Summary Relative Risk Estimates Research Articles

Adjuvant endocrine therapy and risk of contralateral breast cancer: a systematic review and meta-analysis of observational studies.

Randomized clinical trials support reductions in contralateral breast cancer (CBC) risk with use of adjuvant endocrine therapy, however, real-world treatment effects, particularly for subgroups of breast cancer survivors, remain inconclusive. To address this, population-based observational studies of adjuvant endocrine therapy and CBC were synthesized and meta-analyzed. PubMed and Embase databases were systematically searched for observational studies of endocrine therapy use and CBC risk. Random effects meta-analyses estimated summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between endocrine therapy (ever use of tamoxifen and/or aromatase inhibitors (AIs)) and CBC risk. Heterogeneity across studies was assessed using the I2 test. Subgroup analyses were conducted by study design, menopausal status, and CBC estrogen receptor (ER)-status. Seventeen eligible observational studies (n = 287,576 breast cancer survivors) published between 1995 and 2019 were included. Endocrine therapy use was associated with reduced CBC risk (RR:0.62, 95% CI:0.53, 0.73, I2 = 84.8%, p < 0.0001). No heterogeneity was observed by study design (phet = 0.9). Similar reductions were observed in analyses restricted to tamoxifen use. As only two studies assessed AI use, estimates could not be meta-analyzed. In subgroup analyses, there were no differences in CBC risk reduction by menopausal status (phet = 0.22). Endocrine therapy reduced risk of ER-positive (RR:0.55, 95% CI:0.43, 0.70) but not ER-negative CBC (RR:1.26, 95% CI:0.95, 1.66) (phet < 0.001). This meta-analysis of observational studies supports a reduction in CBC risk with endocrine therapy among breast cancer survivors, in concert with evidence synthesized from randomized clinical trials, and highlights differences in endocrine therapy effectiveness by ER-status of CBC.

Association of metabolic obesity phenotypes with risk of overall and site-specific cancers: a systematic review and meta-analysis of cohort studies

BackgroundAdiposity is a known risk factor for certain cancers; however, it is not clear whether the risk of cancer differs between individuals with high adiposity but different metabolic health status. The aim of this systematic literature review and meta-analysis of cohort studies was to evaluate associations between metabolic obesity phenotypes and overall and site-specific cancer risk.MethodsPubMed and Embase databases were used to identify relevant cohort studies up to the 6th of June 2023. Random-effects models were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs) for the association between metabolic obesity phenotypes and cancer risk. Certainty of evidence was assessed using the Cochrane methods and the GRADE tool. This study is registered with PROSPERO, number CRD42024549511.ResultsA total of 15,556 records were screened, and 31 publications covering 15 unique cohort studies were included in this analysis. Of these studies, 22 were evaluated as being at low risk of bias and 9 at moderate risk of bias. Compared to metabolically healthy normal-weight individuals (MHNW), metabolically unhealthy overweight/obese (MUOW/OB) individuals had a higher risk of overall (SRR = 1.21, 95% CI = 1.02–1.44, n = 3 studies, high certainty) and obesity-related cancers (SRR = 1.42, 95% CI = 1.15–1.74, n = 3, very low certainty). Specifically, MUOW/OB individuals were at higher risk of cancers of the postmenopausal breast (SRR = 1.32, 95% CI = 1.17–1.48, n = 7, low certainty), colorectum (SRR = 1.24, 95% CI = 1.16–1.31, n = 6, moderate certainty), endometrium (SRR = 2.31, 95% CI = 2.08–2.57, n = 4, high certainty), thyroid (SRR = 1.42, 95% CI = 1.29–1.57, n = 4, moderate certainty), kidney (SRR = 1.71, 95% CI = 1.40–2.10, n = 3, low certainty), pancreas (SRR = 1.35, 95% CI = 1.24–1.47, n = 3, high certainty), liver (SRR = 1.81, 95% CI = 1.36–2.42, n = 2, moderate certainty), gallbladder (SRR = 1.42, 95% CI = 1.17–1.73, n = 2, high certainty), bladder (SRR = 1.36, 95% CI = 1.19–1.56, n = 2, moderate certainty), and stomach (SRR = 1.50, 95% CI = 1.12–2.01, n = 2, high certainty). In addition, we found elevated risks of most of these cancers among individuals classified as MUNW and MHOW/OB phenotypes compared to those with MHNW phenotype. Our stratified analyses according to metabolic obesity phenotypes suggested that the elevated risks of some cancers were stronger in individuals with MUOW/OB versus those with MHOW/OB or MUNW phenotypes.ConclusionThese findings suggest that both higher adiposity and metabolic dysfunction were independently associated with increased risk of several cancers, with the strongest associations generally observed among those with both metabolic dysfunction and obesity.

