    a    r     G

 .    8

    C    1

   A    b    H    r    o    t    s    e    t    e    c    n    a    r    e    l    o    t

   I    I    I    l    e    v    e    L

   K    U     f    d    o    e     fi    i    a    y    i    t    i    d    r    l    e    i    o    t    b    M   i    r    a    b    g    c    o    e    n    i    r    p    s    m    u    o    e    o    h    r    t    H    F    B    s    g    n    s    n    e    i    o    s    v    m    s    a    i    A    h    S

   )    5    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R    (

   x    i    d    n    e    p    p    a    o    t    r    e    )     f    e    4    V    R    (     C

   B    e    d    a    r     G

   k    s    i    r

   n    s    w   r    o    o    t    n    c    k    f    a    t    u    k    o    s    i    h    r    t    i    s    w   t    e  ,    0    e    b    3    a    i    ≥    d

   n    w    o    n    k    h    t    i    w   s  ,    r    8    o    t    1    c    a    ≥    f

   )    H    F    (    a    i    m    e    l    o    r    e    t    s    e    l    o    l    h    a    i    c    l    i    r    e    m   p    a    y    F    H

 .    L    1    l    1    L    /     /    l    o    1    o    m   ≥    m   m   T    m   1    T  .     G    0  .    1    O    7    1    r    L     /    l    ≥    ≥    u    o    o     G    G    H    m    B    B      F    R    2    m

 .    9

   )    7    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R    (

   x    i    d    n    e    p    p    A    o    t    r    e    )     f    e    6    V    R    (     C

   t    o    n    y    l    l    a    r    e    n    g    e    n    g    i    n    s    i    e    g    e    r    n    c    i    t    s    s    r    e    o    t     f    c    d    i    t    e    e    d    n    e    e    e     G    n

   e    c    n    e    r    e     f    e    R

   )    0    1    (

   e    n    c    o     i    n    e    f    t    d    o    a    d     i    v    e    n    E    d    e     f    a    m    o    r    l     G    m    e    o    v    c    e    e    r    L

   I    I    I    l    e    v    e    L

   B    e    d    a    r     G

   I    I    I    l    e    v    e    L

   e    c    n    e    r    e     f    e    R

   B    e    d    a    r     G

   s    r    o    o    t    c    n    a     f    i     f    k    s    s    r    i    a    r    e    s    y    e    t    3    e   -    b    a    i    1    d

   d    i    p    l    i    l    a    e    m    h    r    t    o     f    i    n    y    l    s    i    l    a    e    l    u    fi    n    o    n    r    A    p

   l    a    v    r    e    t    n    I

   )    2    6  ,    1    6  ,    7    5    (

 ,    4    3  ,    )    2    7    2    5  ,    1    1    (

   )    4    3  ,    0    1    (

   I    I    I    l    e    v    e    L

   s    r    h    o    t    i    t    c    w   a    t     f    n    k    e    s    i    u    r    q    s    e    r    e     f    t    e    e    r    b    o    a    i    M   d

   B    e    d    a    r     G

   n    o    i    t    a    t    n    e    s    e    r    p    t    s    r     fi    t    A

   )    3    6      1    6  ,    7    5    (

   )    2    2  ,    1    1    (

  n

   o     i    t    e     f     f    c    o    a    d    o    n    l    e    e    n    e    d    d    e    v    i    a    m    e    v    r    L    E    G    m    o    c    e    r

   s    d    o    h    t    e    m     /    s    l    o    o    T

   )    r    a    e    Y    (    e    g    A    g    n     i    n    e    e    r    c     S

   k    s     i    r    r    a    l    s    u   r    c   o    s    t    a   c    a    v    f    o     i    d    r    a     C

   o    N

   I    I    I    l    e    v    e    L

   A    e    d    a    r     G

   e    l    )     fi    G    o    r    T    p    d    n    d    i    a    p    i    l     C      g    L    n    i    D    t    s    H    a  ,     f     C      e    L    t    e    l    D    p    L    m  ,    o    C     C    T    (

   I    I    I    l    e    v    e    L

   g    n    i    t    s    e    a    s     f    o  ,    c    e    u    l    s    g    o    l    c    a    u    l    r    g    o  ,    d    e    o    s    o    l    o    b    c    u    l    m   g    o    d    d    n    o    a    o    l    R    b

   )    3    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R    (

   n    w    o    n  ,    )    k    T    t    y    r    P    i    s    o    i    H    e    r    p  ,  .    b    o    h    g  .  ,    t    i    e    s    (    e    w   s    t  ,    F    e    8    R    b    1    V    a    i    ≥    C    D

   r    o    n    t    c    w   a    o    f    n    k    k    s    i    h    r    t    i    s    w   t    e  ,    8    e    b    1    a    i    ≥    d

   r    o    i    r    p    t    s    u    F    o    R    h    V    t    i     C    w  ,    n    0    w    4    o    n    ≥    k

   s    u    t    i    l    l    e    M    s    e    t    e    b    a    i    D

   a    i    m    e    a    d    i    p    i    l    s    y    D

 .    7

   A    e    d    a    r     G

 .    8

    C    1

   A    b    H    r    o    t    s    e    t    e    c    n    a    r    e    l    o    t

   I    I    I    l    e    v    e    L

   K    U     f    d    o    e     fi    i    a    y    i    t    d    r    i    l    e    i    o    t    i    b    M   r    a    b    g    c    o    i    e    r    n    p    s    m    u    o    e    h    H    o    r    t    F    B    s    g    n    s    e    n    i    o    s    v    m    s    a    i    A    h    S

   )    5    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R    (

   x    i    d    n    e    p    p    a    o    t    r    e    )     f    e    4    V    R    (     C

   B    e    d    a    r     G

   k    s    i    r    n    w    o    n    k    h    t    i    w   s  ,    r    o    8    t    1    c    a    ≥    f

   n    s    r    w   o    o    t    n    c    k    a    t     f    u    k    o    s    i    h    r    t    i    s    w   t    e  ,    0    e    b    3    a    i    ≥    d

   )    7    V     C    x    i    d    n    e    p    p    A    o    t    r    e     f    e    R    (

   t    o    n    y    l    l    a    r    e    n    e    g    i    g    n    n    s    i    e    g    e    r    c    n    i    s    t    s    r    e    o    t     f    c    d    i    t    e    e    d    n    e    e    e     G    n

   x    i    d    n    e    p    p    A    o    t    r    e    )     f    e    6    V    R    (     C

   )    H    F    (    a    i    m    e    l    o    r    e    t    s    e    l    o    l    h    a    c    i    r    l    i    e    m   p    a    y    F    H

 .    L    1    l    1    L    /     /    l    o    1    o    m   ≥    m   m   T    m   1    T  .     G    0  .    1    O    7    1    r    L    u    /    l    ≥    ≥    o    o     G    G    H    m    B    B      F    R    2    m

 .    9

 Table  T able 3

9 9

1.4

Harm of CVRFs assessment

No systematic review or meta-analysis has been done to evaluate the evidence on clinically important harms associated directly with the screening of CVFRs: false positives, false negatives, psychological effects and socioeconomic impact. An examination of potential harms resulting from pharmacotherapy for hypertension, diabetes mellitus, hypercholesterolaemia, hypercholesterolaemia, smoking cessation and obesity was outside the scope of this screening guideline review.  Although there are no local studies of asymptomatic adults’ values and preferences preferences regarding CVRFs screening, it can be inferred from undertaking the population-based National Health and Morbidity Survey every 10 years, which used similar CVR assessment tools, that the recommended recommended screening tools for common CVRFs are acceptable to the general public.

REFERENCES 1.

2.

3. 4.

5. 6.

7.

8.

9.

10

World Health Organisation. Organisation . Cardiovascular Cardiovascu lar diseases (CVDs). [updated January January 2015; assessed assessed 10th April April 2015]. Available from: http://www.who.int/mediacentre/  factsheets/fs317/en/#. Mendis S, Puska P, P, Norrving Norrvi ng B. Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: WHO, 2011. World Health Organisation. Organisation . Global status report on noncommunicable diseases 2014. Geneva: WHO; 2014. Roth GA, Forouzanfar MH, Moran AE, Barber R, Nguyen G, Feigin VL, et al. Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med 2015;372(14):1333-41. Health Informatics Informatic s Centre, Ministry Ministr y of Health (MOH). Health Facts 2014. Putrajaya, Malaysia; 2014. Institute Institut e for Health Metrics and Evaluation. Evaluation . Country Profile: Malaysia (Global Burden of Disease Study 2010). [updated 5th March 2013; assessed 16th April 2015]. Available from: http://www.healthdata.org/s http://www.healthdata.org/sites/default/  ites/default/  files/files/country_profiles/G files/files/country_profiles/GBD/ihme_gbd BD/ihme_gbd_country_ _country_ report_malaysia.pdf. Raitakari OT, OT, Juonala M, Ronnemaa T, KeltikangasKeltikanga sJarvinen L, Rasanen L, Pietikainen M, et al. Cohort profile: the cardiovascular risk in Young Finns Study. Int J Epidemiol 2008;37(6):1220-6. World Health Organisation. Organisation . Global health risks: Mortality and burden of disease attributable to selected major risks. Geneva: WHO; 2009. Malaysian Society of Hypertension, Hypertensi on, Academy of Medicine Malaysia. Clinical Practice Guidelines: Management

Harm of CVRFs assessment

10.

11.

12.

13. 14.

15.

16.

of Hypertension. 4th ed. Putrajaya: Ministry of Health Malaysia; 2013. National Heart Association of Malaysia, Academy of Medicine Malaysia. Clinical Practice Guidelines: Management of Dyslipidaemia. 4th ed. Putrajaya: Ministry of Health Malaysia; 2011. Malaysian Endocrine & Metabolic Society, Malaysian Association of Diabetes, Academy of Medicine Malaysia. Clinical Practice Guidelines: Management of Type 2 Diabetes Mellitus. 4th ed. Putrajaya: Ministry of Health Malaysia; 2009. National Vascular Disease Prevention Alliance. Guidelines for the assessment of absolute cardiovascular disease risk. Melbourne: National Heart Foundation of Australia; 2009. Scottish Intercollegiate Guidelines Network. Risk estimation and the prevention of cardiovascular disease: A national clinical guideline. Edinburgh: SIGN; 2007. Wan Ahmad WA, Sim KH. Annual report of the Acute Coronary Syndrome (ACS) Registry 2009 and 2010 (Malaysia: National Cardiovascular Disease Database). Kuala Lumpur: National Heart Association of Malaysia and Ministry of Health Malaysia; 2013. Institute Institut e for Public Health. National Health and Morbidity Survey (Interim) 2011 (NHMS 2011). Vol. II: NonCommunicable Diseases. Kuala Lumpur: Ministry of Health Malaysia; 2011. Non-communicable Diseases and Mental Health. Integrated management of cardiovascular risk: Report of a WHO Meeting, Geneva, 9-12 July 2002. Geneva:

17. 18.

19. 20.

21.

22. 23.

24.

25.

26.

27.

World Health Organisation; 2002. Erhardt L, Moller R, Puig JG. Comprehensive cardiovascular risk management--what does it mean in practice? Vasc Health Risk Manag 2007;3(5):587-603. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009;338:1665. World Health Organisation. Organisation . Prevention of cardiovascular cardiovascu lar disease: Guidelines for assessment and management of cardiovascular risk. Geneva: WHO; 2007. National Coordinating Committee on Food and Nutrition, Nutriti on, Ministry of Health. Malaysian Dietary Guidelines [Internet]. 1st ed. Malaysia;2010 [cited 5 May 2015]. Available from: http://dg.cnsoc.org/upload/  affix/20140818104029708.pdf International Internati onal Diabetes Federation. Clinical Guidelines Task Force Global Guideline for Type 2 Diabetes [Internet]. 1st ed. Belgium;2012 [cited 5 May 2015]. Available from: http://www.idf.org/sites/default/files/  IDF%20T2DM%20Guideline.pdf American Diabetes Association. Standards of medical care in diabetes-2015 abridged for primary care providers. Clin Diabetes 2015;33(2):97-111. Mancia G, Fagard R, Narkiewicz Narkiewic z K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013;34(28):2159-219. James PA, PA, Oparil S, Carter BL, Cushman WC, DennisonHimmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311(5):507-20. Cleeman JI. Executive Executive summary summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001;285(19):2486-97. Stone NJ, Robinson JG, Lichtenstein Lichtenstei n AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1-45. Ammerman AS, Lindquist CH, Lohr KN, Hersey J. The efficacy of behavioral interventions to modify dietary fat and fruit and vegetable intake: a review of the evidence. Prev Med 2002;35(1):25-41.

28. Tamakoshi A, Tamakoshi K, Lin Y, Yagyu Yagyu K, Kikuchi S, Group JS. Healthy lifestyle and preventable death: findings from the Japan Collaborative Cohort (JACC) Study. Prev Med 2009;48(5):486-92. 29. National Vascular Vasc ular Disease D isease Prevention P revention Alliance A lliance (NVDPA). Guidelines for the management of absolute cardiovascular disease risk [Internet]. 1st ed. Australia; 2012 [cited 5 May 2015]. Available from: http://  strokefoundation.com.au/site/media/AbsoluteCVD_GL_ webready.pdf 30. Krogsbøll LT LT, Jørgensen KJ, Grønhøj Larsen C, Gøtzsche PC. General health checks in adults for reducing morbidity and mortality from disease. Cochrane Database Syst Rev 2012:Issue 10. 31. Lee H, Cho J, Shin D, Lee S, Hwang S, Oh J et al. Association of cardiovascular health screening with mortality, clinical outcomes, and health care cost: A nationwide cohort study. Prev Med 2015;70:19-25. 32. Sharmini S, Jamaiyah H, Gurpreet K, Gurpreet K, Tee GH, Mohd Adam B, Kee CC, Bots ML. Identification of effective screening strategies for cardiovascular disease prevention in a developing country: using cardiovascular risk-estimation and risk-reduction tools for policy recommendations. BMC Cardiovasc Disord 2013;13:10,2261-13-10Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study. Circulation 2002;105(3):310-5. 33. Goh LG, Chua Chu a T,T, Kang V, V, Kwong KH, Lim WY, Low LP, LP, et al. Ministry of health clinical practice guidelines: screening of cardiovascular disease and risk factors. Singapore Med J 2011;52(3):220-7. 34. Greenland P, P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2010;122(25):2748-64. 35. Cooney MT, Dudina A, D’Agostino R, Graham IM. Cardiovascular risk-estimation systems in primary prevention: do they differ? Do they make a difference? Can we see the future? Circulation 2010;122(3):30010. 36. D’Agostino D’Agostin o RB, Sr., Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 2008;117(6):743-53. 37. D’Agostino D’Agostin o RB, Sr., Sr., Grundy S, Sullivan LM, Wilson P, P, Group CHDRP. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups’ investigation. JAMA 2001;286(2):180-7. 38. Selvarajah S, Kaur G, Haniff J, Cheong KC, Hiong TG,

References

11

REFERENCES

39.

40. 41.

42.

43.

44.

45. 46.

47. 48.

49.

50.

12

van der Graaf Y, et al. Comparison of the Framingham Risk Score, SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population. Int J Cardiol 2014;176(1):211-8. Bastuji-Garin S, Deverly A, Moyse D, Castaigne A, Mancia G, de Leeuw PW, et al. The Framingham prediction rule is not valid in a European population of treated hypertensive patients. J Hypertens 2002;20(10):197380. Pyörälä K. Cardiovascular risk prediction systems have to be adapted and updated to current national conditions. Eur J Cardiovasc Prev Rehabil 2006;13(5):674-5. Liu J, Hong Y, D’Agostino RB, Sr., Wu Z, Wang W, Sun J, et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study. JAMA 2004;291(21):2591-9. Koller MT, Steyerberg EW, Wolbers M, Stijnen T, Bucher HC, Hunink MG, et al. Validity of the Framingham point scores in the elderly: results from the Rotterdam study. Am Heart J 2007;154(1):87-93. Rodondi N, Locatelli I, Aujesky D, Butler J, Vittinghoff E, Simonsick E, et al. Framingham risk score and alternatives for prediction of coronary heart disease in older adults. PloS one 2012;7(3):e34287. Chia YC. Review of tools of cardiovascular disease risk stratification: interpretation, customisation and application in clinical practice. Singapore Med J 2011; 52(2):116-23. Beswick A, Brindle P. Risk scoring in the assessment of cardiovascular risk. Curr Opin Lipidol 2006;17(4):37586. Brindle P, Beswick A, Fahey T, Ebrahim S. Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review. Heart 2006;92(12):1752-9. Dawber TR, Meadors GF, Moore FE, Jr. Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 1951;41(3):279-81. Kannel WB, Feinleib M, McNamara PM, Garrison RJ, Castelli WP. An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol 1979;110(3):281-90. Framingham Heart Study Group. Cardiovascular Disease Risk Function (10-Year Risk): Risk Score Calculators. 2008 [assessed 16th April 2015]. Available from: https://www.framinghamheartstudy.org/risk-functions/  cardiovascular-disease/10-year-risk.php. Goff DC, Jr., Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S49-73.

References

51. De Backer G, Graham I, Cooney MT. Do novel biomarkers add to existing scores of total cardiovascular risk? Eur J Prev Cardiol 2012;19(2 Suppl):14-7. 52. Palomaki GE, Melillo S, Neveux L, Douglas MP, Dotson WD, Janssens AC, et al. Use of genomic profiling to assess risk for cardiovascular disease and identify individualized prevention strategies--a targeted evidence-based review. Genet Med 2010;12(12):77284. 53. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren WM, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012): the Fifth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Prev Cardiol 2012;19(4):585667. 54. Hlatky MA, Greenland P, Arnett DK, Ballantyne CM, Criqui MH, Elkind MS, et al. Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation 2009;119(17):2408-16. 55. Genest J, McPherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, et al. Canadian Cardiovascular Society/  Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult - 2009 recommendations. Can J Cardiol 2009;25(10):567-79. 56. Red Book Taskforce. Guidelines for preventive activities in general practice. 8th ed. East Melbourne: Royal Australian College of General Practitioners; 2012. 57. Malaysian Endocrine & Metabolic Society, Malaysian Association for the Study of Obesity, Academy of Medicine Malaysia. Clinical Practice Guidelines: Management of Obesity. Putrajaya: Ministry of Health Malaysia; 2004. 58. Brauer P, Connor Gorber S, Shaw E, Singh H, Bell N, Shane AR, et al. Recommendations for prevention of weight gain and use of behavioural and pharmacologic interventions to manage overweight and obesity in adults in primary care. CMAJ 2015;187(3):184-95. 59. Yusuf S, Islam S, Chow CK, Rangarajan S, Dagenais G, Diaz R, et al. Use of secondary prevention drugs for cardiovascular disease in the community in highincome, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey. Lancet 2011;378(9798):1231-43. 60. Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011;5(3):133-40.

61. National Clinical Guidelines Centre for Acute and Chronic Conditions. Identification and management of familial hypercholesterolaemia 2008 (Revised 2014). National Institute for Health and Care Excellence; 2014. 62. Watts GF, Sullivan DR, Poplawski N, van Bockxmeer F, Hamilton-Craig I, Clifton PM, et al. Familial hypercholesterolaemia: a model of care for Australasia. Atheroscler Suppl 2011;12(2):221-63.

References

13

 Appendix CV1 Examples of FRS calculator for general CVD risk prediction: A) Web-based FRS Calculators:

14

 Appendix CV1

B) Paper-based FRS Calculators:

Simple Model with Office-based non-laboratory Predictors CVD Points for Women POINTS

 Age

BMI

-3

SBP Not Treated

SBP Treated

Smoker

Diabetic

NO

NO

<120

-2 -1 0

<120

1 2

<25

120-129

25-<30

130-139

30-34

35-39

120-129

 ≥30

3

140-149

4

150-159

130-139  YES

5

40-44

6

45-49

150-159

50-54

160+

160+

140-149

 YES

7 8 9 10

55-59

11

60-64

12

65-69

13 14

70-74

15

75+

TOTAL POINTS

Points  Allotted

Simple Model with Office-based non-laboratory Predictors CVD Risk for Women POINTS

RISK

POINTS

RISK

POINTS

RISK

-2 or less

Below 1%

6

3.4%

14

11.6%

-1

1.0%

7

3.9%

15

13.5%

0

1.1%

8

4.6%

16

15.6%

1

1.5%

9

5.4%

17

18.1%

2

1.8%

10

6.3%

18

20.9%

3

2.1%

11

7.4%

19

24.0%

4

2.5%

12

8.6%

20

27.5%

5

2.9%

13

10.0%

21+

 Above 30%

 Appendix CV1

15

Simple Model with Office-based non-laboratory Predictors CVD Points for Men POINTS

 Age

BMI

-2

SBP Not Treated

SBP Treated

Smoker

Diabetic

NO

NO

<120

-1 0

30-34

1 2

<25

120-129

25-<30

130-139

 ≥30

140-159

120-129

160+

130-139

35-39

3 4 5

<120

140-159

 YES  YES

160+

40-44

6 7

45-49

8

50-54

9 10

55-59

11

60-64

12 13

65-69

14

70-74

15

75+

TOTAL POINTS

Points  Allotted

Simple Model with Office-based non-laboratory Predictors CVD Risk for Men

16

 Appendix CV1

POINTS

RISK

POINTS

RISK

POINTS

RISK

-5 or less

Below 1%

3

4.0%

11

15.7%

-4

1.1%

4

4.7%

12

18.5%

-3

1.4%

5

5.6%

13

21.7%

-2

1.6%

6

6.7%

14

25.4%

-1

1.9%

7

8.0%

15

29.6%

0

2.3%

8

9.5%

16+

 Above 30%

1

2.8%

9

11.2%

2

3.3%

10

13.3%

 Appendix CV2 The following is the listing of key messages proposed in the Malaysian Dietary Guidelines, 2010

Key Message 1

Eat a variety of foods within your recommneded intake

Key Message 2

Maintain body weight in a healthy range

Key Message 3

Be physically active everyday

Key Message 4

Eat adequate amount of rice, other cereal products (preferably whole grain) and tubers

Key Message 5

Eat plenty of fruits and vegetables every day

Key Message 6

Consume moderate amounts of fish, meat, poutry, egg, legumes and nuts

Key Message 7

Consume adequate amounts of milk and milk products

Key Message 8

Limit intake of foods high in fats and minimise fats and oils in food preparation

Key Message 9

Choose and prepare foods with less salt and sauces

Key Message 10

Consume foods and beverages low in sugar

Key Message 11

Drink plenty of water daily

Key Message 12

Practise exclusive breastfeeding

Key Message 13

Consume safe and clean foods

Key Message 14

Make effective use of nutrition information on food labels

(Please refer to the guidelines for details of the recommendations) 

 Appendix CV3 Screening & evaluation of dyslipidaemia (adopted from the Malaysian Clinical Practice Guidelines in Management of Dyslipidemia, 4th Edition)

• •

• •

TC and HDL-C can be measured in fasting and non fasting states. TG is best measured in a fasting sample. LDL-C should be the primary target of  therapy, LDL-C is calculated using the Friedwald’s equation (LDL-C (mmol/l) = TC -HDL-C - TG / 2.2 ). When TG > 2.3mmol/L, non HDL-C is a better indicator of total atherogenic burden. When TG > 4.5 mmol/L, the equation is no longer valid for LDL-C calculation. HDL-C < 1.0 mmol/L & TG > 1.7 mmol/L are considered as major CVD risk factors.

 Appendix CV3

17

 Appendix CV4 Risk factors for type 2 Diabetes Mellitus (T2DM) screening:

•

Symptoms suggestive of DM (tiredness, lethargy, polyuria, polydipsia, polyphagia, weight loss, pruritus vulvae, balanitis)

•

Asymptomatic adults who are overweight or obese (BMI >23 kg/m2 or WC ≥80 cm for women & ≥90 cm for men) with additional risk factors: o Physical inactivity o First-degree relative with diabetes o Hypertension ( ≥ 140/90 mmHg or on therapy for hypertension) o Dyslipidaemia high density lipoprotein (HDL) cholesterol <0.9mmol/L or n triglycerides (TG) >1.7 mmol/L n o HbA1C ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose on previous testing o History of CVD o o o

Other clinical conditions associated with insulin resistance (e.g., severe obesity and acanthosis nigricans) Women with polycystic ovarian syndrome Women who delivered a baby weighing >4 kg or were diagnosed with gestational diabetes mellitus

(Adapted from the American Diabetes Association: Position Statement on Standards of Medical Care in Diabetes 2015)

18

 Appendix CV4

 Appendix CV5 Screening for T2DM at primary care level - without symptoms

(Adopted from the Clinical Practice Guidelines of Management of Type 2 Diabetes Mellitus, 4th Edition)

 ASYMPTOMATIC WITH RISK  Capillary Plasma Glucose

<5.6

≥5.6

Random Venous Plasma Glucose (RPG)

Fasting Venous Plasma Glucose (FPG) <7.8

7.8 to 11.0

NORMAL

OGTT

NORMAL <6.1

≥7.0

6.1 to 6.9

Second FPG

Second RPG

NORMAL <7.0

≥11.1

≥7.0 ≥11.1

NORMAL

DM DM

FPG <6.1

6.1 to 6.9

≥7.0

<7.8

NORMAL

IFG

DM

NORMAL

• • • •  

2 hour PPG 7.8 to 11.0 ≥11.1

IGT

DM

For screening of T2DM, measuring either venous or capillary blood using glucometer is acceptable For diagnosis of T2DM, venous plasma glucose value is required If FPG ≥ 7.0 mmol/L or 2 hour PPG ≥ 11.1 mmol/L, repeat OGTT is required to make the diagnosis of diabetes All values in mmol/L. Capillary whole blood reading is 12% lower than venous plasma glucose

 Appendix CV5

19

 Appendix CV6 Individuals with increased risk of Familial Hypercholesterolaemia (FH):

• History of premature CVD (men aged < 55 years, women aged < 60 years) • Family history of first-degree relative with premature CVD (men aged < 55 years, women aged < 60 years) • Total cholesterol > 7.5 or LDL-cholesterol > 4.9 mmol/L (untreated) • First-degree relative with a total cholesterol > 7.5 or LDL-C > 4.9 mmol/L (untreated) • Presence of physical signs of FH: tendon xanthomata or arcus cornealis at age < 45 years; xanthelasma at age < 25 years

 Appendix CV7 Modified UK Simon Broome Criteria for FH:

1. DNA mutation 2. Tendon xanthomas in patient or first/second-degree relative 3. Family history MI <50 in second-degree or <60 in first-degree relative 4. Family history of cholesterol >7.5 in first- or second-degree relative 5. Cholesterol >7.5 (adult) or >6.7 (age <16 years) 6. LDL-C >4.9 (adult) or >4.0 (age <16 years) Definite FH: (5 or 6) + 1 Probable FH: (5 or 6) + 2 Possible FH: (5 or 6) + (3 or 4)

20

 Appendix CV7

02

Thyroid Dysfunction SUMMARY

There is insufficient evidence to recommend universal screening for subclinical thyroid disorder. The risk of progression from subclinical thyroid dysfunction to overt thyroid disorder is relatively low. Measuring serum TSH and free T4 level should be based on individual merits, i.e., high risk of overt clinical disease.

RECOMMENDATIONS

Routine screening for thyroid dysfunction should not be offered.

2.1

Grade I

Introduction

 Thyroid dysfunction ranges from subclinical to overt thyroid disease. Screening can detect patients with subclinical disease or undiagnosed overt thyroid disease. Patients with overt disease have derangement in both thyroid stimulating hormone and free thyroxine level. Overt thyroid disease is noted to be associated with multiple co-morbidities including adverse cardiovascular, musculo–skeletal, neuropsychiatric, dermatologic and gastrointestinal effects (1). Although the prevalence of overt undiagnosed thyroid dysfunction was reported to vary between countries, it was consistently noted to be less common than subclinical dysfunction (2-4). Subclinical hypothyroidism is defined as an elevated serum thyroid stimulating hormone level (TSH: reference range of 0.45-4.5 mIU/L) with a normal serum free thyroxine (T4) and triiodothyroxine levels (T3) (5). In the United States, the prevalence of subclinical hypothyroidism in adults is noted to range from 4 to 10% (5, 6) Level II. No local data is available at present. Untreated subclinical hypothyroidism progresses to overt hypothyroidism at the rate of 2–5% per year. The rate of progression is faster in patients with higher levels of TSH, older patients, female gender and positive thyroid antibody status (7 -9) Level II-2. The risks of cardiovascular disease and cardiovascular mortality are increased with increasing level of TSH in patients with subclinical hypothyroidism (10)   Level II.  Thyroid Dysfunction

21

Participants with TSH ≥ 10 mIU/L have a significantly increased risk of CHD events (HR, 1.89 [95% CI, 1.28–2.80]) and CHD mortality (HR, 1.58 [95% CI, 1.10–2.27]) but not all-cause mortality (10, 11) Level II. All-cause mortality is increased only among those with cardiovascular risks (RR 1.76, [95% CI 1.36-2.30]) (12, 13) (14)  Level II. However, the associations between subclinical hypothyroidism and other clinical conditions, e.g., neuropsychiatric syndromes and systemic hypothyroid symptoms, are not clear, except dyslipidemia which is increased in patients with a TSH >10 mU/L” (15-18) Level II. Subclinical hyperthyroidism is defined as condition characterized by low serum TSH levels with a normal serum T4 and T3 (13, 19). The prevalence of subclinical hyperthyroidism ranges from 0.6-12.4% (13) Level II. In untreated subclinical hyperthyroidism, a great majority of patients remain subclinically hyperthyroid or revert to euthyroid status (20) Level II-2. It may develop into overt disease at a rate of 1–5% per year especially in elderly patients with multinodular goitre or those with total suppression of TSH level (TSH < 0.1) (11, 21) Level I (22) Level II-2. Furthermore, there is an increased relative risk of atrial fibrillation (RR 2.2, CI 1.4-3.3) in those aged 65 years and above with TSH < 0.1 mU/L (19) Level II-1 (23, 24) Level II-2. However, the evidence for increased cardiovascular disease risk is conflicting (19) Level I (25) Level II-2  (13) Level I (26) Level I. Cardiovascular mortality may be increased only among undetectable  TSH (<0.1 mU/L) (27). It is also associated with reduced BMD in post-menopausal women (13) Level I, but there is no clear evidence to support its association with osteoporotic fracture (13, 19) Level I. In addition, there is no clear evidence linking subclinical hyperthyroidism with mental health (13, 18) Level I or overall mortality risk (25, 28 -32) Level II (14, 26) Level I.

