No Association Linking Short-Term Proton Pump Inhibitor Use to Dementia: Systematic Review and Meta-analysis of Observational Studies.

INTRODUCTION: Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support. METHODS: We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach. RESULTS: We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88-1.37); for Alzheimer dementia only, it was 1.06 (0.72-1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84-1.25) and for Alzheimer dementia only 0.96 (0.82-1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low. DISCUSSION: We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.

Time for a Changing of Guard: From Minimally Invasive Surgery to Endoscopic Drainage for Management of Pancreatic Walled-off Necrosis.

BACKGROUND AND AIMS: Endoscopic drainage (ED) with or without necrosectomy, and minimally invasive surgical necrosectomy (MISN) have been increasingly utilized for treatment of symptomatic sterile and infected pancreatic walled-off necrosis (WON). We conducted this systematic review to compare the safety of ED with MISN for management of WON. METHODS: We searched several databases from inception through November 9, 2017 to identify comparative studies evaluating the safety of ED versus MISN for management of WON. MISN could be performed using video-assisted retroperitoneal debridement or laparoscopy. We evaluated difference in mortality, major organ failure, adverse events, and length of hospital stay. RESULTS: Six studies (2 randomized controlled trials and 4 observational studies) with 641 patients (326 ED and 315 MISN) were included in this meta-analysis. Rates of mortality for ED and MISN were 8.5% and 14.2%, respectively. Pooled odds ratio (OR) with 95% confidence interval was 0.59 (0.35-0.98), I=0% in favor of ED. On subgroup analysis: no difference in mortality was seen based on randomized controlled trials [OR, 0.65 (0.08-5.11)], while ED had improved survival in observational studies [OR, 0.49 (0.27-0.89)]. Development of new major organ failure rates after interventions were 12% and 54% for ED and MISN, respectively. Pooled OR was 0.12 (0.06-0.31), I=25% in favor of ED. For adverse events, pooled OR was 0.25 (0.10-0.67), I=70% in favor of ED. There was no difference in risk of bleeding [OR, 0.68 (0.44-1.05)], while ED was associated with a significantly lower rate of pancreatic fistula formation [OR, 0.20 (0.11-0.37)], I=0%. Length of stay was also lower with ED, pooled mean difference was -21.07 (-36.97 to -5.18) days. CONCLUSIONS: When expertise is available, ED is the preferred invasive management strategy over MISN for management of WON as it is associated with lower mortality, risk of major organ failure, adverse events, and length of hospital stay.

Rifaximin for the prevention of spontaneous bacterial peritonitis and hepatorenal syndrome in cirrhosis: a systematic review and meta-analysis.

Prophylactic antibiotics have been recommended in patients with a previous history of spontaneous bacterial peritonitis (SBP). Recently, there has been interest in the use of rifaximin for the prevention of SBP and hepatorenal syndrome (HRS). We conducted a meta-analysis to evaluate this association of rifaximin. We searched several databases from inception through 24 January 2017, to identify comparative studies evaluating the effect of rifaximin on the occurrence of SBP and HRS. We performed predetermined subgroup analyses based on the type of control group, design of the study, and type of prophylaxis. Pooled odds ratios (ORs) were calculated using a random effects model. We included 13 studies with 1703 patients in the meta-analysis of SBP prevention. Pooled OR [95% confidence interval (CI)] was 0.40 (95% CI: 0.22-0.73) (I=58%). On sensitivity analysis, adjusted OR was 0.29 (95% CI: 0.20-0.44) (I=0%). The results of the subgroup analysis based on type of control was as follows: in the quinolone group, pooled OR was 0.42 (95% CI: 0.14-1.25) (I=55%), and in the no antibiotic group, pooled OR was 0.40 (95% CI: 0.18-0.86) (I=64%). However, with sensitivity analysis, benefit of rifaximin was demonstrable; pooled ORs were 0.32 (95% CI: 0.17-0.63) (I=0%) and 0.28 (95% CI: 0.17-0.45) (I=0%) for the comparison with quinolones and no antibiotics, respectively. Pooled OR based on randomized controlled trials was 0.41 (95% CI: 0.22-0.75) (I=13%). For the prevention of HRS, the pooled OR was 0.25 (95% CI: 0.13-0.50) (I=0%). Rifaximin has a protective effect against the development of SBP in cirrhosis. However, the quality of the evidence as per the GRADE framework was very low. Rifaximin appeared effective for the prevention of HRS.