Abstract P315: Consumption of Potatoes and Risk of Hypertension: A Pooled Analysis of US Cohorts

Background: Limited and inconsistent observational data are available on the association of potato consumption with risk of hypertension. Objective: To test the hypothesis that consumption of total; combined baked, boiled, and mashed; and fried potatoes is associated with incidence of hypertension and that dietary pattern (assessed using the plant-based diet index [PDI]) modifies such association. Methods: We pooled and analyzed harmonized, individual-level data from 5 US cohorts (n=67,146). Frequency of baked, boiled, mashed, and fried potato consumption during the previous year was ascertained using a food frequency questionnaire. We used Cox regression to estimate hazard ratios separately in each cohort adjusting for age, sex, race/ethnicity, education, body mass index, energy intake, physical activity, smoking, alcohol intake, trans fats, and PDI score. We then pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks. Results: Mean age ranged from 25 to 72 years and median total potato consumption ranged from 1.2 to 3.2 times per week across the cohorts. During the follow up, 31,546 new cases of hypertension occurred. Total potato consumption was not associated with the risk of hypertension: adjusted HR (95% CI): 1.00 (ref), 1.01(0.96-1.05), 1.01(0.96-1.05), 1.04(1.00-1.08), and 1.04(0.99-1.08) for total potato intake of 0; 1-2; &gt;2 to &lt;3; 3-&lt;5; and 5+ times per week, respectively. HR (95% CI) for combined baked, boiled, and mashed potato consumption were 1.0 (ref), 1.00 (0.97-1.04), 1.02 (0.98-1.05), and 1.02(0.98-1.07) for intake of 0, 1-2; &gt;2 to &lt;3; and 3+ times/week, respectively. In contrast, intake of fried potatoes was positively associated with hypertension risk (figure). There was no significant interaction between PDI score and potato consumption on HTN risk. Conclusions: Our pooled analysis showed a positive association between fried, but not combined baked, boiled, and mashed, potatoes and incidence of hypertension.

Efficacy, immunogenicity and safety of COVID-19 vaccines in older adults: a systematic review and meta-analysis.

BackgroundOlder adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors.MethodsRandomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456).ResultsOf the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55−89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77−96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80−4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80−96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82−93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45−99.98) and GMT (SMD 6.20, 95% CI: 2.02−10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38−1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups (p > 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22).ConclusionCOVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.

Theoretical attributable risk analysis and Disability Adjusted Life Years (DALYs) based on increased dairy consumption

BackgroundIdentification of modifiable risk factors that may impact chronic disease risk is critical to public health. Our study objective was to conduct a theoretical population attributable risk analysis to estimate the burden of disease from low dairy intake and to estimate the impact of increased dairy intake on United States (US)-based disability adjusted life years (DALYs).MethodsWe conducted a comprehensive literature review to identify statistically significant summary relative risk estimates (SRREs) from recent meta-analyses of dairy consumption and key chronic disease outcomes. The SRREs were applied to preventive fractions using a range of categories (low to high) for population consumption of dairy products. The preventive fraction estimates were then applied to the number of DALYs for each health outcome in the US based on 2019 WHO estimates. The population attributable risk proportion estimates were calculated using the inverse of the SRRE from each meta-analysis using the same range of categories of consumption. These values were subsequently applied to the DALYs estimates to estimate the theoretical burden of disease attributable to low dairy intake.ResultsStatistically significant SRREs were identified in recent meta-analyses of total dairy consumption in relation to breast cancer, colorectal cancer, cardiovascular disease (CVD), type 2 diabetes (T2D), stroke, and hypertension. In this theoretical analysis, nearly 850,000 DALYs (or 5.0% of estimated years of healthy life lost) due to CVD and 200,000 DALYs (4.5%) due to T2D may be prevented by increased dairy consumption. Approximately 100,000 DALYs due to breast cancer (7.5%) and approximately 120,000 DALYs (8.5%) due to colorectal cancer may be prevented by high dairy intake. The numbers of DALYs for stroke and hypertension that may be prevented by increased dairy consumption were approximately 210,000 (6.0%) and 74,000 (5.5%), respectively.ConclusionsConsumption of dairy products has been associated with decreased risk of multiple chronic diseases of significant public health importance. The burden of disease that may potentially be prevented by increasing dairy consumption is substantial, and population-wide improvement in meeting recommended daily dairy intake goals could have a notable public health impact. However, this analysis is theoretical, and thus additional studies providing empirical evidence are needed to further clarify potential relationships between dairy intake and various health outcomes.

