Lifestyle Diseases and Their Risk Factors

(Park's Textbook of Preventive and Social Medicine)

Part A: Enumeration of Lifestyle Diseases

Definition of Lifestyle

"A considerable body of evidence has accumulated which indicates that there is an association between health and lifestyle of individuals. Many current-day health problems especially in the developed countries are associated with lifestyle changes."

• Park's Textbook of Preventive and Social Medicine, Section: Behavioural and Socio-cultural Conditions

Non-Communicable Diseases (NCDs) / Lifestyle Diseases - Enumeration

• The leading NCD killer worldwide
• 17.9 million deaths per year (44% of all NCD deaths in 2016)
• Includes coronary heart disease (CHD), stroke, hypertension, and other heart diseases
• Lifestyle links: tobacco, physical inactivity, unhealthy diet, obesity, raised blood pressure, raised cholesterol

• 9 million deaths per year (16% of NCD deaths in 2016)
• Includes lung cancer, colorectal cancer, stomach cancer, breast cancer, cervical cancer
• Lifestyle links: tobacco (71% of lung cancers), alcohol, unhealthy diet, obesity, physical inactivity, cancer-associated infections (HPV, HBV, HCV, H. pylori)

• 3.8 million deaths per year (9% of NCD deaths in 2016)
• Includes chronic bronchitis, emphysema, asthma, chronic obstructive pulmonary disease (COPD)
• Lifestyle links: tobacco (42% of chronic respiratory disease), air pollution, occupational hazards

• 1.6 million deaths per year (4% of NCD deaths in 2016)
• Unfavourable modification of lifestyle and dietary habits associated with urbanization are the most important factors
• Prevalence of diabetes is approximately twice as high in urban areas than in rural population
• Lifestyle links: unhealthy diet, physical inactivity, obesity

• At least 2.8 million people die each year as a result of being overweight or obese
• Risks of heart disease, stroke and diabetes increase steadily with increasing BMI
• Also increases the risk of certain cancers
• Factors driving this: poor diet and lack of exercise

• Included within Park's enumeration of NCDs (cardiovascular, renal, nervous and mental diseases)
• Lifestyle factors such as alcohol, drug addiction, stress, and sedentary behaviour play a significant role

• Includes arthritis and allied diseases
• Related to lifestyle factors such as obesity, physical inactivity, occupational habits

• Included in Park's enumeration of NCDs
• Closely linked to hypertension and diabetes - both lifestyle-related

• Explicitly listed by Park among "current-day health problems especially in developed countries associated with lifestyle changes"

• Park includes "senility, blindness, obesity and various other metabolic and degenerative diseases and chronic results of communicable diseases" in the NCD category

1. Cardiovascular diseases
2. Cancer
3. Chronic respiratory diseases
4. Diabetes

"Non-communicable diseases (NCDs) include cardiovascular, renal, nervous and mental diseases, musculo-skeletal conditions such as arthritis and allied diseases, chronic non-specific respiratory diseases (e.g., chronic bronchitis, emphysema, asthma), permanent results of accidents, senility, blindness, cancer, diabetes, obesity and various other metabolic and degenerative diseases."

• Park's Textbook of Preventive and Social Medicine, p. 413 (Block 5)

Part B: Risk Factors for Lifestyle Diseases

"Most epidemiologists accept that a set of 'risk factors' are responsible for a major share of adult non-communicable disease morbidity and premature mortality. A large percentage of NCDs are preventable through the changes in these factors."

• Park's Textbook of Preventive and Social Medicine, p. 413

A. Behavioural Risk Factors

• Almost 7 million people die from tobacco use each year, both from direct use and second-hand smoke
• About 600,000 deaths are caused by second-hand smoke; of these, 170,000 are children
• In 2016, there were 1.1 billion smokers worldwide, with over 80% being every-day smokers
• By 2020, tobacco deaths will increase to 7.5 million, accounting for 10% of all deaths
• Smoking causes approximately:
  • 71% of lung cancer
  • 42% of chronic respiratory disease
  • Nearly 10% of cardiovascular disease
• Highest incidence of smoking among men is in lower-middle-income countries

