ObjectiveThe association between the regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomised controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes.MethodThis is a prospective analysis of 204 689 participants free of diabetes in the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications.ResultsWe documented 10 105 incident cases of diabetes over 2 127 471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users (HR 1.24, 95% CI 1.17 to 1.31). The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 (95% CI 0.93 to 1.19) for participants who used PPIs for >0–2 years and 1.26 (95% CI 1.18 to 1.35) for participants who used PPIs for >2 years compared with non-users.ConclusionsRegular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.

Background The training of neonatal resuscitation is an important part in the clinical teaching of neonatology. This study aimed to identify the educational efficacy of high-fidelity simulation compared with no simulation or low-fidelity simulation in neonatal resuscitation training. Methods The PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Chinese databases (CBM, CNKI, WanFang, and Weipu), ScopeMed and Google Scholar were searched. The last search was updated on April 13, 2019. Studies that reported the role of high-fidelity simulation in neonatal resuscitation training were eligible for inclusion. For the quality evaluation, we used the Cochrane Risk of Bias tool for RCTs and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for non-RCTs. A standardized mean difference (SMD) with a 95% confidence interval (CI) was applied for the estimation of the pooled effects of RCTs. Results Fifteen studies (10 RCTs and 5 single arm pre-post studies) were ultimately included. Performance bias existed in all RCTs because participant blinding to the simulator is impossible. The assessment of the risk of bias of single arm pre-post studies showed only one study was of high quality with a low risk of bias whereas four were of low quality with a serious risk of bias. The pooled results of single arm pre-post studies by meta-analysis showed a large benefit with high-fidelity simulation in skill performance (SMD 1.34; 95% CI 0.50–2.18). The meta-analysis of RCTs showed a large benefit in skill performance (SMD 1.63; 95% CI 0.49–2.77) and a moderate benefit in neonatal resuscitation knowledge (SMD 0.69; 95% CI 0.42–0.96) with high-fidelity simulation when compared with traditional training. Additionally, a moderate benefit in skill performance (SMD 0.64; 95% CI 0.06–1.21) and a small benefit was shown in knowledge (SMD 0.39; 95% CI 0.08–0.71) with high-fidelity simulation when compared with low-fidelity simulation. Conclusions Improvements of efficacy were shown both in resuscitation knowledge and skill performance immediately after training. However, in current studies, the long-time retention of benefits is controversial, and these benefits may not transfer to the real-life situations. Electronic supplementary material The online version of this article (10.1186/s12909-019-1763-z) contains supplementary material, which is available to authorized users.

Metabolic syndrome (MetS) and its components may link to pancreatic cancer risk; however, current epidemiological evidence is limited, and the potential mechanisms underlying the associations remain unclear. To investigate this, we carried out this prospective cohort study of 474 929 participants without a diagnosis of cancer based on UK Biobank dataset. MetS was defined according to the International Diabetes Federation criteria and pancreatic cancer was identified through linkage to UK cancer registries (median follow-up time: 6.6 years). We evaluated hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demography and lifestyle factors. Restricted cubic spline was performed for each MetS component to investigate their possible nonlinear associations with risk of pancreatic cancer. During 3 112 566 person-years of follow-up, 565 cases of pancreatic cancer were identified. Individuals with MetS (HR = 1.31, 95% CI, 1.09-1.56), central obesity (HR = 1.24, 95% CI, 1.02-1.50) and hyperglycemia (HR = 1.60, 95% CI, 1.31-1.97) had increased risk of pancreatic cancer. Higher waist circumference (WC) and blood glucose were independently associated with pancreatic cancer, with no evidence against nonlinearity. Although elevated CRP (≥1.00 mg/dL) showed a positive association with the risk for pancreatic cancer, the effect was substantially increased only in participants with MetS and CRP ≥1.00 mg/dL. Our study demonstrated a positive association between MetS and increased risk of pancreatic cancer, with two of the MetS components, WC and blood glucose, showing independent associations in linear manner. Our study also suggested a potential joint effect of MetS and CRP in pancreas tumorigenesis.

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) have a major impact on gut microbiome and immune function, which in turn, may increase the risk of inflammatory bowel disease (IBD). Our aim in this study was to evaluate PPI use and subsequent risk of IBD and subtypes (ie, Crohn's disease and ulcerative colitis). METHODS: This was a pooled analysis of the Nurses' Health Study (NHS, n ¼ 82,869), NHS II (n ¼ 95,141), and UK Biobank (n ¼ 469,397). We included participants with information on personal use of PPIs and free of IBD or cancer at baseline. We evaluated hazard ratios and 95% confidence intervals (CIs) with Cox regression adjusting for lifestyle factors, PPI indications, comorbidities, and other medications. RESULTS: We documented 271 cases of IBD (median follow-up, 12 years) in the pooled NHS cohorts and 1419 cases (median follow-up, 8.1 years) in the UK Biobank. For both pooled NHS cohorts and UK Biobank, regular use of PPIs consistently showed a significantly positive association with IBD, Crohn's disease, and ulcerative colitis risk. Combined analyses of 3 cohorts showed that regular PPI users had an increased risk of IBD as compared with nonusers (hazard ratio, 1.42; 95% CI, 1.22-1.65; number needed to harm, 3770; 95% CI, 3668-4369). Direct comparison with H2 receptor antagonist, a less potent acid suppressor, showed that PPI use was also associated with higher IBD risk (hazard ratio, 1.38; 95% CI, 1.16-1.65). CONCLUSIONS: Regular use of PPIs was associated with an increased risk of IBD and its subtypes. The findings should be interpreted with caution because the absolute risk was low and the clinical benefits of PPIs are substantial.

In VLBW Chinese infants, IVF, GA < 32 weeks, apnea, BPD, sepsis, PDA, and blood transfusion were independent perinatal risk factors for ROP.

Objectives: This study aimed to assess the efficacy of minocycline for the treatment of acute ischemic stroke.Background: While there have been meta-analysis that surveyed the efficacy of minocycline in the treatment of acute stroke, they have some methodological limitations. We performed a new systematic review which was distinct from previous one by adding new outcomes and including new studies.Methods: Document retrieval was executed through PubMed, Cochrane Central Register of Controlled Trials, the Stroke Center, NIH's Clinical Trials, Current Controlled Trials, and the WHO International Clinical Trials Registry Platform Search Portal before Jan 2018. The data meeting the inclusion criteria were extracted. Before meta-analysis, publication bias and heterogeneity of included studies were surveyed. Random and fixed-effects models were employed to calculate pooled estimates and 95% confidence intervals (CIs). Additionally, sensitivity and subgroup analyses were implemented.Result: For clinical studies, 4 trials with 201 patients in the minocycline group, and 195 patients in the control group met the inclusion criteria; 3 were randomized trials. At the end of 90-day follow up or discharge day, results showed that the groups receiving minocycline were superior to the control group, with significant differences in the NIHSS scores (mean difference [MD], −2.75; 95% CI, −4.78, 0.27; p = 0.03) and mRS scores (MD, −0.98; 95% CI, −1.27, −0.69; p < 0.01), but not Barthel Index Score (MD, 9.04; 95% CI, −0.78, 18.07; p = 0.07). For rodent experiments, 14 studies were included. Neurological severity scores (NSS) was significantly improved (MD, −1.38; 95% CI, −1.64, −1.31; p < 0.01) and infarct volume was obviously reduced (Std mean difference [SMD], −2.38; 95% CI, −3.40, −1.36; p < 0.01) in the minocycline group. Heterogeneity among the studies was proved to exist for infarct volume (Chi2 = 116.12, p < 0.01; I2 = 0.89) but not for other variables.Conclusions: Based on the results in our study, minocycline appears as an effective therapeutic option for acute ischemic stroke.

Background & Aims Little is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort. Methods We included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method. Results Over a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27–1.72] and central obesity [HR 1.65, 95% CI 1.18–2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk. Conclusions MetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.

Backgrounds: Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) <5.0% was used to judge the effect of azithromycin MDA on eliminating trachoma as a public health problem. Two researchers independently conducted the selection process and risk of bias assessment. Results: A total of 1543 studies were screened, of which 67 studies including 13 cluster-randomized controlled trials and 54 non-randomized studies were included. The effect of azithromycin MDA on trachoma was closely related to the baseline prevalence in districts. For the districts with baseline prevalence between 5.0% and 9.9%, a single round of MDA achieved a TF <5.0%. For the districts with baseline between 10.0% and 29.9%, annual MDA for 3 to 5 years reduced TF <5.0%. However, for the districts with high level of baseline prevalence (TF >30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF <5.0% even after 5 to 7 years of treatment. Quarterly MDA is more effective in controlling trachoma in these hyperendemic districts. Conclusions: Azithromycin MDA for controlling trachoma depends on the baseline prevalence. The recommendation by the World Health Organization that annual MDA for 3 to 5 years in the districts with TF baseline >10.0% is not appropriate for all eligible districts.