2.2 Benefit of screening and treating subclinical thyroid dysfunction Significant morbidities associated with subclinical thyroid dysfunction are uncommon. No study has looked at the benefit of screening for subclinical thyroid dysfunction (1). There is no clear clinical benefit of treating subclinical hypothyroidism (1, 33 -37) and subclinical hyperthyroidism (38 -43); moreover, the evidence is of poor quality. There could be positive effects on lipid profile (reduced total and LDL cholesterol) with thyroxine treatment but its clinical benefit is uncertain (1, 44). Treating subclinical hyperthyroidism is noted to be associated with a positive benefit of improving daytime blood systolic blood pressure, but a small increase in BMI. Again, however, the quality of evidence is poor (44). There could be benefit in treating patients with TSH > 10mIU/L or those with increased cardiovascular risk, i.e., patients with documented diastolic dysfunction, diastolic hypertension, atherosclerosis, dyslipidemia or diabetes mellitus, and smokers (13) Level III. However, screening of patients with CVD risk factors for thyroid disorders yield low prevalence thus it is not justified.

22

Benefit of screening and treating subclinical thyroid dysfunction

2.3

Screening test

 TSH test is the initial evaluation because of its ability to detect abnormalities prior to abnormal serum free T4 and T3 levels(13). The TSH test has sensitivity above 98% and specificity above 92% in detecting thyroid dysfunction among patients suspected to have thyroid disorder (45). Among healthy people, normal TSH concentration has a high negative predictive value in ruling out thyroid disease (45). Nevertheless, thyroid function results in the elderly (>70 years) should be interpreted with caution as the normal range may be different from that in younger population. (46)

2.4

Harm of screening

 A review by USPFTF finds scarce evidence documenting harm of screening (1). Harm generally associated with screening, such as overtreatment and anxiety resulting from overdiagnosis, is a potential problem.

REFERENCES 1.

2. 3.

4.

5.

6.

Rugge J, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2015;162(1):35. Delitala A, Pilia M, Ferreli L, Loi F, Curreli N, Balaci L et al. Prevalence of unknown thyroid disorders in a Sardinian cohort. Eur J Endocrinol 2014;171(1):143-9. Unnikrishnan A, Bantwal G, John M, Kalra S, Sahay R, Tewari N. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab 2013;17(4):647. Benseñor I, Goulart A, Lotufo P, Menezes P, Scazufca M. Prevalence of thyroid disorders among older people: results from the São Paulo Ageing and Health Study. Cad Saude Publica 2011; 27(1):155-61. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4 and thyroid autoantibodies in the United States population (1988–1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489–99. Canaris G J, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.

7.

Vanderpump M, Tunbrldge W, French J, Appleton D, Bates D, Clark F et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol 1995;43(1):55-68. 8. Diez JJ, Iglesias P. Spontaneous subclinical hypothyroidism in patients older than 55 years: an analysis of natural course and risk factors for the development of overt thyroid failure. J Clin Endocrinol Metab 2004;89(10):4890-7 9. Huber G, Staub JJ, Meier C, Mitrache C, Guglielmetti M, Huber P, Braverman LE. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab 2002;87(7):3221-6. 10. Rodondi N, den Elzen W, Bauer D, Cappola A, Razvi S, Walsh J et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010;304(12):1365. 11. Gencer B, Collet T, Virgini V, Auer R, Rodondi N. Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies. Endocr Metab Immune Disord Drug Targets 2013;13(1):4-12.

References

23

REFERENCES 12. Singh S, Duggal J, Molnar J, Maldonado F, Barsano C, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: A meta-analysis. Int J Cardiol 2008;125(1):418. 13. Biondi B, Cooper D. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76-131. 14. Haentjens P, Van Meerhaeghe A, Poppe K, Velkeniers B. Subclinical thyroid dysfunction and mortality: an estimate of relative and absolute excess all-cause mortality based on time-to-event data from cohort studies. Eur J Endocrinol 2008;159(3):329-41. 15. Kanaya Am, Harris F, Volpato S et al. Association between thyroid dysfunction and total cholesterol level in an older biracial population: the health, aging and body composition study. Arch Intern Med 2002;162:773-9. 16. Bauer Dc, Ettinger B, Browner WS. Thyroid function and serum lipids in older women: A population-based study. Am J Med 1998;6:546-51. 17. Kung AW, Pang RW, Janus ED. Elevated serum lipoprotein (a) in subclinical hypothyroidism. Clin Endocrinol 1995;4:445-9 18. Chaker L, Baumgartner C, Ikram MA, Dehghan A, Medici M, Visser WE, et al. Subclinical thyroid dysfunction and the risk of stroke: a systematic review and metaanalysis. Eur J Epidemiol 2014;29(11):791-800. 19. Helfand M. Screening for subclinical thyroid dysfunction in non-pregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2004;140(2):128. 20. Vadiveloo T, Donnan P, Cochrane L, Leese G. The thyroid epidemiology, audit, and research study (TEARS): the natural history of endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 2011;96(1):E1-E8. 21. Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012;172(10):799-809. 22. Díez J, Iglesias P. An analysis of the natural course of subclinical hyperthyroidism. Am J Med Sci 2009;337(4):225-32. 23. Cappola A, Fried L, Arnold A, Danese M, Kuller L, Burke G et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295(9):1033. 24. Palmeiro C, Davila MI, Bhat M, Frishman WH, Weiss IA. Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment. Cardiol Rev 2013;21(6):300-8. 25. Vo¨lzke H, Schwahn C, Wallaschofski H, Do¨rr M. Review: the association of thyroid dysfunction with all-cause and circulatory mortality: is there a causal relationship? J Clin Endocrinol Metab 2007;92:2421–9. 26. Ochs N, Auer R, Bauer DC, et al. Meta-analysis:

24

References

27.

28.

29.

30.

31.

32.

33. 34.

35.

36.

37.

38.

Subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med 2008;148(11):832-45. Biondi B. How could we improve the increased cardiovascular mortality in patients with overt and subclinical hyperthyroidism? Eur J Endocrinol 2012;167(3):295-9. Singh S, Duggal J, Molnar J, Maldonado F, Barsano C, Arora R. Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: A meta-analysis. Int J Cardiol 2008;125(1):418. Boekholdt S, Titan S, Wiersinga W, Chatterjee K, Basart D, Luben R et al. Initial thyroid status and cardiovascular risk factors: The EPIC-Norfolk prospective population study. Clin Endocrinol 2010;72(3):404-10. Flynn R, Bonellie S, Jung R, MacDonald T, Morris A, Leese G. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab 2010;95(1):186-93. Ittermann T, Haring R, Sauer S, Wallaschofski H, Dorr M, Nauck M et al. Decreased serum TSH levels are not associated with mortality in the adult northeast German population. Eur J Endocrinol 2009;162(3):579-85. Sgarbi J, Matsumura L, Kasamatsu T, Ferreira S, Maciel R. Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study. Eur J Endocrinol 2009;162(3):569-77. Villar HCCE, Saconato H, Valente O, Atallah ÁN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Libr 2007. Razvi S, Shakoor A, Vanderpump M, Weaver J, Pearce S. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a meta-analysis. J Clin Endocrinol Metab 2008;93(8):2998-3007. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver J. The beneficial effect of l-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab 2007;92(5):1715-23. Iqbal A, Jorde R, Figenschau Y. Serum lipid levels in relation to serum thyroid-stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromso study. J Intern Med 2006;260(1):53-61. Völzke H, Schwahn C, Wallaschofski H, Dörr M. The association of thyroid dysfunction with all-cause and circulatory mortality: is there a causal relationship? J Clin Endocrinol Metab 2007;92(7):2421-9. Forfar J, Feek C, Miller H, Toft A. Atrial fibrillation and isolated suppression of the pituitary-thyroid axis:

39.

40.

41.

42.

43.

44.

45. 46.

response to specific antithyroid therapy. Int J Cardiol 1981;1(1):43-8. Kaminski G, Michalkiewicz D, Makowski K, Podgajny Z, Szalus N, Ruchala M et al. Prospective echocardiographic evaluation of patients with endogenous subclinical hyperthyroidism and after restoring euthyroidism. Clin Endocrinol (Oxf) 2011;74(4):501-7. Sgarbi J, Villaça F, Garbeline B, Villar H, Romaldini J. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J Clin Endocrinol Metab 2003;88(4):1672-7. Faber, Jensen, Petersen, Nygaard, Hegedus, SiersbaekNielsen. Normalization of serum thyrotrophin by means of radioiodine treatment in subclinical hyperthyroidism: effect on bone loss in postmenopausal women. Clin Endocrinol (Oxf) 1998;48(3):285-90. Yönem Ö, Dökmetas H, Aslan S, Erselcan T. Is antithyroid treatment really relevant for young patients with subclinical hyperthyroidism? Endocr J 2002;49(3):30714. Mudde A, Houben A, Kruseman A. Bone metabolism during anti-thyroid drug treatment of endogenous subclinical hyperthyroidism. Clin Endocrinol (Oxf) 1994;41(4):421-4. Rugge B, Balshem H, Sehgal R. Screening and subclinical screening and treatment of subclinical hypothyroidism or hyperthyroidism. Agency Healthc Res Qual US Dep Heal Hum Serv 2007;24. British Thyroid Association. UK guidelines for the use of thyroid function tests. Consultant 2006. Brenner AP, Feddema P, Leedman PJ, et al. J Clin Endocrinol Metab 2012; 97(5): 1554-62.

References

25

03

Osteoporosis SUMMARY

Osteoporotic fracture is associated with high morbidity and mortality. Treatment for osteoporosis reduces the incidence of osteoporotic fracture for women but evidence for the benefit of screening is yet to be established. Evidence for any benefit in treating and screening men for osteoporosis is insufficient. High risks of future osteoporotic fractures include age >50 with previous fragility fracture or loss of height. DEXA scan is the recommended screening tool.

RECOMMENDATIONS

Screening for osteoporosis using DEXA scan should only be indicated for women at high risk of osteoporotic fracture.

Grade C

Routine screening for osteoporosis should not be offered to men.

Grade I

3.1

Introduction

Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequence of increased bone fragility and susceptibility to fracture (1). Clinically, WHO working groups defines osteoporosis in women based on the following criteria: Table 1: The World Health Organisation (WHO) Working Group classification of osteoporosis (2) Normal

Bone mineral density (BMD) within 1 SD of young adult reference range (T score > –1)

Osteopenia

BMD more than 1 SD but less than 2.5 SD below the young adult mean (T score between –1 and –2.5)

Osteoporosis

BMD value of 2.5 SD or more below the young adult mean (T score < –2.5)

Severe/ Established

BMD value of 2.5 SD or more below the young adult mean Osteoporosis with the presence of 1 or more fragility fractures

• T score is the standard deviation (SD) in comparison with young adult BMD 

26

Introduction

 The aim of managing osteoporosis is to reduce the risk of future osteoporotic fracture. Hip fracture is associated with a higher mortality rate in women aged 50 years compared to those without. It is also associated with a mortality rate of up to 20% in the first year. The majority of those who survive are disabled and only 25% will resume normal activities (3) Level II-3 . Osteoporosis-related fractures are estimated to cause 6.7% of women to become dependent in basic activities of daily living and 7.8% requiring nursing home care for an average of 7.6 years (4). In Malaysia, the incidence of hip fracture for individuals over 50 years old have increased over the years from 70 per 100,000 population in 1989 to 90 per 100,000 in 1996 and 1997 (5, 6). In 1997, the age-adjusted rates of osteoporotic fracture for men and women in Malaysia were 88 and 218 per 100,000, which were lower than the rates for US Whites (7 -9). Race-specific incidence data have shown that fracture rates are highest among Chinese Malaysians (160/100 000) followed by ethnic Indians (150/100 000) and Malays (30/100 000) (6). Females are twice as commonly affected compared to males. Countries with a high incidence of osteoporotic hip fracture have rates over 250/100 000 (9).  The important factors associated with an increased risk of osteoporotic fracture are (10 -17):   • • • • • • • • • •

age prior fragility fracture low body mass index low BMD parental history of hip fracture smoking use of systemic corticosteroids excess alcohol intake low calcium and vitamin D intake sedentary life-style

 Age is the single most important risk factor. Prior fragility fracture, including a vertebral fracture, and documented reduced height poses a high risk for another osteoporotic fracture. Increased risk of a fall is also associated with osteoporotic fracture.

3.2

Benefit of screening and treating osteoporosis

Meta-analyses and reviews have shown that treating  post-menopausal women with established osteoporosis using various agents reduces the rates of osteoporotic fracture (18 -22) Level I. Effective treatments include calcium and vitamin D (23), bisphophanates (22), SERMs, teriparatide (24) and denosumab (25). Treating old and frail women with osteoporotic fracture also reduces their mortality rate (26). Most meta-analyses have included secondary

Benefit of screening and treating osteoporosis

27

prevention studies on patients who have had a prior fragility fracture. The benefit of reducing fracture risk in primary prevention, i.e., without prior fracture, is smaller or not significant compared with secondary prevention (27 -30). In men with osteoporosis, meta-analyses have shown a reduction of vertebral and non-vertebral fractures with alendronate and risedronate treatments (31, 32)  Level I. On the other hand, the benefit of screening is less uncertain. RCTs on screening programmes to reduce fracture rates in the community show conflicting results. One RCT on osteoporosis screening in women aged 45-54 followed by treatment showed reduced osteoporosis fracture (HR = 0.741, 95% CI = 0.551-0.998) (33) but the absolute benefit was small.  Another screening programme using risk score and spinal radiograph for those at risk did not show any significant short-term (12 months) benefit in reducing osteoporotic vertebral fracture (34). Data on the cost-effectiveness of any particular strategy is lacking. Cost-effectiveness assessment on osteoporosis screening followed by treatment in a cohort study indicated that non-adherence with osteoporosis medications substantially increases the incremental cost-effectiveness ratio of osteoporosis screening (35) Level II-2. A RCT on the benefit of osteoporosis screening using fracture risk scoring is still ongoing (36).

3.3

Screening tests

 Annual measurements of height to detect possible risk vertebral fracture is simple and can be used to identify patients for lateral spinal radiograph and BMD assessment (37). Those with high risk of osteoporosis, such as age > 50 with previous fragility fracture and high risk of fall, should be offered BMD assessment (37). Dual energy X-ray absorptiometry (DEXA) is the gold standard for diagnosing osteoporosis and is the recommended screening test, if indicated (38, 39). Quantitative Ultrasound (QUS) for diagnosing and monitoring treatment is not recommended because there is a diversity of techniques and a lack of standardised reference range.  The criteria for diagnosis and recommending treatment based on ultrasound are not well established (40) Level II-2.  There are many risk scoring systems to predict the risk of osteoporosis. However, no tool is good enough and validated yet for selecting patients for therapy and improving fracture outcome. Most tools are reported to have sensitivity of 80-90% and specificity of 50% in detecting osteoporosis (41). Simple tools, such as the Osteoporosis Self-assessment  Tool (OST), Osteoporosis Risk Assessment Instrument (ORAI), and Garvan Fracture Risk Calculator (Garvan), fare as well or better than more complex tools, such as the Simple 28

Screening tests

Calculated Risk Estimation Score [SCORE], WHO Fracture Risk Assessment Tool [FRAX] (http://www.shef.ac.uk/FRAX/index.jsp ), and Qfracture, in predicting osteoporosis (42), or osteoporotic fracture (41). RCTs evaluating the use of FRAX tool in prevention of osteoporotic fracture are still ongoing (36).

3.4

Harm of screening

Screening programmes have been shown to consistently increase the chance of treatment but with uncertain fracture risk reduction (33, 34, 43). Meta-analyses on osteoporotic treatment found harms of increased risk of serious infection with denosumab [OR (95% CI) 4.45 (1.15 to 17.14), p=0.03] (44), and a possible association with adverse cardiovascular outcomes (45) with calcium intake. However, the risk of harm is small (46).

REFERENCES 1. 2.

3.

4.

5. 6. 7.

Consensus Development Conference. Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1993;94:646-50. WHO technical Report Series 843. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva, World Health Organisation 1994. Clayer MT, Bauze RJ. Morbidity and mortality following fractures of femoral neck and trochanteric region: analysis of risk factors journal of trauma-injury infection & critical care. J Trauma 1989;29(12):1673-8. Chrischilles EA, Butler CD, Davis CS, Wallace RB. A model of lifetime osteoporosis impact. Arch Intern Med 1991;151(10):2026-32. Lee CM, Sidhu JS, Pan KL. Hip fracture incidence in Malaysia 1981-1989. Acta Orthop Scand 1993;64(2):178-80. Lee JK, Khir ASM. The incidence of hip fracture in Malaysians above 50 years of age: variation in different ethnic groups. J Rheumatol 2007;10(4):300-5. Lau EM, Lee JK, Suriwongpaisal P, et al. The incidence of hip fracture in Four Asian countries: the Asian Osteoporosis Study (AOS). Osteoporos Int 2001;12(3):239-43.

8. 9.

10.

11. 12. 13.

14. 15.

Cummings S, Melton L. Epidemiology and outcomes of osteoporotic fractures. The Lancet 2002;359(9319):1761-7. Kanis J, Odén A, McCloskey E, Johansson H, Wahl D, Cooper C. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 2012;23(9):2239-2256. Lau EM, Suriwongpaisal P, Lee JK, et al. Risk factors for hip fracture in Asian men and women: the Asian Osteoporosis Study. J Bone Miner Res 2001;16(3):57280. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005;16(6):581-9. Kanis JA, Johansson H, Johnell O, et al. Alcohol intake as a risk factor for fracture. Osteoporos Int 2005;16(7):737-42. Kanis JA, Johnell O, Oden A, et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int 2005;16(2):15562. Kanis JA, Johnell O, Oden A, et al. A family history of fracture and fracture risk: a meta-analysis. Bone 2004;35(5):1029-37. De Laet C, Kanis JA, Odén A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos References

29

REFERENCES 16. 17.

18.

19.

20.

21.

22.

23.

24.

25.

26. 27.

28.

30

Int 2005;16(11):1330-8. Lim PS, Ong FB, Adeeb N, et al. Bone health in urban midlife Malaysian women: risk factors and prevention. Osteoporos Int 2005;16(12):2069-79. Loh KY, Shong KH, Soo NL, et al. Risk factors for fragility fracture in Seremban district, Malaysia: a comparison of patients with fragility fracture in the orthopedic ward versus those in the outpatient department. Asia Pac J Public Health 2008;20(3):251-7. Adachi JD, Rizzoli R, Boonen S, et al. Vertebral fracture risk reduction with risedronate in post-menopausal women with osteoporosis: a meta-analysis of individual patient data. Aging Clin Exp Res 2005;17(2):150-6. Fraser LA, Vogt KN, Adachi JD, Thabane L. Fracture risk associated with continuation versus discontinuation of bisphosphonates after 5 years of therapy in patients with primary osteoporosis: a systematic review and meta-analysis. Ther Clin Risk Manag 2011;7:157-66. Kanis JA, Johansson H, Oden A, McCloskey EV. A metaanalysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX. Osteoporos Int 2011;22(8):2347-55. Boonen S, Laan RF, Barton IP, Watts NB. Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies. Osteoporos Int 2005;16(10):1291-8. Murad M, Drake M, Mullan R, Mauck K, Stuart L, Lane M et al. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 2012;97(6):1871-80. Avenell A, Mak JC, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev 2014;4:Cd000227. Han S, Wan S. Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials. Int J Clin Pract 2012;66(2):199-209. Silva-Fernández L, Rosario M, Martínez-López J, Carmona L, Loza E. Denosumab for the treatment of osteoporosis: A systematic literature review. Reumatología Clínica 2013;9(1):42-52. Bolland MJ, Grey AB, Gamble GD, Reid IR. Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol Metab 2010;95(3):1174-81. Holder KK, Kerley SS. Alendronate for fracture prevention in postmenopause. Am Fam Physician 2008;78(5):57981. Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev

References

29.

30.

31.

32. 33.

34.

35.

36.

37.

38.

39.

40.

2008(1):Cd004523. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008(1):Cd003376. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008(1):Cd001155. Sawka AM, Papaioannou A, Adachi JD, et al. Does alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of antifracture efficacy in women. BMC Musculoskelet Disord 2005;6:39. Zhong ZM, Chen JT. Anti-fracture efficacy of risedronic acid in men: A meta-analysis of randomized controlled trials. Clin Drug Investig 2009;29(5):349-57. Barr RJ, Stewart A, Torgerson DJ, Reid DM. Population screening for osteoporosis risk: a randomised control trial of medication use and fracture risk. Osteoporos Int 2010;21(4):561-8. Clark EM, Gould V, Morrison L, Ades AE, Dieppe P, Tobias JH. Randomized controlled trial of a primary carebased screening program to identify older women with prevalent osteoporotic vertebral fractures: Cohort for Skeletal Health in Bristol and Avon (COSHIBA). J Bone Miner Res 2012;27(3):664-71. Hiligsmann M, Gathon HJ, Bruyere O, et al. Cost effectiveness of osteoporosis screening followed by treatment; the impact of medication adherence. Value in Health 2010;13(4):394-401. Shepstone L, Fordham R, Lenaghan E, Harvey I, Cooper C, Gittoes N, et al. A pragmatic randomised controlled trial of the effectiveness and cost-effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study. Osteoporos Int 2012;23(10):2507-15. Care C. Overview—Appraisal Process [Internet]. Canadian Task Force on Preventive Health Care. 2015 [cited 2 March 2015]. Available from: http://  canadiantaskforce.ca/appraised-guidelines/overview/  Uspreventiveservicestaskforce.org. Home - US Preventive Services Task Force [Internet]. 2015 [cited 2 March 2015]. Available from: http://www. uspreventiveservicestaskforce.org/  Acadmed.org.my. Academy of Medicine of Malaysia - Clinical Practice Guidelines (CPGs) [Internet]. 2015 [cited 2 March 2015]. Available from: http://www. acadmed.org.my/index.cfm?&menuid=67 Flöter M, Bittar CK, Zabeu JL, et al. Review of comparative studies between bone densitometry and quantitative ultrasound of the calcaneus in osteoporosis.

41.

42.

43.

44.

45.

46.

Acta Reumatol Port 2011;36(4):327-35. Rubin KH, Friis-Holmberg T, Hermann AP, Abrahamsen B, Brixen K. Risk assessment tools to identify women with increased risk of osteoporotic fracture: complexity or simplicity? A systematic review. J Bone Miner Res 2013;28(8):1701-17. Nayak S, Edwards DL, Saleh AA, Greenspan SL. Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density. Osteoporos Int 2015. McConaha JL, Berdine HJ, Skomo ML, Laux RV, Higginbotham SK, O’Neil CK. Impact of the fracture risk assessment on patient and physician behavior in osteoporosis prevention. J Pharm Pract 2014;27(1):2530. Anastasilakis AD, Toulis KA, Goulis DG, Polyzos SA, Delaroudis S, Giomisi A, et al. Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a metaanalysis. Horm Metab Res 2009;41(10):721-9. Rojas-Fernandez CH, Maclaughlin EJ, Dore NL, Ebsary S. Assessing the potential adverse consequences of supplemental calcium on cardiovascular outcomes: should we change our approach to bone health? Ann Pharmacother 2012;46(5):696-702. Varenna M, Bertoldo F, Di Monaco M, Giusti A, Martini G, Rossini M. Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature. Reumatismo 2013;65(4):143-66.

References

31

04

Chronic Obstructive Pulmonary Disease (COPD) SUMMARY

Chronic obstructive pulmonary disease (COPD) is characterised by progressive, partially reversible airflow obstruction and lung hyperinflation. The main factor associated with COPD is cigarette smoking. An established screening tool is not available. Early diagnosis management with pharmacological agents does not improve mortality and morbidity. Smoking cessation remains the most effective strategy in reducing mortality and morbidity associated with COPD.

RECOMMENDATIONS

Routine screening of adults for COPD is not indicated.

4.1

Grade D

Introduction

Chronic obstructive pulmonary disease (COPD) is characterised by progressive, partially reversible airflow obstruction and lung hyperinflation (1). It is mainly caused by cigarette smoking. COPD may initiate or worsen many co-morbid diseases, such as ischemic heart disease, congestive heart failure, osteoporosis, anaemia, lung cancer, depression and diabetes. In turn, these diseases may worsen COPD, which leads to increased hospitalizations, mortality and healthcare costs (2, 3) Level II-3. Population-based surveys from seven countries reported overall prevalence of COPD ranging from 4.5% to 21.1% (4). The estimated prevalence rates of COPD in Asia Pacific and Malaysian adults were 6.3% and 4.6%, respectively (5) Level III. The estimation was based on a model calculation of patients with at least moderately severe COPD. COPD is currently the fifth leading cause of death worldwide (6). In a cross sectional study at primary care settings in Malaysia, airflow limitation (defined as FEV1/FVC of < 0.7) was noted in 10.6% of adults over than 40 years with ≥ 10 pack-years of smoking history. (7)

32

Introduction

4.2

Benefit of treatment or early intervention

 The mainstay of COPD management is smoking cessation, which has been shown to reduce mortality and morbidity at any stage of disease severity (8) Level I. Other management strategies, such as inhaled bronchodilators, corticosteroids and vaccinations, have been shown to reduce exacerbations in patients with severe COPD and have a small effect on all–cause mortality (9 -17) Level I.

4.3

Screening tests

 The diagnosis of COPD should be based on careful history-taking on the presence of symptoms and assessment of airway obstruction (or airflow limitation) (18). The available screening tools include spirometry and questionnaires. Spirometer is the validated tool for measuring lung function. Case Finding Questionnaire (CFQ) and COPD Diagnostic Questionnaire (CDQ) have been developed and studied to identify high-risk chronic smokers (19). CDQ consists of five questions on symptoms of COPD, with each question carrying one point. With a score of three and above as the cut-off for COPD, CFQ has a wide range of sensitivity and specificity of 59%-80% and 58%-77%, respectively, in predicting COPD (19) Level III. CDQ, which was assessed in various countries in Europe and the UK, as well as in Australia recently, has shown poor validity (19 -22). None of these tools has been formally tested in Malaysia.

4.4

Harm of screening

 There is no evidence to conclude potential benefits of early diagnosis and management of asymptomatic patients through screening (19). Screening may also result in potential harms, such as false-positive results, leading to subsequent unnecessary therapy with adverse effects (19, 24, 25) Level II-B. Since, smoking cessation is the only effective intervention to improve morbidity and mortality among COPD patients, it is arguably more useful to screen patients for smoking and advise on smoking cessation.

Harm of screening

33

REFERENCES 1.

2. 3.

4.

5.

6. 7.

8.

9.

10.

11.

12.

13.

14.

34

Agusti A. systemic effects of chronic obstructive pulmonary disease: What we know and what we don’t know (but should). Proc Am Thorac Soc 2007;4(7):5225. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33(5):116585. Soriano JB, Visick GT, Muellerova H, Payvandi N, Hansell AL. patterns of comorbidities in newly diagnosed COPD and asthma in primary care. Chest 2005;128(4):2099107. Wilt TJ, Niewoehner D, Kim C, et al. Use of spirometry for case finding, diagnosis, and management of chronic obstructive pulmonary disease (COPD). Summary, Evidence Report/Technology Assessment:121. 2005. Agency for Healthcare Research and Quality, Rockville, MD. Regional COPD working group. COPD prevalence in 12 Asia-pacific countries and regions: Projections based on the COPD prevalence estimation model. Respirology 2003;8:192-8. Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. The Lancet 2007;370(9589):765-73. Ching SM, Pang YK, Price D, et al. Detection of airflow limitation using a handheld spirometer in a primary care setting. Respirology 2014;19(5):689-93 Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE. The effects of a smoking cessation intervention on 14.5-year mortality. Ann Int Med 2005;142(4):233. Wongsurakiat P, Maranetra KN, Wasi C, Kositanont U, Dejsomritrutai W, Charoenratanakul S. Acute respiratory illness in patients with copd and the effectiveness of influenza vaccination. Chest 2004;125(6):2011-20. Burge PS, Calverley PMA, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 2000;320(7245):1297303. Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356(8):775-89. Sin DD, Wu L, Anderson JA, Anthonisen NR, Buist AS, Burge PS, et al. Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease. Thorax 2005;60(12):992-7. Sestini P, Renzoni E, Robinson S, Poole P, Ram FS. Shortacting beta 2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002;4. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular

References

15.

16.

17. 18.

19.

20. 21.

22.

23.

24. 25.

effects of beta-agonists in patients with asthma and COPD. Chest 2004;125(6):2309-21. Salpeter SR, Buckley NS, Salpeter EE. Metaanalysis: Anticholinergics, but not beta agonists, reduce severe exacerbations and respiratory mortality in COPD. J Gen Intern Med 2006;21 (10):1011-9. Barr RG, Bourbeau J, Camargo Jr CA. Inhaled tiotropium for stable chronic obstructive pulmonary disease. Cochrane Libr 2005. Ferguson GT, Funck-Brentano C, Fischer T, Darken P, Reisner C. Cardiovascular safety of salmeterol in COPD. Chest 2003;123(6):1817-24. Global Initiative for Chronic Obstructive Lung Disease (GOLD), Spirometry for health care providers [Internet]. 2010 (cited 2012 May 12). Available from: http://  www.goldcopd.org/uploads/users/files/GOLD_ Spirometry_2010.pdf Hill K, Hodder R, Blouin M, Heels-Ansdell D, Guyatt G, Goldstein R. Identifying adults at risk of COPD who need confirmatory spirometry in primary care. Do symptombased questions help? Can. Fam. Physician 2011; 57: e51–7. Price DB, Tinkelman DG, Nordyke RJ. Scoring system and clinical application of COPD diagnostic questionnaires. Chest 2006;129(6):1531. Kotz D, Nelemans P, van Schayck CP, Wesseling GJ. External validation of a COPD diagnostic questionnaire. Eur Respir J 2008;31(2):298-303. Stanley AJ, Hasan I, Crockett AJ, van Schayck OCP, Zwar NA. Validation of the COPD diagnostic questionnaire in an Australian general practice cohort: a cross-sectional study. Prim Care Respir J 2014;23(1):92-7. Lin K, Watkins B, Johnson T, Rodriguez JA, Barton MB. Screening for chronic obstructive pulmonary disease using spirometry: summary of the evidence for the US Preventive Services Task Force. Ann Int Med 2008;148(7):535-43. Vedal S, Crapo RO. False positive rates of multiple pulmonary function tests in healthy subjects. Bull Eur Physiopathol Respir 1983;19(3):263-6. Hardie JA, Buist AS, Vollmer WM, Ellingsen I, Bakke PS, Mørkve O. Risk of over-diagnosis of COPD in asymptomatic elderly never-smokers. Eur Respir J 2002;20(5):1117-22.

