Central obesity and risks of pre‐ and postmenopausal breast cancer: a dose–response meta‐analysis of prospective studies

Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist‐to‐hip ratio (WHR), and risks of pre‐ and postmenopausal breast cancer (BC). A dose–response meta‐analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random‐effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR _{per 10‐cm increase} = 1.06, 95% CI: 1.04–1.09, I² = 29.9%) and WHR (15 studies, RR _{per 0.1‐unit increase} = 1.07, 95% CI: 1.01–1.14, I² = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR _{per 10‐cm increase} = 1.05, 95% CI: 0.99–1.10, I² = 0%) nor WHR (11 studies, RR _{per 0.1‐unit increase} = 1.07, 95% CI: 0.95–1.21, I² = 59.7%) were associated with premenopausal BC. The WHR‐postmenopausal BC association lost statistical significance after correcting publication bias (RR _{per 0.1‐unit increase} = 1.06, 95% CI: 0.99–1.13). When considering BMI‐adjusted RRs, WC was associated with both pre‐ (five studies, RR _{per 10‐cm increase} = 1.09, 95% CI: 1.02–1.16, I² = 0%) and postmenopausal BC (seven studies, RR _{per 10‐cm increase} = 1.05, 95% CI: 1.02–1.08, I² = 6.3%), whereas WHR was not associated with either pre‐ (seven studies, RR _{per 0.1‐unit increase} = 1.12, 95% CI: 0.94–1.34, I² = 70.9%) or postmenopausal BC (eight studies, RR _{per 0.1‐unit increase} = 1.05, 95% CI: 0.98–1.13, I² = 57.3%). Among non‐current (former or never) users of hormone replacement therapy, the summary RR _{per 10‐cm increase} of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03–1.05, I² = 69.2%, seven studies; BMI‐adjusted RR = 1.05, 95% CI: 1.02–1.09, I² = 22.8%, four studies). This meta‐analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre‐ and postmenopausal BC independent of general obesity.     

Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis

Background: Minimal hepatic encephalopathy(MHE) is an early and reversible form of hepatic encephalopathy. The documentations on the treatment with probiotics are inconsistent. The present meta-analysis was to verify the role of probiotics in the treatment of cirrhotic patients with MHE.Data sources: Seven electronic databases were searched for relevant randomized controlled trials(RCTs)published until July 2015. The effects of probiotics on serum ammonia, endotoxin, and MHE were evaluated.Results: A total of 14 RCTs(combined n = 1132) were included in the meta-analysis. When probiotics were compared to placebo or no treatment, probiotics were more likely to reduce values in the number connection test(NCT; week 4: MD =-30.25, 95% CI:-49.85 to-10.66), improve MHE(week 4: OR = 0.18,95% CI: 0.07 to 0.47; week 12: OR = 0.15, 95% CI: 0.07 to 0.32), and prevent overt HE progression(week4: OR = 0.22, 95% CI: 0.07 to 0.67) in patients with liver cirrhosis. When probiotics was compared to lactulose, probiotics tended to reduce serum ammonia levels(week 4: MD =-0.33 μmol/L, 95% CI:-5.39 to 4.74; week 8: MD = 6.22 μmol/L, 95% CI:-24.04 to 36.48), decrease NCT(week 8: MD = 3.93, 95% CI:-0.72 to 8.58), improve MHE(week 4: OR = 0.93, 95% CI: 0.45 to 1.91; week 12: OR = 0.73, 95% CI: 0.35 to 1.51) and prevent the development of overt HE(week 4: OR = 0.96, 95% CI: 0.17 to 5.44; week 12:OR = 2.7, 95% CI: 0.50 to 14.64) in patients with liver cirrhosis. However, lactulose appears to be more effective in reducing NCT values as compared to probiotics(week 4: MD = 6.7, 95% CI: 0.58 to 12.82).Conclusion: Probiotics can decrease serum ammonia and endotoxin levels, improve MHE, and prevent overt HE development in patients with liver cirrhosis.     

