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Concept: Study design

197

Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.

Concepts: Tobacco smoking, Study design, Medical statistics, Neurodegenerative disorders, Odds ratio, Risk, Cancer, Epidemiology

164

BACKGROUND: Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case–control and cohort studies to investigate the association between coffee consumption and liver cancer. METHODS: We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case–control studies and seven cohort studies. RESULTS: The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42–0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40–0.63) for case–control studies and 0.48 (95% CI: 0.38–0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25–0.56) in males and 0.60 (95% CI: 0.33–1.10) in females. The OR was 0.45 (95% CI: 0.36–0.56) in Asian studies and 0.57 (95% CI: 0.44–0.75) in European studies. The OR was 0.39 (95% CI: 0.28–0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46–0.66) after adjustment for a history of liver disease. CONCLUSIONS: The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.

Concepts: Study design, Odds ratio, Infectious disease, Evidence-based medicine, MEDLINE, Cochrane Library, Cancer, Epidemiology

114

Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design.

Concepts: Epidemiology, Oncology, Carcinogen, Cancer, Study design, Case-control study, Benzene, Leukemia

65

Low muscle strength has been found in late adolescence in individuals diagnosed with Parkinson disease (PD) 30 y later. This study investigated whether this lower muscle strength also may translate into increased risks of falling and fracture before the diagnosis of PD.

Concepts: Osteoporosis, Experimental design, Study design, Actuarial science, Epidemiology

56

The aim of the present systematic review and meta-analysis was to gain further insight into the effects of adherence to Mediterranean Diet (MedD) on risk of overall cancer mortality, risk of different types of cancer, and cancer mortality and recurrence risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and Scopus until 25 August 2017. We included randomized trials (RCTs), cohort (for specific tumors only incidence cases were used) studies, and case-control studies. Study-specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effects model. Observational studies (cohort and case-control studies), and intervention trials were meta-analyzed separately. The updated review process showed 27 studies that were not included in the previous meta-analysis (total number of studies evaluated: 83 studies). An overall population of 2,130,753 subjects was included in the present update. The highest adherence score to a MedD was inversely associated with a lower risk of cancer mortality (RRcohort: 0.86, 95% CI 0.81 to 0.91, I² = 82%; n = 14 studies), colorectal cancer (RRobservational: 0.82, 95% CI 0.75 to 0.88, I² = 73%; n = 11 studies), breast cancer (RRRCT: 0.43, 95% CI 0.21 to 0.88, n = 1 study) (RRobservational: 0.92, 95% CI 0.87 to 0.96, I² = 22%, n = 16 studies), gastric cancer (RRobservational: 0.72, 95% CI 0.60 to 0.86, I² = 55%; n = 4 studies), liver cancer (RRobservational: 0.58, 95% CI 0.46 to 0.73, I² = 0%; n = 2 studies), head and neck cancer (RRobservational: 0.49, 95% CI 0.37 to 0.66, I² = 87%; n = 7 studies), and prostate cancer (RRobservational: 0.96, 95% CI 0.92 to 1.00, I² = 0%; n = 6 studies). Among cancer survivors, the association between the adherence to the highest MedD category and risk of cancer mortality, and cancer recurrence was not statistically significant. Pooled analyses of individual components of the MedD revealed that the protective effects appear to be most attributable to fruits, vegetables, and whole grains. The updated meta-analysis confirms an important inverse association between adherence to a MedD and cancer mortality and risk of several cancer types, especially colorectal cancer. These observed beneficial effects are mainly driven by higher intakes of fruits, vegetables, and whole grains. Moreover, we were able to report for the first time a small decrease in breast cancer risk (6%) by pooling seven cohort studies.

Concepts: Random effects model, Oncology, Study design, Relative risk, Experimental design, Metastasis, Epidemiology, Cancer

45

This case-control study was nested in a prospective birth cohort to evaluate whether the presence of enteroviruses in stools was associated with the appearance of islet autoimmunity in the Type 1 Diabetes Prediction and Prevention study in Finland.