05

Cervical Cancer SUMMARY

Cervical cancer is the second most common cancer among women in Malaysia. The incidence rate increases with age after 25 years and peaks at 60-69 years old. Treating precancerous cervical lesions costs much less than treating the cancer itself. Screening with cytology has been proven to reduce cervical cancer mortality and morbidity. Co-testing of cytology with HPV DNA every five years confers the benefit of lower incidence of cervical cancer.

RECOMMENDATIONS

Screening should start at 25 years old for women who have ever had sexual activity or 3 years after the initiation of sex

Grade A

Screening can be done using either conventional cytology testing in Pap test or liquid based cytology every 3 years, or co-testing cytology with HPV DNA every 5 years

Grade A

Screening can be discontinued in women at age 65 after 3 negative consecutive tests.

Grade C

Screening should still be offered to women aged 65 and above who have not had any cervical cancer screening

Grade C

5.1

Introduction

Cervical cancer is a health concern worldwide. The incidence rate among Hispanics and African Americans in the USA was reported at 9.0 to 9.8 per 100,000 women in 2011 (1). However, the incidence among Caucasians in the USA is very low (1). In Malaysia, it is the second most common cancer among women age 15-44 years old. The incidence has increased from an agestandardised ratio (ASR) of 12.2 in 2006 to 15.6 per 100,000 in 2012 (2, 3). The incidence rate starts to increase at the age of 25-29 years old years and peaks at 60-69 years old (3). By ethnicity, Chinese Malaysian women have the highest incidence of cervical cancer followed by Indians and Malays (2). Even though it Introduction

35

is not listed in the top ten of hospitalized cases in Malaysia, neoplasm contribute the fourth highest cause of death in Ministry of Health hospitals (4).  The risk factors for cervical cancer include: Early age of sexual debut (5)  Level II-2, (6) Level I, (7) Level I. More than 2 sexual partners (5)  Level II-2, (7) Level I, (8) Level II-2 Multi-parity (8) Level II-2 Persistent and high risk type of HPV infection (9)  Level I, (10) (12) Level II-2, (13) Level II-2 • Smoking factor (14), (15)  Level I • HIV infection (16) Level II-2 • In-utero exposure to diethylstilbestrol (17) Level III • • • •  

Level I

, (11) Level II,

 Almost all cases of cervical cancer are caused by high-risk human papilloma virus (HPV) (3), (18) Level III. Chronic and persistent exposure to high-grade type of HPV precedes cervical metaplasia and dysplasia, and the long duration of its pathology makes screening for cervical cancer feasible. Although HPV vaccination may prevent cervical cancer, there is still no strong evidence that it offers total protection. The vaccination does not cover all types of high-risk HPV. While HPV 16 and 18 are responsible for 70% of cervical cancer cases, there are at least 13 other types of HPV that are linked to the development of cervical cancer (9) Level I . Even though current HPV vaccination has an efficacy of 98% - 100% in preventing HPV 16 and 18 infections, the duration of protection is unclear making the cost-effectiveness of this program as cancer prevention still under investigation (19) Level I. Thus, cervical cancer screening is relevant.

5.2 Benefit of screening and treating cervical abnormalities  The treatment of cervical cancer at an early stage is associated with excellent survival (20).  Therefore, it is imperative to diagnose cervical cancer early as screening for cervical cancer provides great benefits to women (21)  Level I. Screening compared to no screening significantly reduced the risk of invasive cancer (RR: 0.38, 95%CI: 0.23, 0.63) and reduced the mortality from advanced cancer (RR: 0.56, 95%CI: 0.42, 0.75) (22) Level I. In Malaysia, even though the  ASR of cervical cancer has declined, the percentage of cervical cancer patients who had been screened three years before diagnosis was found to be very low (0-12%) (23). Managing precancerous cervical lesions costs much less than cancer treatment (24). The average cost of managing atypical squamous cell of undetermined significance (ASCUS) in Malaysia is estimated to cost RM898 to RM1948 for CIN2/3. This is comparatively much cheaper than the average cost of managing cervical cancer which is estimated at RM10,

36

Benefit of screening and treating cervical abnormalities

540.24. In addition to the cost-effectiveness, the success rate of ablation and excision therapy of the pre-cancerous lesion ranges from 90% to 95% (25).

5.3

Screening tests

Screening tests used for cervical cancer include conventional Pap smear, liquid-based cervical cytology, HPV-DNA test and visual inspection with acetic acid. Conventional Pap smear test is a well-established screening test for cervical cancer (26).  The liquid-based cervical cytology is neither more sensitive nor more specific for detecting high-grade cervical abnormality compared with the conventional Pap test (27) Level I, (28) Level I.  The HPV-DNA test for cervical smear is not useful for younger aged women because of the high rate of clearance observed in infected cases. The infection is shown to decrease after age 29 years and has a clearance rate of 92% within five years (29) Level II-3, (30) Level II-2. However, for women aged 30 years and above, co-testing of Pap smear and HPV DNA is an alternative.  This combination is more useful as it results in a higher detection of positive screening cases (31) Level III. Co-testing for three years increases the detection of CIN3 or cancer compared to Pap smear alone (10% vs 3.1%, p<0.0001) and the increased detection continues to be seen at year 5 (12.15 vs 5.95, p<0.0001) (32)  Level II-2, (33) Level III. In India, a single round of HPV DNA testing followed by management of positive cases compared to cervical cytology with no invitation for screening was associated with a significant reduction in the numbers of CIN2 or advanced cervical cancers and deaths from cervical cancer (22) Level I. In another study in the Netherlands, however, the added benefit of HPV DNA compared to cytology in the incidence of cervical cancer after five years was marginal (4 of 19,579 in the intervention group vs 14 of 19,731; OR: 0.29, 95% CI: 0.10-0.87; p=0·031) (34) Level I. Nonetheless, HPV DNA as a single primary screening test or co-test every three to five years is an alternative for women above 30 years old. However, in view of its high cost, it is not offered regularly.  Visual inspection with acetic acid is also an alternative method of screening. It has high sensitivity and specificity but poor positive predictive value. Furthermore, colposcopy training and other resources are needed before recommending this for routine use (35) Level I, (36) Level II-2 .

 Age of initiation  A cohort study in Manchester showed that the cumulative risk of developing CIN3/cervical cancer begins at age 20 years, after which the incidence increases (37) Level II-2. In a 20052009 cohort analysis in US, the incidence rate of cervical cancer among women younger than 20 years was 0.2%, increasing up to 14% from age 20 years onwards till age 44 after

Screening tests

37

which it decreases (38)

Level II-2

. Despite a high prevalence of HPV infection among younger

age groups following sexual debut, very few infections persist beyond two and a half years.  Those with persistent infection have an increased risk of cervical abnormalities (39)  Level II-3. Furthermore, the prevalence rates of biopsy-proven dysplasia of any grade and cervical cancer were highest among women younger than 30 years of age. Screening women aged 20–24 years old had no detectable impact on reducing cervical cancer rates in women under 30 years. The risk of mortality from screening women age 22-24 years old was not significant either (OR: 1.1, 95% CI: 0.8-1.5) (40). In addition, CIN2 and CIN3 cases peak at 25-29 years old with an incidence rate of 3.8 and 4.1 /1000 smears, respectively. Screening women starting at the age of 25 confers benefit in reducing cervical cancer mortality and morbidity (40).

Interval of screening In a cohort of women followed up every year for three years in a Pap smear programme, the prevalence of CIN2 and 3 decreased after two consecutive screenings (41) Level II-2. Among younger age groups, there was little difference in the prevalence of dysplasia between women who had one negative test compared to two negative tests but screening once every three years after the last negative test was anticipated to result in an average of five extra cases of cancer per 100,000 women (41) Level II-2. For women aged 25 and above, screening with cytology every three years is adequate. A shorter interval of screening is associated with increased unnecessary colposcopy (42).  Among women aged 30 to 64 years who have had three or more negative cervical cancer results from prior screening done once in three years have an excess cancer risk of no more than 3 in 100,000 compared to annual screening (41) Level II-2. A vast majority of cervical cancers in older women occurred in those who were not previously screened or who did not have three consecutive normal cytology results (17) Level III. Screening women above 65 years old who have had two previous normal smears confers minimum benefit (42). Women aged above 65 who have not had regular cytology screening benefit from three consecutive screens.

5.4

Harm of screening

Harm from screening for cervical cancer may occur when cervical abnormalities are overinterpreted, especially in women with low risk of developing invasive cancer. CIN1 has to be managed as CIN1 and not looked at as a positive endo–cervical curettage because most episodes of CIN1 are transient and do not usually progress to CIN3. Similarly, with the high prevalence of HPV and cervical abnormalities among younger women, the American Society for Colposcopy and Cervical Pathology in 2011 has made some changes to be

38

Harm of screening

more conservative with younger women with CIN (25). Approximately 55,000 cytologies are required to detect one case of cervical cancer in women aged less than 24 years old which does not justify close follow-up for minor cervical abnormalities. When a young woman knows that she carries a high-risk type HPV, the effect on her emotional health can be detrimental. The distress that comes from receiving the news may be accompanied by feelings of shame and also impose a stigma even though subsequent follow up is reassuring (41, 43). Some studies have indicated a negative effect on pregnancy when treating a pre-cancerous lesion. A meta-analysis has shown some evidence of increase in preterm delivery, perinatal mortality and low birth weight with ablation therapy for pre-cancerous lesion. Loop excision also carries a small risk (44).

REFERENCES 1. 2.

3.

4.

5.

6.

7.

Watson M, Saraiya M, Benard V, et al.Burden of cervical cancer in the United States from 1998 -2003. Cancer 2008;113(10 Suppl):2855-64. Zainal Ariffin O, Zainudin MA, Nor Saleha IT. Malaysia cancer statistics-data and figure Peninsular Malaysia 2006.National Cancer Registry 2006, Ministry Of Health Malaysia. Bruni L, Barrioneuvo-Rosas L, Albero G, and et al. ICO information centre on HPV and Cancer (HPV infornation centre). Human Papillomavirus and related diseases in Malaysia. Summary report 2015-03-02. Data accessed on 10th April 2015. Ministry of Health Malaysia. Annual Health Report 2011 [Internet]. Putrajaya; 2011. (cited 29 April 2015). Available from: http://vlib.moh.gov.my/  cms/documentstorage/com.tms.cms.document. Document_433472a1-a02c4149-1b47cc20e49f321e/2012%20(English).pdf Cooper D, Hoffman M, Carrara H, et al. Determinants of sexual activity and its relation to cervical cancer risk among South African women. BMC Public Health 2007;7:341. Louie KS, de Sanjose S, Diaz M, et al. Early age at first sexual intercourse and early pregnancy are risk factors for cervical cancer in developing countries .Br J Cancer 2009;100(7):1191-7. International Collaboration of Epidemiological Studies

8.

9. 10.

11.

12.

13.

of Cervical Cancer. Cervical Carcinoma and Sexual Behavior: collaborative re-analysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies. Cancer Epidemiol Biomarkers Prev 2009;18:1060-9. Parazzini F, Chatenoud L, La Vecchia C, et al.Determinants of risk of invasive cervical cancer in young women. Br J Cancer 1998;77(5):838-41. Muñoz N, Bosch FX, de Sanjosé S, et al.Epidemiologic classification of Human Papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518-27. Smith JS, Lindsay L, Hoots B, et al.Human Papillomavirus type distribution in invasive cervical cancer and highgrade cervical lesions: a meta-analysis update. Int J Cancer 2007;121:621-32. Lacey JV Jr, Swanson CA, Brinton LA, et al. Obesity as a potential risk factor for adenocarcinomas and squamous cell carcinomas of the uterine cervix. Cancer 2003;98:814-21. Kjaer SK, van den Brule AJ, Paull G, et al. Type specific persistence of high risk Human Papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study. BMJ 2002;325:1-7. Brown DR, Shew ML, Qadadri B, et al. A longitudinal study of genital Human Papillomavirus infection in a

References

39

REFERENCES

14.

15.

16.

17.

18.

19.

20. 21. 22. 23.

24.

25.

26.

40

cohort of closely followed adolescent women. J Infect Dis 2005;191(2):182-92. McIntyre-Seltman K, Castle PE, Guido R, et al. Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic Human Papillomavirus DNA-positive women with equivocal or mildly abnormal cytology. Cancer Epidemiol Biomarkers Prev 2005;14(5):116570. International Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer 2006;120:88591. Adjorlolo-Johnson G, Unger ER, Boni-Ouattara E, et al. Assessing the relationship between HIV infection and cervical cancer in Côte d’Ivoire: A case-control study. BMC Infect Dis 2010;10:242. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number 109, December 2009: Cervical cytology screening. Obstet Gynecol 2009;114: 1409-20. Du J, Näsman A, Carlson JW, et al. Prevalence of Human Papillomavirus (HPV) types in cervical cancer 2003 - 2008 in Stockholm, Sweden, before public HPV vaccination. Acta Oncol 2011;50(8):1215-9. Damm O, Nocon M, Roll S, et al. Human Papillomavirus (HPV) vaccination for the prevention of HPV 16/18 induced cervical cancer and its precursors. GMS Health Technol Assess 2009; 5:4. Steven E Waggoner. Cervical cancer. Lancet 2003; 361: 2217–25 Peirson L, Fitzpatrick-Lewis D, Cliliska D, Warren R. Screening for cervical cancer: A systematic review and meta-analysis. Systematic Reviews 2013;2:35. Sankaranarayanan R, Nene BM, Shastri SS, et al. HPV screening for cervical cancer in rural india. N Engl J Med 2009;360(14):1385-93. Othman N, Beena CRV, Halimah Y. Cervical Cancer Screening; patient’s understanding in major hospitals in Malaysia. Asian Pac J Cancer Prev 2009;10:569-74. Aljunid S, Zafar A, Saperi S, Amrizal M. Burden of disease associated with cervical cancer in Malaysia and potential costs and consequences of HPV vaccination. Asian Pac J Cancer Prev 2010;11(6):1551-9. Massad LS, Einstein AH, Huh WK and et al. 2012 Updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17:S1-27. Waxman AG. Guidelines for cervical cancer screening: history and scientific rationale. Clin Obstet Gynecol 2005;48(1):77–97

References

27. Arbyn M, Bergeron C, Klinkhamer P, et al. Liquid compared with conventional cervical cytology: a systematic review and meta-analysis. Obstet & Gynecol 2008 ;111(1):167-77. 28. Evelyn P. Whitlock, MPH; Kimberly K. Vesco, MD, MPH; Michelle Eder, PhD; Jennifer S. Lin, MD, MCR; Caitlyn A. Senger, MPH; and Brittany U. Burda, MPH LiquidBased Cytology and Human Papillomavirus Testing to Screen for Cervical Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:687-97. 29. Elfgren K, Kalantari M, Moberger B, et al. A populationbased five-year follow-up study of cervical human papillomavirus infection. Am J Obstet Gynecol 2000;188(3):561-7. 30. Datta SD, Koutsky LA, Ratelle S, et al. Human Papillomavirus infection and cervical cytology in women screened for cervical cancer in the United States, 20032005. Ann Intern Med 2008;148:493-500. 31. Moyer VA, U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. preventive Services Task Force Recommendation Statement. Ann Intern Med 2012;156;880-91. 32. Katki HA, Kinney WK, Fetterman B, et al. Cervical cancer risk for women undergoing concurrent testing for Human Papillomavirus and cervical cytology: a population-based study in routine clinical practice.The Lancet Oncology 2011;12(7):663-72. 33. Noormah MD, Chandriah H, Rosliza L. HPV DNA based screening test for cervical cancer. Health Technology Assessment Report 2010. Ministry of Health Malaysia. 34. Rijkaart DC, Berkhof J, Rozendaal L, et al. Human papillomavirus testing for the detection of high-grade cervical intra-epithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol 2012;13:78–88 35. Sauvaget C, Favette JM, Muwone R, et al. Accuracy of visual inspection with acetic acid for cervical cancer screening. Intl J Gynecol & Obstet 2011;113(1):14-24. 36. Arbyn M, Sankaranarayanan R, Muwonge R, et al. Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India. Inlt J Cancer 2008;123(1):153-60. 37. Peto J, Gilham C, Deacon J, et al. Cervical HPV infection and neoplasia in a large population-based prospective study: the Manchester cohort. Br J Cancer 2004;91:942-53. 38. U.S. Department of Health and Human Services National Cancer Institute, (NCI) cancer incidence surveillance, epidemiology, and end results (SEER 18) registries research data (adjustments for areas impacted by Hurricanes Katrina and Rita, 2005). National Cancer Institute, Surveillance Systems Branch, Bethesda, USA. 39. Rodriguez AC, Burk R, Herrero R, et al. The natural

40.

41.

42.

43. 44.

history of Human Papillomavirus infection and cervical intraepithelial neoplasia among young women in the guanacaste cohort shortly after initiation of sexual life. Sexually Transmitted Diseases 2007;34(7):494-502. Care Canada. Screening for Cervical Cancer (2013) [Internet]. Canadian Task Force on Preventive Health Care. 2013 [cited 28 April 2015]. Available from: http://  canadiantaskforce.ca/ctfphc-guidelines/2013-cervicalcancer/  Sawaya GF, McConnell KJ, Kulasingam SL, et al. Risk of cervical cancer associated with extending the interval between cervical-cancer screenings. N Engl J Med 2003;349(16):1501-9. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, And American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Ca Cancer J Clin 2012;62:147-72. Rogstad KE. The psychological impact of abnormal cytology and colposcopy. BJOG 2002;109:364–8 Arbyn M, Kyrigiou M, Simoens S et al. Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis. BMJ 2008;337:a1284.

References

41

06

Breast Cancer SUMMARY

Breast cancer is the most common cancer among women in Malaysia. Breast cancer in Malaysia starts at a relatively early age from 30-39 years old and presents at an advanced stage. Compared to women 50 years and above, screening women aged 40-49 years leads to a relative reduction in mortality but requires a higher number of women to be screened to prevent one death.

RECOMMENDATIONS

For women below 50 years of age, the decision to offer screening depends upon the discussion on harm, benefit, risk and patient’s preference. For women aged 50 -74 years, screening with mammogram is indicated every two years.

Grade B

For women aged above 75 years, routine screening is not indicated. Instructing women on self-breast examination should only be incorporated as breast health awareness.

6.1

Introduction

Breast cancer is still the most common cancer among women even though the rate has reduced from an age standardized ratio (ASR) of 47.4 per 100,000 population in 2003 to an ASR of 39.3 per 100,000 population in Malaysia in2005 (1, 2). Although the incidence rate in Malaysia is comparable to some of the  ASEAN countries, it has one of the highest annual mortality rates at 6% per year over the period 1997-2008 (3). While it peaks at 50-59 years, the incidence in Malaysia starts to rise at a lower age from 30-39 years compared to the United States where the risk increases from 40 years onwards (2, 4). In Malaysia, women with breast cancer tend to present late. Specifically, a substantial number (up to 40%) of women with breast cancer in this country present at an advanced stage, with only 14% presenting at stage 1 (3, 5). On 42

Introduction

average, women present with a 4cm lump, mostly at stage 2 of the disease (1, 5, 6,). A larger tumour is associated with a higher staging of tumour. It was thought that the breast lumps of women with breast cancer would be smaller if screening modalities were strengthened (7). However, the recommendations for breast cancer screening remain controversial.  The risk of breast cancer can be stratified according to the table shown below: Low Risk  (RR 1.0 - 1.4)

o Alcohol consumption o Reproductive factors: • Increasing age at first full term pregnancy > 30 years • Hormone replacement   therapy • Oral contraceptive pills o Obesity

Moderate Risk  (RR 1.5 - 2.0)

High Risk  (RR > 2.0)

o Increasing age from 40 years old o Reproductive factors: • Early menarche (< 12 years old) (RR 1.02) • Late menopause (> 55 years old) (OR 2.4) • Nulliparity o Benign breast disease with proliferation without atypia o Dense breast

o Personal history of invasive breast cancer o Lobular Carcinoma In Situ (LCIS) and Ductal Carcinoma In Situ (DCIS) o Benign breast disease with atypical hyperplasia o Ionising radiation from treatment of breast cancer, Hodgkin’s disease, etc o Carrier of BRCA1 and 2 genetic mutation o Significant family history, i.e., first degree family with breast cancer

*RR-relative risk compared to the normal population without risk   Adapted from Clinical Practice Guideline 2010, Malaysia (8) with permission from Health Technology Assessment, Ministry of Health Malaysia.

6.2

Benefit of screening and treating breast cancer

 A systematic review of trials have identified up to eight randomised controlled trials (RCT) assessing cancer mortality with screening. In general, a 20% decrease in the relative risk of breast cancer mortality is expected from systematic cancer screening (9). A Canadian  Task force found a reduction in breast cancer mortality with screening at a median of 11.4 years of follow-up (RR:0.81, 95%CI:0.74-0.88) (10). Another meta-analysis has also shown a reduction in breast cancer mortality across all ages (RR:0.81, 95%CI:0.74-0.87). However, due to variations in the quality of randomisation, a sub-analysis of the trials with high qualities did not reveal a similar significant reduction (RR:0.90, 95%CI:0.79-1.02) (11). Similarly, a recent RCT in Canada did not demonstrate a reduction in breast cancer mortality with mammography screening for women aged 40-59 even after25 years of follow-up (RR: 1.05 (95% CI:0.85 to 1.30) (12). In countries with high breast cancer awareness, it has been argued that screening adds little benefit to cancer mortality. Women with tumours detected through mammogram have a better survival rate compared to those detected through routine clinic care (70.6% of Benefit of screening and treating breast cancer

43

25-year survival compared to 62.8%). This is because a mammogram can detect smaller tumour sizes, and not because of the screening programme per se. The Canadian breast screening study shows that the mean size of tumour found during screening was significantly smaller (19mm) compared to the size from routine clinical care (21mm). Also, women with tumours less than 20mm have a 25-year survival of 77% compared to 54% among those with tumours greater than 20mm (HR:0.46, 95% CI:0.37-0.58). However, once palpable, the 25-year survival for women who have had mammography was similar to the control group (66.3% versus 62.8%) (12). It was concluded that the benefit seen in screening was due to a higher number of elderly women being diagnosed with tumours which were non-palpable in the intervention group (12). In the USA, there has been a very small decrease in advanced cancer mortality attributable to screening (13). Despite the incidence of early-stage breast cancer in USA increasing from 112 cases in 1976 to 234 cases per 100,000 women in 2008 (a 109% increase), the incidence of late-stage cancer has decreased only by 8%, from 102 to 94 cases per 100,000 women, while the incidence of distant metastases has remained similar (11). The declining trend in breast cancer mortality is thought to be due to advancements in the treatment regime, which is seen to affect all stages of the disease, and is independent of tumour characteristics (11). There have been considerable recent advancements in treatment. Treatments using anti-hormones and new poly chemotherapy are noted to be effective even when the cancer has metastasized (14). Hence, for tumours beyond 20mm, screening does not confer any benefit in terms of its detection rate (15). It should be noted that this trend is seen among countries with a high awareness of breast cancer. In view of the many controversies with regards to the absolute benefit of screening, especially with mammography, the decision for or against mammography should be individualized. It should involve an exchange of information on risks, benefits and alternatives, and consideration of patients’ preference, values and reservations (9). Support for the decisionmaking process has been reported to increase women’s knowledge in screening risks and benefits. Individuals with better knowledge seem to be less likely to go for unnecessary screening (9). In a country with a high rate of late presentation and large tumour size at diagnosis, screening may be beneficial because many would not seek treatment early despite having clinically palpable tumours (8).

6.3

Screening tests

Over the past many years, a few modalities have been used to screen for breast cancer. In the general population, there is no evidence to show that clinical breast examination or breast self-examination reduces mortality from breast cancer or from any other cause (16). Breast self-examination (BSE) appears to be ineffective in reducing breast cancer mortality (17). A systematic review did not show any reduction in breast cancer mortality associated with teaching regular breast self-examination to women aged 31–64 years. Instead, 44

Benefit of screening and treating breast cancer

increased harm was seen from detecting benign biopsies (RR 1.5, 95% CI 1.1–1.9) (16, 17). BSE is recommended for raising awareness among women at risk rather than as a screening method. In fact, increasing breast cancer awareness seems to have been an important motivation for women. In Denmark, before the era of screening, the average tumour size at diagnosis in 1978-79 was larger at 33 mm compared to 24 mm average at diagnosis in 1988-89. This difference is greater than the size difference found with screening which was only 5 mm (11, 14). Current evidence is insufficient to assess the additional benefits and harms of clinical breast examination (CBE) (18). Studies involving CBE have shown promising outcomes to downstage the cancer upon diagnosis but the studies have not taken into consideration the effect of over-diagnosis from other concomitant screening tests nor the quality of the process done (19). A review on CBE showed many poorly executed CBE performance (19). A recent RCT has suggested that screening using mammography may have a higher detection rate if a thorough physical breast examination is done (12). Therefore, CBE can still be used as part of a screening method as per normal practice especially for women from countries who present with advanced stage cancer. Screening using MRI scans for women with average breast cancer risk has not been evaluated compared with mammography, CBE or SBE. Thus, screening women at average risk using MRI scans is not recommended (16, 18).

Mammography for women aged 40-49 years  The net benefit of screening this group with mammography is small compared to screening higher risk groups. In addition to queries on the quality of the supporting evidence, a higher risk of false-positive results has been noted. (11). The USPSTF has stated that screening with mammography results in a 15% reduction in breast cancer mortality among women aged 39-49 years old (18). In one systematic review that excluded trials with suspected flawed randomization, the risk of dying from breast cancer was lower with screening (RR: 0.84, 95%CI: 0.75-0.96)(9). As estimated, if 10,000 of these women had an annual screening done for 10 years, about 190 would be diagnosed with invasive cancer and up to 16 deaths could be prevented. At the same time, however, an estimated 6,130 women would have more than one false positive result over 10 years of screening (9). Meta-analysis also showed that to prevent one death from breast cancer among women in this age group, 1,904 women would have to be screened (9).  The Canadian Task Force also agreed that mammography is associated with a reduction in breast cancer mortality but in view of the lower risk of developing cancer in this age group, the absolute risk benefit is much lower than for older age groups. The Task Force estimated that 2,108 women needed to be screened with mammography every two years for a median of 11 years to prevent one cancer death. In the same analysis, 690 women would have a

Screening tests

45

false-positive result from a mammogram, leading to 75 women having a potentially avoidable biopsy of their breasts (16).  Thus, the net benefit of screening young women is small and the harm is high with a high number needed to screen to prevent death. It should be noted, however, that the evidence described is mostly derived from developed countries. The recommendation on screening women aged less than 50 in Malaysia needs to consider the tendency for breast cancer to be diagnosed at younger ages, the high mortality rate and the advanced stage of presentation seen in this country compared to developed countries. At present, the Malaysian clinical guideline does not recommend routinely screening women aged 40-49 years old with average risk but these women should not be denied this procedure if they prefer to have it done (8). The decision to execute screening has to consider the risks, benefit and harm from mammography in this age group.

Mammography for women aged 50-69 years  The risk reduction for women aged 50-59 is reported to be similar to younger women (RR: 0.86, 95%CI: 0.75-0.99) but the benefit of screening is estimated to be higher (9). To prevent one death from breast cancer, 1,339 women need to be screened (9, 18). Similarly, if 10,000 of these women underwent a screening every year for 10 years, a higher number of invasive cancers would be detected and deaths prevented compared to screening younger women; an estimated 302 cases and up to 32 deaths. The estimated number of false positive results would be similar to the one estimated for younger women (6,130) (9).  A review of seven studies by the Canadian Task Force demonstrated that, screening leads to a reduction in breast cancer mortality (RR 0.79, 95% CI 0.68-0.90) among women aged 50 to 69 years. However, the decrease in risk becomes non-significant when the metaanalysis was restricted to properly randomized studies (RR 0.91, 95% CI 0.74–1.11) (10).  The Canadian Task Force also stated that in order to prevent one death among women 5069 years old, 720 women would have to be screened, 204 of which would produce false positive results resulting in 26 unnecessary biopsies (16). Regardless, this is more efficient than screening the younger age group. In Denmark, after over 17 years of observations, screening for breast cancer is offered only to 20% of women. A 10-year follow-up cohort study of screened women aged 55 to 74 years showed no reduction in mortality. In fact, a significant reduction was seen among women who came from non-screened areas (RR: 0.98, 95%CI: 0.97-0.99). In its conclusion, this reduction was attributed to the use of Tamoxifen as a treatment since changes were already seen at a premature stage of the screening programme (13). Screening at more than 24-month intervals resulted in more mortality reduction than the ones at less than 24 months intervals (RR: 0.86; 95%CI 0.75–0.98 vs RR: 0.67; 95%CI: 0.51–0.88). Furthermore, screening every 33 months portrayed a similar trend in benefit even though the finding was not statistically significant (RR: 0.70; 95%CI: 0.45-1.09) (16). 46

Screening tests

Mammography for women aged over 74 years Routine screening for breast cancer is not recommended for women this age group. A systematic review revealed that a meta-analysis of two studies on mammography screening for women aged ≥70 years found a non-significant reduction in breast cancer mortality (RR 0.68, 95% CI 0.45–1.01) (10). Similarly, a comparative study in Denmark showed no significant changes between the screened and non-screened group of women age 75 to 84 years (13). These women are more likely to die due to other conditions then breast cancer (18).

