Comparative maintenance performance of all biologic agents and small molecules in ulcerative colitis: a network meta-analysis.

BACKGROUND AND AIMS: Βiologic agents and small molecules have expanded the therapeutic armamentarium of moderate to severe ulcerative colitis (UC). However, their comparative efficacy and safety performance as maintenance treatments have not been sufficiently explored. We performed a systematic review and network meta-analysis (NWM) to assess the comparative efficacy and safety of all approved and emerging treatments for maintenance in moderate to severe UC. METHODS: We searched Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through April 2023. The primary endpoint was clinical remission at the end of the maintenance therapy. Data were analyzed by means of a Bayesian NWM. The ranking probability concerning efficacy and safety was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: There were 20 eligible RCTs with 7660 patients randomized to 20 treatments. RCTs were grouped into two study designs, that is, re-randomization of patients after an induction period and treat-through patients. Concerning efficacy, in re-randomized patients, upadacitinib 30 mg/day was ranked first (SUCRA 94.9%) whereas in treat-through patients etrasimod 2 mg/day was ranked first (SUCRA 91.1%). The integrated efficacy-safety hierarchical analysis, showed that tofacitinib 10 mg had the best efficacy-safety therapeutic profile in re-randomized patients, whereas in treat-through patients infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety profile. CONCLUSION: For maintenance treatment, in moderate to severe UC, this NWM showed that upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked best for efficacy in re-randomized and treat-through patients respectively. Tofacitinib 10 mg/day and infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety therapeutic profile in re-randomized and treat-through patients respectively.

[THE IMPACT OF REGULATION AND CENTRAL MANAGEMENT ON PATIENT SAFETY IN ISRAEL].

INTRODUCTION: An adverse event is defined as an unwanted and unexpected occurrence in a medical process that may end in harm to the patient. In the USA the number of deaths due to failures reaches 253,000 per year. In Israel, over 10,000 deaths occur per year due to errors in the medical treatment of hospitalized patients, the third most common cause of death after heart disease and cancer. The main cause of failures in medical diagnosis and treatment is the complexity of the medical profession. A large number of caregivers in different medical disciplines are needed to treat one patient, therefore there are many errors, especially regarding communication between therapists. The Israeli health system has been operating with a budget deficit for many years and an addition of at least NIS 20 billion is needed to bring it to optimal functioning. The number of doctors, nurses, and hospital beds per 1000 inhabitants is significantly less than the average of the OECD countries. When there was a 30% increase in the population of Israel it was necessary to enhance the existing situation, with the addition of 7700 hospital beds, but only 1400 were added. This caused a decrease from 2.1 beds per 1000 residents to 1.8 beds per 1000 residents. There is an urgent need to change the elements of treatment safety in the Ministry of Health's strategic plan. An administration for quality, treatment safety, risk management in medicine, and accreditation should be established which, in addition to the care quality division, will include a safety division with investigation and monitoring units and will prepare strategic improvement plans, and a university-level research institute with researchers, computing, statistics, and information gathering units. The institute will receive all reports of adverse events, results of investigations, inspection committees, control and quality committees, relevant verdicts, and updated literature reviews, for research and systemic learning. Strategic plans will be prepared to prevent failures in diagnosis and medical treatment, leading to a decrease in mortality due to adverse events and the significant expenses involved.

The Effects of Gluten-free Diet on Body Mass Indexes in Adults with Celiac Disease: A Systematic Review and Meta-analysis of Observational Studies.

