Jayadeep Patra

Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders

Alcohol consumption has been identified as an important risk factor for chronic disease and injury. In the first paper in this Series, we quantify the burden of mortality and disease attributable to alcohol, both globally and for ten large countries. We assess alcohol exposure and prevalence of alcohol-use disorders on the basis of reviews of published work. After identification of other major disease categories causally linked to alcohol, we estimate attributable fractions by sex, age, and WHO region. Additionally, we compare social costs of alcohol in selected countries. The net effect of alcohol consumption on health is detrimental, with an estimated 3.8% of all global deaths and 4.6% of global disability-adjusted life-years attributable to alcohol. Disease burden is closely related to average volume of alcohol consumption, and, for every unit of exposure, is strongest in poor people and in those who are marginalised from society. The costs associated with alcohol amount to more than 1% of the gross national product in high-income and middle-income countries, with the costs of social harm constituting a major proportion in addition to health costs. Overall, we conclude that alcohol consumption is one of the major avoidable risk factors, and actions to reduce burden and costs associated with alcohol should be urgently increased.

THE RELATION BETWEEN DIFFERENT DIMENSIONS OF ALCOHOL CONSUMPTION AND BURDEN OF DISEASE - AN OVERVIEW

AIMS As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. METHODS Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. RESULTS Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose-response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. CONCLUSIONS Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol-disease relationships.

Alcohol as a Risk Factor for Type 2 Diabetes A systematic review and meta-analysis

OBJECTIVE To clarify the dose-response relationship between alcohol consumption and type 2 diabetes. RESEARCH DESIGN AND METHODS A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group. RESULTS The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76–1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71–1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52–0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83–1.26]). CONCLUSIONS Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women.

Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis.

INTRODUCTION AND AIMS Alcohol is an established risk factor for liver cirrhosis. It remains unclear, however, whether this relationship follows a continuous dose-response pattern or has a threshold. Also, the influences of sex and end-point (i.e. mortality vs. morbidity) on the association are not known. To address these questions and to provide a quantitative assessment of the association between alcohol intake and risk of liver cirrhosis, we conducted a systematic review and meta-analysis of cohort and case-control studies. DESIGN AND METHODS Studies were identified by a literature search of Ovid MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, ETOH and Google Scholar from January 1980 to January 2008 and by searching the references of retrieved articles. Studies were included if quantifiable information on risk and related confidence intervals with respect to at least three different levels of average alcohol intake were reported. Both categorical and continuous meta-analytic techniques were used to model the dose-response relationship. RESULTS Seventeen studies met the inclusion criteria. We found some indications for threshold effects. Alcohol consumption had a significantly larger impact on mortality of liver cirrhosis compared with morbidity. Also, the same amount of average consumption was related to a higher risk of liver cirrhosis in women than in men. DISCUSSION AND CONCLUSIONS Overall, end-point was an important source of heterogeneity among study results. This result has important implications not only for studies in which the burden of disease attributable to alcohol consumption is estimated, but also for prevention.

Dose-response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight, preterm birth and small for gestational age (SGA)—a systematic review and meta-analyses

Please cite this paper as: Patra J, Bakker R, Irving H, Jaddoe V, Malini S, Rehm J. Dose–response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight, preterm birth and small for gestational age (SGA)—a systematic review and meta‐analyses. BJOG2011;118:1411–1421.

Hours and Days of Sale and Density of Alcohol Outlets: Impacts on Alcohol Consumption and Damage: A Systematic Review

AIMS The aim of this study was to examine recent research studies published from 2000 to 2008 focusing on availability of alcohol: hours and days of sale and density of alcohol outlets. METHODS Systematic review. RESULTS Forty-four studies on density of alcohol outlets and 15 studies on hours and days of sale were identified through a systematic literature search. The majority of studies reviewed found that alcohol outlet density and hours and days of sale had an impact on one or more of the three main outcome variables, such as overall alcohol consumption, drinking patterns and damage from alcohol. CONCLUSIONS Restricting availability of alcohol is an effective measure to prevent alcohol-attributable harm.

