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Purpose Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS. Methods The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality. Results We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72–0.95, ARR 8.0%, 95% CI 2.2–12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course. Conclusion The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.

Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non–COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.

PurposeMotivated by a new randomized trial (the PEPTIC trial) that raised the issue of an increase in mortality with proton pump inhibitors (PPIs) relative to histamine-2 receptor antagonists (H2RAs), we updated our prior systematic review and network meta-analysis (NMA) addressing the impact of pharmacological gastrointestinal bleeding prophylaxis in critically ill patients.MethodsWe searched for randomized controlled trials that examined the efficacy and safety of gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. We performed Bayesian random-effects NMA and conducted analyses using all PEPTIC data as well as a restricted analysis using only PEPTIC data from high compliance centers. We used the GRADE approach to quantify absolute effects and assess the certainty of evidence.ResultsSeventy-four trials enrolling 39 569 patients proved eligible. Both PPIs (risk ratio (RR) 1.03, 95% credible interval 0.93 to 1.14, moderate certainty) and H2RAs (RR 0.98, 0.89 to 1.08, moderate certainty) probably have little or no impact on mortality compared with no prophylaxis. There may be no important difference between PPIs and H2RAs on mortality (RR 1.05, 0.97 to 1.14, low certainty), the 95% credible interval of the complete analysis has not excluded an important increase in mortality with PPIs. Both PPIs (RR 0.46, 0.29 to 0.66) and H2RAs (RR 0.67, 0.48 to 0.94) probably reduce clinically important gastrointestinal bleeding; the magnitude of reduction is probably greater in PPIs than H2RAs (RR 0.69, 0.45 to 0.93), and the difference may be important in higher, but not lower bleeding risk patients. PPIs (RR 1.08, 0.88 to 1.45, low certainty) and H2RAs (RR 1.07, 0.85 to 1.37, low certainty) may have no important impact on pneumonia compared with no prophylaxis.ConclusionThis updated NMA confirmed that PPIs and H2RAs are most likely to have a similar effect on mortality compared to each other and compared to no prophylaxis; however, the possibility that PPIs may slightly increase mortality cannot be excluded (low certainty evidence). PPIs and H2RAs probably achieve important reductions in clinically important gastrointestinal bleeding; for higher bleeding risk patients, the greater benefit of PPIs over H2RAs may be important. PPIs or H2RAs may not result in important increases in pneumonia but the certainty of evidence is low.

The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections. In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study (n = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza (n = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference −1.62, 95% CI −3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence). Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.

The cleaning device is an important part of combine harvesters, as its superior or inferior performance directly affects the performance of the combine harvester greatly. With an increasing rice yield, the current single-duct cleaning performance declines greatly, and causes a large grain sieve loss level and a direct grain loss for the farms. To optimize the existing single-duct cleaning device to meet the large feeding rate requirement, firstly, the terminal velocity of rice grain and MOG (material other than grain) for different varieties was experimentally measured by the custom-made device. The effects of the moisture content of rice grains and the length of short straws on terminal velocity were studied in detail. Then, the gas–solid two-phase flow theory was comprehensively applied by utilizing the discrete element method (DEM) and computational fluid dynamics (CFD) to study the working mechanism of the existing single-duct cleaning unit, and the cleaning performance was evaluated from the view of the motion law of the threshing output within the cleaning shoe. At last, a multi-duct cleaning device was put forward, and a field experiment was performed to assess the performance of the newly developed cleaning device. The results showed that the grain sieve losses ratio and grain impurity ratio improved dramatically, proving that structure optimization of the cleaning device was feasible.

Depression frequently comorbidities with cancer, adversely affecting survivors’ quality of life. Liver dysfunction is also prevalent among cancer survivors. However, the association between these two conditions remains unclear. This study aimed to explore the relationship between depression and liver function biomarkers in US cancer survivors. A cross-sectional study was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2005–2020. Cancer survivors were screened and depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and 18 liver function biomarkers were included. Survey-weighted generalized linear models with multiple covariables adjusted were employed to examine the associations between depression and liver function biomarkers. A total of 4118 cancer survivors were included, representing a weighted population of 21 501 237. After adjusted with age, gender, race, marital status, education level, family income-to-poverty ratio, and number of cancer types, 8 biomarkers demonstrated positive correlations with depression in cancer survivors, included alanine aminotransferase (ALT, OR = 1.007, 95% CI: 1.000 to 1.013), alkaline phosphatase (ALP, 1.006 [1.002, 1.010]), gamma glutamyl transferase (GGT, 1.004 [1.001, 1.007]), lactate dehydrogenase (LDH, 1.004 [1.000, 1.009]), total protein (TP, 1.040 [1.009, 1.072]), globulin (GLB, 1.060 [1.030, 1.091]), total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio (1.162 [1.050, 1.286]), and low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (1.243 [1.012, 1.526]); while 4 other biomarkers exhibited negative correlations, included HDL-C (0.988 [0.980, 0.997]), total bilirubin (TBi, 0.501 [0.284, 0.883]), aspartate aminotransferase (AST) to ALT ratio (0.588 [0.351, 0.986]), albumin (ALB) to GLB ratio (0.384 [0.229, 0.642]). Following sensitivity analysis, 5 biomarkers included LDH, HDL-C, TBi, AST/ALT and LDL-C/HDL-C lost their statistical significance for the association. This study identified certain associations between 7 liver function biomarkers and depression in US cancer survivors. Further research, particularly prospective longitudinal studies, is warranted to elucidate the causal relationships and explore the potential of improving liver function for the management of depression in cancer patients.