Statins in Hepatitis B or C Patients Is Associated With Reduced Hepatocellular Carcinoma Risk: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma is the world's leading cause of cancer-related death. Chronic hepatitis B virus and hepatitis C virus infection cause liver cancer. The aim of this study was to investigate the relationship between statins and the risk of hepatocellular carcinoma in patients with hepatitis B or C. We systematically searched Web of Science, Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database from their inception to January 2019. We included studies that reported the hepatocellular carcinoma incidence among hepatitis B virus- or hepatitis C virus-infected patients or hepatitis B virus- or hepatitis C virus-related cirrhotic patients, evaluated and clearly defined exposure to statins, provided effective comparison groups, and reported risk estimates. Inclusion was not otherwise restricted. Summary relative risk estimates with 95% CIs were calculated using a random-effects model. Meta-analysis of 10 studies showed that statin users had a significantly lower risk of hepatocellular carcinoma (relative risk = 0.47, 95% CI = 0.38-0.56) with significant heterogeneity. In 7 hepatitis studies, using statin was associated with a 53% reduction in the incidence of hepatocellular carcinoma (relative risk = 0.47, 95% CI = 0.43-0.50) with substantial heterogeneity. In 3 cirrhosis studies, the incidence of hepatocellular carcinoma in statin users was significantly reduced by 55% (relative risk = 0.45, 95% CI = 0.30-0.61) with no heterogeneity. Statins reduce the hepatocellular carcinoma risk among patients infected with hepatitis B virus or hepatitis C virus. This chemoprotective association is more pronounced in hepatitis B virus or hepatitis C virus-associated cirrhotic patients.

Background exposure to polychlorobiphenyls and mortality: A systematic review and meta-analysis

Abstract Polychlorinated biphenyls (PCBs) are a family of 209 congeners known to be highly persistent in the environment and with long-range transport leading to a ubiquitous pollution. This group of persistent organic pollutants is known to be carcinogenic and to have endocrine-disrupting properties. Due to bioaccumulation along the food chain, the main route of exposure in general population is through diet. High level toxicity was well characterized with mass poisoning episodes and occupational cohort but the association with PCBs exposure at low doses with mortality in general population is uncertain. We conducted a systematic review and meta-analysis to assess whether background exposure levels of PCBs increase all-cause and cancer- and cardiovascular-specific mortality risk in the general population, following the National Toxicology Program/Office of Health Assessment and Translation framework. Studies were identified by searching PubMed, Embase and Web of Science up to 1st of January, 2021. Random-effects meta-analysis was used to estimate summary relative risks (SRRs). Eight prospective cohort studies met our inclusion criteria, leading to 72,852 participants including 17,805 deaths. Overall exposure to PCBs was not statistically significantly associated with all-cause mortality (SRR=1.13, 95% CI = 0.90-1.41, n = 7 studies, low certainty); however, dietary exposure to PCBs was associated with an increased risk of cardiovascular-specific mortality (SRR=1.38, 95% CI = 1.14-1.66, n = 3 studies, moderate certainty), while no association was found with cancer-specific mortality. Bayesian meta-analysis and subgroup analyses confirmed these findings. Our meta-analysis suggests that background exposure to PCBs is associated with an increased risk of cardiovascular-specific mortality in the general population with a “moderate” level of evidence. This should be interpreted with caution given the small number of studies on mortality in the general population. Key messages This meta-analysis fails to highlight any clear association between background level of PCB exposure and all-cause and cancer-specific mortality, probably due to the limited number of studies. This study brings new evidence of an increased risk of cardiovascular-specific mortality associated with a higher exposure to PCBs in the general population, with a moderate level of certainty.

