Body fatness, diabetes, physical activity and risk of kidney stones: a systematic review and meta-analysis of cohort studies

Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose–response meta-analysis Abstract Epidemiological evidence on the association of soy intake with breast cancer risk is still inconsistent due to different soy intake levels across previous studies and small number of breast cancer cases. We aimed to investigate this issue by analyzing data from the China Kadoorie Biobank (CKB) study and conducting a dose–response meta-analysis to integrate existing evidence. The CKB study included over 300,000 women aged 30–79 from 10 regions across China enrolled between 2004 and 2008, and followed-up for breast cancer events until 31 December 2016. Information on soy intake was collected from baseline, two resurveys and twelve 24-h dietary recalls. We also searched for relevant prospective cohort studies to do a dose–response meta-analysis. The mean (SD) soy intake was 9.4 (5.4) mg/day soy isoflavones among CKB women. During 10 years of follow-up, 2289 women developed breast cancers. The multivariable-adjusted relative risk was 1.00 (95% confidence interval [CI] 0.81–1.22) for the fourth (19.1 mg/day) versus the first (4.5 mg/day) soy isoflavone intake quartile. Meta-analysis of prospective studies found that each 10 mg/day increment in soy isoflavone intake was associated with a 3% (95% CI 1–5%) reduced risk of breast cancer. The CKB study demonstrated that moderate soy intake was not associated with breast cancer risk among Chinese women. Higher amount of soy intake might provide reasonable benefits for the prevention of breast cancer.

Predicted lean body mass, fat mass and risk of lung cancer: prospective US cohort study Abstract An inverse association between body mass index (BMI) and risk of lung cancer has been reported. However, the association of body composition such as fat mass (FM) and lean body mass (LBM) with risk of lung cancer has not been fully investigated. Using two large prospective cohort studies (Nurses’ Health Study, 1986–2014; Health Professionals Follow-up Study, 1987–2012) in the United States, we included 100,985 participants who were followed for occurrence of lung cancer. Predicted FM and LBM derived from validated anthropometric prediction equations were categorized by sex-specific deciles. During an average 22.3-year follow-up, 2615 incident lung cancer cases were identified. BMI showed an inverse association with lung cancer risk. Participants in the 10th decile of predicted FM and LBM had a lower risk of lung cancer compared with those in the 1st decile, but when mutually adjusted for each other, predicted FM was not associated with lung cancer risk (adjusted hazard ratio [aHR] = 0.98, 95% confidence interval [CI] 0.72–1.35; P(trend) = 0.97) whereas predicted LBM had an inverse association (aHR = 0.73, 95% CI 0.53–1.00; P(trend) = 0.03), especially among participants who were current smokers or had smoked in the previous 10 years (aHR = 0.55, 95% CI 0.36–0.84; P(trend) = 0.008). In conclusion, BMI was inversely associated with lung cancer risk. Based on anthropometric prediction equations, low LBM rather than low FM accounted for the inverse association between BMI and lung cancer risk.

Pregnancy, pregnancy loss and the risk of diabetes in Chinese women: findings from the China Kadoorie Biobank Abstract Pregnancy and pregnancy loss may be associated with increased risk of diabetes in later life. However, the evidence is inconsistent and sparse, especially among East Asians where reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy and pregnancy loss (miscarriage, induced abortion, and still birth) with the risk of incident diabetes in later life among Chinese women. In 2004–2008, the nationwide China Kadoorie Biobank recruited 302 669 women aged 30–79 years from 10 (5 urban, 5 rural) diverse localities. During 9.2 years of follow-up, 7780 incident cases of diabetes were recorded among 273,383 women without prior diabetes and cardiovascular disease at baseline. Cox regression yielded multiple-adjusted hazard ratios (HRs) for the risk of diabetes associated with pregnancy and pregnancy loss. Overall, 99% of women had been pregnant, of whom 10%, 53%, and 6% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Among ever pregnant women, each additional pregnancy was associated with an adjusted HR of 1.04 (95% CI 1.03; 1.06) for diabetes. Compared with those without pregnancy loss, women with a history of pregnancy loss had an adjusted HR of 1.07 (1.02; 1.13) and the HRs increased with increasing number of pregnancy losses, irrespective of the number of livebirths; the adjusted HR was 1.03 (1.00; 1.05) for each additional pregnancy loss. The strength of the relationships differed marginally by type of pregnancy loss. Among Chinese women, a higher number of pregnancies and pregnancy losses were associated with a greater risk of diabetes.