6.4

Harm of screening

 Across all ages, the cumulative risk of a false-positive result for women after 10 mammograms ranges from about 21% to 49%. This rate is most commonly seen among younger women; 97.8 per 1,000 women aged 40-49 years, when their risk for invasive cancer is the lowest (1.8 per screening round). In Japan, even though the rate is reported to be lower than in Europe, younger women still have the highest rate of false positive results (20). Over-diagnosis occurs when tumours with limited malignant potential are diagnosed and treated, such as cancer in situ, or tumours are diagnosed in women who are at higher risk of dying from other causes such, as old age (9, 18). A meta-analysis of studies from six European countries revealed an over-diagnosis of 52% from mammography screening programmes (21). Over-diagnosis and overtreatment expose women diagnosed with breast cancer to unnecessary psychological distress. Women with false positive biopsy results also suffer unnecessary psychological distress and the effect is prolonged. The severity of the psychological distress in women with a false positive biopsy result was noted to be between that for healthy women and those with breast cancer even three years after they have been declared free from cancer (22). Many women (26%-77%) reported experiencing varying degrees of pain during a mammogram and some women decline from going to the second round of screening primarily due to the pain from a previous mammography (23). Even though there has been no study evaluating the effect of mammography in inducing cancer, radiotherapy from the treatment of breast cancer among women aged 70 has been noted to increase relative mortality due to heart failure and lung cancer by 27% and 78%, respectively (24). This is particularly important for women with cancer detected through by screening because the cancer may be over diagnosed and over treated in almost a third of women (11, 21, 25).

Harm of screening

47

REFERENCES 1.

2.

3. 4. 5.

6. 7.

8.

9. 10.

11. 12.

13. 14.

15. 16.

48

Maznah D, Sofea R, Awang MB. Breast cancer prevention and control programs in Malaysia. Asian Pacific Journal of Cancer Prevention 2011;12:1-4. Malaysian Cancer Statistics - Data and figure Peninsular Malaysia 2006 [Internet]. 1st ed. National Cancer Registry, Ministry of Health Malaysia; 2006 [cited 4 May 2015]. Available from: http://www.moh.gov.my/images/  gallery/Report/Cancer/MalaysiaCancerStatistics2006. pdf Youlden DR, Cramb SM, Yip CH, Baade PD. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med 2014;11(2) Jemal A, Siegel R, Ward E, et al. Cancer Statistic 2008. CA Cancer J Clin 2008;58:71-96. Yip CH, Taib NA, Ibrahim M. Epidemiology of breast cancer in Malaysia. Asian Pacific J Cancer Prev 2006;7:369-74 Leong BDK, Chuah JA, Kumar VM, et al. Trends of breast cancer treatment in Sabah, Malaysia: a problem with lack of awareness. Singapore Med J 2009;50(8):772-6. Taib NA, Yip CH, Ibrahim M, et al. Breast cancer in Malaysia: Are our women getting the right message? A 10 year experience in a single institution in Malaysia. Asian Pac J Cancer Prev 2007;8(1):141-5. Clinical Practice Guidelines (CPG); Management of Breast Cancer [Internet]. 2nd ed. Malaysia: Ministry of Health (MOH), Malaysia; 2010 [cited 5 May 2015]. Available from: http://www.moh.gov.my/attachments/6915.pdf Pace LE and Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014;311(13):1327-35 Breast Cancer Screening [Internet]. 1st ed. Canada: Canadian Task Force on Preventive Health Care (CTFPHC); 2011 [cited 5 May 2015]. Available from: http://canadiantaskforce.ca/files/guidelines/2011breast-cancer-systematic-review-en.pdf Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;Issue 6. Miller AB, Wall C, Baine, Ping Sun, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 2014;348 Jørgensen K. Is the tide turning against breast screening?. Breast Cancer Research 2012;14(4):107. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15year survival: an overview of the randomised trials. The Lancet, 2005;365(9472):1687-717. Jørgensen KJ, Zahl P, Gøtzsche PC. Breast cancer mortality in organised mammography screening in Denmark: comparative study. BMJ 2010:340;1241 The Canadian Task Force on Preventive Health Care (CTFPHC). Recommendations on screening for breast

References

17. 18.

19. 20.

21.

22.

23.

24.

25.

cancer in average-risk women aged 40–74 years. CMAJ 2011;183(17):1991-2001. Kösters JP, Gøtzsche PC. Regular self-examination or clinical examination for early detection of breast cancer. Cochrane Database Syst Rev 2003;Issue 2. US Preventive Services Task Force. Recommendation Summary - US Preventive Services Task Force [Internet]. 2009 [cited 5 May 2015]. Available from: http://  www.uspreventiveservicestaskforce.org/Page/Topic/  recommendation-summary/breast-cancer-screening Miller AB, Baines CJ. The role of clinical breast examination and breast self-examination. Prev Med 2011;53:118-20. Suzuki A, Ishida T and Ohuchi N. Controversies in breast cancer screening for women. Jpn J Clin Oncol 2014;44(7):613-18 Jørgensen KJ, Gøtzsche PC. Over-diagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ 2009;339:2587 Brodersen J, Siersma VD. Long-term psychosocial consequences of false-positive screening mammography. Ann Fam Med 2013;11(2):106-15. Armstrong K, Moye E, William S, Berlin JA and Reynolds EE. Screening mammography in women 40 to 49 years of age: A systematic review for the American College of Physicians. Ann Intern Med. 2007;146:516-26 Ring A, Reed M, Leonard R, et al. The treatment of early breast cancer in women over the age of 70. Br J Cancer 2011; 105, 189 -193. Kalager M, Adami HO, Bretthauer M, and Tamimi RM. Over-diagnosis of invasive breast cancer due to mammography screening: results from the Norwegian screening program. Ann Intern Med. 2012;156:491-9.

07

Colorectal Cancer SUMMARY

In Peninsular Malaysia, colorectal cancer (CRC) is the most common cancer in males and the second most common, after breast cancer, in females. CRC is a slow growing disease for approximately 10 years from adenomatous polyps to invasive cancer, thus, providing an opportunity for screening. A few modalities of screening tests are available with varying degrees of sensitivity and specificity. Faecal occult blood tests (FOBT), followed by colonoscopy, after positive test results has been shown to reduce CRC mortality by 13-21% after 8-13 years of screening, and 25% after adjusting for attendance to screening. Harm associated with screening procedures including colonoscopy is small <1% (10/1,000 procedures).

RECOMMENDATIONS

In average-risk individuals aged 50 to 75 years old, yearly screening using gFOBT or iFOBT is indicated.

Grade A

Alternative screening strategies for average risk individuals are colonoscopy every 10 years or sigmoidoscopy every 5 yearly plus FOBT every 3 years.

Grade A

In increased-risk individuals, colonoscopy is indicated every 5 years from age 40 years or at an age 10 years younger than the age of first diagnosis of CRC in family.

Grade A

7.1

Introduction

Colorectal cancer (CRC) is a worldwide problem with an annual incidence of approximately one million cases and an annual mortality of more than 500,000 worldwide (1). In Malaysia, the published incidence of cancer in 2007 showed CRC is the second most common cancer in males after trachea, bronchus and lung cancer and the second most common in females after breast cancer (2). In 2007, there were 2,246 cases of CRC, which represents 12.3% of all cases registered with the National Cancer Registry. The incidence was slightly higher Introduction

49

among males (ASR 13.4/100,000) compared to females (ASR 10.2/100,000 population).  The incidence was highest among Chinese Malaysians with ASR of 19.4/100,000 and 14.6/100,000 for male and female respectively, and lower among Malays and Indians with  ASR of 10.1/100,000 (male) and 7.5/100,000 (female), 10.2/100,000 (male) and 6.9/100,000 (female) respectively (2). In Malaysia, the incidence of the CRC is shown to increase exponentially with age then plateaus in the sixth decade. More than 80% of CRC occurred above 50 years of age and peaked at the age of 60 years. Only 5%-8% of cases reported were below 40 years of age (2, 3). The incidence peaked at a younger age group in males compared to females - 60-69 years in male (29.1%) and above 70 years in females (30.5%), respectively (4). CRC is a slow growing disease that may present without symptoms for several years. In most cases, up to 70-90% of CRC arise from the formation of small, non-cancerous or adenomatous polyps (5, 6). The average time from onset of a polyp (<1cm) to onset of carcinoma –the dwell time –is about 10-15 years (7, 8). However, the dwell time appears to vary with the location of the cancer. It is longer in the distal colon than in the proximal colon and it is shortest in the recto-sigmoid segment (5). Given that adenomatous polyps are precursors to cancer and that polyps and early cancers are usually asymptomatic, there is strong rationale to support screening asymptomatic individuals for early cancer detection and prevention.  Three categories of risk for colorectal cancer are suggested: (9, 10) Low Risk

Asymptomatic individuals aged < 50 years with negative family history

Average risk

Increased risk  

Asymptomatic individuals aged ≥ 50 years • with negative family history, Or • with 1 first degree relative diagnosed with CRC aged ≥ 60 years* Or • with non-first degree relative with CRC

Asymptomatic individuals at any age with • 1 first degree relative diagnosed with CRC < 60   years Or • 2 first or second degree relatives diagnosed with CRC at any age

* an individual with one first degree relative diagnosed with CRC at the age of 60 has a similar risk of CRC 10 years earlier then general population (11) 

 The following individuals are at higher risk of CRC than general population and require disease specific surveillance: • Individual with suspected or genetically diagnosed familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC)

50

Introduction

• Patients with Inflammatory bowel disease, chronic ulcerative colitis and Crohn’s  

colitis

 The surveillance should be undertaken in secondary or tertiary care settings.

7.2

Benefit of screening and treating colorectal cancer

 The main treatment modality for CRC is surgery with adjuvant chemotherapy or radiotherapy.  The prognosis after CRC treatment is very good. The 5-year survival rate for early-stage cancers is greater than 90%, whereas the 5-year survival rate for those diagnosed with widespread cancer is less than 10% (12). Screening program for CRC has been shown to reduce the incidence of CRC and improve CRC mortality. Two large RCTs using FOBT as the screening test showed a reduction of CRC mortality by 13-21% after 8-13 years of screening. The benefit in mortality can be delayed as the other two RCTs did not show mortality benefit until after 15-18 years of screening. Combined results from these four RCTs showed a 16% reduction in CRC mortality (RR 0.84; CI: 0.78-0.90) and three of the studies that used biennial screening interval showed a 15% reduction (RR 0.85, CI: 0.78-0.92). The non-compliance rate, however, for those RCTs ranged from 33-46% for the first screen and between 22-40% for at least one round of screening. After adjusting for attendance at screening, the relative risk mortality reduction was 25% (RR 0.75, CI: 0.66 - 0.84) for those screened (13) Level I. No study has evaluated whether screening colonoscopy alone reduces the incidence of or mortality from CRC in people at average risk (14-17) but polypectomy colonoscopy has been shown to reduce the incidence of CRC by 76-90% (18-20) Level II-2. Case-control studies of sigmoidoscopy have also reported a 59-80% reduction in mortality with a screening frequency of 5 and 10 years (21-24) Level II-2. The benefit of colorectal cancer screening for individuals with a life expectancy less than 10 years, however, was noted to be small (27).

Starting age for screening  The percentage of CRC among males is highest in the 60-69 years age group (29.1%) and among females, in ≥70 years age group (30.5%) (2). Due to the estimated 10-year timescale for the adenoma-carcinoma sequence, experts agree that screening should target those over 50 years (25). Moreover, screening colonoscopy in people aged 40–49 years confirms that CRC are uncommon in this age group and supports the recommendation that screening of average-risk individuals should begin at age 50 years (26). Routine screening in asymptomatic individuals aged above 75 years is not recommended due to small benefit and potential increased harms.

Benefit of screening and treating colorectal cancer

51

Screening interval   Yearly screening is more effective than biennial screening and individuals who follow through with screening will have a greater benefit. Although the sensitivity of a single gFOBT is low (30-50%), a programme of repeated annual testing can detect as many as 92% of cancers (27). After 18 years of follow-up, yearly FOBT resulted in a cumulative reduction of CRC deaths by 33% compared to 21% reduction from biennial testing (28). For individuals who have undergone polyp excision, a cohort study showed that development of advanced neoplasia was rare up to 5 years after a negative colonoscopy (18). In summary, average risk individuals should benefit from any of the following: (29-31) 1. FOBT annually between 50 to 75 years old 2. Colonoscopy every 10 years 3. Sigmoidoscopy every 5 years and FOBT every 3 years  Among increased risk individuals, e.g., with family history in a first degree relative, the risk of CRC parallels the risk in persons with no family history but precedes it by about 10 years (11). Hence, they would benefit from starting screening at younger age and at shorter intervals of screening. Generally, it is recommended to have colonoscopy every five years from age 40 years or at an age 10 years younger than the age of first diagnosis of CRC in the family.

7.3

Screening Tests

Screening tests for CRC broadly fall into two categories. In one category are the faecal tests, i.e., guaiac-based faecal occult blood test (gFOBT), immunochemical faecal occult bleeding test (iFOBT), and stool DNA test (sDNA), which are primarily effective in identifying CRC. In the second category are the partial or full structural examinations, i.e., flexible sigmoidoscopy, colonoscopy, double-contrast barium enema (DCBE), and computed tomography colonography (CT colonography), which are effective at detecting cancer and premalignant adenomatous polyps. These tests differ in complexity and accuracy for the detection of CRC and advanced neoplasia (33) (Appendix 1). Generally, the sensitivity of the tests in the order of the least to the most sensitive test are gFOBT < iFOBT < flexible < sigmoidoscopy < colonoscopy. The specificity for tests are also varied. In order from the least to the most specific tests are iFOBT≈ gFOBT < flexible sigmoidoscopy ≈ colonoscopy (32). Operator dependent tests such as flexible sigmoidoscopy, CT colonography and colonoscopy may have variations in the validity of the test from one setting to another. DCBE is not preferred because of poor sensitivity despite the hassle of bowel preparation. CT colonography is also not recommended because of the variability in reporting standard outside research settings (30). Up to now, only FOBT screening has been evaluated directly in RCTs for the mortality benefit of CRC cancer.

52

Screening Tests

Choices of FOBT  Special consideration is needed for FOBT. Three consecutive stools testing for the presence of occult blood is needed because identifying two positive test results has been shown to reduce the risk of CRC mortality (28, 29, 34, 35). Rehydration of gFOBT is not recommended.  Although rehydration of the guaiac-based slides increases sensitivity, the readability of the test is unpredictable, and rehydration substantially increases the false-positive rate (36, 37). Newer guaiac-based and immunochemical tests are available with improved sensitivity and acceptable specificity. Dietary restrictions during testing are recommended to reduce the false-positive rate for the more sensitive guaiac-based tests but are not necessary for the immunochemical and less sensitive guaiac-based tests. gFOBT requires three repeated samples while iFOBT requires only one sample. Single sample iFOBT was shown to have comparable specificity but better sensitivity than gFOBT (38). The participation rate for iFOBT and detection rate was also shown to be higher than with gFOBT, (38, 39) presumably because iFOBT is more convenient as it does not require dietary restriction and only a single sample.

7.4

Harm of Screening

Harms from colorectal cancer screening are related to false positive results and further testing with colonoscopy (31). Anxiety with false positive results has been documented but relief and assurance appeared to outweigh the initial negative emotion after the diagnostic workout (40). From a review for the US Preventive Service Task force, the estimated rate of serious harm from colonoscopy in the general population was 2.8/1,000 procedures. The serious outcomes included perforation, haemorrhage, diverticulitis, cardiovascular complications, abdominal pain and death (31). The risk of similar serious complications was almost 10 times lower in flexible sigmoidoscopy at 0.34/1,000 procedures (31). The estimates of harm from the reviews were lower than observed in several cohorts of colorectal cancer screening programmes outside controlled trial settings. The risks of adverse events associated with colonoscopy from screening programmes were 4.7-7.5/1,000 procedures for major events (41, 42) Level III and 100/1,000 for minor events (41). The main major adverse events reported include perforation or haemorrhage (41, 42). However, the majority of adverse events were associated with therapeutic procedures during colonoscopy (41, 42). Older individuals over 65 years old had a higher risk of complications (42). Based on a questionnaire survey among 10,078 individuals from Hong Kong, about half had reported bodily discomfort and physical harms from the screening (43) Level III. The survey findings were observational and based on a self-reported questionnaire from participants in a CRC screening programme. The bodily discomfort and physical harms were not defined.  Although CT colonoscopy may overcome the challenges related to endoscopic procedure

Harm of screening

53

and has an advantage over examining extracolonic anatomy, the risk of radiation has been noted, and uncertainty in the benefit of discovering extracolonic abnormalities. The radiation risk ri sk is small but could be significant signific ant at population level where whe re widespread CT-based CT-based screening is undertaken. Extracolonic abnormalities abnormalities findings are common (up to 1 in every 4 procedures) procedures) with 7-16% of patients with these abnormalities requiring further evaluation (31). In summary, summary, there is lack of published literature on benefits and harms of colorectal cancer screening locally. From the review of evidence from developed countries, the benefit of colorectal cancer screening was estimated to outweigh the harm (44). Although harms were commonly reported in the study based in Hong Kong, the degree of harm was not defined.

54

Harm of screening

 Appendix CRC1 T e st

FOBT

Validity gFOBT Sensitivity: 25–50% (28, 31) Specificity: 98–99% (37)

Potential advantages and disadvantages

• Simple, non-invasive, inexpensive, high   acceptance • Not diagnostic

iFOBT Sensitivity: 61-91% (31) Specific: 91-98% (31)

sDNA 

Sensitivity: 52% (45) Level II-2 Specificity 95% (45) Level II-2

• Improved sensitivity over gFOBT, but with no difference in specificity • No dietary modifications are needed, improved patient acceptance

Flexible sigmoidoscopy

Sensitivity ranges from 73.3% for small polyps to 96.7% for cancer and large polyps (46) Level I

• More expensive than gFOBT • Peri-procedural discomfort. • Serious complications, e.g., death, perforation, major bleeding, severe abdominal symptoms, and syncope have been reported.

Colonoscopy

Specificity ranges from 92% for small polyps to 94% for cancer and large polyps (46)  Level I

• Enable complete visualization of the entire colon, detection and removal of polyps and diagnostic sampling of cancers • Inconvenience of bowel preparation Operator dependent result, • Complications of procedure include sedation, perforation, • Availability of the services may be limited

Relative sensitivity of colonoscopy for colorectal cancer (95%) was greater than that for barium enema (82.9%) (47) Level II-2

DCBE

Sensitivity is 53% for polyps 6-10 mm in size and 48% for those >1 cm in size compared to colonoscopy (48) Level I

• • • • •

Enables evaluation of the entire colon Perforation rate is lower than that of colonoscopy Complete bowel prep is required Diagnostic sensitivity is inferior to colonoscopy Lacks therapeutic capability

CT colonography

Sensitivity was 94% for polyps of at least 10 mm in diameter and 94% for polyps of at least 8 mm and 89% for polyps at least 6 mm in diameter and specificity was 96%, 92% and 80% respectively (49) Level II

• • • • •

Higher patient acceptance Better imaging of the colon Enable visualization of extra-colonic findings, Risk of radiation exposure Availability of the services may belimited

Guaiac-based faecal occult blood test (gFOBT), immunochemical faecal occult bleeding test (iFOBT), and stool DNA test (sDNA].

 Appendix CRC1

55

REFERENCES 1. 2. 3.

4. 5.

6. 7. 8. 9. 10.

11. 12.

13.

14. 15.

16.

17.

56

World Health Organisation (WHO). Global cancer rate. Geneva 2003. Zainal Ariffin O, Nor Saleha IT. IT. NCR Report 2007. Kuala Lumpur: National Cancer Registry, Ministry of Health, Malaysia, 2011 Reis L, Eisner MR, Kosary CL. SEER Cancer statistic review 1975-2002. National Cancer Institute, Bethesda, USA 2007. MR Hassan, W Lim (eds). The first annual report of the National Cancer Patient Registry-Colorectal Cancer, 2007-2008. Kuala Lumpur, Malaysia 2010. Launoy G, Smith TC, Duffy SW, SW, et al. Colorectal cancer mass-screening: Estimation of faecal occult blood test sensitivity, taking into account cancer mean sojourn time. Int J Cancer 1997;73(2):220-4. Peipins LA, Sandler RS. Epidemiology of colorectal adenomas. Epidemiol Rev 1994;16(2):273-97. Stryker S, Wolff B, Culp C, et al. Natural history of untreated colonic polyps. gastroenterol 1987;93(5):1009-13. Morson BC. The evolution of colorectal carcinoma. Clinical Radiology 1984;35(6):425-31. Tejpar S. Risk stratification stratificat ion for colorectal cancer and implications for screening. Acta gastro-enterologica Belgica 2005;68(2):241. Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale—update based on new evidence. Gastroenterology 2003;124(2):544-60. Fuchs CS, Giovannucci Giovannucc i EL, Colditz GA, et al. A prospective study of family history and the risk of colorectal cancer. N Engl J Med 1994;331(25):1669-74. O’Connell JB, Maggard MA, Ko CY. CY. Colon cancer survival rates with the new American Joint Committee on cancer sixth edition staging. J Natl Cancer Inst 2004;96(19):1420-5. Hewitson P, P, Glasziou P, P, Irwig L, et al. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2011(2): CD001216. Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening: Clinical guidelines and rationale. Gastroenterol 1997;112(2):594-642. Smith RA, von Eschenbach AC, Wender R, et al. American Cancer Society guidelines for the early detection of cancer: Update of early detection guidelines for prostate, colorectal and endometrial cancers. CA Cancer J Clin 2001;51(1):38-75. U.S. Preventive Services Task Force. Screening for colorectal cancer: Recommendation and rationale. Ann Inter Med 2002;137(2):129-31. Rex DK, Johnson DA, Lieberman DA, et al. Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology. Am J Gastroenterol 2000;95(4):868-77.

References

18. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993;329(27):1977-81. 19. Citarda F, F, Tomaselli G, Capocaccia R, et al. The Italian Multicentre Study group. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001;48(6):812-5. 20. Thiis-Evensen Thiis-Evens en E, Hoff GS, Sauar J, et al. Populationbased surveillance by colonoscopy: effect on the incidence of colorectal cancer. Telemark Polyp Study I. Scand J Gastroenterol 1999;34(4):414-20. 21. Selby JV, Friedman GD, Quesenberr y CP, CP, Weiss Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326(10):653-7. 22. Muller AD, Sonnenberg A. Protection by endoscopy against death from colorectal cancer: A casecontrol study among veterans. Arch Intern Med 1995;155(16):1741-8. 23. Newcomb PA, Storer BE, Morimoto LM, et al. Long-term efficacy of sigmoidoscopy in the reduction of colorectal cancer incidence. J Natl Cancer Inst 2003;95(8):622-5. 24. Kavanagh AM, Fuchs CS, Giovannucci EL, Colditz GA. Screening endoscopy and risk of colorectal cancer in United States men. Cancer Causes Control 1998;9(4):455-62. 25. Radzi M, Lim W, Khamizar W, W, et al. The first annual report of the National Cancer Patient Registry - colorectal cancer 2007-2008. Med J Malaysia 2009;64 (Supp B 61). 26. Imperiale TF, TF, Wagner DR, Lin CY, CY, et al. Results of screening colonoscopy among persons 40 to 49 years of age. N Engl J Med 2002;346(23):1781-5. 27. Lee SJ, Boscardin WJ, Stijacic-Cenzer Stijacic-C enzer I, Conell-Price J, O’Brien S, Walter LC. Time lag to benefit after screening for breast and colorectal cancer: meta-analysis of survival data from the United States, Sweden, United Kingdom, and Denmark. BMJ 2013; 346:e8441. 28. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. N Engl J Med 1993;328(19):1365-71. 29. Mandel JS, Church TR, Ederer F, F, Bond JH. Colorectal cancer mortality: Effectiveness Of biennial screening for fecal occult blood. J Natl Cancer Inst 1999;91(5):434-7. 1999;91(5):434-7. 30. Sung JJ, JJ , Lau JY, JY, Young GP, GP, Sano Y,Y, Chiu H, Byeon J, et al. Asia Pacific consensus recommendations for colorectal cancer screening. Gut 2008;57(8):1166-76. 31. Whitlock EP, EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: a targeted, updated systematic review for the US Preventive Services Task Force. Ann Intern Med 2008; 149(9):638-58. 32. Pignone M, Sox HC. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149(9):627-37.

33. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: A joint guideline from the American Cancer Society, The US Multi-Society Task Force on colorectal cancer, and the American College Of Radiology. Gastroenterol 2008;134(5):157095. 34. Hardcastle JD, Chamberlain JO, Robinson MHE, et al. Randomised controlled trial of faecal-occultblood screening for colorectal cancer. Lancet 1996;348(9040):1472-7. 35. Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occultblood test. Lancet 1996;348(9040):1467-71. 36. Young GP, St John JB, Winawer SJ, Rozen P. Choice of fecal occult blood tests for colorectal cancer screening: Recommendations based on performance characteristics in population studies. Am J Gastroenterol 2002;97(10):2499-507. 37. Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult blood tests for colorectalcancer screening. N Engl J Med 1996;334(3):155-60. 38. Van Rossum LG, van Rijn AF, Laheij RJ, et al: Random comparison of guaiac and immunochemical faecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 2008;135:82-90. 39. Hol L, van Leerdam ME, van Ballegooijen M, et al: Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. Gut 2010;59:62-8. 40. McGovern PM, Gross CR, Krueger RA, Engelhard DA, Cordes JE, Church TR. False-positive cancer screens and health-related quality of life. Cancer Nurs. 2004;27(5):347-52. 41. Denis B, Gendre I, Sauleau EA, Lacroute J, Perrin P. Harms of colonoscopy in a colorectal cancer screening programme with faecal occult blood test: a populationbased cohort study. Dig Liver Dis 2013;45(6):474-80. 42. Rutter CM, Johnson E, Miglioretti DL, Mandelson MT, Inadomi J, Buist DS. Adverse events after screening and follow-up colonoscopy. Cancer Causes Control. 2012;23(2):289-96. 43. Wong M, Ching J, Hirai H, Lam T, Griffiths S, Chan F et al. Perceived obstacles of colorectal cancer screening and their associated factors among 10,078 Chinese participants. PLoS ONE 2013;8(7):e70209. 44. Richardson AK, Potter JD. Screening for colorectal cancer and prostate cancer: challenges for New Zealand. N Z Med J 2014;127(1395):23-30. 45. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351(26):2704-14.

46. Markowitz A, Winawer S. Screening and surveillance for colorectal cancer. Semin Oncol 1999;26:485-98. 47. Rex DK, Rahmani EY, Haseman JH, et al. Relative sensitivity of colonoscopy and barium enema for detection of colorectal cancer in clinical practice. Gastroenterol 1997;112(1):17-23. 48. Winawer SJ, Stewart ET, Zauber AG, et al. A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. N Engl J Med 2000;342(24): 1766-72. 49. Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349(23):2191-200.

References

57

08

Prostate Cancer SUMMARY

Prostate cancer is common in aging men. Screen-detected cancer often has an indolent clinical course. There is conflicting evidence on whether prostate cancer screening using PSA Level for the general population reduces mortality effectively. A large number of men need to be screened and treated to prevent one death from prostate cancer. The sensitivity and specificity of PSA test vary with different cut-off values. A cutoff value of 4ng/ml has a high false positive rate. Prostate cancer screening is associated with a high number of false positive and significant complications from prostate biopsy and treatment of screen detected prostate cancer.

RECOMMENDATIONS

Screening prostate cancer with PSA test is not indicated for the general population.

8.1

Grade D

Introduction

Prostate cancer is the second most common cancer among men worldwide with an age-standardized rate (ASR) of 28.5 cases per 100,000 persons in 2008 (1). In the United States of America (US), it is the most commonly diagnosed cancer with ASR of 66.2 per 100,000 persons per year, and the second leading cause of cancer death among American men (1, 2). In Malaysia, from the National Cancer Registry 2007, prostate cancer was the fourth most common cancer among men at 6.2% with men of Chinese ethnicity having the highest rate at 8.7 per 100,000 men followed by Indian (5.8) and Malay (4.8) (3). Comparatively, the incidence among men in the United States (US) or European countries is higher than in Asia. However, deaths from prostate cancer among the latter group are projected to increase compared to declining mortality rate in the US (2, 4). The increasing incidence and declining mortality rate among Americans and Europeans can be attributed to the higher screening pattern or improved 58

Introduction

treatment options (4, 5).  The prevalence of undiagnosed prostate cancer at autopsy is estimated to be as high as 70% at the age of 70 – 79 years old (5). The estimated lifetime risk of prostate cancer is 15.9%, but the lifetime risk of dying from prostate cancer is only 2.8% (6). Only a small proportion of men with prostate cancer presents with symptoms and dies from the disease. Most cases of prostate cancer progress slowly and are not life-threatening (5). In Sweden, where a high number of men undertake screening, most of the tumours diagnosed are localised with intermediate risk and an indolent clinical course (7). The risk factors for prostate cancer include:

• Increasing age (8) Level II-3, (9) Level III, (10) Level II-3 • Ethnicity - In Malaysia, Chinese men have the highest risk of developing prostate cancer followed by Indians and Malays (2, 10) Level II-3 • Positive family history of prostate cancer (OR: 2.5, 1.1-2.9)(8, 12) Level II-2; higher risk with a positive family history involving first degree relative, brother or more than two family members (13) Level I • Current smokers, especially heavy smoker (14)

Level I

In Malaysia, according to the 2007 National Cancer Registry, most of the prostate cancers in Malaysia were diagnosed at stage 3 or higher (15) The economic burden of prostate cancer treatment is high (4, 16) and even higher with advanced disease. Although late diagnosis and the high cost of treatment in late disease, determining the net benefit of screening for prostate cancer in developing Asian countries is challenging (5) because benefit of early detection from prostate cancer screening is controversial.

