Does Famotidine Reduce the Risk of Progression to Severe Disease,Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis

Background

Famotidine was reported to potentially provide benefits to Coronavirus Disease 2019 (COVID-19) patients. However, it remains controversial whether it is effective in treating COVID-19.

Aims

This study aimed to explore whether famotidine use is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

Methods

This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42020213536). A comprehensive search was performed to identify relevant studies up to October 2020. I-squared statistic and Q-test were utilized to assess the heterogeneity. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated through the random effects or fixed effects model according to the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also conducted.

Results

Five studies including 36,635 subjects were included. We found that famotidine use was associated with a statistically non-significant reduced risk of progression to severe disease, death, and intubation for Coronavirus Disease 2019 (COVID-19) patients (pooled RR was 0.82, 95% CI?=?0.52–1.30, P?=?0.40).

Conclusion

Famotidine has no significant protective effect in reducing the risk of developing serious illness, death, and intubation for COVID-19 patients. More original studies are needed to further clarify whether it is associated with reduced risk of the severity, death, and intubation for COVID-19 patients.

     

Clopidogrel With Proton Pump Inhibitors: Safe or Not?

Gastrointestinal (GI) bleeding is a serious complication associated with use of antiplatelet therapy, and proton pump inhibitors (PPIs) are known to be beneficial in decreasing such risk. Several studies in the recent past have suggested concerns regarding interaction between clopidogrel and PPIs, presumably due to inhibition of clopidogrel activity and thus attenuation of its antiplatelet activity. A web-based literature and guidelines search was done using the keywords "clopidogrel," "omeprazole," "proton pump inhibitors" and "interaction." Of the available results, relevant studies (n = 11) were then systematically reviewed and summarized. The studies were categorized based on their retrospective or prospective nature. Most of the retrospective, observational studies suggested a link between the 2; however, recent prospective studies have shown no interaction, as well as a positive influence of PPIs in preventing the GI side effects of antiplatelet therapy. There is currently insufficient clinical evidence to suggest interaction between clopidogrel and PPIs and decision to add PPI therapy to clopidogrel should be guided by its clinical indications rather than as a routine prophylactic measure.     

Cost-Effectiveness of Chemoprevention with Proton Pump Inhibitors in Barrett’s Esophagus

Background

Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus. PPIs are prescribed for virtually all patients with Barrett’s esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated.

Aim

The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett’s esophagus without reflux.

Methods

We designed a state-transition Markov microsimulation model of a hypothetical cohort of 50-year-old white men with Barrett’s esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios.

Results

Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %.

Conclusions

Chemoprevention with PPIs in patients with Barrett’s esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett’s esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma.     

Alcohol for the Prevention of Type 2 Diabetes Mellitus?

While diabetes mellitus is recognized clinically as a complication of alcohol dependence, in the last 15 years several large prospective studies have demonstrated a significant reduction in risk of incident type 2 diabetes in moderate drinkers. In this article, we review prospective studies on the association between alcohol consumption and incidence of diabetes. Few prospective studies have demonstrated an unequivocal positive association between alcohol use and incidence of diabetes. A number of large prospective studies have now demonstrated an inverse association: typically a 40% risk reduction after controlling for other major risk factors. Studies based on cohorts of health professionals have not demonstrated an increased risk of diabetes with heavier consumption, but these cohorts contain few heavy drinkers. Some cohorts drawn from the general population have shown a J- or U-shaped association between level of alcohol consumption and incidence of diabetes. Frequent moderate drinking has been reported to be associated with lower risk than infrequent drinking. There have been contradictory reports on the importance of the type of alcoholic beverage and whether the effect of alcohol differs according to the bodyweight of the drinker. We conclude that like many other chronic diseases, there is a delicate balance between the harmful and beneficial effects of alcohol on the incidence of diabetes. In moderate amounts, drinking is associated with a reduced risk of diabetes, whereas in higher amounts with an increased risk.     

Does Root Development Status Affect the Outcome of Tooth Autotransplantation? A Systematic Review and Meta-Analysis