The efficacy and safety of tiotropium in Chinese patients with stable chronic obstructive pulmonary disease: A meta-analysis

Background and objective: Tiotropium is the only long‐acting inhaled anticholinergic bronchodilator currently available in China, but information about its clinical effect in this population is limited. This meta‐analysis assessed the efficacy and safety of tiotropium in Chinese patients with stable COPD. Methods: An electronic search of the literature was undertaken to identify randomized controlled trials (RCTs) of tiotropium in Chinese patients, which were then assessed for inclusion in a meta‐analysis. The efficacy and safety of tiotropium was compared with placebo and ipratropium, using the outcomes of FEV₁, FEV₁%, symptoms, frequency of exacerbations, adverse events and safety. Results: Eleven RCTs recruiting 1006 patients were included in the meta‐analysis. Compared with both placebo and ipratropium, tiotropium significantly improved FEV₁[weighted mean difference (WMD) = 304 mL, 95% CI 271–337], FEV₁% (WMD = 8.35%, 95% CI 5.40–11.31) and symptoms [relative risk (RR) = 2.00, 95% CI 1.61–2.49]. Tiotropium significantly reduced the risk of exacerbations (RR = 0.07, 95% CI 0.01–0.54) compared with placebo, and there was a non‐significant reduction in the risk of exacerbations compared with ipratropium (RR = 0.70, 95% CI 0.13–3.75). Tiotropium was well tolerated with a similar safety profile to placebo and ipratropium (RR = 1.16, 95% CI 0.76–1.77, P = 0.49). Conclusions: Tiotropium improved pulmonary function and symptoms, reduced exacerbations and was well tolerated and safe. On the basis of its efficacy and safety profile, tiotropium appears to be a reasonable first‐line choice for the management of Chinese patients with stable COPD. Additional long‐term RCTs are required to further evaluate the efficacy and safety of tiotropium.     

Early enteral nutrition compared with parenteral nutrition for esophageal cancer patients after esophagectomy: a meta‐analysis

Early postoperative enteral nutrition (EN) after esophagectomy in esophageal cancer patient has been reported to be correlated with a better rehabilitation than parenteral nutrition (PN). However, a robust conclusion has not been achieved. Therefore, we performed a meta‐analysis to compare the postoperative EN and PN in patients with esophageal cancer undergoing esophagectomy. Three electronic databases were searched for eligible studies to be included in the meta‐analysis. The summary relative risk/weighted mean difference (RR/WMD) estimates and corresponding 95% confidence interval (CI) were calculated using fixed‐ and random‐effects models. Ten studies met the inclusion criteria. The analysis demonstrated that the early postoperative EN could significantly decrease the pulmonary complications (RR = 0.37, 95% CI = 0.22–0.62, P = 0.00, test for heterogeneity: I² = 0.0%, P = 0.89) and anastomotic leakage (RR = 0.46, 95% CI = 0.22–0.96, P = 0.04, test for heterogeneity: I² = 0.0%, P = 0.66) compared with PN. On the eighth postoperative day, the EN group had a higher levels of albumin (WMD = 1.84, 95% CI = 0.47–3.21, P = 0.01, test for heterogeneity: I² = 84.5%, P = 0.00) and prealbumin (WMD = 12.96, 95% CI = 3.63–22.29, P = 0.01, test for heterogeneity: I² = 0.0%, P = 0.63) compared with the PN group. However, there was no difference in digestive complications between these two approaches (RR = 1.30, 95% CI = 0.79–2.13, P = 0.30, test for heterogeneity: I² = 0.0%, P = 0.97). For patients with esophageal cancer following esophagectomy, the early postoperative EN support could decrease the morbidity of severe complications, such as pulmonary complications and anastomotic leakage, and maintain patients at a better nutritional status than parenteral nutrion support.     