8.2

The benefit of screening and treating prostate cancer

 There is conflicting evidence on whether PSA, used as a prostate cancer screening modality for the general population, can reduce mortality effectively. Screening for prostate cancer detects more localised disease (17) Level I. In a report from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, among patients aged 55 to 74 years, the incidence of death from prostate cancer was low and did not differ between the group assigned to prostate specific antigen (PSA) and digital rectal examination (DRE) screening (2.0/10,000 person-years), and the control group (1.7/10,000 person-years) (18) Level I. In another randomised controlled trial with 20 years of follow-up in Sweden, among men aged 50-69 years, it was noted that there was no difference in the prostate cancer mortality rate between men assigned to screening with PSA and DRE (81%) and those not assigned to screening (86%) (19) Level I. On the contrary, the European Randomised Study of Screening and Prostate Cancer (ERSPC) mortality conducted among men aged 50-74 years old showed that, after

 The benefit of screening and treating prostate cancer

59

11 years of follow-up, the death rate from prostate cancer was reduced by 21% with PSA based screening (relative risk ratio 0.79, 95% CI: 0.68-0.91). However, in order to prevent one death from prostate cancer, 1,055 men needed to be screened and an additional 37 men needed to be treated. (20) A meta-analysis of 5 randomised controlled trials on the use of PSA as a screening for prostate cancer after more than 10 years initiating screening did not show convincing evidence of benefit in using PSA as an effective screening tool (21)

Level I

.

Given the various disease progressions of screened detected prostate cancer, the management of early prostate cancer is debatable. Management options include watchful waiting, active surveillance, surgery and radiation. No consensus has been made so far on the optimal management (6).

8.3

Screening tests

Prostate Specific Antigen (PSA) PSA test has high sensitivity but poor specificity and positive predictive value in diagnosing prostate cancer. The sensitivity and specificity vary with different cut off values. One study reported sensitivity of 73.9% and specificity of 51.9% for prostate cancer prediction when using a value less than 4ng/mL but lower sensitivity and higher specificity with a higher cut off value (22) Level III. Another study found that prostate cancer among men with PSA Level less than 0.5 and up to 4ng/mL was not unusual (6.6% with PSA at 0.5ng/mL to 26.9% with PSA 4ng/mL) (23) Level I. In other words, no Level of PSA can exclude prostate cancer (5). In the Prostate Cancer Prevention Trial (PCPT), PSA values at 1.1, 2.1, 3.1, 4.1 ng/mL yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of 38.9%, 72.5%, 86.7%, and 93.8%, respectively, in detecting prostate cancer (24)  Level I. There is no specific cut-off point of PSA for monitoring healthy men for their risk of prostate cancer and for suggesting biopsy. It is more of a continuum of risks at all values (24) Level I. Prediction of cancer by PSA is slightly better in men less than 70 years old compared to older men (Area Under the ROC 0.669±0.013, compare to 0.663±0.13, p=0.03) (24) Level III. Overall, the predictive value of PSA is not optimal.

Digital Rectal Examination (DRE) DRE has lower sensitivity than PSA in detecting prostate cancer. The sensitivity and specificity of DRE was 37% and 91%, respectively. The sensitivity was lower when the PSA is less than 3ng/mL but increased with higher PSA Levels. The positive predictive value of DRE when used in men with PSA less than 3ng/mL ranged from 4-11% but increased to 33-83% when the PSA exceeds 3ng/mL (25) Level I. Abnormal DRE findings may be useful in a selected population with abnormal PSA to avoid unnecessary biopsies and over-diagnosis.

60

Harm of screening

• The positive predictive value of an abnormal DRE (48.6%) done as an adjunct to PSA test for prostate cancer is higher in than when the DRE is normal (22.4%) (26) Level I . • High percentages of abnormal DRE (71.0%-85.7%) done as an adjunct to PSA test detects prostate cancer with poorer staging; Gleason score >7 (26) Level I • The detection rate of prostate cancer using DRE alone was 2.5%. It helped to detect 17% of the prostate cases that may not be detected when screened with PSA alone (25) Level I. In summary, the predictive value of PSA and DRE, either alone or in combination, may predict prostate cancer to a certain degree, but prediction is improved at higher PSA Levels. Despite the ability of prostate biopsy to confirm the diagnosis of prostate cancer, it is difficult to differentiate between indolent and aggressive cancer (6).

8.4

Harm of screening

False positive results are common and vary with different Levels of PSA. One study estimated false positive rates of 11.3% and 19.8% for a threshold of 4.0 and 3.0 ng/mL, respectively (5). In addition, men with false positive results were noted to suffer from persistent worry (6).  About one third of men who went through prostate biopsy experienced pain, fever, bleeding, infection and transient urinary difficulty, while serious complications requiring hospitalization were estimated to occur in 1% (27) to 2.1% (28) of cases. Death from biopsy was estimated to be 0.2% (28). Over-diagnosis of cancer, which is clinically insignificant in most cases, was estimated to be up to 50% in the group of men from the Rotterdam section of the ERSPC trial invited for PSA test (16) Level I. Despite the fact that most screen-detected cancers would remain asymptomatic, most patients and treating doctors will choose active treatment strategies which have a high rate of complications, such as urinary incontinence and erectile dysfunction (up to 40%). The death rate associated with treatment was noted to be as high as 0.5% (6). With non-demonstrable benefit of screening, and high proportions of harm from screening and early treatment of screen-detected prostate cancer, it is concluded that the harms outweigh the benefit of prostate cancer screening (5, 6).

Harm of screening

61

REFERENCES 1.

2. 3. 4.

5.

6.

7.

8. 9. 10. 11.

12.

13.

14.

15. 16.

17.

62

Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127: 2893-917. Jemal A, Siegel R, Ward E, Murray T. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66. Zainal Afriffin, I.T Nor Saleha. National Cancer Registry Report 2007. Ministry of Health Malaysia 2011. Namiki M, Akaza H, Lee SE, et al. The prostate cancer working group report. Jap J Clin Oncol 2010; 40(1):i70-i75. Bell N, Gorber S, Shane A, Joffres M, Singh H, Dickinson J, Shaw E, Dunfield L and Tonelli M. Recommendations on screening for prostate cancer with the prostatespecific antigen test. CMAJ 2014; 186(16): 1225-34. Moyer V. (2012). Screening for prostate cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2012; 157(2):120. Bratt O, Berglund A, Adolfsson J, et al. Prostate cancer diagnosed after prostate specific antigen testing of men without clinical signs of the disease: A population based study from the National Prostate Cancer Register of Sweden. Scand J Urol Nephrol 2010;44:384-90. Mazdak H, Mazdak M, Jamali L, Keshteli AH. Determination of prostate cancer risk factors in Isfahan, Iran: a case - control study. Med Arh 2012;66(1):45-8. American Cancer Society. Cancer facts and figures 2012. Atlanta 2012. Lim GCC, Rampal S, Halimah Y. Cancer incidence in Peninsular Malaysia, 2003 - 2005. National Cancer Registry. Kuala Lumpur 2008. Yanke BV, Carver BS, Bianco FJ Jr, et al. AfricanAmerican race is a predictor of prostate cancer detection: incorporation into a pre-biopsy nomogram. BJU Int 2006 Oct;98(4):783-7. Mohd Nizam S, Shamsul AS, Zulkifli MZ. Risk factors for prostate cancer in Universiti Kebangsaan Malaysia Medical Centre: a case-control study. Asian Pacific J Cancer Prev 2009;10:1015-20. Kiciński M, Vangronsveld J, Nawrot TS. An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. PLoS One 2011;6(10):e27130. Huncharek M, Haddoc KS, Reid R, Kupelnick B. Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health 2010;100693-701. Zainal Ariffin O, Nor Saleha IT. NCR Report 2007. Kuala Lumpur: National Cancer Registry, Ministry of Health, Malaysia, 2011 Stokes ME,Ishak J, Proskorovsky I, et al. Lifetime economy burden of prostate cancer. BMC Health Services Research 2011;11:349. Draisma G, Boer R, Otto SJ, et al. Lead time and over detection due to prostate specific antigen screening; estimates from the European Randomised Study of

References

18. 19.

20. 21. 22. 23.

24.

25. 26.

27.

28.

screening for prostate cancer. J Natl Cancer Inst 2003;95:868-78. Andriole GL, Crawford ED, Grubb III RL, et al. Mortality results from a randomised prostate-cancer screening trial. N Engl J Med 2009;360: 1310-9. Sandblom G, Varenhorst E, Rosell J, et al. Randomised prostate cancer screening trial: 20 year follow up. BMJ 2011;342:d1539. Schroder FH, Hugosson J, Roobol MJ et al. Prostatecancer mortality at 11 years of follow-up.N Engl J Med 2012; 366: 981–90 Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database of Syst Rev 2013: 1. de Abreu DS. Bio-impedence and chronoamperometry as an adjunct to prostate specific antigen screening for prostate cancer. Cancer Manag Res 2011;3:109-16. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate specific antigen Level ≤4.0ng/Ml. N Engl J Med 2004;350(22):2239-46. Thompson IM, Ankerst DP, Chen Chi, et al. Operating characteristics of prostate specific antigen in men with an initial PSA Level of 3.0 ng/mL or lower. JAMA 2005;291(1):66-71. Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a Randomised European Study. N Engl J Med 2009:360;1320-8. Gosselaar C, Roobol MJ, Roemeling S, Schroder FH. The role of the digital rectal examination in subsequent screening visits in the european randomized study of screening for prostate cancer (ERSPC). Eur Urology 2008;54:581-8. Rosario DJ, Lane JA, Metcalfe C, Donovan JL, Doble A, Goodwin L, et al. Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study. BMJ 2012;344:d7894. Screening for prostate cancer with prostate specific antigen and treatment of early-stage or screen-detected prostate cancer: a systematic review of the clinical benefits and harms [Internet]. 1st ed. Canada: Canadian Task Force on Preventive Health Care (CTFPHC); 2014 [cited 18 May 2015]. Available from: http://  canadiantaskforce.ca/files/guidelines/2014-prostatecancer-systematic-review-en.pdf

09

Tobacco SUMMARY

Tobacco usage (including smoking) is prevalent in Malaysia. Smoking cessation and abstinence result in substantial morbidity and mortality benefit. Recording smoking status as part of vital sign assessment in the clinic improves the intervention and abstinence rate. The 5A strategy (Ask, Advise, Assess, Assist, and Arrange) is an effective intervention to improve the rate of smoking abstinence.

RECOMMENDATIONS

Screening for tobacco abuse by recording smoking status as part Grade A of vital sign assessment in the clinic is indicated annually.

9.1

Introduction

 The Global Adult Tobacco Survey (GATS) 2011 reported a 22% prevalence of current smokers in Malaysia (1). The World Health Organisation has identified tobacco, alcohol and illicit drugs among the top 20 risk factors for ill-health which are responsible for 8.8% of all deaths (2). It is estimated that 10,000 deaths due to smoking-related illnesses are reported in Malaysia every year, making it the primary cause of death in this country since the 1980s. Furthermore, if the trend continues, there will be 30,000 deaths due to smoking-related diseases by the year 2020 (3).

9.2 Benefit of screening and treating tobacco addiction Screening for tobacco smoking has been shown to increase rates of clinician intervention resulting in significant reductions in morbidity and mortality (4 -7) Level I . Recording smoking status as part of vital signs in medical records significantly

Introduction

63

results in a higher rate of brief intervention by primary care doctors. In one study on the effect of screening for smoking, 61.9% of smokers reported receiving any counselling on smoking cessation in intervention practices, compared with 53.4% of smokers at control practices, i.e., a difference of 8.5% (P = .04) (8) Level I. In another study, the effect of recording smoking status routinely resulted in a higher rate of physician interventions for smoking cessation (OR 2.6; 95% CI 1.3-5.2) (9)

Level I

.

Counselling by paramedics has also proven to reduce rates of tobacco abstinence (RR 1.29; 95% CI 1.20 to 1.39) (10). Routine physician screening and counselling may increase quit rates at 6-12 months from 3% (usual care) to 8-11% (11)  Level I.

9.3

Screening tests

 The 5A strategy (Ask, Advise, Assess, Assist, and Arrange) as a screening tool has been shown to improve the rate of smoking abstinence (12) Level I.  The 5A strategies are: • ASK - all patients about smoking • ADVISE - brief, non-judgmental advice about smoking cessation • ASSESS - readiness to stop smoking • ASSIST - offer intervention to help smoking cessation (counselling, nicotine replacement treatment) • ARRANGE –follow-ups and referrals as appropriate.  Therefore, routine recoding of smoking status should be part of the vital sign assessment in primary care.

9.4

Harm of screening

 The published literature on harm of tobacco screening is scarce (13). Harm from the screening test and brief intervention, e.g., 5A strategy, was shown to be minimal (8). Harm from treatment for tobacco dependence is mainly from the side-effects of nicotine replacement therapy and nicotine receptor partial agonist, which are temporary during treatment. Screening for tobacco addiction may strain the resources for counselling services. However, these constraints are small compared to the benefit of tobacco smoking cessation.

64

Harm of screening

REFERENCES 1. 2.

3. 4.

5.

6. 7. 8.

9.

10. 11.

12.

13.

Tee, GH. Epidemiology of tobacco consumption: The Malaysian Perspective. 2012; Malaysia. World Health Organization International (WHO) | The World Health Report 2002 -Reducing risks, promoting healthy life [Internet]. 2002 [cited 22 April 2015]. Available from: http://www.who.int/whr/2002/en/ Disease Control Division, Ministry of Health Malaysia 2003, Clinical practice guidelines on treatment of tobacco use and dependence 2003. Fiore MC, Jorenby DE, Schensky AE, et al. Smoking status as the new vital sign: effect on assessment and intervention in patients who smoke. Mayo Clin Proc 1995; 70(3): 209-13. Katz DA, Muehlenbruch DR, Brown RL, et al. Effectiveness of implementing the agency for healthcare research and quality smoking cessation clinical practice guideline: a randomized control trial. J Natl Cancer Inst 2004; 96(8): 594-603. Ahluwalia JS, Gibson CA, Kenney RE, et al. Smoking status as a vital sign. J Gen Intern Med 1999; 14 (7):402-8. Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev 2004; (1): CD003041. Rothemich SF, Woolf SH, Johnson RE, Burgett AE, Flores SK, Marsland DW, Ahluwalia JS. Effect on cessation counseling of documenting smoking status as a routine vital sign: an ACORN study. Ann Fam Med 2008; 6(1): 60-8 Seale JP. Shellenberger S. Velasquez MM. Boltri JM. Okosun I. Guyinn M. Vinson D. Cornelius M. Johnson JA. Impact of vital signs screening & clinician prompting on alcohol and tobacco screening and intervention rates: a pre-post intervention comparison. BMC Family Practice 2010. 11:18 Rice VH, Hartmann-Boyce J, Stead LF. Nursing interventions for smoking cessation. Cochrane Database Syst Rev 2013, Issue 8. Bernstein S. Preventive Care in the Emergency Department: Diagnosis and management of smoking and smoking-related illness in the emergency department: a systematic review. Acad Emerg Med 2002;9(7):720-9. Bentz CJ, Bayley KB, Bonin KE, et al. Provider feedback to improve 5a’s tobacco cessation in primary care: a cluster randomized control trial. Nicotine Tob Res 2007; 9(3):341-9. Uspreventiveservicestaskforce.org. Home - US Preventive Services Task Force [Internet]. 2009 [cited 23 April 2015]. Available from: http://www. uspreventiveservicestaskforce.org/

References

65

10

 Alcohol SUMMARY

Although the prevalence of alcohol drinking is increasing, the majority are low risk drinkers. There is evidence of benefit in screening and brief intervention for communities in which the majority of drinkers are mild to moderate consumers.

RECOMMENDATIONS

Screening for alcohol consumption should be done among those at risk groups using AUDIT-C.

Grade B

10.1 Introduction  Alcohol consumption in Malaysia has shown a small increase over time. The National Health Morbidity Survey (NHMS) reported increasing prevalence of ever-consumed and current drinkers among those aged 13 years and above in the past five years (ever-drinker: 16.1% in 2006 versus 17.8% in 2011, current drinker: 11.1% in 2006 versus 11.6% in 2011) (1, 2). It was estimated that 76.3 million people worldwide (2004 data) suffer from alcohol use disorders (3). In comparison to global data, Malaysia showed a higher prevalence of low-risk drinkers (49.2%). On the other hand, the other drinkers’ profiles, notably, exdrinker (35.6%), risky (14%) and high-risk drinkers (1.2%) were lower than the global prevalence (2).  At-risk groups of problematic alcohol consumption among patients attending primary care clinics are (4, 5) Level III: • middle-aged males • adolescents • certain occupational groups, such as, business executives, entertainers, sex workers, workers in pubs, and seamen. In Malaysia, a higher prevalence of current drinkers was reported in Kuala Lumpur followed by Sarawak and Sabah, in urban areas, among males, and those in 20-24 years age group. By ethnicity, the highest prevalence of current 66

Introduction

drinkers was among Chinese followed by other Bumiputera and Indians (2).

10.2 Benefit of screening and treating alcohol use For people with a mild to moderate alcohol drinking pattern, brief intervention has proven to be effective at primary care settings (6 -8) Level I A Cochrane review on brief interventions in primary care found a significant reduction in men’s alcohol consumption (mean difference -57 grams/week, 95% CI: -89 to -25, I2 = 56%), but not women’s. (Mean difference: -10 grams/  week, 95% CI: -48 to 29, I2 = 45%) (7). The brief interventions included in the review were carried out either by a general physician, a nurse or a psychologist. Training is needed to do brief interventions for alcohol use (7). In Malaysia, training for brief intervention is available and can be implemented by doctors and paramedics. However, there is insufficient evidence to support alcohol screening and brief intervention for primary-care patients with very heavy drinking or alcohol dependence, especially if this pattern of drinking is prevalent (9) Level I.  They require referral to a specialised unit for management.

10.3 Screening tests  There are several tools to screen for alcohol abuse, such as CAGE, AUDIT and the Brief Michigan Alcohol Screening Test. These tests have almost similar sensitivity (75% -84%) and specificity (87%-90%) (10). The AUDIT was developed by the World Health Organization (WHO). It is a simple method of screening for excessive drinking and to assist in brief assessment. It also comes in a simplified form, AUDIT-C (3 item questionnaire), that mainly asks about consumption and it has almost similar validity to AUDIT (10 item questionnaire) (11). The AUDIT questionnaire, developed together with an intervention programme, has shown to be effective in reducing alcohol problem drinking (12 -16).  A score of ≥ 4 for males and ≥ 3 for females from the total scores is considered positive for hazardous drinkers (17, 18) - refer to appendix for AUDIC-C screening questionnaire.

10.4 Harm of screening  Although the evidence of harm from screening is scarce (19), alcohol use may be associated with stigma in certain cultures. Hence, labelling of alcohol misuse may cause anxiety and have a negative social impact. However, the benefit of treatment outweighs the harm.

Harm of screening

67

 Appendix Alcohol 1

AUDIT-C Questionnaire

Patient Name: 1.

Date of Visit:

How often do you have a drink containing alcohol?

(Score)

2.

a. Never

0

b. Monthly or less

1

c. 2-4 times a month

2

d. 2-3 times a week 3

3

e. 4 or more times a week

4

How many standard drinks containing alcohol do you have on a typical day?

(Score)

3.

a. 1 or 2

0

b. 3 or 4

1

c. 5 or 6

2

d. 7 to 9

3

e. 10 or more

4

How often do you have six or more drinks on one occasion?

(Score) a. Never

0

b. Less than monthly

1

c. Monthly

2

d. Weekly

3

e. Daily or almost daily

4

Total score (sum score of all responses):

68

 Appendiox Alcohol 1

REFERENCES 1. 2. 3. 4.

5.

6.

7.

8. 9.

10.

11. 12.

13. 14.

15.

16.

Ministry of Health Malaysia. The National Health Morbidity Survey III Report. Malaysia; 2006. Ministry of Health Malaysia. The National Health Morbidity Survey 2011. Malaysia; 2011. World Health Organization. Global Status Report On Alcohol And Health. 2004. Murray RM. Screening and early detection instruments for disabilities related to alcohol consumption. AlcoholRelated Disabilities. Geneva, World Health Organization 1977; 2: 89-105. World Health Organization. Problems related to alcohol consumption, Report of a WHO Expert Committee. Tech Report Series 650, Geneva, World Health Organization 1980. Kypri K, Langley JD, Saunders JB, et al. Randomized controlled trial of web-based alcohol screening and brief intervention in primary care. Arch Intern Med 2008; 168(5): 530-6. Kaner EF, Dickinson HO, Beyer F, et al. The Effectiveness of brief alcohol interventions in primary care settings: a systematic review. Drug Alcohol Rev 2009; 28(3): 30123. Riper H, van Straten A, Keuken M, et al. Curbing problem drinking with personalized-feedback interventions a meta-analysis. Am J Prev Med 2009; 36(3): 247-55. Saitz R. Alcohol screening and brief intervention in primary care: absence of evidence for efficacy in people with dependence or very heavy drinking. Drug Alcohol Rev 2010; 29(6): 631-40. Soderstrom CA, Smith GS, Kufera JA, et al. The accuracy of the CAGE, the brief Michigan alcoholism screening test and alcohol use disorder identification test in screening trauma centre patients for alcoholism. J Trauma 1997; 43(6): 962-9. Bradley KA, DeBenedetti AF, Volk RJ, et al. AUDIT-C As a brief screen for alcohol misuse in primary care. Alcohol Clin Exp Res 2007; 31(7): 1208-17. Kelly TM, Donovan JE, Chung T, et al. Alcohol use disorders among emergency department-treated older adolescents: a new brief screen using AUDIT, CAGE, CRAFT And RAPS-QF. Alcohol Clin Exp Res 2004; 28(5): 746-53. Bien TH, Miller WR, Tonigan S. Brief intervention for alcohol problems: a review. Addiction 1993; 88: 31536. Kahan M, Wilson L. Becker L. Effectiveness of physicianbased interventions with problem drinkers: A review. Canadian Med Assoc J 1995; 152(6):851-9. Wilk AI, Jensen NM, Havighurst TC. Meta-analysis of randomized control trials addressing brief interventions in heavy alcohol drinkers. J General Internal Me 1997; 12:274-87. Lee JD, Delbanco B, Wu E, Gourevitch MN. Substance use prevalence and screening instrument comparisons in urban primary care. Subst Abus 2011; 32(3): 128-34.

17. Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT alcohol consumption questions (AUDIT-C): An effective brief screening test for problem drinking. Arch Internal Med 1998; (3): 1789-95. 18. Bradley KA, Bush KR, Epler AJ, et al. Two brief alcohol-screening tests from the Alcohol Use Disorder Identification Test (AUDIT): Validation in a female veterans’ affairs patient population. Arch Internal Med 2003; Vol 163: 821-9. 19. Moyer V. Primary care interventions to prevent tobacco use in children and adolescents: U.S. Preventive Services Task Force Recommendation Statement. Pediatrics. 2013; 132(3):560-5.

References

69

11

Illicit Drugs SUMMARY

Malaysia has a low prevalence of illicit drug use. With strict drug laws, screening for illicit drugs may have legal implications. There is insufficient evidence to support screening for illicit drug use in adults in primary care.

RECOMMENDATIONS

Routine screening for illicit drug use is not indicated.

Grade I

11.1 Introduction  The 2010 National Anti-Drug Agency Report (1) reported a prevalence of 0.08% of illicit drug users in Malaysia. The screening of adolescents in the National Service (PLKN) found that the prevalence of illicit substance use was 1.3% (2). Illicit drugs were responsible for 0.4% of deaths. Although illicit drug use can lead to serious health problems, the prevalence is low in general population. Consequently, screening will have a low detection rate.

11.2 Benefit of screening and treating illicit drug use  The United States Agency for Healthcare Research and Quality states that screening for drug misuse is not useful in populations with a low prevalence of drug use/ misuse (3) Level II-3 (counselling for drug misuse).

11.3 Harm of screening  Although important, screening for illicit drug use among general population adults in a country that has strict drug laws may have potential legal implications. 70

Introduction

REFERENCES 1. 2. 3.

National Anti-Drug Agency (AADK). The national antidrug agency drug report. Malaysia; 2010. Norizzati BIB, Noor Ani A, Noraida MK, et al. Mental health problem among youth in Malaysia. Abstract Book National Public Health Conference 2011. Lanier D, Ko S. Screening in primary care settings for illicit drug use: Assessment of screening instruments - a supplemental evidence update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 58, Part 2. AHRQ Publication No. 08-05108-EF-2. Rockville, Maryland: Agency for Healthcare Research and Quality. 2008.

References

71

12

Human Immunodeficiency Virus Infection SUMMARY

In Malaysia, HIV is concentrated among intravenous drug users, commercial sex workers, men who have sex with men (MSM), and transgender persons. Early detection and treatment have individual and public health benefits. Sequential rapid testing and serum antibody testing strategies are highly accurate.

RECOMMENDATIONS

HIV screening is indicated for individuals with high risk of infection.

Grade B

12.1 Introduction  The overall growth of the global AIDS epidemic appears to have stabilized, with declining incidence each year. In 2009, 2.6 million people were infected, nearly 19% lower than the number in 1999. The success of therapy has reduced annual AIDS-related deaths, from a peak of 2.1 million in 2004 to 1.9 million in 2009. However, the number of new infections is still substantial. This has led to the increasing total number of people living with HIV worldwide; reaching 33.3 million in 2009 (1) Level III. In Malaysia, a similar trend is observed. The annual number of newly reported HIV cases has been steadily decreasing from almost 7,000 in 2002 to 3,479 in 2011. The HIV prevalence among adults (15-49 years) in Malaysia is 0.5% (2) Level III. 26% of reported infections are amongst young people between the ages 13-29 years, 2.4% aged less than 19 years and 1.0% aged less than 13 from 1986 to December 2011 (2) Level III. The percentage of HIV-positive pregnant women detected has been maintained at below 0.04% since the introduction of the National Prevention of Maternal to Child Transmission of HIV Program (PMTCT) in 1998 (3) Level III. Malaysia is classified by the World Health Organisation (WHO) as a country with a concentrated low-level HIV epidemic where the four most-at-risk populations include injecting drug users, female sex workers, men who have sex with men, 72

Introduction

(MSM), and transgender persons. The 2012 prevalence rates by the risk groups was 18.9%, 4.2%, 12.6% and 5.7%, respectively (5)

Level III

.

Numerous studies show that patients with HIV are still presenting at a late stage of the disease. In the United Kingdom, national surveillance data showed that approximately onethird of all HIV infections in adults remain undiagnosed and that approximately 33% of newly diagnosed individuals have a CD4 cell count of less than 200 (an accepted marker of ‘late’ diagnosis) (6)  Level III. Similar findings are also seen in other countries such as those in subSaharan Africa (7) Level II-2, India (8) Level II-2, the United States and Canada (9) Level II-2, and France and Belgium (10) Level II-2. Studies also show that patients who present with advanced HIV disease had missed opportunities for diagnosis in the years prior to being diagnosed (11, 12) Level II-2.

12.2 Benefit of screening and treating HIV infection Early detection and treatment result in significant benefit in HIV morbidity and mortality. Early treatment of HIV infection slows its progression to AIDS (13). Early initiation of antiretroviral therapy has been shown to reduce the rate of sexual transmission of HIV-1 by 96% and clinical events (which were defined as occurrence of pulmonary tuberculosis, severe bacterial infection or death) by 41%, indicating both personal and public health benefits from such therapy (14) Level II-1. With early detection of HIV infection, there is also an opportunity to initiate chemoprophylaxis for the spouse of HIV patients (13). Conversely, late diagnosis of HIV infection has been associated with increased mortality and morbidity, and impaired response to antiretroviral therapy (15) Level II-3. A national audit by the British HIV Association (BHIVA) showed that 24% of deaths occurring amongst HIV-positive adults in the UK in 2006 were directly attributable to the diagnosis of HIV being made too late for effective treatment (16) Level III. Persons with HIV infection who present late, as defined by an initial CD4 count of < 200 cell / mm3, incur a higher cumulative direct HIV treatment expenditure than those who present earlier in the disease process (17, 18) Level II-2.

12.3 Screening tests Screening tests for HIV infection include Enzyme Immunoassay (EIA) and antibody rapid test. EIA test has a sensitivity of >99.5%, and specificity of >99.5% (19). The highly sensitive Rapid Test is a feasible, accurate and quick screening test (20) Level I (21) Level III. Local data have demonstrated that the Rapid Test (Hemo-Strip®) has a sensitivity of 100% and a specificity of 100% (22) Level III. However, a reactive Rapid Test result should be confirmed with another EIA, Particle Agglutination (PA) or the Western Blot (23) Level III. Screening tests

73

 Two strategies can be adopted for screening HIV infection: 1) HIV Antibody Testing Using Single Rapid Test (1RTK Strategy) (Appendix HIV -1) and 2) HIV Antibody Testing (24) (Appendix HIV-2). In both strategies, a first screening test is performed using either the Rapid Test or HIV antibody test. A positive result is followed by a second test using a different method. This sequential rapid testing algorithm has been shown to have high accuracy and cost-effectiveness (25, 26).  As Malaysia is a concentrated low-level epidemic country WHO does not recommend routine screening for patients attending health facilities. (27). Screening should be prioritized as provider-initiated testing and counselling for patients with signs and symptoms suggestive of HIV infection. Special consideration should be also be given to (28): 1. 2. 3. 4. 5. 6.

Patients with sexually transmitted infection Men who have sex with men Sex worker Patients with tuberculosis Injecting drug users Spouse with the above risk factors

12.4 Harm of screening Rapid testing and initial antibody screening may result in anxiety, social stigma and depression if the results are reactive. However, no study has systematically compared the psychological impact of rapid testing and conventional antibody testing (19). Although early diagnosis of HIV infection may expose patients to the side effects of treatment earlier compared to late diagnosis, the benefits of treatment at the optimal time outweigh the risk of medication sideeffects.