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).DesignThis was a retrospective observational study of trends in antibiotic use and AMR in the context of AMS.SettingBeijing Chaoyang Hospital, a 1400-bed tertiary hospital, in China.Data and participantsAntibiotic 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.InterventionsMultiaspect 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 measuresThe 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.ResultsThe 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.ConclusionsAMS had an important role in reducing antibiotic use and surgical antibiotic prophylaxis. The AMR was positively correlated with antibiotic consumption to some extent.

This study aims to assess the efficacy and safety of pharmacoprophylaxis regimens for venous thromboembolism (VTE) in patients undergoing bariatric surgery. A total of 15 studies were included. Low molecular-weight heparins (LMWH) and fondaparinux may be equally effective in reducing VTE risk (OR 1.02, 95% confidence interval [CI] 0.14–7.39). Pooled estimate suggested uncertain effects of augmented LMWH dosing on VTE prophylaxis compared with standard dosing (OR 0.57, 95% CI 0.07–4.39), but may increase major bleeding (OR 3.03, 95% CI 0.38–23.96). Very low-quality evidence showed an inconclusive effect of extended prophylaxis on VTE (OR 0.54, 95% CI 0.15–1.90) and major bleeding (OR 1.24, 95% CI 0.92–1.68) compared with restricted prophylaxis. Standard LMWH dosing may be effective and safe. Current evidences are insufficient to support extended prophylaxis.

Antiviral medications are being given empirically to some patients with coronavirus disease 2019 (COVID-19). To support the development of a COVID-19 management guideline, we conducted a systematic review that addressed the benefits and harms of 7 antiviral treatments for COVID-19. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and 3 Chinese databases (CNKI, WANFANG and SinoMed) through Apr. 19, medRxiv and Chinaxiv through Apr. 27, and Chongqing VIP through Apr. 30, 2020. We included studies of ribavirin, chloroquine, hydroxychloroquine, umifenovir (arbidol), favipravir, interferon and lopinavir/ritonavir. If direct evidence from COVID-19 studies was not available, we included indirect evidence from studies of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for efficacy outcomes and other acute respiratory viral infections for safety outcomes. In patients with nonsevere COVID-19 illness, the death rate was extremely low, precluding an important effect on mortality. We found only very low-quality evidence with little or no suggestion of benefit for most treatments and outcomes in both nonsevere and severe COVID-19. An exception was treatment with lopinavir/ritonavir, for which we found low-quality evidence for a decrease in length of stay in the intensive care unit (risk difference 5 d shorter, 95% confidence interval [CI] 0 to 9 d) and hospital stay (risk difference 1 d shorter, 95% CI 0 to 2 d). For safety outcomes, evidence was of low or very low quality, with the exception of treatment with lopinavir/ritonavir for which moderate-quality evidence suggested likely increases in diarrhea, nausea and vomiting. To date, persuasive evidence of important benefit in COVID-19 does not exist for any antiviral treatments, although for each treatment evidence has not excluded important benefit. Additional randomized controlled trials involving patients with COVID-19 will be needed before such treatments can be administered with confidence.

On Mar. 11, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic. The worldwide spread of COVID-19 represents a profound threat to human health. Patients with COVID-19 present primarily with fever, cough, and myalgia or fatigue, and sometimes initially with predominantly gastrointestinal symptoms. A minority of patients progress to severe pneumonia, and about 15% of these patients to critical illness characterized by acute respiratory distress syndrome (ARDS), which is associated with mortality of about 50%. Here, Zhikang Ye et al. have developed an evidence-based guideline that focuses on both patients with nonsevere and severe COVID-19 and, for use of corticosteroids, patients with ARDS.