GOALS AND BACKGROUND: Gluten-free diet (GFD) includes a higher intake of sugars and fats. Previous studies have investigated its effect on body mass index (BMI) in celiac disease (CD) patients but had contradictive conclusions. Thus, we conducted a systematic review and meta-analysis examining the effect of GFD on BMI in CD patients. STUDY: Systematically, we conducted literature research using Medline, Scopus, and Embase, and we identified 1565 potential studies/abstracts. Only studies of patients with CD under a GFD with recorded BMI before and after dietary intervention were included. Subgroup analyses based on study design and BMI categories were performed. We calculated the pooled odds ratios (ORs) and 95% confidence intervals (Cls) for the number of patients in each BMI group according to the World Health Organization (WHO) definitions after GFD using fixed and random effect meta-analysis. RESULTS: The analysis included 10 studies and 38 sub-studies/data sets, which encompassed 2450 patients from 5 countries. We found nonsignificant odds for changing the BMI group (pooled OR 0.972, 95% CI: 0.858-1.101, P=0.65) after GFD. However, looking specifically at BMI subgroups, we found higher odds for BMI category change after GFD in underweight patients (OR 0.588, 95% CI: 0.479-0.723, P <0.001), and overweight patients,25

Crisis management for Patient Safety Officers: lessons learned from the Covid-19 pandemic.

BACKGROUND: There is no consensus for the role definition for Patient Safety Officers (PSOs) in healthcare during pandemics or other crises as opposed to their routine activities. This study aimed to examine the contribution of personality traits and systemic factors on the performance of PSOs during the pandemic, and to compare these variables during the first and third waves of the Covid-19 pandemic in Israel. METHODS: This cross-sectional study invited 117 PSOs to complete a questionnaire addressing their role during the Covid-19 pandemic. The questionnaire included items concerning: Personal and socio-demographic characteristics; Uncertainty; Personal initiative; Burnout; Professional functioning; Patient Safety and Risk Management policies and practices; Organizational functioning; and Personal Involvement in risk management activities. Qualitative data was collected by two open-ended questions. RESULTS: A total of 78 PSOs (67%) completed the questionnaire. The results revealed that many PSOs reduced their involvement in risk management processes or even left their position temporarily in order to return to their primary specialization as clinicians. Only 51.3% and 57.7% reported practicing risk management in the first and third waves, respectively. The three main factors that kept PSOs functioning were managerial support, mobilization of their team, and the belief in the importance of their position. CONCLUSIONS: A crisis generates uncertainty, a plethora of frequent and urgent tasks, and the need to adapt policy to changing circumstances and to the increased risks. The risk manager must be a member of the crisis management team and participate in every important discussion in order to represent essential staff and patient safety issues and ensure that these are fully addressed already in the early stages of planning.

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg).

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Difference Between COVID-19 Alpha Variant B.1.1.7 and the Original Virus in Gastrointestinal Symptoms and Mortality: Does a Negative Correlation Exist?

BACKGROUND: Up to half the patients diagnosed with acute coronavirus disease 2019 (COVID-19) presented with gastrointestinal symptoms. Gastric mucosal cells, enterocytes, and colonocytes express the viral entry receptor angiotensin-converting enzyme 2 (ACE2) and coreceptor transmembrane protease serine 2 (TMPRSS2) and are prone to infection. Direct infection of gastrointestinal epithelial cells has been demonstrated. COVID-19 disease was first diagnosed in Israel at the end of February 2020 with 842,536 confirmed cases and 6428 deaths by the end of June 2021. In our multicenter, retrospective cohort study, we looked for gastrointestinal signs and symptoms in two periods and correlated them with mortality. Period 1 included the first and second waves and the original virus. Period 2 represented the third wave and the alpha variant. OBJECTIVES: To reveal gastrointestinal signs and symptoms in two periods and correlate them with mortality. METHODS: From 22,302 patients hospitalized in general medical centers, we randomly selected 3582 from Period 1 and 1106 from Period 2. The study was performed before vaccinations were available. RESULTS: Gastrointestinal signs and symptoms, diarrhea, vomiting, abdominal pain, and taste/smell loss were significantly more prevalent during Period 1. Thirty-day mortality and in-hospital mortality were significantly higher in Period 2 than in Period 1, 25.20% vs. 13.68%, and 21.17% vs. 12.87%, respectively (P < 0.001). CONCLUSIONS: Thirty-day mortality and in-hospital mortality rates were 1.84 and 1.64 times higher from 6 November 2020 to 15 January 2021, the alpha variant, and in negative correlation with gastrointestinal symptoms.

Mucin Expression in the Small Bowel of Celiac Disease: A Systematic Review.