74

Harm of screening

 Appendix HIV-1

HIV Antibody Testing Using Single Rapid Test (1RTK strategy)

Request for screening

RTK Screening site

REACTIVE

Report as: Anti– HIV Rapid Test REACTIVE Name of Rapid Test Kit

Results reported in documented form: Fax, postal, telephone

Obtain venous blood sample 3ml in plain tube Fill up Request Form and provide Rapid Test Result on form

Simple Rapid Test using finger prick  Blood / venous blood (regard as 1st sample)

NON–REACTIVE

Report as: Anti– HIV Rapid Test NON– REACTIVE

End

Send to Nearest Hospital Screening centre with EIA/Combo & PA facilities Follow adult confirmation test (next algorithm)

 Appendix HIV1

75

HIV Antibody Testing strategy 

Screening requested (Venous blood sample)

Test 1: EIA HIV 1/2  Antibody test

Reactive (R)

*Test 2: anti-HIV test using different Ab test from 1st test such as PA

Notify to nearest District Health

EIA : Reactive + PA : Detected +

EIA : Reactive + **PA: Not Detected

Report reactive. Make request for fresh sample for patient verification: Do EIA & PA

Non-Reactive (N)

Repeat as necessary

EIA : Reactive + **PA : Inconclusive +

Send blood sample to Regional HIV Testing

Note: *2nd test can be another EIA or PA. **Exclude Prozone reaction in PA. Dotted arrow indicates that Immunoblot maybe required in special circumstances.

Test 3: Immunoblot

Reactive

Immunoblot Negative

Obtain fresh blood from patient for verification.

EIA : Reactive PA : Detected

Patient

76

 Appendix HIV1

EIA : Reactive PA : Not Detected

Immunoblot Indeterminate

Obtain another blood sample for

EIA : Non-Reactive PA : Not Detected

Investigate for: Patient mix up / Sample mix up

REFERENCES 1.

2. 3. 4.

5. 6. 7.

8.

9. 10.

11.

12.

13.

14. 15.

Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS Report On The Global Aids Epidemic 2010 [Internet]. 2010. (cited 29 April 2015). Available from: http://www.unaids.org/globalreport/  documents/20101123_GlobalReport_full_en.pdf. HIV/STI Section, Ministry of Health Malaysia. The Global AIDS Response 2012, Country Progress Response. Malaysia 2012. AIDS/STD Section, Disease Control Division, Ministry of Health Malaysia. Summary of HIV/AIDS cases 2006. Malaysia 2006. AIDS/STD Section, Disease Control Division, Ministry of Health Malaysia. Summary findings of behavioural surveillance survey (BSS) in Malaysia 2006. Commercial Sex Workers, IDUs. Malaysia 2006. Ministry of Health. International behavioural surveillance survey. Malaysia 2012. Sullivan AK, Curtis H, Sabin CA, et al. Newly diagnosed HIV infections: review in UK and Ireland. BMJ 2005;330:1301-2 Kigozi I, Dobkin L, Martin JN. Late disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in Sub-Saharan Africa. J Acquir Immune Defic Syndr 2009;52(2):280 Alvarez-Uria G, Midde M, Pakam R, et al. Factors associated with late presentation of HIV and estimation of antiretroviral treatment need according to CD4 lymphocyte count in a resource-Limited Setting: Data from an HIV Cohort Study in India. Interdiscip Perspect Infect Dis 2012; 2012:293795. Althoff KN, Gange SJ, Klein MB, et al. Late presentation for HIV Care in United States and Canada. Clin Infect Dis 2010;50(11):1512-20. Ndiaye B, Salleron J, Vincent A. Factors associated with presentation to care with advanced HIV disease in Brussels and Northern France: 1997-2007. BMC Infectious Dis 2011;11:11 Lyons MS, Lindsell CJ, Wayne BD. Comparison of missed opportunities for earlier HIV diagnosis in 3 geographically proximate emergency departments. Ann Emerg Med 2011; 58(1 Suppl 1):S17-22.e1. Fetene NW, Feleke A. Missed opportunities for earlier HIV testing and diagnosis at the health facilities of Dessie Town, North East Ethiopia. BMC Public Health 2010, 10:. Ministry of Health (Moh.gov.my). Official Portal for Ministry of Health Malaysia; CPG-Infectious Disease [Internet]. 2014 [cited 24 April 2015]. Available from: http://www.moh.gov.my/english.php/pages/view/214 Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection by early antiretroviral therapy. N Eng J Med 2011;365(6):493-505. Losina E, Schackman BR, Sadownik SN. Racial and gender disparities in life expectancy losses among HIV-infected persons in the United States: impact of risk behavior, late initiation and early discontinuation

16.

17. 18. 19.

20. 21.

22.

23.

24.

25.

26.

27. 28.

of antiretroviral therapy. Clin Infect Dis 2009;49(10): 1570-8. British HIV Association (BHIVA). 2005-6 Full results of mortality audit [Internet]. 2005. (cited 29 April 2015). Available from: http://www.bhiva.org/documents/  ClinicalAudit/FindingsandReports/MortalityAudit.ppt Krentz HB, Auld MC, Gill MJ. The high cost of medical care for patients who present late (CD4<200 cells/μl) with HIV infection. HIV Medicine 2004;5:93-8. Fleishman JA, Yehia BR. The Economic Burden of Late Entry Into Medical Care for Patients With HIV Infection. Med Care 2010;48 (12):10719. Uspreventiveservicestaskforce.org. Recommendation Summary - US Preventive Services Task Force [Internet]. 2013 [cited 23 April 2015]. Available from: http://  www.uspreventiveservicestaskforce.org/Page/Topic/  recommendation-summary/human-immunodeficiencyvirus-hiv-infection-screening?ds=1&s=HIV Moyer V. Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013;159(1):51-60. Lyamuya EF, Aboud S, Urassa WK. Evaluation of simple rapid HIV assays and development of national rapid HIV test algorithms in Dar es Salaam, Tanzania. BMC Infectious Dis 2009;9:19. Ng K, Saw T, Baki A, Singh N, Lyles C. SHORT REPORT Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2. Int J STD AIDS. 1999;10(6):401-4. Centers for Disease Control and Prevention (CDC). Revised recommendations for HIV testing of adults,adolescents, and pregnant women in health-care settings. MMWR 2006; 55/(RR14):1-17. Ministry of Health (Moh.gov.my). Official Portal for Ministry of Health Malaysia. View Listing Circulars, HIV screening test and validation flowchart [Internet]. 2011 [cited 24 April 2015]. Available from: http://www.moh. gov.my/english.php/database_stores/store_view_ page/10/199 Ménard D, Maïro A, Mandeng M, Doyemet P, Koyazegbe T, Rochigneux C et al. Evaluation of rapid HIV testing strategies in under equipped laboratories in the Central African Republic. J. Virol. Methods 2005;126(1-2):7580. Farnham PG, Hutchinson AB, Sansom SL, Branson BM. Comparing the costs of HIV screening strategies and technologies in health-care settings. Public Health Rep 2008;123:Suppl 351–62. WHO Guidance On Provider. Initiated HIV testing and counselling in health facilities. WHO Library Cataloguingin-Publication Data 2007. Palfreeman A, Fisher M, Ong E. Testing for HIV: concise guidance. Clin Med. 2009;9(5):471-6.

References

77

13

Domestic violence SUMMARY

Screening women for domestic violence increases the identification of victims, particularly among pregnant mothers. Risks for domestic violence include female gender, young age, low income, depression, partner with substance abuse and terminating a relationship. Screening for domestic violence, followed by interventions, improves health outcomes. Issues about domestic violence should be explored in a non-judgmental manner and in the absence of the abuser.

RECOMMENDATIONS

Screening for domestic violence may be indicated for women of childbearing age.

Grade C

Screening for domestic violence during obstetric care should occur at the first antenatal visit, at least once per trimester, and at the postpartum check-up.

Grade C

13.1 Introduction Domestic violence is defined by the World Health Organization as any behaviour within an intimate relationship that causes physical, psychological or sexual harm to those in the relationship (1). In Malaysia, the Domestic Violence Act (Act 521) 1994 provides legal protection for victims of domestic violence (2). Victims are reported to be mainly women although the opposite can also occur (3). Studies have shown that up to 41% of women attending primary care consultations have experienced some form of domestic violence in their life (3-8).  The risks for domestic violence include female gender, young age, low income, depression, partner with substance abuse and termination of a relationship (913). A review of prevalence of domestic violence in Peninsular Malaysia noted 39% of women older than age 15 years in 1990 suffered some form of violence and 68% of battered women were beaten while pregnant. The rate of abuse can increase during pregnancy with 32% of pregnant women reporting to have been abused in developing countries (14). 78

Introduction

Domestic violence can result in physical injuries and death to the victims (15-17). Notwithstanding, the biggest burden of domestic violence comes from its psychological implications. Mental health problems contribute to 60% of domestic violence health outcomes (18) including post-traumatic stress disorder (PTSD), depression, panic attacks, insomnia, suicide, substance abuse and alcoholism (15, 19-22). The abusive relationship is also associated with exacerbating chronic diseases, such as hypertension, diabetes mellitus and ischaemic heart disease (23), unwanted and unplanned pregnancy, anaemia, first and second trimester bleeding, poor weight gain, low birth weight and late prenatal care booking (14-24). Furthermore, domestic violence often co-exists with child abuse (25). Children living in homes with domestic violence are likely to have increased risks of behavioural problems and social incompetence (27, 28), as well as experience domestic violence in their adult relationships, (26, 27).

13.2 Benefit of screening and managing domestic violence Identifying domestic violence is the first step in intervention. It can be approached via universal screening or case finding. Systematic reviews have found inadequate evidence to support one approach over another (29, 30)   Level I. Current evidence suggests that the likelihood of identifying abused women increases when screening for domestic violence is conducted (31, 32) Level I.  A recent systematic review reported that screening women for domestic violence, with an intervention, can reduce the recurrence of domestic violence and improve health outcomes (31) Level I. An intervention involving intensive advocacy for abused women who were already in refuges has been shown to reduce physical violence after one to two years of intervention (33) Level I. Among pregnant women, screening for domestic violence followed by a brief intervention has been shown to reduce re-victimizations, improve birth outcomes, reduce pregnancy coercion and to motivate the abused women to discontinue their abusive relationship (34-37) Level I. This brief intervention consists of the following: i.  Validation of domestic violence experience. This is done by listening non-

   

judgmentally and providing appropriate responses such as ‘No one deserves to be abused’, ‘You are not alone and help is available’ ii. Review the safety issues iii. Offer relevant domestic violence information. This includes the nature of an abusive relationship and domestic violence resources, such as the One-Stop-CrisisCentre (OSCC)

Benefit of screening and managing domestic violence

79

13.3 Screening tests  There are many tools for screening domestic violence. Seven screening tools are reported to have high diagnostic accuracy in detecting past, current, or recent domestic violence or predicting the likelihood of future domestic violence (31) Level I. These are: Hurt, Insult,  Threatened, Scream (HITS); Ongoing Violence Assessment Tool (OVAT); Slapped, Threatened, and Throw (STaT); Humiliation, Afraid, Rape, Kicks (HARK); Woman Abuse Screening Tool (WAST); Partner Violence Screen (PVS); Childhood Trauma Questionnaire-Short Form (CTQ).  These screening instruments have sensitivity and specificity ranging from 80-100%. However, none of the above has been validated in Malaysia. A 20 item questionnaire which forms parts of the WHO Women’s Health and Life Experiences Questionnaire, has been translated and pyshometrically validated in Malaysia.(38) However, its sensitivity and specificity has not been established.

Sample domestic violence screening questions (39) Framing Statement

A framing statement in the beginning of the assessment to show that screening is done universally and not only when domestic violence is suspected: “Because violence is common in many women’s lives and because there is available help, I now ask every patient about domestic violence”  Sample Questions

The following questions could be incorporated into the routine medical history-taking: “Within the past one year (or since you have been pregnant), have you been hit, slapped, kicked or otherwise physically hurt by someone?”  “Are you in a relationship with a person who threatens or physically hurts you?”  “Has anyone forced you to have sexual activities that make you feel uncomfortable?” 

Questions regarding domestic violence should only be asked (40, 41): • in the absence of the patient’s partner • in a non-judgmental manner • with clinicians reaffirming the confidentiality of the information given Clinicians are strongly advised against couple counselling without the victim’s permission.

80

Screening tests

13.4 Harm of screening  The potential harm of screening includes shame, guilt feeling, fears of revenge and/  or abandonment by the spouse. Nevertheless, direct evidence of harm has not been demonstrated. A review by the USPSTF on three clinical trials and 11 observational studies did not reveal any significant harm from screening and interventions associated with intimate partner violence (42).

REFERENCES 1.

Krug EG, Mercy JA, Dahlberg LL, Zwi AB. The world report on violence and health. Lancet 2002;360(9339):10838. 2. Attorney-General’s Chambers (AGC) Malaysia. Domestic Violence Act 1994, Malaysia. 3. Sassetti MR. Domestic violence. Prim Care 1993;20(2):289-305. 4. Bradley F, Smith M, Long J, O’Dowd T. Reported frequency of domestic violence: cross-sectional survey of women attending general practice. BMJ 2002;324:271. 5. Brown JB, Lent B, Schmidt G, Sas G. Application of the Woman Abuse Screening Tool (WAST) and WASTShort in the family practice setting. J Fam Pract 2000;49(10):896-903. 6. Hegarty KL, Taft AT. Overcoming the barriers to disclosure and inquiry of partner abuse for women attending general practice. Aust N Z J Public Health 2001;25:433-7. 7. McCauley J, Kern D, Kolodner K, Dill L, Schroeder A, DeChant H, et al. The “Battering Syndrome”: prevalence and clinical characteristics of domestic violence in primary care internal medicine practices. Ann Intern Med 1995;123(10):737-46. 8. Richardson J, Jeremy C, Petruckevitch A, Chung WS, Moorey S, Feder G. Identifying domestic violence: crosssectional study in primary care. BMJ 2002;324:274. 9. Wong YL, Othman S. Early detection and prevention of domestic violence using the Women Abuse Screening Tool (WAST) in primary health care clinics in Malaysia. Asia Pac J Public Health 2008;20(2):102-16. 10. Coker AL, Smith PH, McKeown RE, King MJ. Frequency and correlates of intimate partner violence by type: Physical, sexual, and psychological battering. Am J Public Health 2000;90(4):553-9. 11. Hegarty K, Hindmarsh ED, Gilles MT. Domestic violence in Australia: definition, prevalence and nature of presentation in clinical practice. MJA 2000;173:363-7.

12. Tollestrup K, Sklar D, Frost FJ, Olson L, Weybright J, Sandvig J, et al. Health indicators and intimate partner violence among women who are members of a managed care organization. Prev Med 1999;29:431-40. 13. Vest JR, Catlin TK, Chen JJ, Brownson RC. Multivariate analysis of factors associated with intimate partner violence. Am J Prev Med 2002;22(3):156-64. 14. Campbell JC, Garcia-Moreno C, Sharps P. Abuse during pregnancy in industrialized and developing countries. Violence Against Women 2004;10(7):770-89. 15. Coker AL, Smith PH, Bethea L, King MR, McKeown RE. Physical health consequences of physical and psychological intimate partner violence. Arch Fam Med 2000;9(5):451-7. 16. Campbell JC. Health consequences of intimate partner violence. The Lancet 2002;359(9314):1331-6. 17. Kyriacou DN, Anglin D, Taliaferro E, Stone S, Toni T, Linden JA, et al. Risk factors for injury to women from domestic violence. N Eng J Med 1999;341:1892-8. 18. Vichealth.vic.gov.au. The Health Costs of Violence: Measuring the burden of disease caused by intimate partner violence [Internet]. 2004 [cited 5 May 2015]. Available from: https://www.vichealth.vic.gov.au/  media-and-resources/publications/the-health-costs-ofviolence 19. Pico-Alfonso MA. Psychological intimate partner violence: the major predictor of posttraumatic stress disorder in abused women. Neurosci Biobehav Rev 2005;29:181-93. 20. Dienemann J, Boyle E, Baker D, Wiederhorn N, Campbell JC. Intimate partner abuse among women diagnosed with depression. Issues Ment Health Nurs 2000;21:400513. 21. Jones L, Hughes M, Unterstaller U. Post-traumatic stress disorder (PTSD) in victims of domestic violence: A review of the research. Trauma Violence Abuse 2001;2(2):99119. Harm of screening

81

REFERENCES 22. Golding JM. Intimate partner violence as a risk factor for mental disorders: a meta-analysis. J Fam Violence 1999;14(2):99-132. 23. Ruiz-Pérez I, Plazaola-Castaño J, del Río-Lozano M. Physical health consequences of intimate partner violence in Spanish women. Eur J Public Health 2007;17(5):437-43. 24. Hegarty KL, Gunn J, Chondros P, Small R. Association between depression and abuse by partners of women attending general practice: descriptive, cross sectional survey. BMJ 2004;328:621-4. 25. Appel AE, Holden GW. The co-occurrence of spouse and physical child abuse: A review and appraisal. J Fam Psychol 1998;12(4):578-99. 26. Kitzmann KM, Gaylord NK, Holt AR, Kenny ED. Child witnesses to domestic violence: a meta-analytic review. J Consult Clin Psychol 2003;71(2):339-52. 27. Stiles MM. Witnessing domestic violence: the effect on children. Am Fam Physician 2002;66(11):2052-66. 28. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. Am J Prev Med 1998;14(4):245-58. 29. Feder G, Ramsay J, Dunne D, Rose M, Arsene C, Norman R, et al. How far does screening women for domestic (partner) violence in different health-care settings meet criteria for a screening programme? Systematic reviews of nine UK National Screening Committee criteria. Health Technol Assess 2009;13(16):iii-iv, xi-xiii, 1-113, 37347. 30. U.S. Preventive Services Task Force. Screening for family and intimate partner violence: Recommendation Statement. Am Fam Physician 2004;70(4):747-51. 31. Nelson HD, Bougatsos C, Blazina I. Screening women for intimate partner violence: a systematic review to update the U.S. Preventive services task force recommendation. Ann Intern Med 2012;156(11):796-808. 32. Taft A, O’Doherty L, Hegarty K, Ramsay J, Davidson L, Feder G. Screening women for intimate partner violence in healthcare settings. Cochrane Database Syst Rev 2013, Issue 4. 33. Ramsay J, Carter Y, Davidson L, Dunne D, Eldridge S, Feder G, et al. Advocacy interventions to reduce or eliminate violence and promote the physical and psychosocial well-being of women who experience intimate partner abuse. Cochrane Database Syst Rev 2009(3):CD005043. 34. El-Mohandes AA, Kiely M, Gantz MG, El-Khorazaty MN. Very preterm birth is reduced in women receiving an integrated behavioral intervention: a randomized controlled trial. Matern Child Health J 2011;15(1):1928. 35. El-Mohandes AA, Kiely M, Joseph JG, Subramanian S, Johnson AA, Blake SM, et al. An intervention to 82

References

36.

37.

38.

39. 40. 41. 42.

improve postpartum outcomes in African-American mothers: a randomized controlled trial. Obstet Gynecol 2008;112(3):611-20. Miller E, Decker MR, McCauley HL, Tancredi DJ, Levenson RR, Waldman J, et al. A family planning clinic partner violence intervention to reduce risk associated with reproductive coercion. Contraception 2011;83(3):274-80. Kiely M, El-Mohandes AA, El-Khorazaty MN, Blake SM, Gantz MG. An integrated intervention to reduce intimate partner violence in pregnancy: a randomized controlled trial. Obstet Gynecol 2010;115(2 Pt 1):273-83. Norkhafizah S, Zaharah S, Siti Hawa A, et al. Validity and reliability of the Malay version of WHO Women’s Health and Life Experiences Questionnaire. J Interpers Violence 2013;28(12):2557-80 American College of Obstetricians and Gynecologists. Intimate partner violence: Committee opinion No. 518. Obstet Gynecol 2012;119:412-7. Taket A, Nurse J, Smith K, Watson J, Shakespeare J, Lavis V, et al. Routinely asking women about domestic violence in health settings. BMJ 2003;327:673-6. Taft AJ, Hegarty KL, Feder GS. Tackling partner violence in families. Med J Aust 2006;185(10):535-6. Moyer V. Screening for Intimate Partner Violence and Abuse of Elderly and Vulnerable Adults: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 2013; 58(6):478.

14

Depression SUMMARY

Although prevalent, the detection and treatment of depression in primary care settings remain low. Routine screening using questionnaires for depression, without staff assistance in depression care, has minimal short-term impact on detection and beneficial outcome. Screening can improve outcomes if it is coupled with adequate depression care support.

RECOMMENDATIONS

Screening for depression may be indicated for high-risk patients in primary care settings if staff-assisted depression care support is available.

Grade C

14.1 Introduction Depression is a global public-health issue (1-5) with considerable consequences (6-12). The estimated one-year and lifetime prevalence of major depression in the general population worldwide have been reported to range from 3.2 to 6.7 % (1, 2). In the United States (US), 20.1% of adults reported significant depressive symptoms in national health surveys (3). However, the prevalence of major depression in the primary care setting ranged from 2.2 to 36.1% (2, 4). In the Asia Pacific region, the prevalence of major depression in the general population was reported to range from 1.3 to 5.5% (5). In Malaysia, a recent review on depression prevalence found comparable rates of 6.3% to 13.9% in the community and 6.7% to 14.4% in the primary care setting (6).  The Global Burden of Disease Study ranked depression as the fourth leading cause of disease burden in the year 2000, accounting for 4.4% of total disabilityadjusted life years (DALYs) (7). By 2020, depression is projected to rank second in the leading causes of disease burden (8). Depression increases the risk of morbidity (1, 4, 9, 10) and mortality (12-15). In the US, a 2013 report cites major depression as the most common cause of suicide (15). Moreover, from 1990 to

Introduction

83

2000, the economic burden of depression rose by 7% while its treatment rate increased by over 50% (12).  The risk groups for depression include those with (16-23): • • • • •

physical health problems causing disability past history of depression family history of depression other mental health problems such as substance abuse or dementia adverse psychosocial factors

Other risk factors that have been identified include genetic predisposition, female gender, lower education and poor self-perception of health.

14.1 Benefit of screening and treating depression  Although depression remains under-recognized and under-treated (3, 24), routine screening by clinicians using questionnaires for depression have proven to have minimal and short term impact on its detection and management or outcome (25-27). According to a Cochrane review, screening and feedback to clinicians of the screening scores do not increase the detection of depression (relative risk 1.00; 95% confidence interval 0.89 to 1.13) (25). Although a higher intervention rate on screen-detected cases (relative risk 1.35; 95% confidence interval 0.98 to 1.85) was noted in small studies (25), the benefit of screening programmes was not evident without staff assistance in depression care (25, 27). However, screening coupled with adequate staff-assisted and organisational depression care support (28-30) showed improved outcomes, although it was associated with increased cost (31).  An established treatment for major depression is available and is effective (32). The majority of patients with depression attending primary care have mild symptoms. The benefit of treatment for mild major depression is smaller compared to the benefit of treatment for moderate and severe major depression (33). After 10 to 16 weeks of treatment, a study reported that patients on antidepressants, psychotherapy and in the control group had a remission rate of 46%, 48% and 24.4%, respectively (34). In older adults, treatment with anti-depressants was associated with a higher remission rate compared to the placebo (OR, 2.13 [CI, 1.61 to 2.86]) (35). A meta analysis also found that psychotherapy is effective in achieving remission compared to no treatment (OR, 2.47 [CI, 1.76 to 3.47]) (36).

84

Benefit of screening and treating depression

14.2 Screening tests  Although many screening tools for depression exist, they have different validities in detecting depression (37). Screening for depression should be done using the simplest tool or questionnaire without substantially compromising validity (33). A few studies have looked at the validity of various screening instruments appropriate for primary care settings (Table 1). PHQ-9 (39-43) and PHQ-2 (43, 44) have demonstrated high sensitivity. Other questionnaires, such as GDS-15, GDS-30, BDI, BDI-SF, CES-D, HADS and DASS-21, have also been reviewed (37, 45-52). The construct validity of the translated versions of DASS-21 (BM DASS-21) (53 -55), DASS-24 (BM DASS-24) (56) and PHQ-9 (57) has been tested in Malaysia. They have demonstrated similar validity but with a higher number of items. On the other hand, the adapted PHQ-2, a brief Two Questions With Help Questions (TQWHQ) (42, 58), including the translated TQWHQ (Malay version) (59), has been shown to have good validity. The two questions asked in the TQWHQ are similar in content to the PHQ-2 (44) and  Two Whooley Questions (60, 61), with an addition of a help question, Q3 (Appendix). The addition of the help question has improved the tool’s specificity in diagnosing depression in primary care (42, 58, 59). Therefore, if screening is indicated, the TQWHQ (Malay version) can be considered as the screening tool for local settings provided that referrals for further evaluation and management for patients who are detected to have depression is in place (57).

Table 1: Validity of commonly available screening instruments for depression Assessment tool

1.

PHQ-2 (43, 44)

2.

TQWHQ (42, 60) - adapted PHQ 2

3.

Sensitivity (%)

Specificity (%)

83

83 -92

86 – 96

78 – 89

TQWHQ (Malay version) (59)

87

95

4.

Whooley questions (60, 61)

96 – 97

57-67

5.

PHQ-9 (39-43)

74-85

89 -94

6.

GDS-15 (46, 47)

78 –81

74 –78

7.

GDS-30 (46, 47)

77 -83

65-70

14.3 Harm of screening Screening for depression may impose potential harm, such as false-positive results, the inconvenience of confirmatory assessments, stigmatization, the expenses and adverse effects of treatment in case of misdiagnosis (32). Other potential harms may also comprise treatment avoidance, deterioration in patient-provider relationship and over treatment (62). Harm of screening

85

So far, no evidence of harms from screening for depression in adults has been reported (32, 63). Nevertheless, there is some evidence on the harm from treatment which includes increased suicidal behaviours in younger adults who were on paroxetine for major depressive disorder (MDD) and increased risk for upper gastrointestinal bleeding with SSRI use among older adults (32).

86

Harm of screening

 Appendix – Depression 1

TWO QUESTIONS ON DEPRESION AND ONE QUESTION ON HELP (TQWHQ) MALAY VERSION (52). Question

Q1

Content

Dalam tempoh sebulan yang lalu, adakah anda sering diganggui dengan perasaan murung, sedih atau tiada harapan?

0

 Ya / Yes

1

Tidak / No

0

 Ya / Yes

1

Jika YA kepada satu ataupun kedua-dua soalan ini, adakah anda memerlukan bantuan dengan masalah anda ini?

Tidak / No

0

If YES to either or both of these 2 questions, do you want help with this? 

 Ya, tetapi bukan hari ini / Yes, but not today

1

 Ya / Yes

2

Dalam tempoh sebulan yang lalu, adakah anda sering kehilangan minat atau keseronokan dalam melakukan kerjakerja? During the past month, have you often been bothered by having little interest or pleasure in doing things? 

Q3

Score

Tidak / No

During the past month, have you often been bothered by feeling down, depressed or hopeless? 

Q2

Response

Patients with a positive score (score of 2 or more) on TQWHQ, should then complete the PHQ-9 (37, 53) or be evaluated further (54).

 Appendix - Depression 1

87

REFERENCES 1.

2.

3.

4.

5. 6. 7. 8. 9.

10.

11.

12.

13. 14.

15.

88

Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. The Lancet 2007; 370(9590):851-8. Waraich P, Goldner EM, Somers JM, Hsu L. Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry 2004; 49(2):124-38. Shim RS, Baltrus P, Ye J, Rust G. Prevalence, treatment, and control of depressive symptoms in the United States: results from the National Health and Nutrition Examination Survey (NHANES), 2005 - 2008. J Am Board Fam Pract 2011; 24(1):33-8. Herrman H, Patrick DL, Diehr P, et al. Longitudinal investigation of depression outcomes in primary care in six countries: the LIDO study. Functional status, health service use and treatment of people with depressive symptoms. Psychol Med 2002;32(2002):889–902 Chiu E. Epidemiology of depression in the Asia Pacific region. Australas Psychiatry 2004; 12:4-10. Firdaus M, Tian PSO. A review on the prevalence of depression in Malaysia. Curr Psychiatry Rev 2011:7(3); 234-8 Ustun TB, Ayuso–Mateos JL, Chatterji S, Mathers C, Murray CJ. Global burden of depressive disorders in the year 2000. Br J Psychiatry 2004;184:386–92 Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997;349:1498-504. Spijker J, de Graaf R, Bijl RV, Beekman AT, Ormel J, Nolen WA. Duration of major depressive episodes in the general population: results from The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Br J Psychiatry 2002;181:208-13. William WE, Huibo S, Gerald N, Ben HL, Bienvenu OJ, Peter Z. Population-based study of first onset and chronicity in major depressive disorder. Arch Gen Psychiatry. 2008;65(5):513-20. Berto P, D’Ilario D, Ruffo P, Di Virgilio R, Rizzo F. Depression: cost-of-illness studies in the international literature, a review. J Ment. Health Policy Econ 2000;3(1):3-10 Paul E, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA, Corey-Lisle PKG. The economic burden of depression in the United States: How did it change between 1990 and 2000? J Clin Psychiatry 2003;64(12):1465-75. Lawson RW, George EV, Victoria EW. A systematic review of the mortality of depression. Psychosom Med 1997; 61:6-17. Amanda BJ, Andrew P, Harvey WA. Factors influencing risk of premature mortality in community cases of depression: a meta-analytic review. Epidemiol Res Int 2011;2011:12 American Foundation for Suicide Prevention. Facts and Figures [Internet]. 2013 [cited 29 April 2015]. Available

References

16.

17. 18. 19. 20. 21.

22.

23. 24.

25. 26. 27.

28. 29.