Childhood cancer and residential proximity to petrol stations: a nationwide registry-based case–control study in Switzerland and an updated meta-analysis

PurposeBenzene is a known carcinogen for adult leukemia. Exposure to benzene through parental occupation and the use of household products has been associated with childhood leukemia (CL). Ambient benzene has also been associated with CL and central nervous system (CNS) tumors. We aimed to investigate whether the higher ambient levels of benzene in proximity of petrol stations are associated with a greater risk of childhood cancers, leukemia, and CNS tumors.MethodsWe identified children diagnosed with cancer at age 0–15 years during 1985–2015 from the Swiss Childhood Cancer Registry and selected 10 age and sex-matched controls per case from national censuses. We calculated the distance from children’s home to the nearest petrol station using precise geocodes. We estimated odds ratios using conditional logistic regression adjusting for ambient levels of NO2, distance to highways, level of urbanization, and presence of a cantonal cancer registry. In addition, we ran a meta-analysis pooling current results for CL with those of previous studies.ResultsWe identified 6129 cases, of which 1880 were leukemias and 1290 CNS tumors. 24 cases lived within 50 m from a petrol station. The adjusted odds ratio of a cancer diagnosis for children thus exposed compared to unexposed children (> 500 m) was 1.29 (0.84–1.98) for all cancers combined, 1.08 (0.46–2.51) for leukemia, and 1.30 (0.51–3.35) for CNS tumors. During 2000–2015, when exposure assessment was more precise, the adjusted odds ratio for any cancer diagnosis was 1.77 (1.05–2.98). The summary relative risk estimate for CL in the meta-analysis including four studies was 2.01 (1.25–3.22).ConclusionsOur study provides weak support for an increased risk of childhood cancers among children living close to petrol stations. A meta-analysis including our study suggests an increased risk for CL.

Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies

ObjectivesWe conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in...

Low-Dose Perioperative Corticosteroids Can Be Administered Without Additional Morbidity in Patients Undergoing Bilateral Total Knee Replacement: A Retrospective Follow-up Study of a Randomized Controlled Trial.

Background: Short-term benefits of perioperative corticosteroid injections (CSIs) for bilateral total knee replacement (BTKR) include suppressed inflammation, improved knee motion, and reduced pain. Very little is known about the long-term benefits, complications, and safety of corticosteroids administered in the perioperative period. Purpose: We sought to compare 3-year follow-up outcomes of BTKR patients who received perioperative CSI with those who received placebo. We hypothesized that there would be no statistically significant differences in functional outcomes or adverse events based on whether or not CSIs were administered in the perioperative period. Methods: We conducted a retrospective review of chart and registry data of BTKR patients from a prior randomized controlled trial to compare outcomes in patients who received hydrocortisone vs placebo injections after BTKR (ClinicalTrials.gov: NCT01399268 and NCT01815918). Outcomes were compared at 6 and 12 weeks and at 1, 2, and 3 years. The Knee Injury and Osteoarthritis Outcome Scores (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to evaluate clinical outcomes. Cochran-Mantel-Haenszel tests were used to compare the risk of complications between treatments after adjustment for trial. When possible, summary relative risk estimates were calculated using the Mantel-Haenszel method. Results: No BTKR patients in the treatment group developed an infection. The risk of complications did not increase in patients who received CSI compared with those who received placebo. Patients in the CSI group experienced greater reductions in pain and stiffness, though these results were not statistically significant. There were no statistically significant differences in the KOOS-Symptoms, KOOS-Activities of Daily Living, KOOS-Sports, KOOS-Quality of Life, or WOMAC Function scores. Conclusions: Low-dose corticosteroids can be administered in selected patients who undergo BTKR without increasing the risk of adverse events. At 3-year follow-up, administration of low-dose corticosteroids did not result in superior clinical outcomes scores when compared with placebo.

A systematic review and meta-analysis of the prognostic role of age in oral tongue cancer.

While evidence suggests an increasing incidence of tongue cancer in young adults, published findings regarding the prognostic role of age at diagnosis are inconsistent. We performed a meta‐analysis of the literature to highlight key points that might help in understanding the association between age of oral tongue cancer patients at diagnosis and their prognosis. According to age at diagnosis, a systematic literature review of all published cohort studies assessing the recurrence risks and mortality associated with tongue cancer was conducted. We compared the risk estimates between patients aged >45 years and those aged <45 years at diagnosis. Random‐effects models were used to calculate summary relative risk estimates (SRRs) according to different clinical outcomes and sources of between‐study heterogeneity (I2) and bias. We included 31 independent cohort studies published between 1989 and 2019; these studies included a total of 28,288 patients. When risk estimations were not adjusted for confounders, no significant association was found between age at diagnosis and overall survival (OS). Conversely, after adjustment for confounders, older age at diagnosis was associated with a significantly increased risk of mortality. The difference between SRRs for adjusted and unadjusted estimates was significant (p < 0.01). Younger patients had a significantly higher risk of local recurrence. Younger patients with oral tongue cancer have better OS but a greater risk of recurrence than older patients. These findings should be validated in a large prospective cohort study which considers all confounders and prognostic factors.