BACKGROUND: Mucins, heavily glycosylated glycoproteins, are synthesized by mucosal surfaces and play an important role in healthy and malignant states. Changes in mucin synthesis, expression, and secretion may be a primary event or may be secondary to inflammation and carcinogenesis. OBJECTIVES: To assess current knowledge of mucin expression in the small bowel of celiac disease (CD) patients and to determine possible associations between mucin profile and gluten-free diet. METHODS: Medical literature searches of articles in English were conducted using the terms mucin and celiac. Observational studies were included. Pooled odds ratios and 95% confidence intervals were calculated. RESULTS: Of 31 articles initially generated by a literature search, 4 observational studies that fulfilled the inclusion criteria remained eligible for meta-analysis. These studies included 182 patients and 148 controls from four countries (Finland, Japan, Sweden, United States). Mucin expression was significantly increased in small bowel mucosa of CD patients than in normal small bowel mucosa (odds ratio [OR] 7.974, 95% confidence interval [95%CI] (1.599-39.763), P = 0.011] (random-effect model). Heterogeneity was significant: Q = 35.743, df (Q) = 7, P < 0.0001, I2 = 80.416%. ORs for MUC2 and MUC5AC expression in the small bowel mucosa of untreated CD patients were 8.837, 95%CI 0.222-352.283, P = 0.247 and 21.429, 95%CI 3.883-118.255, P < 0.0001, respectively. CONCLUSIONS: Expression of certain mucin genes in the small bowel mucosa of CD patients is increased and may serve as a diagnostic tool and assist in surveillance programs.

[DEVELOPMENT AND IMPROVEMENT OF THE NATIONAL PLAN FOR QUALITY INDICATORS - COMPARISON OF 2016 AND 2020 RESULTS].

INTRODUCTION: The National Plan for Quality Indicators of hospitals was established in 2012. The aim of the plan was to improve and advance the quality of medical treatment by measuring, comparison of hospitals and publication of the achievements to the public. Aims: To evaluate and compare the quality indicators between 2016 and 2020, characterize the different types and their contribution to the quality of patient care. METHODS: We calculated the proportion of indicators in every category and medical fields. These data were compared between 2016 and 2020 with Chi-squared tests using SAS software. We compared the success of hospitals over this period over 25 indicators shared by them, when details of the numerator and denominator were available. RESULTS: No significant changes were found in the relative portion of cardiology and pediatrics indicators. An increase was demonstrated in obstetrics, neonatology and psychiatry, and a decrease in neurology, geriatrics and surgery. An increase was also found in result indicators, communication and coordination and in public health. The success rate was higher in 2020 with an increase of 26%. In only 2 indicators, measurement of head circumference in neonates and nutritional assessment in chronic ventilated patients, the success rate was lower in 2020, probably due to significant increase in their required aims and the corona pandemic. CONCLUSIONS: The success rate of the quality indicators was significantly higher in 2020 in spite of an annual increase in their aims. Continuous refreshment of the national plan and the addition of safety indicators to the national plan will bring improvement in the quality and safety of patient care.

[CONFIDENTIALITY OF ADVERSE EVENTS INVESTIGATIONS - THE PRESENT STATUS AND WHAT IS NEEDED].

INTRODUCTION: The goal of the medical staff is to provide proper, effective and efficient treatment to the patient and to take care of his well-being. An error in medical care that causes a serious outcome or mortality, can be considered negligence when the caregiver did not meet the requirements of a reasonable physician for reasonable care and did not take the necessary precautions in providing the treatment, in light of the information available to him. The perception of punishment and compensation due to harm, caused to a patient as a result of a medical error, changed dramatically over the years. Starting with direct and severe punishment according to Hammurabi laws and ending with the "no fault" approach that is accepted widely in some countries. Following an adverse event that occurred in medical treatment, a process should be conducted in order to draw lessons to reduce the likelihood of recurrence of similar incidents in the future, by answering 4 questions: What happened? How did it happen? Why did it happen? and What should be done to prevent similar incidents in the future? The Patient Rights Act does not suggest conducting a safety investigation but recommends an examination board in cases of negligence or error in treatment. By law, the protocols of the examination board are confidential and can be removed by the court in case the protocol contains evidence of importance that is unlikely to be found in the medical record. Lack of confidentiality may cause medical staff to be reluctant of conducting a safety investigation due to fear of using its findings for a lawsuit or appointing an examination board whose conclusions will be reported to the victim and his family. The "no fault" method overcomes these barriers by enabling a thorough safety investigation and has important professional, economic and social aspects with a direct impact on the quality and safety of treatment. The method expands the accessibility of victims to compensation, reduces the number of claims and the burden on the courts. Among additional benefits are transparency and consistency in decisions, promoting patient safety due to physicians' willingness to report failures, reduction in "defensive medicine" and spending in the health care system.