• Approximately 1.6 million people die each year due to physical inactivity
• People who are insufficiently physically active have a 20-30% increased risk of all-cause mortality
• Regular physical activity reduces the risk of:
  • Cardiovascular disease
  • High blood pressure
  • Diabetes
  • Breast and colon cancer
  • Depression
• Insufficient physical activity is highest in high-income countries, but is now also seen in middle-income countries, especially among women

• Approximately 3.3 million people die each year from the harmful use of alcohol
• This accounts for about 5.9% of all deaths in the world; 5.1% of DALYs were attributable to alcoholism
• More than half of these deaths occur from NCDs including cancers, cardiovascular disease, and liver cirrhosis
• There is also a close relationship between drinking and violent crime including domestic violence
• Alcohol-related harm is determined by three dimensions:
  • Volume of alcohol consumed
  • Pattern of drinking
  • Quality of alcohol consumed
• Adult per capita consumption is highest in high-income countries

• Adequate consumption of fruit and vegetables reduces risk for cardiovascular diseases, stomach cancer and colorectal cancer
• Most populations consume much higher levels of salt than WHO recommends
  • High salt consumption is an important determinant of high blood pressure and cardiovascular risk
  • 4.1 million deaths from CVD have been attributed to excess salt/sodium intake
• High consumption of saturated fats and trans-fatty acids is linked to heart disease
• Unhealthy diet is rising quickly in lower-resource settings
• Fat intake has been rising rapidly in lower-middle-income countries since the 1980s
• Children are growing up in a society which promotes high energy intake while encouraging physical inactivity

B. Metabolic / Physiological Risk Factors

• Raised blood pressure is estimated to cause 9.4 million deaths, about 12.8% of all deaths
• It is the major risk factor for cardiovascular disease
• Prevalence of raised blood pressure is similar across all income groups
• In 2015, the global prevalence of raised blood pressure in adults 18 years and above was around 22 per cent

• At least 2.8 million people die each year as a result of being overweight or obese
• Risks of heart disease, stroke and diabetes increase steadily with increasing BMI
• Raised BMI also increases the risk of certain cancers
• Prevalence of overweight is highest in upper-middle-income countries
• In 2016: 11% of men and 15% of women aged 18 years and above were obese
• More than 42 million children under the age of 5 years were overweight in 2015
• Factors driving this rise: poor diet and lack of exercise
• Most of these children will become obese adults and more susceptible to NCDs

• Directly linked to both unhealthy diet and physical inactivity
• Urbanization and unfavourable modification of lifestyle and dietary habits are the most important factors

• Raised cholesterol is estimated to cause 2.6 million deaths annually
• It increases the risk of heart disease and stroke
• Raised cholesterol is highest in high-income countries

C. Other Contributing Risk Factors (per Park)

• At least 2 million cancer cases per year (18% of global cancer burden) are attributable to chronic infections
• Principal infectious agents: HPV, Hepatitis B virus, Hepatitis C virus, and Helicobacter pylori
• These are largely preventable through vaccinations and measures to avoid transmission

• Occupational hazards
• Air and water pollution
• Possession of destructive weapons (in case of injuries)

Summary Table: Four Behavioural Risk Factors and the Four Major NCDs (as per Park/WHO)

Important Notes from Park on Risk Factors

1. Multifactorial causation - Most chronic diseases result from multiple causes. Rarely is there a simple one-to-one cause-effect relationship. The term "risk factors" is used in the absence of a known single agent.
2. Cumulative effect - Chronic diseases appear to result from the cumulative effects of multiple risk factors, which may be both environmental and behavioural, or constitutional.
3. Long latent period - A long gap exists between first exposure to suspected cause and eventual development of disease, making it difficult to link causes with outcomes.
4. Lifestyle factors are not all harmful - Park explicitly notes: "Not all lifestyle factors are harmful. There are many that can actually promote health - examples include adequate nutrition, enough sleep, sufficient physical activity."
5. Preventability - A large percentage of NCDs are preventable through changes in these risk factors. This is the fundamental basis of NCD prevention strategy in public health.

"Four behavioural risk factors are responsible for significant proportions of these diseases - tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol."