Meta-analysis of the performance of ultrathin vs. standard colonoscopes.

Background and study aims Colonoscopy should reliably intubate the cecum with minimal patient discomfort and without complications. Use of thinner endoscopes to overcome pain during the procedure has shown promise. However, the use of thinner scopes could lead to excess looping and difficulty with therapeutic procedures. The aim of this meta-analysis was to analyze the performance of ultrathin colonoscopes (UTC) and standard colonoscopes for routine colonoscopy. Patients and methods We searched several electronic databases for all randomized controlled trials and nonrandomized (prospective) studies that compared the efficacies of UTC (diameter ≤ 9.8 mm) and standard colonoscopes. We used fixed effect or random effects models to compare cecal intubation rate, cecal intubation time, pain score, and polyp and adenoma detection rates using standard mean differences (SMD) or odds ratios (OR) with 95 % confidence intervals (CI). Results Seven studies (2191 patients) met the inclusion criteria. There was no significant heterogeneity among studies except for pain scores. The cecal intubation rate was higher with UTC (OR 2.30; 95 %CI 1.31 to 4.03). There was no difference in the cecal intubation time between UTC and standard colonoscopes. Pain scores were significantly lower with UTC than with standard colonoscopes (SMD - 0.59, 95 %CI - 0.93 to - 0.25). Polyp and adenoma detection rates were similar for both types of colonoscope. Conclusion Use of UTC appears to improve the cecal intubation rate and reduce abdominal pain but does not affect polyp detection. Future trials are needed to evaluate the therapeutic performance of UTC vs. standard colonoscopes.

Endoscopic Ultrasound-Guided Biliary Drainage: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Variable success and adverse event rates have been reported for endoscopic ultrasound-guided biliary drainage (EUS-BD) utilizing either extrahepatic or intrahepatic approach. We aimed to conduct a proportion meta-analysis to evaluate the cumulative efficacy and safety of EUS-BD and to compare the two approaches and transluminal methods of EUS-BD. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus from January 2001 through January 5, 2015, to identify studies reporting technical success and adverse events of EUS-BD. A sample size of more than 20 patients was a further criterion. Weighted pooled rate (WPR) for technical success and post-procedure complications was calculated for overall studies and predefined subgroups. Pooled odds ratios were calculated for technical success and adverse events for two approaches and transluminal methods of EUS-BD for distal common bile duct (CBD) strictures. RESULTS: The WPR with 95% confidence interval (CI) for technical success and post-procedure adverse events was 90% (86, 93%) and 17% (13, 22%), respectively, with considerable heterogeneity (I(2) = 77%). For high-quality studies, the WPR for technical success was 94% (91, 96 %), I(2) = 0% and WPR for post-procedure adverse event was 16% (12, 19%), I(2) = 39%. In meta-regression model, distal CBD stricture and transpapillary drainage were associated with higher technical success and intrahepatic access route was associated with higher adverse event rate. There was no difference in technical success using either approach OR 1.27 (0.52, 3.13), I(2) = 0% or transluminal method OR 1.32 (0.51, 3.38), I(2) = 0%. However, the extrahepatic approach appeared significantly safer as compared to the intrahepatic approach OR 0.35 (0.19, 0.67), I(2) = 27%. Likewise, choledochoduodenostomy was found to have less adverse events as compared to hepaticogastrostomy, OR 0.40 (0.18, 0.87), I (2) = 0%. CONCLUSION: In cases of failure of traditional ERC to achieve biliary drainage, EUS-BD appears to be an emerging therapeutic modality with a cumulative success rate of 90% and cumulative adverse events rate of 17%. Randomized controlled trials are required to further evaluate the efficacy and safety of the procedure along with the comparison to traditional modalities like percutaneous transhepatic biliary drainage.