Concepts: Study design, Diabetes mellitus type 1, Diabetes mellitus, Cohort study

41

Successful coexistence between large carnivores and humans is conditional upon effective mitigation of the impact of these species on humans, such as through livestock depredation. It is therefore essential for conservation practitioners, carnivore managing authorities, or livestock owners to know the effectiveness of interventions intended to reduce livestock predation by large carnivores. We reviewed the scientific literature (1990-2016), searching for evidence of the effectiveness of interventions. We found experimental and quasi-experimental studies were rare within the field, and only 21 studies applied a case-control study design (3.7% of reviewed publications). We used a relative risk ratio to evaluate the studied interventions: changing livestock type, keeping livestock in enclosures, guarding or livestock guarding dogs, predator removal, using shock collars on carnivores, sterilizing carnivores, and using visual or auditory deterrents to frighten carnivores. Although there was a general lack of scientific evidence of the effectiveness of any of these interventions, some interventions reduced the risk of depredation whereas other interventions did not result in reduced depredation. We urge managers and stakeholders to move towards an evidence-based large carnivore management practice and researchers to conduct studies of intervention effectiveness with a randomized case-control design combined with systematic reviewing to evaluate the evidence.

Concepts: Number needed to harm, Science, Epidemiology, Study design, Case-control study, Relative risk, Cohort study, Predation

31

Cohort studies can be biased by unmeasured confounding. We propose a hybrid ecologic-epidemiologic design called the trend-in-trend design, which requires a strong time-trend in exposure, but is unbiased unless there are unmeasured factors affecting outcome for which there are time-trends in prevalence that are correlated with time-trends in exposure across strata with different exposure trends. Thus, the conditions under which the trend-in-trend study is biased are a subset of those under which a cohort study is biased. The trend-in-trend design first divides the study population into strata based on the cumulative probability of exposure given covariates, which effectively stratifies on time-trend in exposure, provided there is a trend. Next, a covariates-free maximum likelihood model estimates the odds ratio (OR) using data on exposure prevalence and outcome frequency within cumulative probability of exposure strata, across multiple periods. In simulations, the trend-in-trend design produced ORs with negligible bias in the presence of unmeasured confounding. In empiric applications, trend-in-trend reproduced the known positive association between rofecoxib and myocardial infarction (observed OR: 1.2, 95% confidence interval: 1.1, 1.4), and known null associations between rofecoxib and severe hypoglycemia [OR = 1.1 (0.92, 1.3)] and non-vertebral fracture [OR = 0.84 (0.64, 1.1)]. The trend-in-trend method may be useful in settings where there is a strong time-trend in exposure, such as a newly approved drug or other medical intervention.

Concepts: Normal distribution, Relative risk, Study design, Clinical trial, Epidemiology, Experimental design, Cohort study, Scientific method

31

Studies have reported inconsistent findings on the association between dairy product intake and weight change and obesity. Only a few prospective studies have investigated the role of dairy consumption in both weight change and risk of becoming overweight or obese and whether these associations depend on the initial body weight.

Concepts: Body mass index, Study design, Adipose tissue, Cancer, Overweight, The Association, Body shape, Obesity

30

OBJECTIVES:Constipation is common in the community, and may affect survival adversely. An association between constipation and development of colorectal cancer (CRC) could be one possible explanation. We performed a systematic review and meta-analysis examining this issue.METHODS:We searched MEDLINE, EMBASE, and EMBASE Classic (through July 2012). Eligible studies were cross-sectional surveys, cohort studies, or case-control studies reporting the association between constipation and CRC. For cross-sectional surveys and cohort studies, we recorded number of subjects with CRC according to the constipation status, and for case-control studies, number of subjects with constipation according to CRC status were recorded. Study quality was assessed according to published criteria. Data were pooled using a random effects model, and the association between CRC and constipation was summarized using an odds ratio (OR) with a 95% confidence interval (CI).RESULTS:The search strategy identified 2,282 citations, of which 28 were eligible. In eight cross-sectional surveys, presence of constipation as the primary indication for colonoscopy was associated with a lower prevalence of CRC (OR=0.56; 95% CI 0.36-0.89). There was a trend toward a reduction in odds of CRC in constipation in three cohort studies (OR=0.80; 95% CI 0.61-1.04). The prevalence of constipation in CRC was significantly higher than in controls without CRC in 17 case-control studies (OR=1.68; 95% CI 1.29-2.18), but with significant heterogeneity, and possible publication bias.CONCLUSIONS:Prospective cross-sectional surveys and cohort studies demonstrate no increase in prevalence of CRC in patients or individuals with constipation. The significant association observed in case-control studies may relate to recall bias.Am J Gastroenterol advance online publication, 12 March 2013; doi:10.1038/ajg.2013.52.

Concepts: Constipation, Scientific method, Panel data, Random effects model, Colorectal cancer, Study design, Experimental design, Epidemiology