Serum albumin and atrial fibrillation: insights from epidemiological and mendelian randomization studies Abstract Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Low serum albumin level is linked to the emergence of many cardiovascular diseases, including AF. In this study, we aim to characterize the nature and magnitude of the prospective association between serum albumin and incident AF in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them. ARIC Study is a population-based, prospective, cohort study of cardiovascular risk factors in four US communities, initially consisting of 15,792 participants, aged 45–64 years, recruited between 1987 and 1989 (visit 1). The final sample size was 12,833 in this study. Baseline (visit 1) characteristics were compared between groups using one-way ANOVA test, Chi square test, or Kruskal–Wallis test as appropriate. We used multivariable Cox’ hazard regression models to assess the association between albumin and incident AF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies was used to estimate the causal influence of the serum albumin and incident AF. During a median follow-up of 25.1 years, 2259 (17.6%) participants developed incident AF. After multiple adjustment, serum albumin was inversely associated with incidence of AF [HR = 0.90, 95% CI 0.86–0.94, per SD (0.27 g/dL) increase; HR = 0.80, 95% CI 0.71–0.91, Q4 vs. Q1]. In MR analysis, we detected no evidence for a causal relation between serum albumin level and AF in inverse-variance weighted (IVW) method (odds ratio: 0.996, 95% CI 0.980–1.012, per 1 g/dL increase of albumin; P = 0.620) without evidence of heterogeneity between estimates from individual SNPs (Pheterogeneity = 0.981 [MR-Egger] and Pheterogeneity = 0.860 [IVW]) nor pleiotropy effect (Ppleiotropy = 0.193). The serum albumin level is independently inverse associated with incident AF in a linear pattern. However, MR analyses did not support a causal role of serum albumin in the etiology of AF.

Risk of colorectal cancer in users of bisphosphonates: analysis of population-based electronic health records Abstract The use of bisphosphonates has been associated with a decrease in the risk of colorectal cancer (CRC) in observational studies, but with controversial results and difficult to interpret because of routine concomitant use of calcium and vitamin D. We aimed to assess the association between CRC risk and outpatient exposure to antiosteoporotic drugs using a large cohort with prescription data in Catalonia. A case–control study was performed using the Information System for Development of Primary Care Research (SIDIAP) which is a primary care medical record database that has linked data on reimbursed medication. The study included 25,836 cases with an incident diagnosis of CRC between 2010 and 2015 and 129,117 matched controls by age (± 5 years), sex and healthcare region. A multivariable model was built adjusting for known risk factors and comorbidities that were significantly associated to CRC in the dataset, and a propensity score for bisphosphonates. Tests for interaction for multiple drug use and stratified analysis for tumour location were prospectively planned. Overall 18,230 individuals (11.5%) were users of bisphosphonates. A significant but modest protective effect on CRC was observed for bisphosphonates (OR 0.95, 95% CI 0.91–0.99), that was no longer significant when adjusted for calcium and vitamin D (OR 0.98, 95% CI 0.93–1.03). Bisphosphonates, however, showed a dose–response effect with duration of use even when adjusted for calcium and vitamin D (OR for use > 40 months: 0.90, 95% CI 0.81–1.00, P value for trend: 0.018). The use of bisphosphonates was associated with a modest decrease in the risk of CRC, but this effect was essentially explained by concomitant use of calcium or vitamin D. The observed protective effect was stronger for long durations of use, which deserves further study.