Benefits and Risks of Maintaining Normothermia during Cardiopulmonary Bypass in Adult Cardiac Surgery: A Systematic Review

Cardiopulmonary bypass is associated with significant morbidities, and the ideal temperature management during cardiopulmonary bypass remains uncertain. This review assessed the benefits and risks of maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery. A total of 6731 patients from 44 randomized controlled trials in 14 countries, comparing normothermic (>34°C) and hypothermic (≤34°C) cardiopulmonary bypass in cardiac surgery (>18 years of age), were identified from MEDLINE (1966 to August 10, 2009), EMBASE (1988 to August 10, 2009), and Cochrane controlled trials register and subject to meta‐analysis. Two investigators examined all studies and extracted the data independently. Mortality after normothermic and hypothermic bypass was not significantly different (1.4% vs. 1.9% respectively, relative risk [RR] 1.38, 95% confidence interval [CI] 0.94–2.04, I²= 0%, P= 0.10). Hypothermic bypass was, however, associated with an increased risk of allogeneic red blood cells (RR 1.19, 95% CI 1.07–1.34, I²= 0%, P= 0.002), fresh frozen plasma (RR 1.54, 95% CI 1.06–2.24, I²= 7.7%, P= 0.02), and platelet transfusion (RR 2.53, 95% CI 1.26–5.06, I²= 44%, P= 0.009). The risk of stroke, cognitive decline, atrial fibrillation, use of inotropic support or intra‐aortic balloon pump, myocardial infarction, all‐cause infections, and acute kidney injury after cardiac surgery was not significantly different between the two groups. The differences in the bypass time and targeted perfusion temperature were not significantly related to the risk of mortality and stroke. The current evidence suggests that maintaining normothermia during cardiopulmonary bypass in adult cardiac surgery is as safe as that of hypothermic surgery, and associated with a reduced risk of allogeneic blood transfusion.     

Thiazolidinedione therapy and breast cancer risk in diabetic women: A systematic review and meta‐analysis

Rising experimental evidence suggests that thiazolidinediones (TZDs) exert a protective effect on breast cancer. However, studies concerning this issue were inconsistent and limited. Hence, we performed a meta‐analysis with data from currently available studies to evaluate the effect of TZDs on breast cancer risk among diabetic women. We comprehensively searched for all pertinent studies addressing TZDs use and breast cancer risk published before January 1, 2016, in PubMed, Clinical Trials, and Cochrane Library. Data synthesis was performed in a random‐effects model using Stata version 12.0 (Stata Corp, College Station, Texas). Fourteen independent studies were eventually selected in this meta‐analysis, including 5 randomized controlled clinical trials (RCTs), 7 cohort studies, and 2 case‐control studies. No significant associations of TZD use and risk of breast cancer were observed in the RCTs (pooled risk ratio [RR]: 0.77, 95% confidence interval (CI), 0.39‐1.53, I² = 26%) or case‐control studies (pooled odds ratio, 0.99, 95% CI, 0.76‐1.28, I² = 31%). A 19% reduction in breast cancer risk (pooled RR: 0.81, 95% CI, 0.66‐0.99, I² = 72%) was found in the cohort studies. However, after removing the study with the smallest event number and the greatest effect size, the association became nonsignificant with greatly decreased heterogeneity (pooled RR: 0.94, 95% CI, 0.86‐1.03, I² = 16%). This meta‐analysis did not find any significant association between TZDs use and risk of breast cancer among diabetic women.     

Treatment of clinical insulin resistance in children: a systematic review

The objective of this study was to evaluate the effectiveness of interventions aimed at improving clinical insulin resistance and/or pre‐diabetes in children. This study is a systematic review and meta‐analysis. Five electronic databases were searched for randomized controlled trials of at least 2‐months' duration. The outcomes were fasting insulin, homeostasis model assessment of insulin resistance (HOMA‐IR), body mass index (BMI) and adverse outcomes. Four randomized controlled trials were identified. All compared the effect of 6 months of metformin plus or minus lifestyle intervention with placebo plus or minus lifestyle intervention. After pooling results from three trials, the mean difference after 6 months favoured the intervention with a statistically significant mean decrease in fasting insulin, HOMA‐IR and BMI of 9.6 µU mL⁻¹ (95% confidence interval [CI]: 6.3, 13.0 µU mL⁻¹; I² = 76%), 2.7 (95% CI: 1.7, 3.6; I² = 74%) and 1.7 kg m⁻² (95% CI: 1.1, 2.3 kg m⁻²; I² = 75) respectively. Mild gastrointestinal symptoms were reported in 19% (2–29%; median and range) of participants taking metformin. Metformin improves markers of insulin sensitivity and reduces BMI in children and adolescents with clinical insulin resistance or pre‐diabetes. Stronger evidence from high‐quality studies of longer duration and larger sample size are required before clinical conclusions about the optimal treatment protocol in this population can be drawn.     