COVID-19 and Renal Failure - Adding Insult to Injury? Israel's Experience Based on Nationwide Retrospective Cohort Study.

INTRODUCTION: Renal failure (RF) is a risk factor for mortality among hospitalized patients. However, its role in COVID-19-related morbidity and mortality is inconclusive. The aim of the study was to determine whether RF is a significant predictor of clinical outcomes in COVID-19 hospitalized patients based on a retrospective, nationwide, cohort study. METHODS: The study sample consisted of patients hospitalized in Israel for COVID-19 in two periods. A random sample of these admissions was selected, and experienced nurses extracted the data from the electronic files. The group with RF on admission was compared to the group of patients without RF. The association of RF with 30-day mortality was investigated using a logistic regression model. RESULTS: During the two periods, 19,308 and 2994 patients were admitted, from which a random sample of 4688 patients was extracted. The 30-day mortality rate for patients with RF was 30% (95% confidence interval (CI): 27-33%) compared to 8% (95% CI: 7-9%) among patients without RF. The estimated OR for 30-day mortality among RF versus other patients was 4.3 (95% CI: 3.7-5.1) and after adjustment for confounders was 2.2 (95% CI: 1.8-2.6). Furthermore, RF patients received treatment by vasopressors and invasive mechanical ventilation (IMV) more frequently than those without RF (vasopressors: 17% versus 6%, OR = 2.8, p<0.0001; IMV: 17% versus 7%, OR = 2.6, p<0.0001). DISCUSSION: RF is an independent risk factor for mortality, IMV, and the need for vasopressors among patients hospitalized for COVID-19 infection. Therefore, this condition requires special attention when considering preventive tools, monitoring, and treatment.

Quality of care indicator performance was minimally changed in 2020 despite the COVID-19 pandemic.

BACKGROUND: In 2020, the COVID-19 pandemic affected healthcare systems throughout the world, including the management of patients and compliance rates of quality indicators. OBJECTIVE: To measure the impact in Israel of the COVID-19 pandemic on the indicator-relevant caseload and compliance rates of the quality indicators reported by medical services providers within the Israeli National Program for Quality Indicators (NPQI). METHODS: Data was collected from the reports made to the NPQI by participating hospitals and medical service providers. The indicator results for the number of cases and compliance rates for 2019 were compared to those from 2020. We assessed and compared the results of the quality indicators in general hospitals, geriatric hospitals and departments, psychiatric hospitals and departments, emergency medical services (EMS), and Mother and Baby health centers. RESULTS: We found a decrease in measurable cases in 2020 relative to 2019, especially in geriatric hospitals. In most indicators, compliance rates rose in 2020. Few indicators had lower compliance rates associated with COVID-19 pandemic regulations. CONCLUSIONS AND POLICY IMPLICATIONS: Routine medical activity decreased in Israel in 2020 in comparison to 2019, as reflected by a decrease in cases, but compliance rates were better in most indicators. The results of our study imply that the functioning of healthcare quality measurement programs should not be interrupted during a pandemic. This not only allows measuring of the healthcare system's performance during a crisis, but also may assist in maintaining a high level of healthcare quality.

Comparing Coronavirus Disease 2019 (COVID-19) Pandemic Waves in Hospitalized Patients: A Retrospective, Multicenter, Cohort Study.