• Park's Textbook of Preventive and Social Medicine, The Problem section, Block 5

c) Strategies for Prevention of Lifestyle Diseases

d) National Programme for Prevention and Control of Lifestyle Diseases

(Park's Textbook of Preventive and Social Medicine)

PART C: Strategies for Prevention of Lifestyle Diseases (NCDs)

"The preventive attack on chronic diseases is based on the knowledge that they are multifactorial in causation, so their prevention demands a complex mix of interventions. Previously only tertiary prevention seemed possible to prevent or delay the development of further disability or the occurrence of premature death. But now, with the identification of risk factors, health promotion activities aimed at primary prevention are being increasingly applied in the control of chronic diseases."

• Park's Textbook of Preventive and Social Medicine, Prevention section, Block 5

STRATEGY I: POPULATION (MASS) STRATEGY

"CHD is primarily a mass disease. The strategy should therefore be based on mass approach focusing mainly on the control of underlying causes (risk factors) in whole populations, not merely in individuals. This approach is based on the principle that small changes in risk factor levels in total populations can achieve the biggest reduction in mortality. That is, the aim should be to shift the whole risk-factor distribution in the direction of 'biological normality'."

• Reduction of fat intake to 20-30% of total energy intake
• Consumption of saturated fats limited to less than 10% of total energy intake; some of the reduction in saturated fat may be made up by mono- and poly-unsaturated fats
• Reduction of dietary cholesterol to below 100 mg per 1000 kcal per day
• Increase in complex carbohydrate consumption (vegetables, fruits, whole grains and legumes)
• Avoidance of alcohol consumption
• Reduction of salt intake to 5 g daily or less

• The goal should be to achieve a smoke-free society
• A comprehensive health programme is required including:
  • Effective information and education activities
  • Legislative restrictions
  • Fiscal measures (taxation)
  • Smoking cessation programmes
• Present evidence does not support promotion of the so-called "safer cigarette"

• Even a small reduction in average blood pressure of the whole population by 2 or 3 mm Hg would produce a large reduction in cardiovascular complications
• Goal: to reduce mean population blood pressure levels
• Involves a multifactorial approach:
  • "Prudent diet" (reduced salt intake, avoidance of high alcohol intake)
  • Regular physical activity
  • Weight control

• Approximately 1.6 million people die each year due to physical inactivity
• National physical activity guidelines, school-based physical activity programmes, workplace programmes

• Restricting access to retailed alcohol
• Enforcing bans on alcohol advertising
• Raising taxes on alcohol
• Enforcing drink-driving laws

STRATEGY II: HIGH RISK STRATEGY

"By means of simple tests such as blood pressure and serum cholesterol measurement it is possible to identify individuals at special risk."

• Those who smoke
• Those with strong family history of CHD
• Diabetics
• Obese individuals
• Young women using oral contraceptives

"Having identified those at high risk, the next step will be to bring them under preventive care and motivate them to take positive action against all the identified risk factors."

• Elevated blood pressure should be treated
• Patient should be helped to break the smoking habit permanently (nicotine chewing gum can be used)
• Serum cholesterol concentration should be reduced in those in whom it is raised

"More than half of the CHD cases occur in those who are not apparently at special risk, and this is one limitation of the high-risk strategy. Nevertheless, recognition and treatment of high-risk cases do make an important contribution to prevention."

STRATEGY III: PRIMORDIAL PREVENTION

"A novel approach to primary prevention of CHD is primordial prevention. It involves preventing the emergence and spread of CHD risk factors and life-styles that have not yet appeared or become endemic. This applies to developing countries in particular. These countries should seek to preserve their traditional eating patterns and life-styles associated with low levels of CHD risk factors."

• Aimed at preventing risk factors from appearing in the first place, especially in communities where they are not yet prevalent
• Targeted at children and young adults
• Focuses on socialization of healthy habits from early life

STRATEGY IV: SECONDARY PREVENTION

"Secondary prevention must be seen as a continuation of primary prevention. It forms an important part of an overall strategy. The aim of secondary prevention is to prevent the recurrence and progression of CHD."

