Clinical question What is the role of gastrointestinal bleeding prophylaxis (stress ulcer prophylaxis) in critically ill patients? This guideline was prompted by the publication of a new large randomised controlled trial. Current practice Gastric acid suppression with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) is commonly done to prevent gastrointestinal bleeding in critically ill patients. Existing guidelines vary in their recommendations of which population to treat and which agent to use. Recommendations This guideline panel makes a weak recommendation for using gastrointestinal bleeding prophylaxis in critically ill patients at high risk (>4%) of clinically important gastrointestinal bleeding, and a weak recommendation for not using prophylaxis in patients at lower risk of clinically important bleeding (≤4%). The panel identified risk categories based on evidence, with variable certainty regarding risk factors. The panel suggests using a PPI rather than a H2RA (weak recommendation) and recommends against using sucralfate (strong recommendation). How this guideline was created A guideline panel including patients, clinicians, and methodologists produced these recommendations using standards for trustworthy guidelines and the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. A weak recommendation means that both options are reasonable. The evidence The linked systematic review and network meta-analysis estimated the benefit and harm of these medications in 12 660 critically ill patients in 72 trials. Both PPIs and H2RAs reduce the risk of clinically important bleeding. The effect is larger in patients at higher bleeding risk (those with a coagulopathy, chronic liver disease, or receiving mechanical ventilation but not enteral nutrition or two or more of mechanical ventilation with enteral nutrition, acute kidney injury, sepsis, and shock) (moderate certainty). PPIs and H2RAs might increase the risk of pneumonia (low certainty). They probably do not have an effect on mortality (moderate certainty), length of hospital stay, or any other important outcomes. PPIs probably reduce the risk of bleeding more than H2RAs (moderate certainty). Understanding the recommendation In most critically ill patients, the reduction in clinically important gastrointestinal bleeding from gastric acid suppressants is closely balanced with the possibility of pneumonia. Clinicians should consider individual patient values, risk of bleeding, and other factors such as medication availability when deciding whether to use gastrointestinal bleeding prophylaxis. Visual overviews provide the relative and absolute benefits and harms of the options in multilayered evidence summaries and decision aids available on MAGICapp.

Objectives: ‘National Special Stewardship in the Clinical Use of Antibiotics’ was put forward in July 2011 in China. We aimed to retrospectively evaluate the impact of antimicrobial stewardship (AMS) managed by clinical pharmacists on antibiotic utilisation, prophylaxis and antimicrobial resistance (AMR). Design: This was a retrospective observational study of trends in antibiotic use and AMR in the context of AMS. Setting: Beijing Chaoyang Hospital, a 1400-bed tertiary hospital, in China. Data and participants: Antibiotic prescriptions from 820 doctors included all outpatients (n=17 766 637) and inpatients (n=376 627) during 2010–2016. Bacterial resistance data were from all inpatients (n=350 699) during 2011–2016. Interventions: Multiaspect intervention measures were implemented by clinical pharmacists (13 persons), for example, formulating the activity programme and performance management, advising on antibacterial prescriptions and training. Outcome measures: The proportion of antibiotic prescriptions among outpatients and inpatients, intensity of consumption in defined daily dose (DDD)/100 bed-days, antibiotic prophylaxis in type I incision operations and resistance rates of Escherichia coli , Klebsiella pneumoniae and Pseudomonas aeruginosa were retrospectively analysed. Results: The proportion of antibiotic prescriptions decreased in outpatients (from 19.38% to 13.21%) and in inpatients (from 64.34% to 34.65%), the intensity of consumption dropped from 102.46 to 37.38 DDD/100 bed-days. The proportion of antibiotic prophylaxis decreased from 98.94% to 18.93%. The proportion of rational timing of initial dose increased from 71.11% to 96.74%, the proportion of rational duration rose from 2.84% to 42.63%. Time series analysis demonstrated the resistance rates of E. coli and P. aeruginosa to fluoroquinolones decreased, the incidence rate of methicillin-resistant Staphylococcus aureus also decreased, whereas the resistance rates of E. coli and K. pneumoniae to carbapenems increased. The antibiotic use was partly positively correlated with AMR. Conclusions: AMS had an important role in reducing antibiotic use and surgical antibiotic prophylaxis. The AMR was positively correlated with antibiotic consumption to some extent.