BACKGROUND: Coronavirus disease 2019 was first diagnosed in Israel at the end of February 2020. By the end of June 2021, there were 842 536 confirmed cases and 6428 deaths. Our aim in this multicenter, retrospective, cohort study is to describe the demographic and clinical characteristics of hospitalized patients and compare the pandemic waves before immunization. METHODS: Of 22 302 patients hospitalized in general medical centers, we randomly selected 6329 for the study. Of these, 3582 and 1106 were eligible for the study in the first period (first and second waves) and in the second period (third wave), respectively. RESULTS: Thirty-day mortality was higher in the second period than in the first period, 25.20% vs 13.68% (P < .001). Invasive mechanical ventilation supported 9.19% and 14.21% of patients in the first period and second period, respectively. Extracorporeal membrane oxygenation (ECMO) was used more than twice as often in the second period. CONCLUSIONS: Invasive ventilation, use of ECMO, and mortality rate were 1.5 to 2 times higher in the second period than in the first period. In the second period, patients had a more severe presentation and higher mortality than those in the first period.

Accessing unproven interventions in the COVID-19 pandemic: discussion on the ethics of 'compassionate therapies' in times of catastrophic pandemics.

Since the onset of the SARS-CoV-2 pandemic, an array of off-label interventions has been used to treat patients, either provided as compassionate care or tested in clinical trials. There is a challenge in determining the justification for conducting randomised controlled trials over providing compassionate use in an emergency setting. A rapid and more accurate evaluation tool is needed to assess the effect of these treatments. Given the similarity to the Ebola Virus Disease (EVD) pandemic in Africa in 2014, we suggest using a tool designed by the WHO committee in the aftermath of the EVD pandemic: Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI). Considering the uncertainty around SARS-CoV-2, we propose using an improved MEURI including the Plan-Do-Study-Act tool. This combined tool may facilitate dynamic monitoring, analysing, re-evaluating and re-authorising emergency use of unproven treatments and repeat it in cycles. It will enable adjustment and application of outcomes to clinical practice according to changing circumstances and increase the production of valuable data to promote the best standard of care and high-quality research-even during a pandemic.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Comparative Efficacy and Tolerability of Janus Kinase Inhibitor Therapies for Moderate to Severe Crohn's Disease: Α Network Meta-analysis.

BACKGROUND AND AIMS: A number of Janus kinase (JAK) inhibitors (tofacitinib, filgotinib, upadacitinib) have been tested for moderate and severe Crohn's disease (CD) in randomized control trials (RCTs). However, data on their comparative efficacy and tolerability is lacking. We aimed to study their performance comparatively, by means of network meta-analysis (NWM). METHODS: We searched the Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through March 2021 and data was extracted. A bayesian NWM was performed to investigate the efficacy and tolerability of the above JAK inhibitors and to explore their rank order in treating moderate and severe CD patients. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: Four RCTs were entered into this NWM. They included 811 patients totally, randomized to 11 interventions, i.e. placebo, tofacitinib (1mg BID, 5mg BID, 10mg BID, 15mg BID), filgotinib 200 OD and upadacitinib (3 mg BID, 6 mg BID, 12 mg BID, 24 mg BID and 24mg OD). Two upadacitinib doses (6 mg BID and 24 mg BID) and filgotinib 200 OD, performed best as judged by the relevant forest plots, league matrixes, rankograms, SUCRA values (96.7%, 84,6 %and 78,7%, respectively) and the clustered ranking plots for efficacy and tolerability. CONCLUSIONS: Upadacitinib 6 mg BID, upadacitinib 24 mg BID and filgotinib 200 OD performed better as induction therapies in comparison to control therapies. Consequently, these regimens may play a therapeutic role in CD and therefore they merit further evaluation with well-designed RCTs.

Comparative effectiveness of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a network meta-analysis of randomized controlled studies.