Egg consumption, overall diet quality, and risk of type 2 diabetes and coronary heart disease: A pooling project of US prospective cohorts

Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is real or due to confounding by dietary habits. We tested the hypothesis that frequent egg consumption is associated with a higher risk of T2D and CHD risk after adjustment for overall dietary patterns among adults. We used prospective cohort design to complete time-to-event analyses. We pooled de novo, harmonized, individual-level analyses from nine US cohorts (n=103,811). Cox regression was used to estimate hazard ratios separately in each cohort adjusting for age, ethnicity, body mass index (BMI), exercise, smoking, alcohol intake, and dietary patterns. We pooled cohort-specific results using an inverse-variance weighted method to estimate summary relative risks. Median age ranged from 25 to 72 years. Median egg consumption was 1 egg per week in most of the cohorts. While egg consumption up to one per week was not associated with T2D risk, consumption of ≥2 eggs per week was associated with elevated risk [27% elevated risk of T2D comparing 7+ eggs/week with none (95% CI: 16%-37%)]. There was little evidence for heterogeneity across cohorts and we observed similar conclusions when stratified by BMI. Overall, egg consumption was not associated with the risk of CHD. However, in a sensitivity analysis, there was a 30% higher risk of CHD (95% CI: 3%-56%) restricted to older adults consuming 5-6 eggs/week. Our data showed an elevated risk of T2D with egg consumption of ≥2 eggs per week but not with <2 eggs/week. While there was no overall association of egg consumption with CHD risk, the elevated CHD observed with consumption of 5-6 eggs/week in older cohorts merits further investigation.

A non-linear dose-response relation of female body mass index and in vitro fertilization outcomes.

Obesity, measured by body mass index (BMI), is implicated in adverse pregnancy outcomes for women seeking in vitro fertilization (IVF) care. However, the shape of the dose-response relationship between BMI and IVF outcomes remains unclear. We therefore conducted a dose-response meta-analysis using a random effects model to estimate summary relative risk (RR) for clinical pregnancy (CPR), live birth (LBR), and miscarriage risk (MR) after IVF. A total of 18 cohort-based studies involving 975,889 cycles were included. For each 5-unit increase in BMI, the summary RR was 0.95 (95% CI: 0.94-0.97) for CPR, 0.93 (95% CI: 0.92-0.95) for LBR, and 1.09 (95% CI: 1.05-1.12) for MR. There was evidence of a non-linear association between BMI and CPR (Pnon-linearity < 10-5) with CPR decreasing sharply among obese women (BMI > 30). Non-linear dose-response meta-analysis showed a relatively flat curve over a broad range of BMI from 16 to 30 for LBR (Pnon-linearity = 0.0009). In addition, we observed a J-shaped association between BMI and MR (Pnon-linearity = 0.006) with the lowest miscarriage risk observed with a BMI of 22-25. In conclusion, obesity contributed to increased risk of adverse IVF outcomes in a non-linear dose-response manner. More prospective trials in evaluating the effect of body weight control are necessary.

Hormonal Replacement Therapy and Risk of Thyroid Cancer in Women: A Meta-Epidemiological Analysis of Prospective Cohort Studies.

ObjectivesMany experimental studies have reported that female sex hormones involve thyroid cancer development because the incidence rate of thyroid cancer in women (TCW) is 3 times higher than in men. Three previous systematic reviews reporting no association between hormone replacement therapy (HRT) and TCW risk had the same search year of 2014. The aim was to reevaluate the association between HRT use and TCW risk using a meta-epidemiological study of prospective cohort studies.MethodsThe study preferentially used all studies selected by the existing systematic reviews and then secured an additional cohort from the list citing the studies. The selection criterion was defined as the prospective cohort study assessing the association between HRT and TCW risk by adjusted relative risk and its 95% confidence intervals (CI) from multivariate analysis. A random-effects model meta-analysis was applied to estimate summary relative risk (sRR) and its 95% CI. A publication bias was evaluated by Egger’s test; moreover, the statistical significance level was set at 5%.ResultsNine cohort studies were finally selected. The random-effect model was applied because of heterogeneity (I2 = 64.3%). The sRR and its 95% CI from a random-effects model meta-analysis had no statistical significance in the association between HRT and TCW risk (sRR = 1.11; 95% CI, 0.98–1.26). Additionally, Egger’s test revealed no statistical significance (P = 0.91).ConclusionsHRT is not associated with TCW risk based on the random-effects model meta-analysis of prospective cohort studies published until now.