30.

from: http://www.afsp.org/understanding-suicide/factsand-figures Hirschfeld RMA, Weissman MM. Risk factors for major depression and bipolar disorder. In Davies KL, Charney D, Coyle JT, Nemeroff C. (Eds) Neuropsychopharmacology: Philadelphia: Lippincot Williams and Wilkins, The Fifth Generation of Progress 2002;1017-26. Martin GC, Nandini D. Risk factors for depression among elderly community subjects: a systematic review and meta-analysis. Am J Psychiatry 2003;160:1147-56. Osama AA, Nabilla AS, Elawad NAM. Gender and risk of depression in Saudi Arabia, a systematic review and meta-analysis. J Public Health Africa 2010;1(1) Djernes JK. Prevalence and predictors of depression in populations of elderly: a review. Acta Psychiatr. Scand 2006;113(5):372-87. Riemann D, Voderholzer U. Primary insomnia: a risk factor to develop depression? J Affect Disord 2003;76(1-3):255-9. Nouwen A, Winkley K, Twisk J, Lloyd CE, Peyrot M, Ismail K, Pouwer F, and for the European Depression in Diabetes (EDID) Research Consortium. Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis. Diabetologia 2010;53(12):2480–6. Chang QH, Zheng RW, Yong HL, Yi ZX, Qing XL. Education and risk for late life depression: a metaanalysis of published literature. Int J Psychiatry Med 2010;40 (1):109-24. Bonde JPE. Psychosocial factors at work and risk of depression: a systematic review of the epidemiological evidence: Review Occup Environ Med 2008;65:438-45 Cepoiu M, McCusker J, Cole MG, Sewitch M, Belzile E, Ciampi A. Recognition of depression by non-psychiatric physicians: a systematic literature review and metaanalysis (Structured abstract). J Gen Intern Med 2008;23(1):25-36 Gilbody S, House A, Sheldon T. Screening and case finding instruments for depression. Cochrane Database of Sys Rev 2009(1). Gilbody S, Sheldon T, Wessely S. Should we screen for depression? BMJ 2006;332:1027 O’Connor EA, Whitlock EP, Beil TL, Gaynes BN. Screening for depression in adult patients in primary care settings: a systematic evidence review. Ann Intern Med. 2009;151(11):793-803. Palmer SC, Coyne JC. Screening for depression in medical care: Pitfalls, alternatives, and revised priorities. J Psychosom Res 2003;54(4):179-287 Pignone MP, Gaynes BN, Rushton JL, Burchell CM, Orleans CT, Mulrow CD, Lohr KN. Screening for depression in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;136(10):765-76 Bijl D, van Marwijk HW, de Haan M, van Tilburg W, Beekman AJ. Effectiveness of disease management

31.

32.

33.

34.

35. 36.

37. 38. 39.

40.

41.

42.

43.

44. 45.

programmes for recognition, diagnosis and treatment of depression in primary care. Eur J Gen Pract 2004;10(1):6-12. Gilbody S, Bower P, Whitty P. Costs and consequences of enhanced primary care for depression. Systematic review of randomised economic evaluations. Br J Psychiatry 2006;189:297-308 U.S. Preventive Services Task Force. Screening for depression in adults: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2009;151:784-92. Ministry of Health. Management of Major Depressive Disorder 2007 [Internet]. 1st ed. Malaysia: 2007 [cited 29 April 2015]. Available from: http://www.moh.gov.my/  attachments/3897.pdf Casacalenda N, Perry JC, Looper K. Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions. Am J Psychiatry 2002;159:1354-60 Wilson K, Mottram P, Sivanranthan A, Nightingale A. Antidepressant versus placebo for depressed elderly. Cochrane Database Syst Rev. 2001:CD000561 Pinquart M, Duberstein PR, Lyness JM. Treatments for later-life depressive conditions: a meta-analytic comparison of pharmacotherapy and psychotherapy. Am J Psychiatry 2006;163:1493-501 Williams JW, Noel PH, Cordes JA, Ramirez G, Pignone M. Is this patient clinically depressed? JAMA 2002;287:1160–70. Douglas MM, Screening for depression. Am Fam Physician 2012;85(2):139-44. Kroenke K, Spitzer RL, Williams JBW, Löwe B. The patient health questionnaire somatic, anxiety, and depressive symptom scales: a systematic review. Gen Hosp Psychiatry 2010;32(2010);345–59 Manea L, Gilbody S, McMillan D. Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): a meta-analysis. CMAJ 2012;184(3):E191–6 Wittkampf KA, Naeije L, Schene AH, Huyser J, van Weert HC. Diagnostic accuracy of the mood module of the Patient Health Questionnaire: a systematic review. Gen Hosp Psychiatry 2007;29(2007):388–95 Arroll B, Goodyear-Smith F, Crengle S, Gunn J, Kerse N, Fishman T, Falloon K, Hatcher S. Validation of PHQ2 and PHQ-9 to screen for major depression in the primary care population. Ann Fam Med 2010;8(4):34853 Gilbody S, Richards D, Brealey S, Hewitt C. Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med 2007;22:1596–602. Kroenke K, Spitzer RL, Williams JBW. The Patient Health Questionnaire-2. Validity of a two-item depression screener. Med Care 2003;41(11):1284–92 Wancata J, Alexandrowicz R, Marquart B, Weiss

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

56.

57. 58.

M, Friedrich F. The criterion validity of the Geriatric Depression Scale: a systematic review. Acta Psychiatr Scand 2006;114:398–410 Mitchell AJ, Bird V, Rizzo M, Meader N. Diagnostic validity and added value of the geriatric depression scale for depression in primary care: A meta-analysis of GDS 30 and GDS 15 . J Affect Disord 2010;125(1):10-7 Furlanetto LM, Mendlowicz MV, Bueno J. The validity of the Beck Depression Inventory—Short Form as a screening and diagnostic instrument for moderate and severe depression in medical inpatients. J Affect Disord 2005;86:87–91. Lasaa L, Ayuso-Mateosa JL, Va´zquez-Barqueroa JL, D´ıez-Manriquea FJ, Dowrick CF. The use of the Beck Depression Inventory to screen for depression in the general population: a preliminary analysis. J Affect Disord 1999;57(2000):261–5 Bjellanda I, Dahlb AA, Haugc TT, Neckelmann D. The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res 2001; 52(2002):69–77 Brennan C, Worrall-Davies A, McMillan D, Gilbody S, House A. The hospital anxiety and depression scale: A diagnostic meta-analysis of case-finding ability. J Psychosom Res 2010;69(2010):371–8. Henry JD, Crawford JR. The short-form version of the Depression Anxiety Stress Scales (DASS-21): Construct validity and normative data in a large non-clinical sample. Br J Clin Psychol 2005;44:227–39 Gloster AT, Rhoades HM, Novy D, Jens Klotsche, Senior A, Kunik M, Wilson N, Stanley MA. Psychometric properties of the Depression Anxiety and Stress Scale-21 in older primary care patients. J Affect Disord 2008;110:248– 59 Ramli M, Ariff MF, Zaini Z. Translation, validation and psychometric properties of Bahasa Malaysia version of the Depression, Anxiety and Stress Scales (DASS-21). ASEAN Journal of Psychiatry 2007;8(2):82-9. Ramli M., Salmiah MA, Nurul Ain M. Validation and psychometric properties of Bahasa Malaysia version of the Depression Anxiety and Stress Scales (DASS) among diabetic patients. Malaysian Journal of Psychiatry 2010;18(2):40-5. Ramli M, Roszaman R, Kartini A, Rosnani S. Concurrent validity of the depression and anxiety components in the Bahasa Malaysia version of the Depression Anxiety and Stress Scales (DASS). ASEAN Journal of Psychiatry 2011;12(1) Ramli M, Rosnani S, Aidil Faszrul AR. Psychometric profile of Malaysian version of the Depressive, Anxiety and Stress Scale 42-item (DASS-42). Malaysian Journal of Psychiatry 2012;20(1);3-9. Sherina MS, Arroll B, Goodyear-Smith F. Criterion validity of the PHQ-9 (Malay version) in a primary care clinic in Malaysia. Med J Malaysia 2012;67(3):309-15. Arroll B, Goodyear-Smith F, Kerse N, Fishman T, Gunn References

89

REFERENCES

59.

60. 61. 62.

63.

90

J. Effect of the addition of a “help” question to two screening questions on specificity for diagnosis of depression in general practice: diagnostic validity study. BMJ 2005;331(7521):884. Sherina MS, Arroll B, Goodyear-Smith F, Azhar MDZ. Screening for depression with a brief questionnaire in a primary care setting: validation of the two questions with help question (Malay Version). The Int J.Psychiatry in Medicine 2011;41(2):143-54 Whooley MA, Avins AL, Miranda J, Browner WS. Case finding instruments for depression: Two questions are as good as many. J Gen Int Med 1997;12(7):439-45 Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ 2003;327:1144–6 Uspreventiveservicestaskforce.org. Final Research Plan: Depression in Adults: Screening - US Preventive Services Task Force [Internet]. 2014 [cited 29 April 2015]. Available from: http://www. uspreventiveservicestaskforce.org/Page/Document/  ResearchPlanFinal/depression-in-adults-screening1 Care C. Depression—Systematic Review [Internet]. Canadian Task Force on Preventive Health Care. 2012 [cited 29 April 2015]. Available from: http://  canadiantaskforce.ca/ctfphc-guidelines/2013depression/systematic-review/

References

15

Scoliosis in Adolescents SUMMARY

Scoliosis is not rare among adolescents, especially girls. Early detection with non-surgical intervention improves disease outcome and reduces surgical intervention. Regional data demonstrate the cost benefit of a school-based screening programme for idiopathic scoliosis.

RECOMMENDATIONS

A school-based screening programme for scoliosis using a scoliometer to measure angle of trunk rotation is indicated for girls aged 12 years.

Grade B

15.1 Introduction Scoliosis is defined as a lateral curvature of the spine greater than 10 degrees as measured using the Cobb method on a standing radiograph, and idiopathic scoliosis is the most common type (1) Level III. The reported prevalence of adolescent idiopathic scoliosis (AIS) varies depending on the degree of curvature used in its definition. In general, the prevalence of AIS is relatively low (2) Level II-3, e.g., a review article reported prevalence rates in the USA of 2 to 4% among children and adolescents (3)  Level III. A study in one urban area in Malaysia reported a prevalence of 1.36% and 4.14% among children aged 11 and 15 years, respectively (4) Level II-3

 and a study on schoolchildren in Singapore found an increasing prevalence of  AIS among females between age 9 to 13 years old (5) Level II-3. Scoliosis is more common, and progresses faster, in girls than boys, thus, requiring treatment earlier compared to scoliosis in boys (4) Level II-3. Scoliosis has a significant impact on the physical and psychosocial health of affected individuals.  Thoracic curves are more likely to cause pulmonary complications whereas Introduction

91

lumbar curves are more likely to produce postural problems. A lower marriage rate among patients with scoliosis and their lack of participation in social functions infer that they have poor self-image and are socially isolated (6) Level II-3.

15.2 Benefit of screening and treating adolescent idiopathic scoliosis In Malaysia, one study on untreated idiopathic scoliosis found that most patients present late in adolescence and need surgical intervention (7)  Level II-3. The mean age at presentation was o 15 years and the median rate of curve progression was 7.03  per year. The mean curve size at presentation was 41.6 degrees (7)  Level II-3. Surgical intervention can be avoided if mild to moderate scoliosis is detected early. Progressive Action Short Brace (PASB) and Milwaukee brace are effective in improving thoraco-lumbar curves (8, 9) Level II-3. Countries with screening programmes have noted a reduction in the need to have corrective surgery (10). However, a more recent meta-analysis reported the evidence supporting bracing as an early effective intervention is weak. (11)

15.3 Screening tests Scoliosis can be assessed by measuring the angle of trunk rotation (ATR). ATR is measured by a scoliometer placed on the spine of the adolescent in an Adam forward bent position (Figure 15.1). Asymmetry noted by ATR should cast suspicion on the presence of AIS.

(a)

(b)

Figure 15.1 Adam forward bent position (a), positioning a scoliometer (b) 92

Screening tests

o

 An ATR of ≥7  needs further radiological evaluation (12)

Level III

. In a study on 150 children

referred to hospitals for evaluation of scoliosis, a comparison of the ATR from scoliometer readings with Cobb angle measurements of lateral deviation of the spine found that an ATR o of 7o was significantly correlated with Cobb angle and scoliosis of ≥25  (13) Level III. This is lower than the level to start bracing treatment - 300. The International Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) recommends using the screening o referral criterion of ATR≥7  at any level of the spine for further assessment. Using this criterion reduces the need for referral, spinal radiography and follow-up, thus, maintaining the cost effectiveness of spinal screening programs (12 -16, 19) Level III (18) Level II-3.  Although The US Preventive Screening Task Force recommendations in 2010 - 2011 (20) Level III do not include screening scoliosis in adolescents, screening is recommended in local, regional guidelines (5) Level II-3 (10, 16) Level III, the American Academy of Scoliosis Research, Scoliosis Research Society, the Pediatric Orthopedic Society of North America and the  American Academy of Pediatrics (1)  Level II-3. Some societies have recommended screening twice for girls aged 10 and 12 years and males at the age of 13 or 14 (1) Level II-3. Singapore has recommended yearly screening for adolescent girls (5) Level II-3. The Health Technology  Assessment (HTA) Ministry of Health Malaysia has recommended screening among high risk adolescents especially 12 year-old girls using a combination of Adams forward-bending test and scoliometer (10, 17) Level III because of the late presentation of AIS in the majority of Malaysian patients. A study from Singapore has demonstrated the cost-effectiveness of screening scoliosis among high-risk groups (21) Level III.

15.4 Harm of screening  A review of evidence by HTA in 2009 noted that there was no progression of the curvature in a majority of patients detected through screening, but there was progression in a greater proportion of girls than boys (10). Screening may result in un necessary brace wear and referral for specialty, thus, the USPSTF has concluded that the harms of screening adolescents for  AIS exceed the potential benefits (20). However, the awareness of AIS is probably higher in developed countries compared to developing countries, and screening may not add benefit compared to the natural presentation of patients with AIS. In Malaysia, on the other hand, many of the patients with AIS may not be aware of the early presentation of scoliosis. Hence, although more patients will be unnecessarily followed-up with a screening programme, the benefit of screening likely outweighs the harm.

Harm of screening

93

REFERENCES 1.

2. 3. 4.

5.

6. 7.

8.

9.

10.

11. 12. 13. 14. 15.

94

Richards BS, Vitale MG. Screening for idiopathic scoliosis in adolescents. an information statement. The Orthopaedic Forum. J Bone Joint Surg Am 2008; 90(1): 195-8. Nery LS, Halpern R, Nery PC, et al. Prevalence of scoliosis among school students in a town in Southern Brazil. Sao Paulo Med J 2010; 128(2): 69-73. Reamy BV, Slakey JB. Adolescent idiopathic scoliosis: review and current concepts. Am Fam Physician 2001; 64(1): 111-6. Azlin A. Screening for scoliosis among students age 11 and 15 years old at Kuala Terengganu, Terengganu. Thesis submitted in partial fulfilment for the degree of Masters of Medicine (family medicine) 2005. Yong F, Wong HK, Chow KY. Prevalence of adolescent idiopathic scoliosis among female school children in Singapore. Ann Acad Med Singapore 2009; 38(12): 1056-63. McCarthy RE. Prevention of the complications of scoliosis by early detection. Clin Orthop Relat Res 1987; (222): 73-8. Chuah SI, Kareem BA, Selvakumar K et al. The natural history of scoliosis curve progression of untreated curves of different aetiology with early (mean 2 years) follow up in surgically treated curves. Med J Malaysia 2001; 56 Suppl C: 37-40. Aulisa AG, Guzzanti V, Galli M, et al. Treatment of thoraco-lumbar curves in adolescent females affected by idiopathic scoliosis with a progressive action short brace (PASB): assessment results according to the SRS committee on bracing and non-operative management standardization criteria. Scoliosis 2009; 4: 21. Jiang J, Qiu Y, Mao S, et al. The influence of elastic orthotic belt and sagittal profile in adolescent idiopathic thoracic scoliosis: a comparative radiographic study with Milwaukee. BMC Musculoskelet Disord 2010; 11: 219. Ministry of Health (MOH). Health Technology Assessment Report [Internet]. Malaysia: Ministry of Health; 2009. Available from: http://www.moh.gov.my/  attachments/7508.pdf. Negrini S, Minozzi S, Bettany Saltikov j, et al. Braces for idiopathic scoliosis in adolescents. Cochrane Database Syst Rev 2010: 1 Samuelsson L, Norén L. Trunk Rotation In Scoliosis. The influence of curve type and direction in 150 children. Acta Orthop Scand 1997; 68(3): 273-6. Grivas TB, Wade MH, Negrini S, et al. SOSORT consensus paper: school screening for scoliosis. Where are we today? Scoliosis 2007; 2: 17. Huang SC. Cut-off point of the scoliometer in school scoliosis screening. Spine (Phila Pa 1976) 1997; 22(17): 1985-9. Bunnell WP. Outcome of spinal screening. Spine 1993; 18(12): 1572-1580.

References

16. Forman SF, Emans SJ. Current goals for adolescent healthcare. Hosp Physician 2000;36(1), 27-48 17. Sabirin J, Bakri R, Buang SN, et al. School scoliosis screening programme? A systematic review. Med J Malaysia 2010; 65(4): 261-7. 18. Bunge EM, Juttmann RE, van Blezen FC et al. Estimating the cost effectiveness of screening for scoliosis: a case control study. Pediatrics 2008; 121 (1): 9-14. 19. Yawn BP, Yawn RA. The estimated cost of school screening. Spine 2000; 25 (18): 2387-91. 20. U.S. Preventive Services Task Force. The guide to clinical preventive services 2010 - 2011: Recommendations of the U.S. Preventive Services Task Force. Rockville (MD): Agency for Healthcare Research and Quality (US); 2010 21. Thilagaratnam S. School-based screening for scoliosis: is it cost effective? Singapore Med J 2007; 48(11): 1012.

16

Hearing Loss in Older People SUMMARY

Hearing loss due to presbycusis is common among older people. Hearing loss is associated with impaired quality of life but most cases are treatable. Screening and treatments are non-invasive and generally are safe. There is a high rate of non-use of hearing aids after hearing impairment is detected by screening. Current evidence primarily reports the benefit of using hearing aids for symptomatic people. The evidence is insufficient to assess the balance of benefits and harms of screening for hearing loss in asymptomatic adults aged 60 years or older.

RECOMMENDATIONS

Routine screening for hearing impairment in asymptomatic adults aged 60 years or older is not indicated.

Grade I

Evaluation of hearing impairment should be as indicated clinically.

16.1 Introduction Hearing loss is common in older adults with increasing prevalence and severity with age (1 - 4)  Level III. In the United States, national data showed that hearing impairment affects 25% to 40% of those 65 years or older (3) Level III. In Malaysia, a study in a primary care clinic reported that 24.3% of adults 60 years and above felt they had hearing loss while 36.9% were detected to have hearing loss by pure tone audiometry (5) Level III. Of the adults with hearing loss, majority has mild hearing loss; 26.1% of adults above 60 years had mild hearing loss, 3.6% had moderate hearing loss, 6 (5.4%) had severe hearing loss and 1.8% had profound hearing loss. Severity of hearing loss is defined as mild hearing loss at 26-40 dBHL, moderate hearing loss at 41-60 dBHL, severe hearing loss as 61-80 dBHL and profound hearing loss at 81 dBHL and above by pure tone audiometry (PTA) measurement.(6)  Hearing loss can impact quality of life, ability to function and emotional wellbeing Introduction

95

in older adults (7-10)

Level I & III

 Studies have found that hearing loss is associated with increased

emotional dysfunction, depression, and social isolation (8 -11)

Level III

.

Hearing impairment is often missed and under-diagnosed for various reasons. The older person with a hearing impairment may not be aware of their problem. The most common cause of hearing loss in older persons is age-related hearing loss (presbycusis), a problem which progresses with advancing age. The symptoms may be relatively mild or slowly progressive. In addition, a study has revealed that some people may perceive hearing loss but do not seek medical attention (1) Level III. Other than presbycusis, cerumen impaction and chronic otitis media, which are treatable if detected early, may be present in up to 30% of elderly patients with hearing loss (12) Level III.

16.2 Benefit of screening and treating hearing impairment  The benefits of a hearing aid were well demonstrated in adult patients with sensory neural hearing loss (13) Level I. However, as this high quality review noted, the benefits were less clear among screen-detected patients with presbycusis. Although one RCT showed benefits of better communication ability, social function, life satisfaction, and emotional balance (8), other RCTs (14, 15) were not able to show similar results with certainty (16). The review commented that the RCT, which showed the benefits of hearing aids, recruited patients not typically seen in the community (16) Level II. The findings are supported by a review which showed self-reported hearing disability was the only significant factor affecting all four outcome measures of hearing aid usage: help-seeking, hearing-aid uptake, use, and satisfaction. (17)  There is direct evidence from randomized controlled trials evaluating the effect of screening among adults aged 50 years and above to show that screening is associated with only a small increase in hearing aid used (18). Many cohort studies following up patients after screening and detecting hearing loss also demonstrated low hearing aid use, (19 -22) Level II unless hearing impairment is significant (> 35dB hearing loss) (23) Level III. The small increase in hearing aid usage was not found to have a discernible effect on hearing-related quality of life in secondary analysis (16). Hence, hearing aid benefits only a small group of people with mild hearing lost (> 26-40 dB hearing loss).  A cost analysis study in the United Kingdom found that a simple systematic screen, using two questions concerning hearing problems and audiometric screening instrument, is justifiable and may be cost-effective. The costs of screening and intervention were in the range of £800 -1000 (RM 4000 -5500) per quality-adjusted life-year using the Health Utilities Index (23) Level III . A later study on the cost-effectiveness of screening noted that patients screened with audioscope have a higher hearing aid use after one year, rendering it more cost-effective (24) Level II . However, similar cost-effectiveness study is not available in Malaysia. 96

Benefit of screening and treating hearing impairment

16.3 Screening tests Screening tests that can be used in an office setting include: a) The Single Global Screening Question: “Do you or your family think that you may have hearing loss?” b) The Hearing Handicap Inventory for the Elderly-Screening (HHIES) c) The AudioScope (a handheld otoscope with a built-in function of an audiometer) d) The whispered voice test- if carried out meticulously.  As a screen for mild hearing loss (>25 dB), the Single Global Screening Question and HHIES have almost similar sensitivity (58 -67%) (24). Although the whisper voice test has higher sensitivity (95%), (25)  Level II-2 it is difficult to standardise, and has high inter-observer variability and poor test-retest reliability (26). All four methods have similar specificity (82-89%) (25) Level II-2 .  As a screen for moderate hearing loss (>40 dB), the Single Global Screening Question and HHIES also have comparable sensitivity (72-81%) while the AudioScope has higher sensitivity (96%) (25) Level II-2. Both methods and the AudioScope have similar specificity (72-76%) (25) Level II-2.

16.4 Harm of screening No randomized trial or controlled observational study has evaluated harms associated with screening for hearing loss in older adults. A few case series have reported the potential harms of hearing aids which include dermatitis, accidental retention of mould, cerumen impaction, otitis externa and middle ear problems (27 -29)  Level III. However, hearing aids are non-invasive and are generally believed to be safe.

Harm of screening

97

REFERENCES 1.

2.

3.

4.

5.

6.

7. 8. 9. 10. 11.

12. 13.

14.

15.

98

Cruickshanks KJ, Wiley TL, Tweed TS, et al. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The epidemiology of hearing loss study. Am J Epidemiol 1998; 148(9):879-86. Gates GA, Cooper JC Jr, Kannel WB, Miller NJ. Hearing in the elderly: the Framingham cohort, 1983–1985, part I: basic audiometric test results. Ear Hear 1990; 11(4):247-56. Reuben DB, Walsh K, Moore AA, Damesyn M, Greendale GA. Hearing loss in community-dwelling older persons: national prevalence data and identification using simple questions. J Am Geriatr Soc 1998; 46(8):1008-11. Wallhagen MI, Strawbridge WJ, Cohen RD, Kaplan GA. An increasing prevalence of hearing impairment and associated risk factors over three decades of the Alameda County Study. Am J Public Health 1997;87(3):440-42. Rosdina AK, Leelavathi M, Zaitun A, Lee VKM, Azimah MN, Majmin SH, Mohd KA. Self-reported hearing loss among elderly Malaysians. Malaysian Family Physician 2010;5(2):91-4. World Health Organization fact sheet. Deafness and hearing impairment. In: Organization W.H, editor. World Health Fact Sheet (#300 ed.) Geneva: World Health Organization; 2006. Gates GA, Mills JH. Presbycusis. Lancet 2005; 366(9491): 1111-20. Mulrow CD, Aguilar C, Endicott JE, et al. Quality-of-life changes and hearing impairment: a randomized trial. Ann Intern Med 1990; 113(3): 188-94. Weinstein BE, Ventry IM. Hearing impairment and social isolation in the elderly. J Speech Hear Res 1982; 25(4): 593-9. Carabellese C, Appollonio I, Rozzini R, et al. Sensory impairment and quality of life in a community elderly population. J Am Geriatr Soc 1993; 41(4): 401-7. Appollonio I, Carabellese C, Magni E, Frattola L, Trabucchi M. Sensory impairments and mortality in an elderly community population: a six-year follow-up study. Age and ageing 1995;24(1):30-6. Yueh B, Shapiro N, MacLean CH, Shekelle PG . Screening and management of adult hearing loss in primary care. JAMA 2003;289:1976-85 Chisolm T H JCE, Danhauer J L, Portz L J, Abrams H B, Lesner S, McCarthy P A, Newman C W. A systematic review of health-related quality of life hearing aids: final report of the American Academy of Audiology Task Force on the Health-Related Quality of Life Benefits of Amplication in Adults 2007;18(2):151-83 Yueh B, Souza PE, McDowell JA, Collins MP, Loovis CF, Hedrick SC,et al. Randomized trial of amplification strategies. Arch Otolaryngol Head NeckSurg 2001;127:1197-204. Jerger J, Chmiel R, Florin E, Pirozzolo F, Wilson N. Comparison of conventional amplification and an assistive listening device in elderly persons. Ear Hear 1996;17:490-504.

References

16. Chou R, Dana T, Bougatsos C, Fleming C, Beil T. Screening adults aged 50 years or older for hearing loss: a review of the evidence for the U.S. preventive services task force. Ann Int Med 2011;154(5):347-55. 17. Knudsen LV, Oberg M, Nielsen C, Naylor G, Kramer SE. Factors influencing help seeking, hearing aid uptake, hearing aid use and satisfaction with hearing aids: a review of the literature. Trends Amplif 2010; 14(3):12754 18. Yueh B, Collins MP, Souza PE, Boyko EJ, Loovis CF, Heagerty PJ, et al. Long-term effectiveness of screening for hearing loss: the Screening for Auditory Impairment—Which Hearing Assessment-Test (SAIWHAT) randomized trial. J Am Geriatr Soc 2010;58:42734. 19. Meyer C, Hickson L, Khan A, Hartley D, Dillon H, Seymour J. Investigation of the actions taken by adults who failed a telephone-based hearing screen. Ear Hear 2011;32(6):720-31. 20. Thodi C, Parazzini M, Kramer SE, Davis A, Stenfelt S, Janssen T, et al. Adult hearing screening: follow-up and outcomes. Am J Audiol 2013;22(1):183-5. 21. van den Berg PJ, Prins A, Verschuure H, Hoes AW. Effectiveness of a single and a repeated screen for hearing loss in the elderly. Audiology 1999;38(6):33940. 22. Yasuda K, Furukawa M. [Hearing examination program status in those aged 65 to 74--Knazawa hearing examination program findings]. Nihon Jibiinkoka Gakkai kaiho. 2009;112(2):73-81. 23. Davis A, Smith P, Ferguson M, Stephens D, Gianopoulos I. Acceptability, benefit and costs of early screening for hearing disability: a study of potential screening tests and models. Health technology assessment (Winchester, England) 2007;11(42):1-294. 24. Liu CF, Collins MP, Souza PE, Yueh B. Long-term costeffectiveness of screening strategies for hearing loss. J Rehabil Res Dev 2011;48(3):235-43. 25. Roger Chou, Tracy Dana, Christina Bougatsos, et al. Screening for hearing loss in adults ages 50 years and older : a review of the evidence for the U.S. Preventive Services Task Force. Evidence Syntheses, No. 83. Oregon Evidence-based Practice Center and Kaiser Permanente Center for Health Research. AHRQ Publication No. 11-05153-EF-1. March 2011. 26. Boatman DF, Miglioretti DL, Eberwein C, et al. How accurate are bedside hearing tests? Neurology 2007; 68(16): 1311-4. 27. Kohan D, Sorin A, Marra S, Gottlieb M, Hoffman R. Surgical management of complications after hearing aid fitting. Laryngoscope 2004;114(2):317-22. 28. Sood A, Taylor JS. Allergic contact dermatitis from hearing aid materials. Dermatitis 2004;15(1):48-50. 29. Lear JT, Sandhu G, English JS. Hearing aid dermatitis: a study in 20 consecutive patients. Contact Dermatitis 1998;38(4):212.

17

 Visual Impairment in Older Persons SUMMARY

Visual impairment in older persons is common. Although most of the common causes of visual impairment in older persons can be treated, the overall outcome through screening has not proven beneficial, possibly due to poor adherence to treatment advice. There is insufficient evidence to support routine screening for visual impairment. Visual acuity chart and pinhole test are the usual screening tests easily done in primary care settings.

RECOMMENDATIONS

Routine screening for visual impairment is not indicated.

Grade I

Evaluation of visual impairment should be as indicated clinically.

17.1 Introduction  Visual impairment is defined as a presenting visual acuity of worse than 6/18 but equal or better than 3/60; whereas blindness is diagnosed when visual acuity is worse than 3/60 (1) Level III. The prevalence of visual impairment among older persons in Malaysia was 12.3% (2) Level III. An unpublished finding from National Eye Survey II in 2014 reported a prevalence of low vision (presenting with visual acuity of less than 6/18 to 3/60) of 5.4%. The prevalence worldwide varies from 7 to 34% (3). Visual impairment in older Malaysians is associated with increased risk of falls and low fragility hip fracture (4) Level II-2, as well as reduced visual related quality of life (5) Level III. The common causes of visual impairment include uncorrected refractive error, cataract, and age-related macular degeneration (2, 6) Level III. These conditions can be effectively treated, hence, may result in improved health-related quality of life (7, 8)  Level II-2.