• A rapidly expanding field with much research in progress (drug trials, coronary surgery, use of pacemakers)
• The principles governing secondary prevention are the same as those for primary prevention, with the modification that they apply to persons who have already had a clinical event
• Includes: rehabilitation, treatment of established disease, preventing recurrence

STRATEGY V: IMMEDIATE HIGH-IMPACT INTERVENTIONS (WHO-recommended "Best Buys")

1. Protecting people from tobacco smoke and banning smoking in public places; warning about dangers of tobacco; enforcing bans on tobacco advertising, promotion and sponsorships; raising taxes on tobacco
2. Restricting access to retailed alcohol; enforcing bans on alcohol advertising; raising taxes on alcohol
3. Reduce salt intake and salt content of food
4. Replacing trans-fat in food with polyunsaturated fat
5. Promoting public awareness about diet and physical activity, including through mass media

1. Nicotine dependence treatment
2. Enforcing drink-driving laws
3. Restrictions on marketing of foods and beverages high in salt, fats and sugar
4. Food taxes and subsidies to promote healthy diets
5. Healthy nutrition environments in schools
6. Nutrition information and counselling in health care
7. National physical activity guidelines (school-based programmes for children, workplace programmes for adults)

STRATEGY VI: CANCER-SPECIFIC PREVENTION

• Vaccination against Hepatitis B (major cause of liver cancer)
• Vaccination against HPV (main cause of cervical cancer)
• Protection against environmental or occupational risk factors such as aflatoxin, asbestos, and contaminants in drinking water

STRATEGY VII: INTEGRATED APPROACH

"It is now felt that the principles of prevention of CHD can be applied also to other major non-communicable diseases (NCDs) because of common risk factors. A broader concept is emerging - to develop an overall integrated programme for the Prevention and Control of NCDs as part of primary health care systems, simultaneously attacking several risk factors known to be implicated in the development of non-communicable diseases. Such concerted preventive action should reduce not only cardiovascular diseases but also other major NCDs, with an overall improvement in health and length of life."

• Case finding through screening and health examination
• Application of improved methods of diagnosis, treatment and rehabilitation
• Control of food, water and air pollution
• Reducing accidents
• Influencing patterns of human behaviour and lifestyles through intensive education
• Upgrading standards of institutional care
• Developing and applying better methods of comprehensive medical care including primary health care
• Political approaches: smoking control, control of alcohol and drug abuse, road safety measures, occupational safety, food safety laws

STRATEGY VIII: WHO STEPS SURVEY (Surveillance)

"The WHO has developed a survey methodology known as 'the STEPS Non-communicable Disease Risk Factors Survey' to help countries establish NCD surveillance system."

1. Questionnaire (demographic, health status, health behaviours)
2. Physical measurements
3. Biochemical measurements

PART D: National Programme for Prevention and Control of Lifestyle Diseases

NPCDCS - National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke

"India is experiencing a rapid health transition with large and rising burden of chronic non-communicable diseases especially cardiovascular disease, diabetes mellitus, cancer, stroke, and chronic lung diseases. It is estimated that in 2016 NCDs accounted for 60 per cent of deaths."

• The existing health system was mainly focused on communicable diseases
• Need for a national programme on NCDs was envisaged
• National Programme on Prevention and Control of Diabetes, Cardiovascular Diseases and Stroke was initially created
• Later integrated with National Cancer Control Programme
• Thus, NPCDCS came into existence
• During the 11th Five Year Plan: 100 identified districts in 21 states covered
• During the 12th Five Year Plan: all districts of the country covered in a phased manner

Major Objectives of NPCDCS

1. Prevent and control common NCDs through behaviour and lifestyle changes
2. Provide early diagnosis and management of common NCDs
3. Build capacity at various levels of health care for prevention, diagnosis and treatment
4. Train human resources within the public health set-up (doctors, paramedics, nursing staff)
5. Establish and develop capacity for palliative and rehabilitative care

Strategies under NPCDCS

• Promoting healthy lifestyle through massive health education and mass media efforts at country level
• Opportunistic screening of persons above the age of 30 years
• Establishment of NCD Clinics at Community Health Centre (CHC) and District level
• Development of trained manpower
• Strengthening of tertiary level health facilities
• Service delivery through existing public health infrastructure and systems

1. Increased intake of healthy foods
2. Increased physical activity
3. Avoidance of tobacco and alcohol
4. Stress management

Three-Tier Delivery Structure

• Health promotion for behaviour and lifestyle change by organizing camps, interpersonal communications, posters, banners
• Opportunistic screening of population above 30 years using BP measurement and blood glucose by strip method
• Suspected cases of diabetes and hypertension referred to CHCs for further diagnosis and management