Vitamin D Treatment for the Prevention of Falls in Older Adults: Systematic Review and Meta‐Analysis

OBJECTIVES: To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults. DESIGN: Systematic review and meta‐analysis. SETTING: MEDLINE, CINAHL, Web of Science, EMBASE, Cochrane Library, LILACS, bibliographies of selected articles, and previous systematic reviews through February 2009 were searched for eligible studies. PARTICIPANTS: Older adults (aged ≥60) who participated in randomized controlled trials that both investigated the effectiveness of vitamin D therapy in the prevention of falls and used an explicit fall definition. MEASUREMENTS: Two authors independently extracted data, including study characteristics, quality assessment, and outcomes. The I² statistic was used to assess heterogeneity in a random‐effects model. RESULTS: Of 1,679 potentially relevant articles, 10 met inclusion criteria. In pooled analysis, vitamin D therapy (200–1,000 IU) resulted in 14% (relative risk (RR)=0.86, 95% confidence interval (CI)=0.79–0.93; I²=7%) fewer falls than calcium or placebo (number needed to treat =15). The following subgroups had significantly fewer falls: community‐dwelling (aged <80), adjunctive calcium supplementation, no history of fractures or falls, duration longer than 6 months, cholecalciferol, and dose of 800 IU or greater. Meta‐regression demonstrated no linear association between vitamin D dose or duration and treatment effect. Post hoc analysis including seven additional studies (17 total) without explicit fall definitions yielded smaller benefit (RR=0.92, 95% CI=0.87–0.98) and more heterogeneity (I²=36%) but found significant intergroup differences favoring adjunctive calcium over none (P=.001). CONCLUSION: Vitamin D treatment effectively reduces the risk of falls in older adults. Future studies should investigate whether particular populations or treatment regimens may have greater benefit.     

Revascularization strategies in cardiogenic shock complicating acute myocardial infarction: A systematic review and meta-analysis

BackgroundThe optimal revascularization strategy in patients with multi-vessel disease (MVD) presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remains unclear.ObjectiveTo investigate the comparative differences between culprit-only revascularization (COR) versus instant multi-vessel revascularization (IMVR) in AMI and CS.Methods13 studies were selected using MEDLINE, EMBASE and the CENTRAL (Inception - 31 November2017). Outcomes were assessed at short-term (in-hospital or ≤30 days duration) and long-term duration (≥6 months). Estimates were reported as random effects relative risk (RR) with 95% confidence interval (CI).ResultsIn analysis of 7311 patients, COR significantly reduced the relative risk of short-term all-cause mortality (RR: 0.87; 95% CI, 0.77–0.97; p = 0.01, I² = 50%) and renal failure (RR: 0.75; 95% CI, 0.61–0.94; p = 0.01, I² = 7%) compared with IMVR. There were no significant differences between both the strategies in terms of reinfarction (RR: 1.25; 95% CI, 0.59–2.63; p = 0.56, I² = 0%), major bleeding (RR: 0.88; 95% CI, 0.75–1.04; p = 0.14, I² = 0%) and stroke (RR: 0.77; 95% CI, 0.50–1.17; p = 0.22, I² = 0%) at short term duration. Similarly, no significant differences were observed between both groups regarding all-cause mortality (RR; 1.01; 95% CI, 0.85–1.20; p = 0.93, I² = 61%) and reinfarction (RR: 0.71; 95% CI, 0.34–1.47; p = 0.35, I² = 26%) at long term duration.ConclusionIn MVD patients presenting with AMI and CS, IMVR was comparable to COR in terms of all-cause mortality at long term follow up duration. These results are predominantly derived from observational data and more randomized controlled trials are required to validate this impression.     

Hylan versus hyaluronic acid for osteoarthritis of the knee: A systematic review and meta‐analysis

Objective

To compare the effectiveness and safety of intraarticular high‐molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee.

Methods

We performed a systematic review and meta‐analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain‐related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random‐effects meta‐analysis.

Results

Thirteen trials with a pooled total of 2,085 patients contributed to the meta‐analysis. The pooled effect size was ?0.27 (95% confidence interval [95% CI] ?0.55, 0.01), favoring hylan, but between‐trial heterogeneity was high (I² = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent‐to‐treat analysis had pooled effect sizes near null. The meta‐analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I² = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I² = 0%).

Conclusion

Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

     

Correlation Between Proton Pump Inhibitors and the Complications of Liver Cirrhosis: A Systematic Review and Meta-Analysis

BackgroundMany studies and meta-analyses have investigated the associations among proton pump inhibitors (PPIs), spontaneous bacterial peritonitis (SBP), portosystemic encephalopathy (PSE), and other infections. However, these studies had limitations, including the omission of several relevant studies and drawing conclusions, based on the abstracts without consulting the full-text of the articles. To evaluate the association between PPIs and complications arising from cirrhosis and risks of PPI use in patients with cirrhosis.MethodsData were extracted from the EMBASE, PubMed, Cochrane, and Google Scholar databases. The Newcastle-Ottawa scale was used to assess the quality of the selected studies.ResultsA total of 29 studies (13 case–control and 16 cohort studies) involving 20,484 patients were included in the meta-analysis. The total relative risk (RR) for the 23 studies which investigated SBP was 1.31, and the 95% CI was 1.10-1.55 (I² = 73.0%). The total RR for the 7 studies which examined PSE was 1.25 (95% CI 0.85-1.84, I² = 96.1%). For the 7 studies which analyzed overall infection, the total RR was 1.37 (95% CI 1.07-1.76, I² = 79.3%). The RR for the 2 cohort studies that assessed mortality was 1.39 (95% CI 0.85-2.27, I² = 0.0%).ConclusionPPI use in cirrhosis patients increased the SBP and overall infection risk. PPIs should be considered with appropriate indications when the benefits exceed the risks in cirrhosis patients with ascites.     

Meta-Analysis of Efficacy and Safety of Proton Pump Inhibitors with Dual Antiplatelet Therapy for Coronary Artery Disease

BackgroundThere is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences.Methods and results39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI = 77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56–3.23, P = 0.50, I² = 0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25–3.54, P = 0.92, I² = 56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62–1.51, P = 0.88, I² = 0) or stroke (RR: 1.11, 95% CI, 0.25–5.04, P = 0.89, I² = 26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20–0.52, P < 0.001, I² = 0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11–1.41, P < 0.001, I² = 82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03–1.52, P = 0.02, I² = 71), MI (RR: 1.30, 95% CI, 1.16–1.47, P < 0.001, I² = 82) and stroke (RR: 1.60, 95% CI, 1.43–1.78, P < 0.001, I² = 0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45–1.22, P = 0.24, I² = 79).ConclusionMeta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT.     

Pharmacist- and Nurse-Led Medical Optimization in Heart Failure: A Systematic Review and Meta-Analysis

BackgroundTraditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in patients with heart failure. This study sought to characterize alternative models of care involving nonphysician provider-led GDMT interventions and their associations with therapy use and clinical outcomes.MethodsWe performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing nonphysician provider-led GDMT initiation and/or uptitration interventions vs usual physician care (PROSPERO ID: CRD42022334661). We queried PubMed, Embase, the Cochrane Library, and the World Health Organization International Clinical Trial Registry Platform for peer-reviewed studies from database inception to July 31, 2022. In the meta-analysis, we used RCT data only and leveraged random-effects models to estimate pooled outcomes. Primary outcomes were GDMT initiation and titration to target dosages by therapeutic class. Secondary outcomes included all-cause mortality and HF hospitalizations.ResultsWe reviewed 33 studies, of which 17 (52%) were randomized controlled trials with median follow-ups of 6 months; 14 (82%) trials evaluated nurse interventions, and the remainder assessed pharmacists’ interventions. The primary analysis pooled data from 16 RCTs, which enrolled 5268 patients. Pooled risk ratios (RR) for renin-angiotensin system inhibitor (RASI) and beta-blocker initiation were 2.09 (95% CI 1.05–4.16; I² = 68%) and 1.91 (95% CI1.35-2.70; I² = 37%), respectively. Outcomes were similar for uptitration of RASI (RR 1.99, 95% CI 1.24-3.20; I² = 77%) and beta-blocker (RR 2.22, 95% CI 1.29–3.83; I² = 66%). No association was found with mineralocorticoid receptor antagonist initiation (RR 1.01, 95% CI 0.47–2.19). There were lower rates of mortality (RR 0.82, 95% CI 0.67–1.04; I² = 12%) and hospitalization due to HF (RR 0.80, 95% CI 0.63–1.01; I² = 25%) across intervention arms, but these differences were small and not statistically significant. Prediction intervals were wide due to moderate-to-high heterogeneity across trial populations and interventions. Subgroup analyses by provider type did not show significant effect modification.ConclusionsPharmacist- and nurse-led interventions for GDMT initiation and/or uptitration improved guideline concordance. Further research evaluating newer therapies and titration strategies integrated with pharmacist- and/or nurse-based care may be valuable.     

Is COPD associated with increased mortality and morbidity in hospitalized pneumonia? A systematic review and meta‐analysis

This review aimed to investigate whether chronic obstructive pulmonary disease (COPD) is associated with increased mortality and morbidity in patients hospitalized with community‐acquired pneumonia (CAP). EMBASE, PubMed and Web of Science were searched for cohort studies and case–control studies investigating the impact of COPD on CAP. The primary outcome was all‐cause mortality, and secondary outcomes included length of hospital stay, intensive care unit (ICU) admission and need for mechanical ventilation. Methodological quality was assessed using the Newcastle–Ottawa Scale. The Mantel–Haenszel method and inverse variance method were used to calculate pooled relative risks (RRs) and mean differences (MD), respectively. Eleven studies (nine cohort studies and two case–control studies), involving 257 958 patients, were included. The overall methodological quality was high. COPD was not associated with increased mortality in hospitalized CAP patients (RR, 1.20; 95% confidence interval (CI): 0.92–1.56; P = 0.19; I² = 55%) in cohort studies, and was associated with reduced mortality in case–control studies (RR, 0.82; 95% CI: 0.74–0.90; P < 0.0001; I² = 80%). COPD was not associated with longer hospital stay (MD, 0.11; 95% CI: ?0.42 to 0.64; P = 0.68; I² = 21%), more frequent ICU admission (RR, 0.97; 95% CI: 0.70–1.35; P = 0.87; I² = 65%), and more need for mechanical ventilation (RR 0.91, 95% CI: 0.71–1.16; P = 0.44; I² = 4%).The current available evidence indicates that COPD may not be associated with increased mortality and morbidity in patients hospitalized with CAP. This conclusion should be re‐evaluated by prospective population‐based cohort studies.     

Male circumcision for the prevention of heterosexually acquired HIV infection: a meta-analysis of randomized trials involving 11,050 men

Objectives

Observational studies and a small collection of randomized controlled trials (RCTs) suggest that male circumcision may significantly reduce HIV transmission between sero‐discordant contacts. The Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization have recently announced recommendations to scale up male circumcision in countries with generalized epidemics and low levels of male circumcision. However, no meta‐analysis has been conducted to determine the effectiveness of this intervention.

Methods

We conducted a systematic review of medical literature, and included any RCTs assessing male circumcision to prevent heterosexually acquired HIV infection among males. We used the DerSimonian–Laird random effects method to pool study outcomes. We calculated the relative risk (RR), risk difference, number needed to treat (NNT) and I², all with 95% confidence intervals (CIs).

Results

We identified three RCTs that met our inclusion criteria, involving a total of 11 050 men. The pooled RR was 0.44 (95% CI 0.33–0.60, P<0.0001, I²=0%, 95% CI 0–35%). The risk difference was 0.014 (95% CI 0.07–0.21), yielding a NNT of 72 (95% CI 50–143).

Conclusions

Male circumcision is an effective strategy for reducing new male HIV infections. Its impact on a population level will require consistently safe sexual practices to maintain the protective benefit.     

Neurological Complications After Renal Transplantation: A Systematic Review and Meta‐Analysis

The aim of this systematic review and meta‐analysis was to evaluate the prevalence of neurological complication after renal transplantation. The searches were conducted by two independent researchers in the international (PubMed, Web of Science, Scopus, and Google Scholar) and national databases (Magiran and SID) to find the relevant studies published in English and Persian languages since the creation of the databases until January 2019 (without time limitations). The keywords used in the search strategy were: neurologic complication, central nervous system, peripheral nervous system, tremor, CVA, encephalopathy, neurological complications, renal transplantation, renal failure, kidney transplantation, immunosuppression, neurotoxicity, opportunistic infections, CNS, cerebrovascular disease, chronic kidney disease, cognitive impairment, and end‐stage renal disease, which were combined using the AND, OR, and NOT operators. Finally, a meta‐analysis was conducted in STATA14 statistical software. Based on the random effect model, the total prevalence of neurologic complications in 4674 patients who had undergone the renal transplantation surgery was 7.9% (95% confidence interval [CI]:7.2%,8.7%, I² = 90.1%). The prevalence of infectious, non‐infectious and treatment associated neurologic complications was 9.5% (95% CI –8.9, 10.2), 91.8% (95% CI –91.3, 92.4) and 97% (95% CI‐95.7%,98.4%) of all neurologic complications in renal transplant patients, respectively. And according to the present subgroup analysis, peripheral neuropathy with a prevalence about 30% (29%) (95% CI –27.6%, 30.4%, I² = 99.4%) was the most common neurological disorder in renal transplant patients followed by tremor with a prevalence of 19.5% (CI –17.6%, 21.3%, I² = 97.1%), cerebrovascular events with a prevalence of 15.1% (95% CI –13.9%, 16.4%, I² = 96.5%), encephalopathy with the prevalence of 13% (95% CI –12%, 14%, I² = 99.3%), headache with a prevalence of 8.3% (95% CI –6.8%, 9.8%, I² = 97.3%) and seizure with a prevalence of 7.4% (CI – 6.5%, 8.3%, I² = 94.6%). The results of the present systematic review and meta‐analysis, suggests that post‐kidney transplantation neurological disorders, with a prevalence rate about 8%, are relatively common; most of them are caused by immunosuppressive drugs and can be treated by decreasing the dose or switching the immunosuppressive drugs. Neurological disorders are associated with increased mortality; thus, differential diagnosis should be conducted for each individual patient with neurological symptoms after transplantation. It is important for all health care providers to become familiar with the symptoms of neurological disorders that may occur after organ transplants. Recognizing and monitoring these symptoms can reduce the risk of death in kidney transplant recipients. Further research is needed to help the transplant community to identify these issues and problems better in order to achieve the ultimate goal of helping renal patients and sending them back into their normal lives.     

Body weight gain and risk of colorectal cancer: a systematic review and meta‐analysis of observational studies

While the relationship between body mass index as an indicator of excess body weight and the risk of colorectal cancer (CRC) is well established, the association between body weight gain in adulthood and risk of CRC remains unresolved. We quantified this association in a meta‐analysis of 12 observational studies published until November 2014 with a total of 16,151 incident CRC cases. Random effect models were used to obtain summary relative risks (RR) and 95% confidence intervals (95% CIs). Between‐study heterogeneity was assessed using I² statistics. Overall, the summary RR (95% CI) was 1.22 (1.14–1.30) for high body weight gain (midpoint: 15.2 kg) compared with stable weight (P for heterogeneity = 0.182; I² = 21.2%). In a dose‐response analysis, each 5 kg weight gain was associated with a 4% (95% CI: 2%–5%) higher risk of CRC. The association persisted after adjustment for body weight at younger age and was present for both men and women, as well as for colon and rectal cancer. Differences by sex were detected for colon cancer (P for interaction = 0.003, with higher risk for men than women), but not for rectal cancer (P for interaction = 0.613). In conclusion, these data underscore the importance of body weight management from early adulthood onwards for the prevention of CRC development.     

Body mass index and risk of pneumonia: a systematic review and meta‐analysis

The aims of our meta‐analysis were to examine the pattern and gender's influence on body mass index (BMI) – pneumonia relationship. Published studies were searched from PubMed, Web of Science, Cochrane Library databases using keywords of pneumonia, BMI and epidemiologic studies. Random‐effects analysis was applied to estimate pooled effect sizes from individual studies. The Cochrane Q‐test and index of heterogeneity (I²) were used to evaluate heterogeneity, and Egger's test was used to evaluate publication bias. Random‐effects meta‐regression was applied to examine the pattern and gender's influence on BMI–pneumonia relationship. A total of 1,531 studies were initially identified, and 25 studies finally were included. The pooled relative risk (RR) and meta‐regression model revealed a J‐shaped relationship between BMI and risk of community‐acquired pneumonia (underweight, RR 1.8, 95% confidence interval [CI], 1.4–2.2, P < 0.01; overweight, 0.89, 95%CI, 0.8–1.03, P, 0.1; obesity, 1.03, 95% CI, 0.8–1.3, p. 8) and U‐shaped relationship between BMI and risk of influenza‐related pneumonia (underweight, RR 1.9, 95% CI, 1.2–3, P < 0.01; overweight, 0.89, 95% CI, 0.79–0.99, P, 0.03; obesity, 1.3, 95% CI, 1.05–1.63, p. 2; morbidity obesity, 4.6, 95% CI, 2.2–9.8, P < 0.01); whereas, no difference in risk of nosocomial pneumonia was found across the BMI groups. Gender difference did not make significant contribution in modifying BMI–pneumonia risk relationship.     

Mobile phone applications and self‐management of diabetes: A systematic review with meta‐analysis,meta‐regression of 21 randomized trials and GRADE

We conducted a systematic review with meta‐analysis of randomized controlled trials that evaluated the effect of diabetes mobile phone applications. A total of 1550 participants from 21 studies were included. For type 1 diabetes, a significant 0.49% reduction in HbA1c was seen (95% CI, 0.04‐0.94; I² = 84%), with unexplained heterogeneity and a low GRADE of evidence. For type 2 diabetes, using diabetes apps was associated with a mean reduction of 0.57% (95% CI, 0.32‐0.82; I² = 77%). The results had severe heterogeneity that was explained by the frequency of HCP feedback. In studies with no HCP feedback, low frequency and high frequency HCP feedback, the mean reduction is 0.24% (95% CI, 0.02‐0.49; I² = 0%), 0.33% (95% CI, 0.07‐0.59; I² = 47%) and 1.12% (95% CI, 0.91‐1.32; I² = 0%), respectively, with a high GRADE of evidence. There is evidence that diabetes apps improve glycaemic control in type 1 diabetes patients. A reduction of 0.57% in HbA1c was found in type 2 diabetes patients. However, HCP functionality is important to achieve clinical effectiveness. Future studies are needed to explore the cost‐effectiveness of diabetes apps and the optimal intensity of HCP feedback.     

Probiotics for Prevention of Atopy and Food Hypersensitivity in Early Childhood: A PRISMA-Compliant Systematic Review and Meta-Analysis of Randomized Controlled Trials

Most studies investigated probiotics on food hypersensitivity, not on oral food challenge confirmed food allergy in children. The authors systematically reviewed the literature to investigate whether probiotic supplementation prenatally and/or postnatally could reduce the risk of atopy and food hypersensitivity in young children.PubMed, Embase, the Cochrane Central Register of Controlled Trials, and 4 main Chinese literature databases (Wan Fang, VIP, China National Knowledge Infrastructure, and SinoMed) were searched for randomized controlled trials regarding the effect of probiotics on the prevention of allergy in children. The last search was conducted on July 11, 2015.Seventeen trials involving 2947 infants were included. The first follow-up studies were analyzed. Pooled analysis indicated that probiotics administered prenatally and postnatally could reduce the risk of atopy (relative risk [RR] 0.78; 95% confidence interval [CI] 0.66–0.92; I² = 0%), especially when administered prenatally to pregnant mother and postnatally to child (RR 0.71; 95% CI 0.57–0.89; I² = 0%), and the risk of food hypersensitivity (RR 0.77; 95% CI 0.61–0.98; I² = 0%). When probiotics were administered either only prenatally or only postnatally, no effects of probiotics on atopy and food hypersensitivity were observed.Probiotics administered prenatally and postnatally appears to be a feasible way to prevent atopy and food hypersensitivity in young children. The long-term effects of probiotics, however, remain to be defined in the follow-up of existing trials. Still, studies on probiotics and confirmed food allergy, rather than surrogate measure of food hypersensitivity, are warranted.