Introduction

99

17.2 Benefit of screening visual impairment and treating common causes of visual impairment Corrective lenses (9) and cataract surgeries have been shown to be beneficial interventions for refractive errors and aged-related cataract (9, 10). In addition, a lower rate of progression of vision loss has also been demonstrated in patients who undertook treatment for agerelated macular degeneration (9).  The aim of screening for visual impairment is to improve visual function. Cluster and randomised controlled trials have showed that vision screening using visual acuity testing followed by the necessary intervention does not improve visual acuity, other clinical or functional outcomes, and vision-related quality of life when compared to no or delayed screening (11 - 14) Level I. In a meta-analysis, three to five years after screening, the risk ratio for visual acuity less than 6/18 in the universal screening group compared to a targeted screening group with healthrelated problems was 1.07 (95% CI 0.84 to 1.36, p = 0.58). The visual function difference of 0.4 (95% CI -1.7 to 2.5, p = 0.69) between the universal and targeted screening groups was also not significant (15)  level I. Adherence to treatment advice after identification of visual impairment in many trials was noted to be poor (9). The common reasons for poor adherence were disbelief in the test results, not having financial support and not knowing the need to see an eye care provider (16).

17.3 Screening tests In primary care, the screening tests for measuring visual acuity of both distance and reading acuity in older persons include the visual acuity chart and pinhole test (17) Level III. The visual acuity chart has higher sensitivity in detecting reading acuity (sensitivity: 98%; specificity: 3%) than the distance visual acuity (sensitivity: 47%; specificity: 84%). The pinhole test has a sensitivity of 34% and specificity of 86% in detecting refractive error (18)  Level III. Screening questions have weak validity (9) as patients may overestimate the adequacy of their vision (19).

17.4 Harm of screening  There is no evidence on serious harm from vision screening of asymptomatic older persons (9) besides the potential general harm caused by screening, such as anxiety and complications of treatment following screen-detected visual impairment. Posterior capsule opacification of 100

Benefit of screening visual impairment and treating common causes of visual impairment

intra-ocular lenses, which is reported and can be treated easily, is uncommon after cataract surgery. Other complications of cataract surgery are also uncommon (1% or less) (9). Notably, a small increased risk of falls is associated with the use of multifocal lenses in older adults (9) and after screening by optometrists (12). Some guidelines have recommended vision screening of community-dwelling older persons annually because treatment is available for most causes of visual impairment (20)   Level III. However, this recommendation is based on the clinical experience of the guidelines group.  Vision screening in older persons as part of a periodic health examination in the primary care setting is not recommended because of insufficient direct evidence on the benefit of screening (9, 21) Level III. Nevertheless, physicians should individualise the decision to screen patients with subjective decrease in vision.

Harm of screening

101

REFERENCES 1. 2.

3. 4.

5.

6. 7.

8. 9.

10. 11. 12. 13. 14.

15. 16.

102

World Health Organization. ICD update and revision platform: Change the definition of blindness. Geneva, WHO, 2010. Zainal M, Ismail SM, Ropilah AR, et al. Prevalence of blindness and low vision in Malaysian population: Results from the national eye survey 1996. Br J Ophthalmol 2002;86(9):951-6. Evans BJ, Rowlands G. Correctable visual impairment in older people: a major unmet need. Ophthalmic Physiol Opt 2004;24(3):161-80. Chew FLM, Yong C-K, Ayu SM, Tajunisah I. The association between various visual function tests and low fragility hip fractures among the elderly: a Malaysian experience. Age Ageing 2010;39(2):239-45. Omar R, Knight VF, Sazlina K, Syarifah N SA. Effect of visual disturbances on daily activities and quality of life among elderly in the Klang Valley. No date (Assessed 2015 Apr 27). Available from: http://ukm.academia. edu/RokiahOmar/Papers/247039/Effect_of_Visual_ Disturbances_on_a daily_activities_and_quality_of_ life_among_elderly_in_the_Klang_Valley. Jessa Z, Evans B, Thomson D, Rowlands G. Vision screening of older people. Ophthalmic Physiol Opt 2007;27(6):527-46. Owsley C, McGwin G, Scilley K, et al. Effect of refractive error correction on health-related quality of life and depression in older nursing home residents. Arch Ophthalmol 2007;125(11):1471-7. Owsley C, McGwin G, Scilley K, et al. Impact of cataract surgery on health related quality of life in nursing home residents. Arch Ophthalmol 2007;91:1359-63. Chou R, Dana T, Bougatsos C. Screening older adults for impaired visual acuity: a review of evidence for the U.S Preventive Services Task Force. Ann Intern Med 2009;151:44-58. Riaz Y, Mehta J, Wormald R, Evans J, Foster A, Ravilla T et al. Surgical interventions for age-related cataract. Am J Ophthalmol 2007;143(4):733-4. Swamy B, Cumming RG, Ivers R et al. Vision screening for frail older people: a randomised trial. Br J Ophthalmol 2009;93(6):736 -41. Cumming RG, Ivers R, Clemson L, et al. Improving vision to prevent falls in frail older people: a randomized trial. J Am Geriatric Society 2007;55:175-81. Smeeth L, Fletcher AE, Hanciles S, et al. Screening older people for impaired vision in primary care: cluster randomised trial. BMJ 2003;327(7422):1027. Eekhof J, De Bock G, Schaapveld K, Springer M. Effects of screening for disorders among the elderly: an intervention study in general practice. Fam Pract 2000;17(4):329 -33. Smeeth L, Iliffe S. Community screening for visual impairment in the elderly. Cochrane Database Syst Rev 2006(3):Cd001054. Mansberger SL, Edmunds B, Johnson CA, Kent KJ, Cioffi GA. Community visual field screening: prevalence

References

17. 18. 19. 20. 21.

of follow-up and factors associated with follow-up of participants with abnormal frequency doubling perimetry technology results. Ophthalmic Epidemiol 2007;14(3):134-40. Chu-Ai Teh R, Lim WS, Basri R, Ismail NH. Utility of a patient-response screening question for visual impairment. J Am Geriatr Soc 2006;54(2):370-2. Ivers RQ, Macaskill P, Cumming RG, Mitchell P. Sensitivity and specificity of tests to detect eye disease in an older population. Ophthalmol 2001;108:968-75 Long CA, Holden R, Mulkerrin E, Sykes D. Opportunistic screening of visual acuity of elderly patients attending outpatient clinics. Age ageing 1991;20(6):392-5. Ministry of Health, Singapore. Functional screening for older adults in the community. Ministry of Health, Singapore: Chung Printing; 2010. American Academy of Family Physicians. Visual- clinical preventive services: Recommendations, Resources & Policies [Internet]. No date (Assessed 2015 Apr 27). Available from: http://www.aafp.org/online/en/home/  clinical/exam/visual.html.

18

Risk of fall in older people SUMMARY

Falls are common among older people and are associated with a substantial risk of morbidity and mortality. There are many risk factors associated with falls especially history of previous falls. However, there is no single reliable screening test to adequately predict the risk of falls. Structured exercise and Vitamin D supplementation are noted to reduce the risk of falls. In the local context, there is no evidence to support the effectiveness of falls prevention intervention. Moreover, there are limited resources in the primary care setting to conduct multi-factorial fall risk assessment and intervention.

RECOMMENDATIONS

Identification of intrinsic and extrinsic risk factors, followed by subsequent interventions to reduce the risk is indicated for highrisk patients with relevant medical co-morbidities.

Grade C

Screening, followed by a comprehensive fall risk assessment and structured intervention (balance and strengthening exercise), is indicated if facilities are available.

Grade I

18.1 Introduction Falls are common among the older people (1). In the United States, up to 40% of older persons aged 65 years and above in the community had one or more falls in the previous 12 months (2, 3 Level III ). A tenth of the older people in the community and a fifth of institutionalised older people sustained an injury secondary to their falls (4). In Malaysia, a study on the prevalence of falls among older people attending an urban primary care clinic was reported to be 47% (5 Level III  ). Most of them had experienced recurrent falls with the majority occurring in their homes. From various studies, it can be summarized that the risks of falls are related to both intrinsic and extrinsic factors (4, 6, 7, 8)  Level III, the majority of which are Introduction

103

preventable (9, 10)

Level III

.

Intrinsic risk factors include medical co-morbidities of (4, 9, 11, 12, 13): i. vision impairment ii. iii. iv. v.

muscular-skeletal and gait imbalance cognitive impairment polypharmacy a history of fall

Extrinsic factors, which are related to environmental hazards, include rugs, slippery flours, inadequate handrails and unsuitable footwear (4, 8). Falls could lead to significant morbidity, and mortality, as well as affect the quality of life of the older persons (1 Level III ). Fall in older people is the main risk factor for fragility fracture and hence the morbidity and mortality associated with it (4). It is also a risk factor for intracranial haemorrhage, functional limitations, soft tissue injuries and dislocation. Hence, the healthcare cost after falls and mortality are substantial (6).

18.2 Benefit of screening and intervention for fall prevention  A few effective primary care interventions to prevent falls and recurrent falls among I community dwelling older persons have been shown. (9, 14 -17  Level  ). Exercise in the form of strength training and balance, gait, and coordination training, either carried out as a single intervention or as part of a multi-component, has proven beneficial in preventing falls (16) Level III . Specifically, the systematic review found the benefit of physical therapy or exercise intervention (OR 0.87 (0.81–0.94) to be moderate (16) Level I. Similarly, a moderate benefit with vitamin D supplementation (0.83 (0.77–0.89) (16) Level I. In a multi-factorial clinical assessment with comprehensive management of identified risk factors, however, there was only a small reduction in the risk of falls (RR 0.89, CI 95%, 0.76 -1.00) (16) Level I. The USPSTF has defined multi-factorial assessment and management as “a clinical assessment of ≥2 domains of functioning, generally supplemented by assessment of falls-related or general geriatric risk factors or conditions, with assessment results used as a basis for remedial management (16, 18).  The benefits of other single intervention strategies, such as visual correction, medication assessment and withdrawal and home-hazard modification, have not been demonstrated (16).

104

Benefit of screening and intervention for fall prevention

Many of the trials on fall risk intervention involved older people with high risk identified through clinical assessment (16). In summary, stronger evidence of benefit was seen in single specific intervention than comprehensive multi-factorial intervention (18). Treating risk factors for falling can reduce falls by 30 to 40% (15) Level I. However, the benefit of falls intervention can be subject to cultural variations because it is related to customary activities by the community (19). Given that the participants in trials have a high risk of falls and there is no consistency in selecting trial participants, direct evidence to support the benefit of screening compared to non-screening cannot be concluded (16).

18.3 Screening tests While the risks of falls have been identified and many screening tools to assess these risks have been developed, no single tool can adequately predict falls (20, 21) Level III. Most tools discriminate poorly between fallers and non-fallers. The common tests used, such as Timed Up and Go Test, and Functional Reach Test, are based on clinical judgment and have cutoff values for the standardized times that have not been validated locally (17, 18, 21) Level III.  Therefore, screening by asking if the individual has fallen in the past year is suggested (9, 17, 22) Level III. This questioning has a sensitivity of 93% to 95% and specificity of 20% to 21% in predicting a single fall in the subsequent year (21) Level III. A history of ever-fall has a sensitivity of 77% and specificity of 55% to predict recurrent falls (21)  Level III. The American Geriatrics Society/British Geriatrics Society guideline for falls prevention also recommends enquiring about gait or balance problems (9)

Level III

.

 A positive answer to any of the above questions improves falls prediction and warrants a multi-factorial fall assessment, where available (16) Level III. Multi-factorial assessment includes medication review, gait and balance, visual acuity, heart rate and rhythm, postural hypotension, feet and footwear, and environmental hazards assessment (9)   Level III. The treatment of individual risk factors can be undertaken by trained clinicians. The optimal benefit of screening is seen if multi-factorial assessments and interventions are undertaken.

18.4 Harm of screening  The reported harms arising from physical therapy and exercise intervention, such as a paradoxical increase in falls and increased physician visits, are small (18) Level III. According to the USPSTF, there are no reports on the side effects of vitamin D supplementation. However, concomitant administration of calcium and vitamin D supplementation has a small increased risk of renal calculi (HR 1.17, 95% CI 1.02 to 1.34). There is also no evidence of serious harms associated with multi-factorial clinical assessment with comprehensive management of identified risk factors (18) Level III. Harm of screening

105

REFERENCES 1. 2.

3. 4. 5.

6. 7. 8.

9.

10.

11.

12. 13.

14.

15.

16.

106

Ozcan A, Donat H, Gelecek N, et al. The relationship between risk factors for falling and the quality of life in older adults. BMC Public Health 2005;5:90. Centers for Disease Control and Prevention (CDC). Selfreported falls and falls at home among person more or equal 65 years - United States 2006. MMWR Morb Mortal Wkly Rep 2008;57:225-9. Rubenstein LZ, Josephson KR. The epidemiology of falls and syncope. Cli Geriatric Med 2002;18:141-58. Karlsson MK, Magnusson H, von Schewelov T, Rosengren BE. Prevention of falls in the elderly -a review. Osteoporos Int 2013;24:747–62 Sazlina SG, Krishnan R, Samsul AS, et al. Prevalence of falls among older people attending a primary care clinic in Kuala Lumpur Malaysia. Malaysian Journal of Community Health 2008;14(1):11-5. Kannus P, Saevanen H, Palavanen M, et al. Prevention of falls and consequent injuries in elderly people. Lancet 2005;366:1885-93. Tinetti ME. Clinical Practice. Preventing falls in elderly. N Engl J Med 2003;348:42-9. Connelv BR, Wolf SL. Environmental and behavioural circumstances associated with falls at home among healthy elderly individuals. Atlanta FICSIT Group. Arch Phys Med Rehabil 1997;78:179-86. Panel for Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society. Summary of the updated American Geriatrics Society/  British Geriatrics Society Clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc 2011;59(1):148-57. National Institute for Health and Clinical Excellence. The assessment and prevention of falls in older people. London: National Institute for Health and Clinical Excellence 2004. Tromp AM, Pluijm SMF, Smit JH, Deeg DJH, Bouter LM, Lips PTAM. Fall-risk screening test: a prospective study on predictors for falls in community-dwelling elderly. J Clin Epidemiol 2001;54(8):837-44. Chu LW, Chi I, Chiu AY. Incidence and predictors of falls in the Chinese elderly. Ann Acad Med Singapore 2005;34(1):60-72. Deandrea S, Lucenteforte E, Bravi F, Foschi R, La Vecchia C, Negri E. Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis. Epidemiology. 2010;21(5):658-68 Gillespie LD, Gillespie WJ, Robertson MC, et al. Interventions for preventing falls in older people living in the commmunity. Cochrane Database Syst Rev 2012;9:CD007146. Chang JT, Morton SC, Rubenstein LZ, et al. Interventions for the prevention of falls in older adults: systematic review and metaanalysis of randomised clinical trials. BMJ 2004;328:680. Michael YL, Whitlick EP, Lin JS, et al. Primary Care Relevant interventions to prevent falling in older adults:

References

17.

18.

19.

20.

21.

22.

a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 2010;153:815-25. The Royal Australian College of General Practitioners. Guidelines for preventive activities in general practice. 7th edn. Melbourne: The Royal Australian College of General Practitioners 2009. Moyer VA. Prevention of falls in community-dwelling older adults: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2012;157:197-204. Tan P, Khoo E, Chinna K, Hill K, Poi P, Tan M. An individually-tailored multifactorial intervention program for older fallers in a middle-income developing country: Malaysian Falls Assessment and Intervention Trial (MyFAIT). BMC Geriatr. 2014;14(1):78. Scott V, Votova K, Scanlan A, Close J. Multifactor and mobility assessment tools for falls risk among older adults in community, home support long term patient care setting. Age Ageing 2007;36:130-9. Simon Gates, Lesley A Smith, Joanne A Fisher, et al. Systematic review of accuracy of screening instrument for predicting falls among independent older adults. J Rehabil Res Dev 2001;45:1105-16. Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ. Will my patient fall? JAMA 2007;297(1):77-86.

19

Dementia in Older People SUMMARY

Dementia is common among older persons. The burden of dementia is high, especially those with behavioural and psychological symptoms of dementia. Evidence is lacking on the benefit of screening asymptomatic older person. There are potential psychological, social and ethical impacts on persons with a positive screening test but who do not meet the criteria for dementia after evaluation. There is insufficient evidence to recommend screening for dementia in asymptomatic people aged 60 and above at primary care.

RECOMMENDATIONS

Routine screening for dementia in individuals aged 60 and above is not indicated. Evaluation of dementia should be as indicated clinically.

Grade I

19.1 Introduction Dementia is defined as an acquired syndrome of decline in memory and at least one other cognitive domain, such as language, visual-spatial or executive function, sufficient to interfere with social or occupational functioning in an alert person (1) Level III. Alzheimer’s disease and vascular dementia are the two most common causes of dementia. In Malaysia, the NMHS-III study showed that 11.2% of the adult population has some form of psychiatric morbidity (2) Level III.  The prevalence of dementia in Malaysia (3) Level III was found to be 9.5% (in 60-69 age group), which is similar to a study in Thailand (9.88%) (4) Level III but higher than the prevalence in Singapore (5.2%) (5) Level III. Our estimate of the prevalence of dementia is higher than the age-standardized prevalence of 5-7% in most world regions (6). The variation in the estimates is likely due to different tools used in the studies. Dementia affects individuals functioning in various stages depending on the degree of ailment. In the early stages, instrumental activities of daily living and organizational ability are affected, while in later stages, activities of daily Introduction

107

living are also affected and, ultimately, are dependent on caregivers for almost all aspects of living. In one study, patients with dementia living at home were noted to have a high level of unmet needs in care for their daytime activities and psychological distress (7). Therefore, the caregivers’ burden is significant. In middle and low income countries, the caregivers of patients with dementia experience substantial strains and adverse economic impact similar to those in high income countries (6). Level III Mild cognitive impairment (MCI) is a clinical entity that may predict later development of dementia. Hence, detecting MCI is argued to result in early detection of risk of dementia, which allows for early intervention to improve prognosis, and facilitate decision-making while patients still retain their decision-making capacity (8).

19.2 Benefit of screening and treating dementia  There is some evidence to suggest that early detection and active treatment at the point of sharp decline in cognitive function delays the subsequent need for nursing home care and reduces the risk of misdiagnosis and inappropriate management (9) Level III. However, the established modalities for treatment, i.e., cholinesterase inhibitors, confer only modest benefits in terms of clinicians’ global impression of change in cognition, function, and behaviour in mild to moderate Alzheimer’s disease (10)   Level I. Current evidence does not support the use of cholinesterase inhibitors in the treatment of mild cognitive impairment (11)  Level I. Although diagnosing dementia provides an opportunity for non-pharmacological interventions, such as caregiver support, the evidence for any benefit in early detection is lacking.

19.3 Screening tests  The Mini-Mental State Examination (MMSE) is the best-studied screening instrument for primary care settings with a sensitivity of 88.3% (95% CI, 81.3% to 92.9%) and specificity of 86.2% (CI, 81.8% to 89.7%) using the most commonly reported MMSE cut-off scores of 23/24 or 24/25 (12)  Level III, (13) Level II for detecting dementia. A drawback of the MMSE is that its accuracy depends upon the age, education, and ethnicity of the individual. In this regard, it is most accurate for Caucasians with at least a high school education (14) Level III, (15) Level IIII. Other instruments with adequate test performance to detect dementia include the Clock Drawing Test, Mini-Cog, Memory Impairment Screen, Abbreviated Mental Test, 7-Minute Screen and Informant Questionnaire on Cognitive Decline in the Elderly. These tests are promising but need further testing in primary care populations (13) Level III.

108

Screening tests

19.4 Harm of screening Concerns have been raised about the potential psychological, social and ethical impact on persons with a positive screening test but who do not meet the criteria for dementia after evaluation. Stress-inducing practical, social and psychological difficulties have been reported among patients coping with an uncertain diagnostic label (16) Level III, (17) Level III.  There are ethical concerns of exposing, otherwise well, screen-positive individuals to possible morbidity from current pharmacological modalities of treatment (18) Level II-2, (19) Level III . A recent study reported that new users of cholinesterase inhibitors are associated with increased rates of hospital visits for syncope and bradycardia, pacemaker insertion, and hip fracture among community-dwelling older people with dementia (18) Level II-2. The risk of these previously under-recognised serious adverse events must be weighed carefully against the drugs’ high costs and the generally modest benefits.  Thus, current evidence does not support routine screening of dementia in asymptomatic older people in primary care setting due to lack of evidence on positive health outcomes with screening (20) Level II-2.

Harm of screening

109

REFERENCES 1. 2. 3.

4.

5. 6.

7.

8.

9.

10.

11.

12.

13.

110

American Psychiatric Association, ed. Diagnostic and statistical manual of mental disorders. Washington D.C 1994. Institute of Public Health. Psychiatric Morbidity, a report of the Third National Health and Morbidity Survey. Ministry of Health Malaysia 2006. Hamid TA, Krishnaswamy S, Abdullah SS, Momtaz  YA. Socio-demographic risk factors and correlates of dementia in older Malaysians. Dement Geriatr Cogn Disord 2010;30(6):533-9. Chiam PC, Ng TP, Tan LL, et al. Prevalence of dementia in Singapore--results of the national mental health survey of the elderly 2003. Ann Acad Med Singapore 2004;33(5 Suppl):S14-5. Senanarong V, Poungvarin N, Sukhatunga K, et al. Cognitive status in the community dwelling Thai elderly. J Med Assoc Thai 2001;84(3):408-16. Prince M, Brodaty H, Uwakwe R, Acosta D, Ferri C, Guerra M et al. Strain and its correlates among carers of people with dementia in low-income and middleincome countries. A 10/66 Dementia Research Group population-based survey. Int J Geriatr Psychiatry 2012;27(7):670-82. Miranda-Castillo C, Woods B, Galboda K, Oomman S, Olojugba C, Orrell M. Unmet needs, quality of life and support networks of people with dementia living at home. Health Qual Life Outcomes 2010;8(1):132. Lin JS, O’Connor E, Rossom R, Perdue LA, Burda BU, Thompson M, Eckstrom E. Screening for cognitive impairment in older adults: An evidence update for the U.S. Preventive Services Task Force. Evidence Report No. 107. AHRQ Publication No. 14-05198-EF1. Rockville, MD: Agency for Healthcare Research and Quality; 2013. Dementia: a NICE-SCIE guideline on supporting people with dementia and their careers in health and social care. Social Care Institute for Excellence (2006) National Institute for Health and Clinical Excellence. The British Psychological Society and Gaskell. National Clinical Practice Guideline 2006. McDowell I, Kristjansson B, Hill GB, Hebert R. Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared. J Clin Epidemiol 1997;50(4):377-83. Jennifer S, Elizabeth O, Rebecca C, Leslie A, Elizabeth E. Screening for cognitive impairment in older adults: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:601-12. Sahadevan S, Lim PP, Tan NJ, Chan SP. Diagnostic performance of two mental status tests in the older Chinese: influence of education and age on cut-off values. Int J Geriatr Psychiatry 2000;15(3):234-41. Ng TP, Niti M, Chiam PC, Kua EH. Ethnic and educational differences in cognitive test performance on mini-mental state examination in Asians. Am J Geriatr Psychiatry 2007 Feb;15(2):130-9.

References

14. Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet 2006;367(9518):1262-70. 15. Banningh L, Vernooij-Dassen M, Rikkert MO, et al. Mild cognitive impairment: coping with an uncertain label. Int J Geriatr Psychiatry 2008;23(2):148-54. 16. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006. 17. Doody RS, Ferris SH, Salloway S, et al. Donepezil treatment of patients with MCI: 48-week randomized, placebo-controlled trial. Neurology 2009;72:1555-61. 18. Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med 2009;169(9): 867-73. 19. Whitehouse PJ, Juengst ET. Anti-aging medicine and mild cognitive impairment: practice and policy issues for geriatrics. J Am Geriatr Soc 2005 Aug;53(8):1417-22. 20. Borson S, Scanlan J, Hummel J, et al. Implementing routine cognitive screening of older adults in primary care: process and impact on physician behavior. J Gen Intern Med 2007;22(6):811-7.

20

Urinary Incontinence in Older People SUMMARY

Urinary incontinence is common among older persons in the community. The causes of urinary incontinence can be potentially treated, but the evidence for quality of life improvements following treatment is limited. Simple validated screening questions are available for use on selected patients. The evidence is insufficient to assess the balance of benefits and harms of screening for urinary incontinence in asymptomatic adults aged 60 years or older.

RECOMMENDATIONS

Routine screening for urinary incontinence for adults aged 60 years or older is not indicated. Evaluation of urinary incontinence should be as indicated clinically.

Grade I

20.1 Introduction  The International Continence Society defines urinary incontinence as a condition where there is any involuntary loss or leakage of urine which is a social or hygienic problem (1). Urinary incontinence can be classified as urge, stress, overflow, functional, or mixed incontinence. Reversible causes of incontinence should be ruled out. These include delirium, infection (UTI), atrophic vaginitis, pharmaceuticals, psychological causes such as depression, excess urinary output due to, e.g., hyperglycaemia, restricted mobility and stool impaction (2) Level III . The prevalence of urinary incontinence ranges from 4.6 to 42% in the community (3 -6) Level III and is higher in institutions (6) Level III. In a rural community in Selangor, the prevalence was noted to be 9.9% (7) Level III. A high rate of urinary incontinence in the general population suggests that screening for this condition should be increased in general practice (8, 9) Level III. Urinary incontinence is associated with the development of decubitus ulcers, sepsis, renal failure and increased mortality (9) Level III. Psychosocial implications include loss of selfesteem, restriction of social and sexual activities and depression (9) Level III. It is a key factor in deciding on nursing home placement (10)

Level III

.

Introduction

111

20.2 Benefit of screening urinary incontinence and treating urinary incontinence Behavioural therapy has been shown to reduce incontinence episodes and reduced quantity of urine loss in patients with stress and urge urinary incontinence (11) Level III. However, the role of medications in urge urinary incontinence has shown only a small effect in improving symptoms (12) Level I. There is limited evidence on quality of life improvements among patients treated for urinary incontinence.

20.3 Screening tests  The following questions have been validated for use as a screening tool for urinary incontinence as they are simple and efficient. “In the last one year, have you ever lost urine and gotten wet?” “If yes, have you lost urine on six separate days?”  The sensitivity of these questions is reported to be 65.5%, specificity 96%, positive predictive value 93.7%, and negative predictive value 81.7% (13) Level III. Urinary incontinence can also be screened using the International Consultation on Incontinence Questionnaire Urinary Incontinence -Short Form (ICIQ-UI-SF) (14) Level III. This has a sensitivity and specificity of 92.1% and 55.6%, respectively, and positive predictive value and negative predictive value of 88.3% and 65.9%, respectively. This questionnaire represents a good compromise between scientific expectations and practicality (14). However, using a screening questionnaire like the ICIQ-UI-SF would be time consuming because older adults may not be fluent in English (13) level III which could lead to misinterpretation of the results/findings by the assessors if they are untrained (13) Level III. Furthermore, using ICIQ-UI-SF requires permission from ICIQ group.

20.4 Harm of screening  There is no randomised trial or controlled observational study evaluating harms associated with screening for incontinence among older adults. Some guidelines recommend screening for urinary incontinence because it causes considerable impairment leading to a reduced quality of life (9, 14) Level III. This recommendation was based on the clinical experience of the guideline group. Urinary incontinence screening in the primary care setting is not recommended because of insufficient direct evidence on its benefit. However, physicians should individualise the decision-making process to screen for urinary incontinence among older persons. 112

Harm of screening

REFERENCES 1.

2. 3.

4. 5. 6. 7.

8.

9. 10.

11. 12.

13.

14.

Foldspang A, Mommens S. The International Continence Society (ICS) Incontinence definition: Is the social and hygienic aspect appropriate for etiologic research? J Clin Epidemio 1997; 50(9): 1055-60. The Royal Australian College of General Practice. Clinical practice guidelines on managing incontinence in general practice. 1st Edition 2002. Homma Y, Imajo C, Takahashi S, et al. Urinary symptoms and urodynamics in a normal elderly population. Scand J Urol Nephrol Suppl 1994; 157: 27-30. Andrews G, Cheok F. The Australian longitudinal study of aging: key findings of a multidimensional pilot survey study. Adelaide: Center for Aging Studies; 1990:1- 25. Kok AL, Voorhorst FJ, Burger CW, et al. Urinary and faecal incontinence in community-residing elderly women. Age & Ageing 1992; 21(3): 211-5. Chan CJ, Lee KS, Anne M, et al. Urinary incontinence among the elderly people of Singapore. Age & Ageing 1991; 20(4): 262-6. Sherina Mohd Sidik. The prevalence of urinary incontinence among the elderly in a rural community in Selangor. Malays J Med Sci 2010; 17(2): 18-23. Scottish Intercollegiate Guidelines Network (SIGN). Clinical Guidelines - Numerical List: Management of urinary incontinence in primary care [Internet]. 2015 [cited 27 April 2015]. Available from: http://www.sign. ac.uk/guidelines/published/numlist.html Weiss BD. Diagnostic evaluation of urinary incontinence in geriatric patients. Am Fam Physician 1998; 57(11): 2675-84 Johnson TM II, Bernard SL, Kincade JE, et al. Urinary incontinence and risk of death among community-living elderly people: results from the National Survey on SelfCare and Aging. J Aging Health 2000;12:25-46 Fantl J. Efficacy of bladder training in older women with urinary incontinence. JAMA 1991;265(5):609-13. Shamliyan T, Wyman J, Ramakrishnan R, Sainfort F, Kane R. Benefits and harms of pharmacologic treatment for urinary incontinence in women. Ann Intern Med 2012;156(12):861. Ministry of Health, Singapore. Clinical practice guidelines on functional screening for older adults in the community. Singapore 2010. Avery K, Donovan J, Peters TJ, Shaw c, Gotoh M, Abrams P. ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol Urodyn 2004;23(4):322-30

References

113