Alcohol consumption and the risk of morbidity and mortality for different stroke types - a systematic review and meta-analysis

BackgroundObservational studies have suggested a complex relationship between alcohol consumption and stroke, dependent on sex, type of stroke and outcome (morbidity vs. mortality). We undertook a systematic review and a meta-analysis of studies assessing the association between levels of average alcohol consumption and relative risks of ischemic and hemorrhagic strokes separately by sex and outcome. This meta-analysis is the first to explicitly separate morbidity and mortality of alcohol-attributable stroke and thus has implications for public health and prevention.MethodsUsing Medical Subject Headings (alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke), a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science databases between 1980 to June 2009 was performed followed by manual searches of bibliographies of key retrieved articles. From twenty-six observational studies (cohort or case-control) with ischemic or hemorrhagic strokes the relative risk or odds ratios or hazard ratios of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and life time abstention (manually estimated where data for current abstainers were given) was used as the reference group. Two reviewers independently extracted the information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, risk estimates and key criteria of study quality using a standardized protocol.ResultsThe dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity.ConclusionsThese results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed.

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review.

BackgroundIn 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship.MethodsA systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken.ResultsThere is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol.ConclusionThe epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.

Alcohol and hypertension: gender differences in dose-response relationships determined through systematic review and meta-analysis.

AIMS To analyze the dose-response relationship between average daily alcohol consumption and the risk of hypertension via systematic review and meta-analysis. DESIGN A computer-assisted search was completed for 10 databases, followed by hand searches of relevant articles. Only studies with longitudinal design, quantitative measurement of alcohol consumption and biological measurement of outcome were included. Dose-response relationships were assessed by determining the best-fitting model via first- and second-degree fractional polynomials. Various tests for heterogeneity and publication bias were conducted. FINDINGS A total of 12 cohort studies were identified from the literature from the United States, Japan and Korea. A linear dose-response relationship with a relative risk of 1.57 at 50 g pure alcohol per day and 2.47 at 100 g per day was seen for men. Among women, the meta-analysis indicated a more modest protective effect than reported previously: a significant protective effect was reported for consumption at or below about 5 g per day, after which a linear dose-response relationship was found with a relative risk of 1.81 at 50 g per day and of 2.81 at an average daily consumption of 100 g pure alcohol per day. Among men, Asian populations had higher risks than non-Asian populations. CONCLUSIONS The risk for hypertension increases linearly with alcohol consumption, so limiting alcohol intake should be advised for both men and women.

Alcohol consumption and non-communicable diseases: Epidemiology and policy implications

AIMS This paper summarizes the relationships between different patterns of alcohol consumption and various on non-communicable disease (NCD) outcomes and estimates the percentage of NCD burden that is attributable to alcohol. METHODS A narrative review, based on published meta-analyses of alcohol consumption-disease relations, together with an examination of the Comparative Risk Assessment estimates applied to the latest available revision of Global Burden of Disease study. RESULTS Alcohol is causally linked (to varying degrees) to eight different cancers, with the risk increasing with the volume consumed. Similarly, alcohol use is related detrimentally to many cardiovascular outcomes, including hypertension, haemorrhagic stroke and atrial fibrillation. For other cardiovascular outcomes the relationship is more complex. Alcohol is furthermore linked to various forms of liver disease (particularly with fatty liver, alcoholic hepatitis and cirrhosis) and pancreatitis. For diabetes the relationship is also complex. Conservatively, of the global NCD-related burden of deaths, net years of life lost (YLL) and net disability adjusted life years (DALYs), 3.4%, 5.0% and 2.4%, respectively, can be attributed to alcohol consumption, with the burden being particularly high for cancer and liver cirrhosis. This burden is especially pronounced in countries of the former Soviet Union. CONCLUSIONS There is a strong link between alcohol and non-communicable diseases, particularly cancer, cardiovascular disease, liver disease, pancreatitis and diabetes, and these findings support calls by the World Health Organization to implement evidence-based strategies to reduce harmful use of alcohol.