Does endoscopic sphincterotomy reduce the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis after biliary stenting? A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic biliary sphincterotomy (ES) is often carried out prior to placement of a biliary stent apparently to reduce the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, the protective effect of ES prior to biliary stenting is controversial. The objective of this meta-analysis is to compare the risk of PEP and other complications after the placement of biliary stent with or without ES in patients with biliary obstruction and bile leak. METHODS: We carried out a systematic search in several electronic databases for randomized controlled trials (RCT) and observational studies (OS) comparing the risk of PEP after biliary stenting with or without ES. The Mantel-Haenszel method was used to pool data of adverse outcomes into fixed or random effect model meta-analyses. RESULTS: Seventeen studies (five RCT and 12 OS) with a total of 2710 patients met the inclusion criteria. No significant difference was observed in the risk of PEP with biliary stenting with and without ES (RD -0.01; 95% confidence interval [CI] -0.03, 0.01). In a subgroup analysis of stenting for biliary obstruction, no difference in the risk of PEP was observed with or without ES. However, ES was associated with lower risk of PEP in patients undergoing biliary stenting for bile leak (RD -0.05; CI -0.10, -0.01). CONCLUSIONS: ES shows risk reduction in prevention of PEP in patients undergoing endoscopic stenting for bile leak. However, placement of biliary stent without ES is not associated with an increased risk of PEP in patients with distal bile duct obstruction with involvement of pancreatic duct.

Systematic review and meta-analysis of the possible association between pharmacological gastric acid suppression and spontaneous bacterial peritonitis.

BACKGROUND: Observational studies have presented conflicting results with regard to an association between gastric acid suppression and spontaneous bacterial peritonitis (SBP). Our aim was to carry out a meta-analysis investigating the possible association between the use of proton pump inhibitors or H2-receptor antagonists and SBP. METHODS: We searched several databases from inception through 15 December 2014 to identify observational studies that provided data on the association of gastric acid suppression with SBP as their primary outcome, and carried out random effects meta-analyses. RESULTS: Fourteen observational studies (six case-control and eight cohort) evaluating the association between proton pump inhibitors and SBP revealed a pooled odds ratio (OR) of 2.32 [95% confidence interval (CI) 1.57-3.42, I(2)=82%]. The subgroup analysis based on study design revealed a pooled OR of 2.52 (95% CI 1.71-3.71, I(2)=16%) for case-control studies, and a pooled OR of 2.18 (95% CI 1.24-3.82, I(2)=89%) for cohort studies. Sensitivity analysis including only the peer-reviewed publications in the cohort subgroup revealed a pooled OR of 1.49 (95% CI 1.15-1.95, I(2)=27%). The subgroup analysis for high-quality studies revealed a pooled OR of 1.49 (95% CI 1.19-1.88, I(2)=21%). The pooled OR for H2-receptor antagonists and SBP was 1.93 (95% CI 1.15-3.24, I(2)=0%). CONCLUSIONS: There appear to be statistically significant, but quantitatively small, associations between gastric acid suppression and SBP. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Furthermore, the quality evidence in support of the association, as per the GRADE framework, was very low.

Cardioprotective role of ischemic postconditioning in acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests that ischemic postconditioning (IPoC) may reduce the extent of reperfusion injury. We performed a meta-analysis of randomized controlled trials, which compared the role of IPoC during primary percutaneous coronary intervention (PCI) to PCI alone (control group) in ST-segment elevation myocardial infarction. METHODS: Several databases were searched, which yielded 19 studies. The outcomes of interest were measures of myocardial damage (serum cardiac enzymes and infarct size by imaging) and left ventricular function (left ventricular ejection fraction and wall motion score index). Mean difference (MD) and standardized mean difference (SMD) were used to assess the treatment effect. An inverse variance method was used to pool data into a random-effects model. RESULTS: Ischemic postconditioning demonstrated a decrease in serum cardiac enzymes (SMD -0.48, 95% CI -0.92 to -0.05, I(2) = 92%), reduction in infarct size by imaging (SMD -0.30, 95% CI -0.58 to -0.01, I(2) = 80%), wall motion score index (MD -0.19, 95% CI -0.29 to -0.09, I(2) = 44%), and showed improvement in left ventricular ejection fraction (IPoC 52 ± 0.4, control 49.7 ± 0.4) (MD 2.78, 95% CI 0.66-4.91, I(2) = 69%). All included studies were limited by high risk of performance and publication bias. CONCLUSIONS: Ischemic postconditioning during PCI in ST-segment elevation myocardial infarction appears to be superior to PCI alone in reduction of both myocardial injury or damage and improvement in global and regional left ventricular function. The effect seems to be more pronounced when a greater myocardial area is at risk. Given the limitations of the current available evidence, additional data from large randomized controlled trials are warranted.