Diabetes, Hypertension, Body Mass Index, Smoking and COVID-19-Related Mortality: A Systematic Review and Meta-Analysis of Observational Studies

Background: Patients who smoke and with preexisting comorbidities have a greater risk of developing severe coronavirus disease 2019 (COVID-19) and have a higher mortality rate. However, the number of deaths attributable to diabetes, hypertension, obesity, or smoking have never been estimated. We conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19.Methods: Relevant observational studies were identified by searches in the PubMed and Embase databases through October 29, 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). We further estimated the proportion of deaths attributable to these conditions. Certainty of evidence was assessed using the Cochrane methods and the GRADE framework. This study is registered with PROSPERO, CRD42020218115.Findings: A total of 186 studies representing 210,447 deaths among 1,304,587 patients with COVID-19 were included in this analysis. The SRR for death in COVID-19 patients was 1.54 (95% CI=1.44-1.64, I2=92%, n=145, low certainty) for diabetes and 1.42 (95% CI=1.30-1.54, I2=90%, n=127, low certainty) for hypertension compared to patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI=1.31-1.61, I2=91%, n=54, high certainty) for patients with BMI ≥30kg/m2 compared to those with BMI Interpretation: Our findings suggest that diabetes, hypertension, obesity and smoking are major contributors to COVID-19 mortality accounting for nearly 30% of COVID-19 deaths.Funding Statement: There was no funding source for this study.Declaration of Interests: We declare no competing interests.

Endometriosis and cancer: a systematic review and meta-analysis.

Endometriosis is an often chronic, inflammatory gynaecologic condition affecting 190 million women worldwide. Studies have reported an elevated cancer risk among patients with endometriosis. However, prior research has included methodologic issues that impede valid and robust interpretation. We conducted a meta-analysis of studies investigating the association between endometriosis and cancer risk and analysed the results by methodologic characteristics. We discuss the implications of cancer screening in patients and management challenges faced by clinicians. We searched PubMed and Embase databases for eligible studies from inception through 24 October 2019. We included cohort and case-control studies examining the association between endometriosis and cancer risk; cross-sectional studies and case reports were excluded. Publications had to present risk/rate/odds estimates with 95% CI. Random effects meta-analysis was used to estimate summary relative risks (SRR) and CIs. Heterogeneity across studies was assessed by the Q test and I2 statistics, and publication bias using Egger's and Begg's tests. Risk of bias and quality of the included studies were assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Forty-nine population-based case-control and cohort studies were included. Twenty-six studies were scored as having a 'serious'/'critical' risk of bias, and the remaining 23 'low'/'moderate'. Cancer-specific analyses showed a positive association between endometriosis and ovarian cancer risk (SRR = 1.93, 95% CI = 1.68-2.22; n = 24 studies) that was strongest for clear cell (SRR = 3.44, 95% CI = 2.82-4.42; n = 5 studies) and endometrioid (SRR = 2.33, 95% CI = 1.82-2.98; n = 5 studies) histotypes (Pheterogeneity < 0.0001), although with significant evidence of both heterogeneity across studies and publication bias (Egger's and Begg's P-values < 0.01). A robust association was observed between endometriosis and thyroid cancer (SRR = 1.39, 95% CI =1.24-1.57; n = 5 studies), a very small association with breast cancer (SRR = 1.04, 95% CI =1.00-1.09; n = 20 studies) and no association with colorectal cancer (SRR = 1.00, 95% CI =0.87-1.16; n = 5 studies). The association with endometrial cancer was not statistically significant (SRR = 1.23, 95% CI =0.97-1.57; n = 17 studies) overall and wholly null when restricted to prospective cohort studies (SRR = 0.99, 95% CI =0.72-1.37; n = 5 studies). The association with cutaneous melanoma was also non-significant (SRR = 1.17, 95% CI =0.97-1.41; n = 7 studies) but increased in magnitude and was statistically significant when restricted to studies with low/moderate risk of bias (SRR = 1.71, 95% CI = 1.24-2.36, n = 2 studies). The most robust finding both in terms of statistical significance and magnitude of effect was an inverse association with cervical cancer (SRR = 0.68, 95% CI =0.56-0.82; n = 4 studies); however, this result has a high potential to reflect heightened access to detection of dysplasia for women who reached an endometriosis diagnosis and is thus likely not causal. Several additional cancer types were explored based on <4 studies. Endometriosis was associated with a higher risk of ovarian and thyroid, and minimally (only 4% greater risk) with breast cancer, and with a lower risk of cervical cancer. However, this meta-analysis confirms that: a majority of studies had severe/critical risk of bias; there is impactful heterogeneity across studies-and for ovarian cancer, publication bias; and causal inference requires temporality, which in many studies was not considered. We discuss the implications of these potential associations from the perspectives of patients with endometriosis, clinicians involved in their care, and scientists investigating their long-term health risks.