Cell cycle checkpoint kinase 2 (CHEK2) is a checkpoint kinase that plays an important role in the DNA damage signaling network. Numerous epidemiological studies have evaluated the association between the CHEK2 I157T variant and cancer susceptibility. However, the results of these studies on the association remain conflicting. The main purpose of this study was to integrate previous results and explore whether the CHEK2 I157T variant is associated with cancer susceptibility. PubMed, Embase (before 2012-10-1), Google Scholar, and CBMdisc were searched for studies on the relationship of the CHEK2 I157T variant and the incidence of cancer. Eligible articles were included for data extraction. The main outcome was the frequency of CHEK2 I157T polymorphisms between cases and controls. Comparison of the distribution of SNP was mainly performed using Review Manager 5.0. The odds ratio (OR) and its 95% confidence interval (95% CI) were used to assess the strength of association. In total, 26,336 cases and 44,219 controls from 18 case–control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19–1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42–1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24–2.26, p=0.0008). We also found an association of the CHEK2 I157T variant with familial cases (OR=1.85, 95% CI=1.51–2.26, p<0.00001). However, the association was not established for other types of cancer (OR=1.09, 95% CI=0.75–1.57, p=0.66). This meta-analysis demonstrates that the CHEK2 I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.

Objective: To determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.Design: Systematic review and network meta-analysis.Data sources: Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.Eligibility criteria for selecting studies and methods: We included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.Results: Seventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).Conclusions: For higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.Systematic review registration: PROSPERO CRD42019126656.

Metabolic syndrome is a common extrapulmonary comorbidity in patients with chronic obstructive pulmonary disease (COPD). However, the reported relationship of COPD with dyslipidemia, an important component of metabolic syndrome, is ambiguous. The aim of this meta-analysis is to investigate the association between COPD and the serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG). The PubMed and Embase databases were searched to find potential studies using the search terms of (“dyslipidemia” or “HDL” or “LDL” or “cholesterol” or “triglyceride”) and COPD. We also performed subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia. Mean differences (MD) with 95% confidence intervals (CI) were estimated with random effects models. A total of 11 studies comprising 615 cases and 471 controls were included in the study. No significant differences were found in the HDL (MD = −2.55, 95% CI [−6.03, 0.93], P = 0.15), LDL (MD = −2.25, 95% CI [−13.36, 8.86], P = 0.69), TC (MD = −2.69, 95% CI [−13.30, 7.92], P = 0.62), and TG (MD = 6.90, 95% CI [−2.81, 16.60], P = 0.16) levels of the 2 groups. However, subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia showed that TG levels were higher in patients with stable COPD than in healthy individuals (MD = 16.35, 95% CI [5.90, 26.80], P = 0.002). Excluding the impact of hypolipidemic treatment on serum lipid profile, TG levels were higher in patients with COPD than in healthy individuals. This meta-analysis suggested that physicians should screen COPD patients for elevated TG levels to reduce the risk of cardiovascular morbidity and mortality.

Hypothyroidism disorders and gestational diabetes are among the most common endocrinopathies during pregnancy. We conducted a meta-analysis to investigate whether hypothyroidism in pregnancy is associated with gestational diabetes risk. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. Seven articles described the relationship between hypothyroidism and risk of gestational diabetes. This meta-analysis revealed that overt hypothyroidism was associated with an increased risk of gestational diabetes (OR 1.892, 95% CI 1.679-2.132, p < 0.001). The relative risk of gestational diabetes was also increased in subclinical hypothyroidism, with the OR of 1.558 (95% CI 1.292-1.877, p < 0.001). There was no evidence of significant association between hypothyroxinemia and risk of gestational diabetes (OR 1.394, 95% CI 0.753-2.580, p = 0.291). The OR for all of the hypothyroidism was 1.749 (95% CI 1.586-1.928, p < 0.001), and an association was found. Results of this meta-analysis indicate that hypothyroidism may be a risk factor for gestational diabetes.