BACKGROUND: There is evidence demonstrating the beneficial effects of 5-hydroxytryptamine 3 receptor antagonists (5-HT3) for the treatment of non-constipated irritable bowel syndrome (NC-IBS). We aimed to determine the comparative effectiveness of 5-HT3 antagonists in NC-IBS, as evidenced by the results of a network meta-analysis (NWM) of published relevant randomized controlled trials (RCTs). METHODS: We searched the PubMed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through September 2020 and data from each selected RCT were extracted. A Bayesian NWM was then performed to investigate the efficacy of 5-HT3 antagonists and to explore the effectiveness rank order in treating NC-IBS patients. RESULTS: Twenty-one eligible RCTs were identified and entered into this NWM. They included a total of 10,421 NC-IBS patients, randomized to alosetron, cilansetron, ondansetron, ramosetron, placebo, and mebeverine. The cumulative ranking probability for each intervention at the end of treatment period, was evaluated by means of surfaces under cumulative ranking (SUCRA) values. These results showed that alosetron had the best performance for global symptom improvement (SUCRA 0.82), cilansetron showed the best performance (SUCRA 0.90) for abdominal pain/discomfort improvement, while ondansetron (SUCRA 0.98) was by far the best choice concerning bowel habits/consistency improvement. The control regimens (mebeverine and placebo) represented the least efficacious interventions. CONCLUSIONS: This NWM showed that 5-HT3 receptor antagonists performed better in comparison to control drugs. Consequently, this class of drugs may play an important role in improving the debilitating symptoms in NC-IBS patients, in particular those with diarrhea.

Susceptibility-guided versus empirical treatment for Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND AND AIM: Empirical therapy for Helicobacter pylori infection is limited by increasing antibiotic resistance and suboptimal eradication rates. Studies of the relative effectiveness of susceptibility-guided therapy have produced conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine whether susceptibility-guided therapy is superior to empirical therapy for H. pylori infection. METHODS: We searched articles listed in PubMed, MEDLINE, EMBASE, and Web of Science through May 25, 2020, RCTs comparing susceptibility-guided versus empirical therapy for H. pylori infection. Outcomes, including effectiveness and safety, were analyzed in a meta-analysis. RESULTS: Our final analysis included 16 studies, comprising 2374 patients who received susceptibility-guided therapy and 2451 patients who received empirical treatment. In previously untreated subjects, susceptibility-guided therapy was slightly more effective than empirical therapy (intent to treat risk ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21; P < 0.0001, I2  = 75%). Susceptibility-guided therapy was superior to first-line clarithromycin-based triple therapy only when clarithromycin resistance exceeded 20% (RR, 1.18; 95% CI, 1.07-1.30; P = 0.001, I2  = 81%). Susceptibility-guided therapy was not more effective than empirical quadruple therapy (RR, 1.02; 95% CI, 0.92-1.13; P = 0.759, I2  = 80%). Three RCTs were performed exclusively among previously treated subjects, and were highly heterogeneous. CONCLUSIONS: Our findings suggest that susceptibility-guided treatment may be slightly superior to empirical first line triple therapy. Susceptibility- guided treatment does not appear to be superior to empirical first-line quadruple therapy or empirical rescue therapy.

Sex differences in the case-fatality rates for COVID-19-A comparison of the age-related differences and consistency over seven countries.

BACKGROUND: Early in the COVID-19 pandemic, it was noted that males seemed to have higher case-fatality rates than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in seven countries. METHODS: Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the national official agencies from Denmark, England, Israel, Italy, Spain, Canada and Mexico. Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the seven countries, for all age-groups. Meta-regression and sensitivity analysis were conducted to evaluate the age and country contribution to differences. RESULTS: The CFRs were consistently higher in males at all ages. The pooled M:F CFR ratios were 1.71, 1.88, 2.11, 2.11, 1.84, 1.78 and 1.49, for ages 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80+ respectively. In meta-regression, age group and country were associated with the heterogeneity in the CFR ratios. CONCLUSIONS: The sex differences in the age-specific CFRs are intriguing. Sex differences in the incidence and mortality have been found in many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the consistently greater case-fatality rates in males at all ages suggests that sex-related factors impact on the natural history of the disease. This could provide important clues as to the mechanisms underlying the severity of COVID-19 in some patients.