Progress against inequalities in mortality: register-based study of 15 European countries between 1990 and 2015 Abstract Socioeconomic inequalities in mortality are a challenge for public health around the world, but appear to be resistant to policy-making. We aimed to identify European countries which have been more successful than others in narrowing inequalities in mortality, and the factors associated with narrowing inequalities. We collected and harmonised mortality data by educational level in 15 European countries over the last 25 years, and quantified changes in inequalities in mortality using a range of measures capturing different perspectives on inequality (e.g., ‘relative’ and ‘absolute’ inequalities, inequalities in ‘attainment’ and ‘shortfall’). We determined which causes of death contributed to narrowing of inequalities, and conducted country- and period-fixed effects analyses to assess which country-level factors were associated with narrowing of inequalities in mortality. Mortality among the low educated has declined rapidly in all European countries, and a narrowing of absolute, but not relative inequalities was seen in many countries. Best performers were Austria, Italy (Turin) and Switzerland among men, and Spain (Barcelona), England and Wales, and Austria among women. Ischemic heart disease, smoking-related causes (men) and amenable causes often contributed to narrowing inequalities. Trends in income inequality, level of democracy and smoking were associated with widening inequalities, but rising health care expenditure was associated with narrowing inequalities. Trends in inequalities in mortality have not been as unfavourable as often claimed. Our results suggest that health care expansion has counteracted the inequalities widening effect of other influences.

A quarter century of decline of autopsies in the Netherlands Abstract Objective Autopsy rates have been declining worldwide. The present study reports the outcome of a retrospective analysis of all non-forensic autopsies in the Netherlands over a course of 25 years, and compares these with the most recent Dutch study. Method Retrospectively, 25 years of data on clinical autopsies from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA) was paired with the mortality registry (Statistics Netherlands). Results The crude prevalence of autopsies declined from 7.07% in 1991 to 2.73% in 2015. After adjusting for age at death, there was no difference in autopsy rate between males and females. An increasing age significantly decreased the autopsy rate. Conclusion In the Netherlands, clinical autopsies have been declining over the last quarter century. Age at death, but not sex, was associated with the autopsy rate. These different results stress the importance of correct collection and analysis methods of data.

Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies Abstract The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism (VTE) is divergent. We conducted a systematic review and meta-analysis of published observational prospective cohort studies evaluating the associations of physical activity with VTE risk. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched until 26 February 2019. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus minimal amount of physical activity groups were pooled using random effects meta-analysis. Twelve articles based on 14 unique prospective cohort studies comprising of 1,286,295 participants and 23,753 VTE events were eligible. The pooled fully-adjusted RR (95% CI) of VTE comparing the most physically active versus the least physically active groups was 0.87 (0.79–0.95). In pooled analysis of 10 studies (288,043 participants and 7069 VTE events) that reported risk estimates not adjusted for body mass index (BMI), the RR (95% CI) of VTE was 0.81 (0.70–0.93). The associations did not vary by geographical location, age, sex, BMI, and methodological quality of studies. There was no evidence of publication bias among contributing studies. Pooled observational prospective cohort studies support an association between regular physical activity and low incidence of VTE. The relationship does not appear to be mediated or confounded by BMI.

A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research Abstract To inform evidence-based practice in health care, guidelines and policies require accurate identification, collation, and integration of all available evidence in a comprehensive, meaningful, and time-efficient manner. Approaches to evidence synthesis such as carefully conducted systematic reviews and meta-analyses are essential tools to summarize specific topics. Unfortunately, not all systematic reviews are truly systematic, and their quality can vary substantially. Since well-conducted evidence synthesis typically involves a complex set of steps, we believe formulating a cohesive, step-by-step guide on how to conduct a systemic review and meta-analysis is essential. While most of the guidelines on systematic reviews focus on how to report or appraise systematic reviews, they lack guidance on how to synthesize evidence efficiently. To facilitate the design and development of evidence syntheses, we provide a clear and concise, 24-step guide on how to perform a systematic review and meta-analysis of observational studies and clinical trials. We describe each step, illustrate it with concrete examples, and provide relevant references for further guidance. The 24-step guide (1) simplifies the methodology of conducting a systematic review, (2) provides healthcare professionals and researchers with methodologically sound tools for conducting systematic reviews and meta-analyses, and (3) it can enhance the quality of existing evidence synthesis efforts. This guide will help its readers to better understand the complexity of the process, appraise the quality of published systematic reviews, and better comprehend (and use) evidence from medical literature.