Background: Tooth autotransplantation is defined as the surgical repositioning of an autogenous tooth in another surgical site within the same individual. Aim: The aim of this research was to analyze the outcome of tooth transplantation using immature donor teeth compared with closed apex teeth and to compare differences between donor tooth positions on the arch. Methods: Electronic and manual literature searches were performed in different databases, including the National Library of Medicine (MEDLINE), EMBASE (OVID), Cochrane Central (CENTRAL), and the digital library of the Universitat Internacional de Catalunya (UIC University) from 1978 to March 2021. Studies were selected when they fulfilled the following criteria: only human prospective clinical studies, minimum sample size of 10 patients, minimum follow-up of 1 year, studies reporting or with at least deducible data on survival rates, immediate tooth autotransplantation with completed or incomplete root formation, and publications in the English language. A meta-analysis of random effects was developed to estimate the global effect measure of the survival rate, success rate, and root resorption involving the total sample, as well as open- and closed-apex groups. Results: Twenty-four articles were eligible for analysis. The Cohen’s kappa corresponding to this review was 0.87, and the risk assessment was considered low–moderate for the included studies. Overall survival and success rates were 95.9% and 89.4%, respectively, with a mean follow-up of 4 years and an overall mean age of 25.2 ± 12.3 years. Closed apex teeth showed a survival rate of 3.9% lower than that of open apex teeth. Higher complication rates were found for both inflammatory external root resorption and replacement root resorption in the closed-apex group, without reaching statistical significance. Conclusions: Tooth autotransplantation is a viable treatment alternative, regardless of the apical condition, with high survival and success rates after a mean follow-up of 4 years. Open-apex donor teeth could be considered the gold-standard option, showing lower complication rates when compared to closed-apex donor teeth. Future randomized controlled clinical studies are needed to examine the long-term prognosis of this technique.     

A Systematic Review and Meta-Analysis of the Treatment for Barrett’s Esophagus

As evidence-based strategies to the clinical management of Barrett’s esophagus (BE) are lacking, we have carried out a systematic review and meta-analysis of all published randomized controlled trials with the aim of evaluating the value of different approaches in the treatment of BE. Searches were conducted in the databases PUBMED, EMBASE, and Cochrane Library. Thirteen randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were assessed in more detail. Based on our search, neither the pharmacological nor surgical therapies currently available for reflux appear to achieve complete regression of BE and the elimination of the cancer risk associated with it. In contrast, endoscopic ablative techniques are capable of achieving endoscopic and histological reversal of BE, with ablation by argon plasma coagulation (APC) appearing to be more effective than treatment with photodynamic therapy (PDT) [odds ratio (OR) 3.46, 95% confidence interval (CI) 1.67–7.81, P = 0.0008]. There was no statistically significant difference between APC and multipolar electrocoagulation (MPEC) in terms of the efficacy to achieve regression of BE (OR 2.01, 95% CI 0.77–5.23, P = 0.15). In conclusion, there have been only a limited number of randomized controlled trials that compare treatments for BE. The pharmacological therapy, antireflux surgery, and endoscopic ablative techniques are promising in terms of treating BE, but the studies carried out to date have had no adequate power to assess the effect of treatment on reducing and preventing progression to adenocarcinoma.     

Is POEM the Answer for Management of Spastic Esophageal Disorders? A Systematic Review and Meta-Analysis

Background and Aims

Spastic esophageal disorders (SEDs) include spastic achalasia (type III), diffuse esophageal spasm (DES), and nutcracker/jackhammer esophagus (JH). Per-oral endoscopic myotomy (POEM) has demonstrated efficacy and safety in the treatment of achalasia. Recently, POEM has been indicated for the treatment of SEDs. We conducted a systematic review and meta-analysis to determine the clinical success and safety of POEM in SEDs.

Methods

We searched several databases from 01/01/2007 to 01/10/2016 to identify studies (with five or more patients) on POEM for the treatment of SEDs. Weighted pooled rates (WPRs) for clinical success and adverse events (AEs) were calculated for all SEDs. Clinical success was defined as Eckardt scores of ≤3 and/or improvement in severity of dysphagia based on achalasia disease-specific health-related quality of life questionnaire. The WPRs for clinical success and AEs were analyzed using fixed- or random-effects model based on heterogeneity. The proportionate difference in clinical success and post-procedure adverse event rates among individual types of SEDs was also calculated.

Results

A total of eight observational studies with 179 patients were included in the final analysis. Two studies were of good quality and six were of fair quality based on the National Institutes of Health quality assessment tool. The WPR with 95% confidence interval (CI) for cumulative clinical success of POEM in all SEDs was 87% (78, 93%), I ² = 37%. The total number of patients for individual disorders, i.e., type III achalasia, JH, and DES, was 116, 37, and 18, respectively. The WPRs for clinical success of POEM for type III achalasia, DES, and JH were 92, 88, and 72%, respectively. Proportion difference of WPR for clinical success was significantly higher for type III achalasia in comparison with JH (20%, P = 0.01). The WPR with 95% CI for AEs of POEM in all SEDs was 14% (9, 20%), I ² = 0%. The WPRs for post-procedure adverse events for type III achalasia, DES, and JH were 11, 14, and 16%, respectively. There was no difference in safety of POEM among individual SEDs.

Conclusion

POEM is an effective and safe therapeutic modality for the treatment of spastic esophageal disorders.

     

Do Calcium Channel Blockers Increase the Risk of Cancer?