• NCD Clinic at CHC performs diagnosis by required investigations (blood sugar, lipid profile, ultrasound, X-ray, ECG)
• Management and stabilization of common CVD, diabetes and stroke cases (outpatient and inpatient)
• Nurses undertake home visits for bedridden cases
• Complicated cases referred to District Hospital

• Screening persons above age of 30 years for diabetes, hypertension, CVDs
• Identifies individuals at high-risk for further investigation
• Provides regular management and annual assessment of persons suffering from cancer, diabetes and hypertension
• Manages persons with established cardiovascular diseases
• Provides home based palliative care for chronic, debilitating and progressive patients
• Health education and counselling to patients and their attendants

Urban Health Check-up Scheme for Diabetes and High Blood Pressure

1. To screen urban slum population for diabetes and high blood pressure
2. To create a database for prevalence of diabetes and high blood pressure in urban slums
3. To sensitize the urban slum population about healthy lifestyle

NCD Cells

• National NCD Cell established at the Centre
• State NCD Cells and District NCD Cells monitor and implement NPCDCS
• As of September 2015: 36 State NCD Cells, 195 District NCD Cells, 201 District NCD Clinics, 1362 CHC NCD Clinics

Guidelines for Referral and Treatment (Operational Guidelines, 2016)

1. Systolic BP >140 mmHg and diastolic BP >90 mmHg, or random blood sugar ≥140 mg/dl - referred to medical officer at nearest facility for confirmation and treatment
2. Those positive for cancer/precancerous lesions - referred to appropriate PHC/CHC/District Hospital
3. Once diagnosis of hypertension/diabetes established - at least one month's supply of drugs from PHC

New Initiatives under NPCDCS

1. Intervention for prevention and control of Rheumatic Heart Disease under NPCDCS and Rashtriya Bal Swasthya Karyakram (RBSK)
2. Integration of AYUSH with NPCDCS
3. Integration of RNTCP with NPCDCS to articulate a national strategy for management of TB and diabetes comorbidities in India

WHO Global Action Plan for the Prevention and Control of NCDs (2013-2020)

"The Global Action Plan provides member states with a road map and menu of policy options which, when implemented collectively between 2013 and 2020, will contribute to progress on 9 global NCD targets."

1. 25% relative reduction in risk of premature mortality from CVD, cancer, diabetes and chronic respiratory disease
2. At least 10% relative reduction in harmful use of alcohol
3. 10% relative reduction in prevalence of insufficient physical activity
4. 10% relative reduction in mean population intake of salt/sodium
5. 30% relative reduction in prevalence of current tobacco use (persons aged 15+ years)
6. 25% relative reduction in prevalence of raised blood pressure
7. Halt the rise of diabetes and obesity
8. At least 50% of eligible people receive drug therapy and counselling (including glycaemic control) to prevent heart attacks and strokes
9. 80% availability of affordable basic technology and essential medicines (including generics) to treat major NCDs in both public and private facilities

Cohort Study: Alcohol Intake and Acute Pancreatitis

(Park's Textbook of Preventive and Social Medicine)

I. WHY IS A COHORT STUDY THE MOST APPROPRIATE DESIGN?

"Cohort study is another type of analytical (observational) study which is usually undertaken to obtain additional evidence to refute or support the existence of an association between suspected cause and disease."

Distinguishing Features that Make It Suitable Here

• In this study, adults aged 30-50 years are identified first, classified by alcohol intake, and then followed up. None have developed acute pancreatitis at baseline - this ensures temporal sequence (exposure precedes disease), which is essential to establish causality.

• The 2-year follow-up allows direct calculation of incidence rates of acute pancreatitis in both the exposed (alcohol drinkers) and unexposed (non-drinkers) cohorts.

• Unlike a case-control study which works backwards (effect to cause), a cohort study works from "cause to effect." This is the fundamental basis for establishing a causal relationship between alcohol and acute pancreatitis.

Indications for Cohort Studies (per Park)

1. When there is good evidence of an association between exposure and disease, derived from clinical observations and supported by descriptive and case-control studies
2. When the incidence of disease is high among exposed, e.g., special exposure groups
3. When attrition of study population can be minimized (follow-up is easy, cohort is stable, cooperative and easily accessible)
4. When ample funds are available

Why NOT a Case-Control Study Here?