Non-vitamin K oral anticoagulants and risk of fractures: a systematic review and meta-analysis.

Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk. PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian-Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75-0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71-0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60-0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74-1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs. This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture.

The relationship between physical activity and lymphoma: a systematic review and meta analysis

BackgroundThe literature suggests an increased risk between anthropometrics including higher body mass index and lymphoma incidence; however, the association with physical activity remains unclear. A systematic review/meta-analysis was therefore performed to examine this association with physical activity (total, recreational or occupational).MethodsPubMed, Web of Science and Embase were reviewed from inception to October 2019 identifying relevant observational studies. Non-Hodgkin lymphoma (NHL) including subtypes diffuse large B cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma (HL) were analyzed. Included studies reported activity, lymphoma cases, effect size and variability measures, and were restricted to human subjects of any age. Data was pooled generating summary relative risk (RR) estimates with 95% confidence intervals (CI) using random-effects models with primary outcome of histologically confirmed incident lymphoma.ResultsOne thousand four hundred studies were initially identified with 18 studies (nine cohort, nine case-control) included in final analysis. Comparing highest vs. lowest activity categories was protective for all lymphoma (RR 0.89, 95%CI 0.81–0.98). Sensitivity analysis demonstrated effect persistence within case-control studies (RR 0.82, 95% CI 0.71–0.96), but not cohort studies (RR 0.95, 95%CI 0.84–1.07). Borderline protective effect was seen for NHL (RR 0.92, 95%CI 0.84–1.00), but not HL (RR 0.72, 95%CI 0.50–1.04). Analysis by NHL subtype or gender showed no effect. Dose response analysis demonstrated a protective effect (p = 0.034) with a 1% risk reduction per 3 MET hours/week (RR 0.99, 95%CI 0.98–1.00).ConclusionsPhysical activity may have a protective effect against lymphoma development; further studies are required to generate recommendations regarding health policy.Trial registrationThis study was registered prospectively at PROSPERO: CRD42020156242.

Adiposity and the risk of rheumatoid arthritis: a systematic review and meta-analysis of cohort studies

Several studies have investigated associations between overweight/obesity and risk of developing rheumatoid arthritis, however, the evidence is not entirely consistent, and previous meta-analyses mainly included case–control studies, which can be affected by various biases. We therefore conducted a systematic review and meta-analysis of cohort studies on adiposity and risk of rheumatoid arthritis. Relevant studies were identified by searching PubMed and Embase databases. Random effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for rheumatoid arthritis in relation to different measures of adiposity. Thirteen cohort studies (10 publications) were included. The summary RR per 5 kg/m2 increase in body mass index (BMI) was 1.11 (95% CI 1.05–1.18, I2 = 50%), but the association was restricted to women (1.15, 95% CI 1.08–1.21, I2 = 17%) and not observed in men (0.89, 95% CI 0.73–1.09, I2 = 58%). The summary RR per 5 kg/m2 increment in BMI at age 18 years was 1.17 (95% CI 1.01–1.36, I2 = 26%, n = 3), and per 10 cm increase in waist circumference was 1.13 (95% CI 1.02–1.25, I2 = 44%, n = 2). Higher BMI in middle age, BMI at age 18 years, and waist circumference were associated with increased rheumatoid arthritis risk, suggesting adiposity could be targeted for primary prevention.

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose\u2013response meta-analysis of prospective studies

Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose–response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose–response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17–1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13–1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19–1.67), and 1.57 (0.64–3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk.