Diabetes mellitus and the risk of pancreatitis: A systematic review and meta-analysis of cohort studies

BackgroundDiabetes mellitus has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association. We conducted a systematic review and meta-analysis of prospective studies on diabetes mellitus and pancreatitis to clarify the association.MethodsPubMed and Embase databases were searched for studies on diabetes mellitus and pancreatitis up to 8^th of January 2020. Cohort studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes diagnosis and pancreatitis were included and summary RRs (95% CIs) were calculated using a random effects model.ResultsEight cohort studies were included in the meta-analysis, and seven of these were included in the analysis of diabetes mellitus and acute pancreatitis (14124 cases, 5.7 million participants). Comparing diabetes patients with persons without diabetes the summary RRs (95% CIs) were 1.74 (95% CI: 1.33–2.29, I² = 95%) for acute pancreatitis, 1.40 (95% CI: 0.88–2.22, I² = 0%, n = 2) for chronic pancreatitis, and 1.39 (95% CI: 1.07–1.80, I² = 54%, n = 3) for pancreatitis overall. Although there was some indication of publication bias in the analysis of acute pancreatitis this appeared to be explained by one outlying study which when excluded did not substantially alter the association. The results persisted in several subgroup and sensitivity analyses.ConclusionsThese results suggest that diabetes patients are at an increased risk of acute pancreatitis. Further studies are needed on diabetes and risk of chronic pancreatitis, pancreatitis overall and on gallstone-related and non-gallstone-related pancreatitis.     

A Prospective Cohort Study of Smoking in Acute Pancreatitis

Background/Aims: Little is known about risk factors for acute pancreatitis other than gallstones and alcohol consumption. The aim of this study was to investigate if smoking or body mass index (BMI) are associated with acute pancreatitis and to determine relative risks (RR) for acute pancreatitis related to smoking, BMI, and alcohol consumption. Methods: From 1974 to 1992, selected birth-year cohorts of residents in Malmö, Sweden (born 1921–1949) were invited to a health-screening investigation including physical examination, blood sampling and a questionnaire. In total, 33,346 individuals participated. Cases of acute pancreatitis were identified from diagnosis registries (n = 179). Incidence rates were calculated in different risk factor categories. A Cox's analysis revealed RR. Results: Current versus never smoking at baseline was associated with acute pancreatitis (RR 2.14, 95% confidence interval (CI) 1.48–3.09) after adjustment for age, sex, BMI and alcohol consumption. This association was stronger in heavy smokers (20–30 cigarettes/day) (RR 3.19, 95% CI 2.03–5.00). Smoking was associated with a RR of 3.57 (95% CI 0.98–13.0) for acute pancreatitis in subjects who reported no alcohol consumption. An increased risk for acute pancreatitis was also found for high versus low risk, self-reported alcohol consumption (RR 2.55,95% CI 1.59–4.08) and for γ-GT levels in the highest versus the lowest quartile (RR 2.14,95%CI 1.32–3.49). There was alsoa weakcorrelation between BMI and acute pancreatitis. Conclusions: Smoking is associated with the incidence of acute pancreatitis in a dose-response manner.     

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.     

Smoking cessation reduces postoperative complications: a systematic review and meta-analysis

Objective

We aimed to review randomized trials and observational evidence to establish the effect of preoperative smoking cessation on postoperative complications and to determine if there is an optimal cessation period before surgery.

Methods

We conducted a systematic review of all randomized trials evaluating the effect of smoking cessation on postoperative complications and all observational studies evaluating the risk of complications among past smokers compared with current smokers. We searched independently, in duplicate, 10 electronic databases and the bibliographies of relevant reviews. We conducted a meta-analysis of randomized trials using a random effects model and performed a meta-regression to examine the impact of time, in weeks, on the magnitude of effect. For observational studies, we pooled proportions of past smokers in comparison with current smokers.

Results

We included 6 randomized trials and 15 observational studies. We pooled the 6 randomized trials and demonstrated a relative risk reduction of 41% (95% confidence interval [CI], 15-59, P = .01) for prevention of postoperative complications. We found that each week of cessation increases the magnitude of effect by 19%. Trials of at least 4 weeks' smoking cessation had a significantly larger treatment effect than shorter trials (P = .04). Observational studies demonstrated important effects of smoking cessation on decreasing total complications (relative risk [RR] 0.76, 95% CI, 0.69-0.84, P < .0001, I² = 15%). This also was observed for reduced wound healing complications (RR 0.73, 95% CI, 0.61-0.87, P = .0006, I² = 0%) and pulmonary complications (RR 0.81, 95% CI, 0.70-0.93, P = .003, I² = 7%). Observational studies examining duration of cessation demonstrated that longer periods of cessation, compared with shorter periods, had an average reduction in total complications of 20% (RR 0.80, 95% CI, 3-33, P = .02, I² = 68%).

Conclusion

Longer periods of smoking cessation decrease the incidence of postoperative complications.     

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.     

Active and passive smoking and risk of death from pancreatic cancer: Findings from the Japan Collaborative Cohort Study

BackgroundThere is uncertainty in the risk of pancreatic cancer with particular aspects of smoking, such as a dose–response relationship and cumulative amount, in Japanese men and women. Very few studies have addressed the role of passive smoking in pancreatic cancer among Japanese women.MethodsWe examined the association between active or passive smoking and the risk of death from pancreatic cancer using data from the Japan Collaborative Cohort Study. The cohort participants (46,395 men and 64,190 women) were followedup for mortality from baseline (1988–1990) through December 31, 2009. Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI).ResultsDuring follow-up, we recorded 611 pancreatic cancer deaths. After adjustment for potential confounding factors, current smokers had a significantly increased risk of death from pancreatic cancer compared with non-smokers, with an RR of 1.70 (95% CI: 1.33–2.19). The risk of death from pancreatic cancer significantly increased with increasing numbers of cigarettes smoked per day. Exposure to environmental tobacco smoke (ETS) in public spaces was not associated with risk of death from pancreatic cancer. The RR for women who reported ETS exposure was 1.20 (95% CI: 0.87–1.67). Women exposed to ETS during childhood or adolescence had 1.21-fold increased risk, but the association was statistically insignificant.ConclusionsCigarette smoking is associated with an approximately 70% increase in the risk of death from pancreatic cancer. Further studies with improved exposure assessment are needed to better quantify the association between passive smoking and pancreatic cancer.     

Clinical Outcomes of Sentinel Cerebral Protection System Use During Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis

ObjectiveTo compare the clinical outcomes following transcatheter aortic valve replacement (TAVR) with and without the use of the Sentinel Cerebral Protection System (Sentinel CPS).BackgroundStroke occurs in 2–5% of patients at 30 days after TAVR and increases mortality >3 fold. The Sentinel CPS is the only FDA (Food and Drug Administration) approved cerebral embolic protection device.MethodsThe Cochrane Library, PubMed and Web of Science were searched for relevant studies for inclusion in the meta-analysis. Two authors independently screened and included studies comparing the clinical outcomes after TAVR with and without the Sentinel CPS. Risk of bias was assessed using the Cochrane tools (RoB2.0 and ROBINS-I).ResultsFour studies comparing 606 patients undergoing TAVR with Sentinel CPS to 724 without any embolic protection device were included. Sentinel CPS use was associated with lower rates of 30-day mortality [0.8% vs 2.7%; RR 0.34 (95% CI 0.12, 0.92) I² = 0%], 30-day symptomatic stroke [3.5% vs 6.1%; RR 0.51 (95% CI 0.29, 0.90) I² = 0] and major or life-threatening bleeding [3.3% vs 6.6%; RR 0.50 (0.26, 0.98) I² = 16%]. There was no significant difference between the two arms in the incidence of acute kidney injury [0.8% vs 1%; RR 0.85 (95% CI 0.22, 3.24) I² = 0%] and major vascular complications [5.1% vs 6%; RR 0.74 (0.33, 1.67) I² = 45%].ConclusionThe results suggest that Sentinel CPS use in TAVR is associated with a lower risk of stroke, mortality and major or life-threatening bleeding at 30 days.     

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.     

Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis of Randomized Controlled Trials

IntroductionTranscatheter aortic valve replacement (TAVR) has become the standard treatment option for patients with symptomatic severe aortic stenosis (AS) with high surgical risk and a reasonable option for intermediate surgical risk as an alternative to surgical aortic valve replacement (SAVR). The role of TAVR in lower risk patients is less established but has been the focus of recent randomized controlled trials (RCTs). We performed a meta-analysis of RCTs to assess TAVR outcomes among low surgical risk patients.Methods and resultsSystematic search of RCTs was done using PubMed, EMBASE, and Cochrane Library databases. Statistical analysis was performed with RevMan v5.3 software using a random effects model to report risk ratio (RR) with 95% confidence interval (CI). A total of three RCTs including 2698 patients (1375 TAVR and 1323 SAVR) were analyzed. Compared to SAVR, TAVR was not associated with all-cause mortality [RR 0.86 (95% CI 0.61–1.19); P = 0.36; I² = 8%] or stroke [RR 0.82 (0.48–1.43); P = 0.49; I² = 42%]. However, TAVR was significantly associated with lower risk of acute kidney injury [RR 0.27 (0.13–0.54); P = 0.0002; I² = 0%], new-onset atrial fibrillation [RR 0.26 (0.18–0.39); P < 0.00001; I² = 80%], and life-threatening or disabling bleeding [RR 0.35 (0.22–0.55); P < 0.00001; I² = 57%], but a higher risk of moderate-severe paravalvular leak [RR 4.40 (1.22–15.86); P = 0.02; I² = 26%] and permanent pacemaker insertion [RR 2.73 (1.41–5.28); P = 0.003; I² = 83%].ConclusionsThere is no difference in all-cause mortality or stroke between TAVR and SAVR, but TAVR is associated with lower risk of other perioperative complications except for moderate-severe paravalvular leak and the need for permanent pacemaker implantation.     

Brief opportunistic smoking cessation interventions: a systematic review and meta-analysis to compare advice to quit and offer of assistance

Aims This study aimed to assess the effects of opportunistic brief physician advice to stop smoking and offer of assistance on incidence of attempts to stop and quit success in smokers not selected by motivation to quit. Methods We included relevant trials from the Cochrane Reviews of physician advice for smoking cessation, nicotine replacement therapy (NRT), varenicline and bupropion. We extracted data on quit attempts and quit success. Estimates were combined using the Mantel–Haentszel method and heterogeneity assessed with the I² statistic. Study quality was assessed by method of randomization, allocation concealment and follow‐up blind to allocation. Results Thirteen studies were included. Compared to no intervention, advice to quit on medical grounds increased the frequency of quit attempts [risk ratio (RR) 1.24, 95% confidence interval (CI): 1.16–1.33], but not as much as behavioural support for cessation (RR 2.17, 95% CI 1.52–3.11) or offering NRT (RR 1.68, 95% CI: 1.48–1.89). In a direct comparison, offering assistance generated more quit attempts than giving advice to quit on medical grounds (RR 1.69, 95% CI: 1.24–2.31 for behavioural support and 1.39, 95% CI: 1.25–1.54 for offering medication). There was evidence that medical advice increased the success of quit attempts and inconclusive evidence that offering assistance increased their success. Conclusions Physicians may be more effective in promoting attempts to stop smoking by offering assistance to all smokers than by advising smokers to quit and offering assistance only to those who express an interest in doing so.     

Smoking and the risk of psoriasis in women: Nurses' Health Study II

Background

Psoriasis is a common, chronic, inflammatory skin disorder. Smoking may increase the risk of psoriasis, but no prospective data are available on this relation.

Methods

We prospectively examined over a 14-year time period (1991-2005) the relation between smoking status, duration, intensity, cessation, and exposure to secondhand smoke, and incident psoriasis in 78,532 women from the Nurses Health Study II. The primary outcome was incident, self-reported, physician-diagnosed psoriasis.

Results

We documented 887 incident cases of psoriasis. Compared with those who had never smoked, the multivariate relative risk (RR) of psoriasis was 1.78 (95% confidence interval [CI], 1.46 to 2.16) for current smokers and 1.37 (95% CI, 1.17 to 1.59) for past smokers. Compared with nonsmokers, the multivariate RR of psoriasis was 1.60 (95% CI, 1.31 to 1.97) for those who had smoked 11-20 pack-years and 2.05 (95% CI, 1.66 to 2.53) for those who had smoked ≥21 pack-years. Compared with never smokers, the multivariate RR of psoriasis was 1.61 (95% CI, 1.30 to 2.00) for those who quit smoking <10 years ago, 1.31 (95% CI, 1.05 to 1.64) for 10-19 years ago, and 1.15 (95% CI, 0.88 to 1.51) for ≥20 years ago. Prenatal and childhood exposure to passive smoke was associated with an increased risk of psoriasis.

Conclusions

In this prospective analysis, current and past smoking, and cumulative measures of smoking were associated with the incidence of psoriasis. The risk of incident psoriasis among former smokers decreases nearly to that of never smokers 20 years after cessation.     

Efficacy of endovascular embolization of arterial pseudoaneurysms in pancreatitis: A systematic review and meta-analysis

BackgroundThere is a significant variability in the reported outcomes following endovascular embolization of arterial pseudoaneurysms in pancreatitis. The objective of this systematic review and meta-analysis is to evaluate the efficacy of endovascular embolization of pancreatitis-related pseudoaneurysms.MethodsSearches of MEDLINE, EMBASE, and SCOPUS databases were performed through July 1, 2019 in accordance with PRISMA guidelines. All studies with ≥10 patients reporting technical success, clinical success, complications, and mortality were included. Generalized linear mixed method with random effects model was used for assessing pooled incidence rates and corresponding 95% confidence intervals (CIs).ResultsA total of 29 studies (n = 840 with 638 pseudoaneurysms) were included. The pooled incidence rates of pseudoaneurysms in acute and chronic pancreatitis were 0.05% and 0.03%, respectively (odds ratio, 0.91, 95% CI-0.24–3.43). The most common site of pseudoaneurysm was splenic artery (37.7%). The most common embolization agent was coil (n = 415). The follow up period was 54.7 months (range, 21 days to 40.5 months). Pooled technical success rate was 97% (95% CI-92-99%, I² 83%). Clinical success rates at ≤3 months, 3–12 months, and >12 months were 82% (95% CI-70-90%, I² 42%), 86% (95% CI-75-92%, I² 44%), and 88% (95% CI-83-91%, I² 0%), respectively. There was no significant difference in the technical or clinical success between acute and chronic pancreatitis on subgroup analysis. Mortality was lower in chronic pancreatitis (OR 4.27 (95% CI 1.35–13.53, I² 0%)). Splenic infarction was the most common complication (n = 47).ConclusionEndovascular embolization is associated with a high technical and clinical success.     

The association of chronic liver disorders with exacerbation of symptoms and complications related to COVID‐19: A systematic review and meta‐analysis of cohort studies

IntroductionThe aim of this review was to combine the results of published cohort studies to determine the exact association between chronic liver disorders, and the severe form of COVID‐19, and its associated complications.MethodsThis meta‐analysis employed a keyword search (COVID‐19 and chronic liver disorders) using PubMed (Medline), Scopus, Web of Sciences, and Embase (Elsevier). All articles related from January 2019 to May 2022 were reviewed. The STATA software was used for analysis.ResultsThe risk of death in COVID‐19 patients with chronic liver disorders was higher than in ones without the chronic liver disease (RR: 1.52; CI 95%: 1.46–1.57; I ²: 86.14%). Also, the risk of acute respiratory distress syndrome (ARDS) and hospitalization in COVID‐19 patients with chronic liver disorders was higher than in ones without the chronic liver disease ([RR: 1.65; CI 95%: 1.09–2.50; I ²: 0.00%] and [RR: 1.39; CI 95%: 1.23–1.58; I ²: 0.20%]). Also, the meta‐analysis showed cough, headache, myalgia, nausea, diarrhea, and fatigue were 1.37 (CI 95%: 1.20–1.55), 1.23 (CI 95%: 1.09–1.38), 1.25 (CI 95%: 1.04–1.50), 1.19 (CI 95%: 1.02–1.40), 1.89 (CI 95%: 1.30–2.75), 1.49 (CI 95%: 1.07–2.09), and 1.14 (CI 95%: 0.98–1.33), respectively, whereas the risk of all these symptoms was higher in COVID‐19 patients with chronic liver diseases than ones without chronic liver disorders.ConclusionThe mortality and complications due to COVID‐19 were significantly different between patients with the chronic liver disease and the general population.     

Risk factors for chronic and recurrent pancreatitis after first attack of acute pancreatitis

Objective: To study the outcome of acute pancreatitis and risk factors for recurrent and chronic pancreatitis in a population based cohort of patients with first-time acute pancreatitis.

Methods: All patients with first-time acute pancreatitis from 2006–2015 in Iceland were retrospectively evaluated. Medical records were scrutinized and relevant data extracted.

Results: 1102 cases of first-time acute pancreatitis were identified: mean age 56yr, 46% female, 41% biliary, 21% alcohol, 26% idiopathic, 13% other causes, mean follow-up 4yr. 21% had ≥1 recurrent acute pancreatitis which was independently related to alcoholic (vs. biliary hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.51–3.46), male gender (HR 1.48, 95%CI 1.08–2.04), and smoking (HR 1.62, 95%CI 1.15–2.28). 3.7% developed chronic pancreatitis. Independent predictors were recurrent acute pancreatitis (HR 8.79, 95%CI 3.94–19.62), alcoholic (vs. biliary HR 9.16, 95%CI 2.71–30.9), local complications (HR 4.77, 95%CI 1.93–11.79), and organ-failure (HR 2.86, 95%CI 1.10–7.42).

Conclusions: Recurrent acute pancreatitis occurred in one-fifth of patients. Development of chronic pancreatitis was infrequent. Both recurrent acute pancreatitis and chronic pancreatitis were related to alcoholic acute pancreatitis, while recurrent acute pancreatitis was associated with smoking and male gender, and chronic pancreatitis to recurrent acute pancreatitis, organ-failure, and local complications.     

Prasugrel vs Ticagrelor for DAPT in Patients with ACS Undergoing PCI: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

IntroductionDual antiplatelet therapy (DAPT) with a P2Y12 inhibitor added to aspirin is considered the standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Prasugrel and ticagrelor are commonly used P2Y12 inhibitors, and a few head-to-head randomized control trials (RCTs) have been performed. We performed a systematic review and meta-analysis of these RCTs to compare the efficacy and adverse effects between these two agents when used in patients with ACS undergoing PCI.MethodsWe searched PubMed/MEDLINE and Cochrane library for RCTs comparing prasugrel to ticagrelor in ACS. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, major bleeding, and all bleeding event. Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI).ResultsSix trials with 6807 patients were included. There were no significant difference of MACE (RR 0.93; 95% CI [0.72–1.20]; p = 0.59; I² = 26%), all-cause mortality (RR 0.92; 95% CI [0.73–1.17]; p = 0.51; I² = 0%), cardiovascular mortality (RR 0.99; 95% CI [0.75–1.31]; p = 0.96; I² = 0%), MI (RR 0.87; 95% CI [0.60–1.27]; p = 0.48; I² = 27%), stent thrombosis (RR 0.64; 95% CI [0.39–1.04]; p = 0.07; I² = 0%), major bleeding (RR 0.94; 95% CI [0.70–1.26]; p = 0.68; I² = 6%), and all bleeding event (RR 0.92; 95% CI [0.77–1.09]; p = 0.32; I² = 0%) for prasugrel compared with ticagrelor.ConclusionThere are no significant difference of MACE, all-cause mortality, cardiovascular mortality, MI, stent thrombosis, and bleeding between prasugrel and ticagrelor when added to aspirin among patients with ACS undergoing PCI.     

Cumulative Marijuana Use and Carotid Intima-Media Thickness at Middle Age: The CARDIA Study

BackgroundLong-term cardiovascular health effects of marijuana are understudied. Future cardiovascular disease is often indicated by subclinical atherosclerosis for which carotid intima-media thickness is an established parameter.MethodsUsing the data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of 5115 Black and white women and men at Year 20 visit, we studied the association between carotid intima-media thickness in midlife and lifetime exposure to marijuana (1 marijuana year = 365 days of use) and tobacco smoking (1 pack-year = 20 cigarettes/day for 365 days). We measured carotid intima-media thickness by ultrasound and defined high carotid intima-media thickness at the threshold of the 75th percentile of all examined participants. We fit logistic regression models stratified by tobacco smoking exposure, adjusting for demographics, cardiovascular risk factors, and other drug exposures.ResultsData was complete for 3257 participants; 2722 (84%) reported ever marijuana use; 374 (11%) were current users; 1539 (47%) reported ever tobacco smoking; 610 (19%) were current smokers. Multivariable adjusted models showed no association between cumulative marijuana exposure and high carotid intima-media thickness in never or ever tobacco smokers, odds ratio (OR) 0.87 (95% confidence interval [CI]: 0.63-1.21) at 1 marijuana-year among never smokers and OR 1.11 (95% CI: 0.85-1.45) among ever tobacco smokers. Cumulative exposure to tobacco was strongly associated with high carotid intima-media thickness, OR 1.88 (95%CI: 1.20-2.94) for 20 pack-years of exposure.ConclusionsThis study adds to the growing body of evidence that there might be no association between the average population level of marijuana use and subclinical atherosclerosis.     

Smoking,alcohol and family history of cancer as risk factors for small intestinal neuroendocrine tumors: a systematic review and meta-analysis

Objectives: Risk factors for small intestinal neuroendocrine tumors (SI-NETs) are not well understood. The aim of this systematic literature review was to identify risk factors for SI-NET and to further assess these by meta-analysis.

Material and methods: PubMed and abstracts from the ENETS and NANETS were searched for studies published until May 2015. Eligible studies were selected according to the PRISMA statement.

Results: Seven studies evaluating six individual populations were included (study accrual period 1980–2012) in the meta-analysis, involving 765 (range 17–325) cases and 502,282 (range 52–498,376) controls. All studies were case–control by design. The following risk factors were reported in ≥2 studies: family history of any cancer, family history of colorectal cancer, ever alcohol use and ever smoking. The pooled OR was 1.34 (95% CI: 1.12–1.60; p?<?.01; I²?=?0.0%) for family history of any cancer, 1.43 (95% CI: 1.15–1.79; p?<?.01; I²?=?0.0%) for family history of colorectal cancer, 1.04 (95% CI: 0.63–1.72; p?=?.87; I²?=?65.0%) for ever alcohol use and 1.40 (95% CI: 1.06–1.86; p?<?.05; I²?=?49.3%) for ever smoking.

Conclusions: Family history of any cancer, family history of colorectal cancer and history of ever smoking were associated with an increased risk of SI-NET by meta-analysis. Alcohol consumption was not a significant risk factor for SI-NET. However, the studies reporting smoking and alcohol had a high degree of heterogeneity. Therefore, further studies are needed for clarification of smoking and alcohol as risk factors for the occurrence of SI-NET.     

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.     

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.     

Decreased risk of esophageal cancer owing to cigarette and alcohol cessation in smokers and drinkers: a systematic review and meta-analysis

Smoking cigarettes and drinking alcoholic beverages are considered very important risk factors for adverse health effects, such as many types of cancer and cardiovascular disease. In this study, we evaluated the influence of smoking and drinking cessation on risk of esophageal cancer, by means of meta-analysis. We extracted 205 studies by conducting a systematic literature search. Thirty-five studies that estimated risk reduction following smoking cessation and 18 studies conducted following drinking cessation were identified in the literature review. Former smokers had a significantly lower summary risk ratio (RR) than current smokers [RR 0.74, 95% confidence interval (CI) 0.68–0.80]. In subgroup analysis of Japanese smokers, squamous cell carcinoma, and adenocarcinoma, RRs for former smokers versus current smokers were 0.65 (95% CI 0.51–0.83), 0.60 (95% CI 0.50–0.72), and 0.93 (95% CI 0.84–1.03), respectively. The summary RR between former alcohol drinkers and current drinkers was not significant (RR 1.09, 95% CI 0.94–1.26). In our analysis of time since drinking cessation, drinkers who had stopped consuming alcohol for 5 years or more had a significantly lower summary RR than current drinkers (RR 0.78, 95% CI 0.66–0.93). Summary RR for drinkers who stopped for 10 years or more versus current drinkers was 0.65 (95% CI 0.57–0.74). Our investigation found that smoking cessation lowers esophageal cancer incidence. We also found that esophageal cancer incidence risk could be decreased in current drinkers by cessation of alcohol consumption for 5 years or more.