• Both exposure and outcome have already occurred before the study starts
• The study proceeds backward from effect to cause
• They are prone to recall bias

II. STEPS OF CONDUCTING THE COHORT STUDY

"The elements of a cohort study are: (1) Selection of study subjects, (2) Obtaining data on exposure, (3) Selection of comparison groups, (4) Follow-up, and (5) Analysis."

STEP 1: Selection of Study Subjects

• Adults aged 30-50 years who consume alcohol regularly (above a defined threshold - e.g., as per WHO definition of harmful alcohol use: >14 standard drinks/week for men, >7 for women)
• Free from acute pancreatitis, chronic pancreatitis, gallstone disease, or other known causes of pancreatitis at baseline
• Must have baseline investigations: serum amylase, lipase, abdominal ultrasound to confirm absence of pancreatitis

• Adults aged 30-50 years who are non-drinkers or minimal drinkers
• Matched or comparable in age, sex, BMI, smoking status, diet
• Same exclusion criteria as exposed group

• Both cohorts must be comparable in all variables except alcohol exposure
• Both should be free from the disease (pancreatitis) at the start of study
• Sufficient sample size must be ensured (based on expected incidence in unexposed population and expected relative risk)
• Informed consent must be obtained from all participants

STEP 2: Obtaining Data on Exposure

• According to whether or not they have been exposed (drinker vs. non-drinker)
• According to the level or degree of exposure (light, moderate, heavy drinkers - dose-response relationship)

STEP 3: Selection of Comparison Groups

STEP 4: Follow-up (2 Years)

"One of the problems in cohort studies is the regular follow-up of all the participants. Therefore, at the start of the study, methods should be devised depending upon the outcome to be determined (morbidity or death)."

• (a) Periodic medical examination of each member - this yields the greatest amount of information
• (b) Reviewing physician and hospital records - hospital admissions for acute pancreatitis
• (c) Routine surveillance of records
• (d) Mailed questionnaires, telephone calls, periodic home visits - preferably all three on an annual basis

• A certain percentage of losses are inevitable (death, change of residence, migration, withdrawal)
• These losses may bias the results
• It is necessary to build a system for obtaining basic outcome information for those who cannot be followed in full detail
• Park's recommendation: achieve as close to a 95% follow-up as possible

STEP 5: Analysis

III. TWO KEY CONSIDERATIONS

Key Consideration 1: Exposure Definition and Measurement

• A standard drink must be clearly defined (e.g., 10 g pure alcohol per standard unit)
• Threshold for "exposure" must be pre-specified using internationally validated tools (AUDIT score)
• Biological markers (GGT, CDT) should supplement self-reported data to reduce misclassification
• Dose-response assessment is important: light drinkers vs moderate vs heavy drinkers in exposed cohort allows internal comparison and strengthens causal inference

Key Consideration 2: Attrition and Loss to Follow-up

• Die from causes unrelated to pancreatitis
• Change residence or migrate
• Withdraw from the study
• Change their drinking habits (former drinkers who quit)

• Collect multiple contact details at baseline (address, phone, emergency contact)
• Regular (6-monthly) contact by mailed questionnaire, telephone, home visits
• Maintain a 95% follow-up rate as recommended by Park
• Analyze characteristics of those lost to follow-up vs those retained, to assess whether bias has occurred
• Proper documentation of change in exposure status (if a drinker quits during follow-up)

IV. POTENTIAL BIASES, CONFOUNDERS AND THEIR CONTROL

A. BIASES

"Bias is any systematic error in the determination of the association between the exposure and disease. The relative risk estimate may increase or decrease as a result of the bias; it reflects some type of non-comparability between the study and control groups."