Calcium channel blockers can block calcium signals that trigger cell differentiation and apoptosis, which are important mechanisms of cancer growth regulation. To ascertain whether calcium channel blocker use was associated with an increased risk of cancer, 750 hypertensive persons age ≥ 71 years, with no history of cancer at baseline, were followed from 1988 through 1992. The patients were using either β-blockers, angiotensin converting enzyme inhibitors or calcium channel blockers (verapamil, nifedipine, and diltiazem; mainly of the short-acting variety). Compared to β-blockers (n = 424, 28 events), after adjusting for age, gender, race, smoking, body mass index, and number of hospital admissions not related with cancer, the relative risks of cancer (95% confidence interval) for angiotensin converting enzyme inhibitors (n = 124, 6 events) and calcium channel blockers (n = 202, 27 events) were 0.73 (0.30 to 1.78) and 2.02 (1.16 to 3.54), respectively. These findings indicate that calcium channel blocker therapy might increase the risk of cancer. New data are needed in patients using modern calcium channel blocker agents with more gradual absorption. This report should encourage further study of cancer outcomes in elderly patients who are vulnerable to cancer and who are receiving calcium channel blockers. Am J Hypertens 1996;9:695–699     

Projected Cardiovascular Impact of Obesity in Children and Adolescents: Will Obesity Increase the Cardiovascular Risk of Women to That of Men?

Far too many girls suffer from overweight, obesity, and even severe obesity in childhood and adolescence. The early establishment of excess adiposity is associated with the development of cardiovascular disease (CVD) through complex metabolic aberrations that manifest as components of the metabolic syndrome at young ages. When combined with exposure to other independent CVD risk factors, overweight and obese girls face an elevated risk of cardiovascular morbidity and mortality in adulthood. Additionally, due to their reproductive capacity, women face a different series of risks with regards to the development of CVD compared with men. The risk of CVD accumulates across the lifespan of women, and without a special emphasis in terms of prophylaxis and treatment in younger girls and women, their risk of CVD is likely to equal or even surpass that of men in the future.     

Do Statins Impair Cognition? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND

In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.

METHODS

We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.

RESULTS

We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95 % confidence interval, CI, −0.01 to 0.03, p = 0.42) or Alzheimer’s disease subjects (standardized mean difference −0.05, 95 % CI −0.19 to 0.10, p = 0.38).

CONCLUSIONS

Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-014-3115-3) contains supplementary material, which is available to authorized users.KEY WORDS: statins, systematic review, meta-analysis, randomized control trials, cognition     

Is the Risk and Nature of CVD the Same in Type 1 and Type 2 Diabetes?

The incidence of both type 1 and type 2 diabetes is increasing globally, most likely explained by environmental changes, such as changing exposures to foods, viruses, and toxins, and by increasing obesity. While cardiovascular disease (CVD) mortality has been declining recently, this global epidemic of diabetes threatens to stall this trend. CVD is the leading cause of death in both type 1 and type 2 diabetes, with at least a two- to fourfold increased risk in patients with diabetes. In this review, the risk factors for CVD are discussed in the context of type 1 and type 2 diabetes. While traditional risk factors such as dyslipidemia, hypertension, and obesity are greater in type 2 patients than in type 1 diabetes, they explain only about half of the increased CVD risk. The role for diabetes-specific risk factors, including hyperglycemia and kidney complications, is discussed in the context of new study findings.     

A Systematic Review and Meta-Analysis of Medical Students’ Perspectives on the Engagement in Research

Engaging students in active learning lies at the center of effective higher education. In medical schools, students’ engagement in learning and research has come under increasing attention. The objective of this study was to synthesize evidence on medical students’ perspectives on the engagement in research. We performed a systematic review and meta-analysis.Relevant studies were searched in electronic databases. The methodological quality of the included studies was assessed. Overall, 14 observational studies (with 17 data sets) were included. In general, many studies did not use the same questionnaires and the outcome measurements were not consistently reported; these presented some difficulties in pooling the results. Whenever data permitted, we performed pooled analysis for the 4 education outcomes. A Bayesian meta-analytical approach was supplemented as a measure of uncertainty.A pooled analysis showed that 74% (95% confidence interval [CI]: 1.57%–11.07%; I²: 95.2%) of those students who engaged in research (while at the medical school) had positive attitudes toward their research experiences, whereas 49.5% (95% CI: 36.4%–62.7%; I²: 93.4%) had positive attitudes toward the study of medical sciences, 62.3% (95% CI: 46.7%–77.9%; I²: 96.3%) had self-reported changes in their practices, and 64% (95% CI: 30.8%–96.6%; I²: 98.5%) could have published their work. There was substantial heterogeneity among studies. We acknowledged the caveats and the merit of the current review.Findings showed that engagement in research resulted in favorable reactions toward research and academic learning. Future well-designed studies using standardized research tools on how to engage students in research are recommended.