• The exposed and unexposed cohorts may not be representative of the general population
• Heavy drinkers who volunteer may be healthier than non-volunteer heavy drinkers (healthy volunteer effect)
• Control: Ensure that both cohorts are selected from the same source population with pre-specified eligibility criteria; both groups should be comparable in baseline characteristics

• Subjects may underreport alcohol intake (social desirability bias) leading to misclassification of exposure
• Control: Use validated questionnaires + objective biochemical markers (GGT, CDT, MCV); use standardized interviews; validate self-reported intake against records

• Less relevant in prospective cohort studies since data is collected prospectively; however, information on past alcohol history may be subject to recall error
• Control: Collect baseline data prospectively; use structured interviews and biological markers

• If participants who develop pancreatitis are more or less likely to drop out from one group compared to the other, results will be distorted
• Control: Vigorous follow-up procedures; achieve 95% follow-up; analyze characteristics of those lost; use intention-to-treat analysis

• If the interviewer knows who is in the exposed group, they may be more thorough in probing for pancreatitis symptoms
• Control: Blinding the outcome assessors to the exposure status of participants; using standardized criteria (ATLANTA criteria for acute pancreatitis)

• If hospital-based cohorts are used, this may occur because of different rates of hospital admission for different diseases
• Control: Use community-based cohort instead of hospital-based cohort

B. CONFOUNDERS

• Associated with the exposure (alcohol)
• Independently associated with the disease (acute pancreatitis)
• Not in the causal pathway

• Smokers are more likely to drink heavily
• Smoking is independently associated with pancreatitis
• Control: Match exposed and unexposed cohorts on smoking status OR measure smoking at baseline and adjust for it in the analysis (stratification, multivariate regression)

• Gallstones are the other major cause of acute pancreatitis
• Persons with gallstones may drink differently
• Control: Exclude persons with gallstone disease at baseline through abdominal ultrasound; OR adjust for gallstones in analysis

• Elevated triglycerides are an independent cause of pancreatitis
• May be linked to alcohol use
• Control: Measure lipid profiles at baseline; adjust in analysis

• Diet is both linked to alcohol consumption habits and to pancreatitis risk
• Control: Collect detailed dietary history at baseline; adjust for diet in analysis

• Age and sex affect both alcohol consumption patterns and pancreatitis incidence
• Control: Restrict to 30-50 years (already done); match groups by sex or stratify by sex in analysis

• Obesity increases pancreatitis risk and is associated with heavy drinking
• Control: Measure BMI at baseline; match or adjust in analysis

"This bias (confounding) can be removed by matching in case control studies."

1. Matching: Match each exposed subject with a non-exposed subject of the same age, sex, smoking status, BMI, etc.
2. Restriction: Restrict the study to subjects who share similar values of potential confounders (e.g., non-smokers only)
3. Stratification in analysis: Analyse results separately in strata (e.g., smokers vs. non-smokers) and then combine using Mantel-Haenszel method
4. Multivariate analysis (logistic/Cox regression): Simultaneously adjust for all confounders mathematically

V. MEASURES OF ASSOCIATION TO INTERPRET STUDY RESULTS

"Having calculated the incidence rates, the next step is to estimate the risk of outcome (e.g., disease or death) in the exposed and non-exposed cohorts. This is done in terms of two well-known indices: (a) relative risk, (b) attributable risk."

1. INCIDENCE RATES (Primary Measure)

• Incidence in exposed = a / (a+b)
• Incidence in non-exposed = c / (c+d)

2. RELATIVE RISK (RR)

"Relative risk (RR) is the ratio of the incidence of the disease (or death) among exposed and the incidence among the non-exposed."

• RR = 1: No association between alcohol and pancreatitis
• RR > 1: Alcohol is associated with increased risk of pancreatitis
• RR < 1: Alcohol appears to be protective (unlikely in this case)

"Relative risk is important in aetiological enquiries. Its size is a better index than is attributable risk for assessing the aetiological role of a factor in disease. The larger the relative risk, the stronger the association between cause and effect."

3. ATTRIBUTABLE RISK (AR) / Risk Difference

"Attributable risk is the amount of disease in the exposed group that can be attributed to the exposure."

"Attributable risk gives a better idea than does relative risk of the impact a successful preventive or public health programme might have in reducing the problem."

4. POPULATION ATTRIBUTABLE RISK (PAR)

"The concept of population attributable risk is useful in that it provides an estimate of the amount by which the disease could be reduced in that population if the suspected factor was eliminated or modified."

5. RELATIVE RISK vs ATTRIBUTABLE RISK - Which to Use When?

"Relative risk does not reflect the potential public health importance as does the attributable risk."

• RR is used to assess whether alcohol is a cause of acute pancreatitis and by how much it multiplies the risk
• AR is used to assess how many cases of pancreatitis could be prevented in the community by reducing alcohol consumption

Summary of Measures