Search

Abstract We performed a systematic review and meta‐analysis to re‐evaluate the effectiveness of angiotensin‐converting enzyme inhibitors (ACE‐I) in the reduction of pneumonia risk. We searched relevant publications in five databases. All studies included patients older than 18 years, who had used ACE‐I as an intervention, and had assessed pneumonia. Seven RCTs (n = 8704) and 38 observational studies (n = 1,705,030) were included. The overall risk of bias was high. ACE‐I‐treated patients were associated with a slightly lower risk of pneumonia, both from pooled estimates of RCTs [pooled odds ratio (OR), 0.75; 95% confidence interval (CI), 0.62–0.90; low certainty of evidence] and observational studies (pooled OR, 0.85; 95% CI, 0.78–0.92; very low certainty of evidence). Considering the small effect size of ACE‐I in preventing pneumonia and the low quality of the evidence, routine use of ACE‐I for pneumonia prevention is not recommended.

Abstract Background Although many quality indicator (QI) sets have been developed for acute cardiovascular diseases, a comprehensive summary is lacking. In this scoping review we aimed to summarize the available evidence on the QI sets for acute cardiovascular diseases, and assess the QI set development process. We followed the Joanna Briggs Institute framework and the PRISMA extension for scoping reviews. Methods We conducted a systematic search of MEDLINE, EMBASE, and major international guidelines on QIs for acute major cardiovascular diseases. The study included articles published after 2000. Results Among the 3112 articles screened, 18 were included in this scoping review. Among the 18 articles included, 12 were on acute coronary syndrome (ACS), five on acute heart failure (AHF), and two on acute aortic dissection (AAD); one article included QIs for both ACS and AHF. Only four of these studies conducted a systematic search with a search strategy. From the 18 articles, 268 QIs containing duplication between articles were identified (191 QIs were for ACS, 57 were for AHF, and 20 were for AAD) and QI measurements varied across articles. Conclusions This scoping review provides a comprehensive list of QIs for acute cardiovascular diseases. Our results may be helpful to clinicians and organizations seeking to develop QIs for acute cardiovascular care in the future.

Objectives Researchers have identified cases in which newspaper stories have exaggerated the results of medical studies reported in original articles. Moreover, the exaggeration sometimes begins with journal articles. We examined what proportion of the studies quoted in newspaper stories were confirmed.Methods We identified newspaper stories from 2000 that mentioned the effectiveness of certain treatments or preventions based on original studies from 40 main medical journals. We searched for subsequent studies until June 2022 with the same topic and stronger research design than each original study. The results of the original studies were verified by comparison with those of subsequent studies.Results We identified 164 original articles from 1298 newspaper stories and randomly selected 100 of them. Four studies were not found to be effective in terms of the primary outcome, and 18 had no subsequent studies. Of the remaining studies, the proportion of confirmed studies was 68.6% (95% CI 58.1% to 77.5%). Among the 59 confirmed studies, 13 of 16 studies were considered to have been replicated in terms of effect size. However, the results of the remaining 43 studies were not comparable.Discussion In the dichotomous judgement of effectiveness, about two-thirds of the results were nominally confirmed by subsequent studies. However, for most confirmed results, it was impossible to determine whether the effect sizes were stable.Conclusions Newspaper readers should be aware that some claims made by high-quality newspapers based on high-profile journal articles may be overturned by subsequent studies within the next 20 years.

Abstract Background This article is a duplicated publication from the Japanese version of “2019 JSDT Guidelines for Peritoneal Dialysis” with permission from the Japanese Society for Dialysis Therapy (JSDT). This clinical practice guideline (CPG) was developed primarily by the Working Group on Revision of Peritoneal Dialysis (PD) Guidelines of the Japanese Society for Dialysis Therapy. Recently, the definition and creation process for CPGs have become far more rigorous; traditional methods and formats no longer adhere to current standards. To improve the reliability of international transmission of our findings, CPGs are created in compliance with the methodologies developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Part 2 of this PD guideline is the first CPG developed by our society that conforms to the GRADE approach. Methods Detailed processes were created in accordance with the Cochrane handbook and the GRADE approach developed by the GRADE working group. Results Clinical question (CQ)1: Is the use of renin-angiotensin system inhibitors (RAS inhibitors), such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), effective in PD patients? Recommendation: We suggest the usage of RAS inhibitors (ACEI and ARB) in PD patients (GRADE 2C). CQ2: Icodextrin or glucose solution: which is more useful as a dialysate among patients with PD? Recommendation: We suggest using icodextrin when managing body fluids in PD patients (GRADE 2C). CQ3: Is it better to apply or not apply mupirocin/gentamicin ointment to the exit site? Recommendation: We suggest not applying mupirocin/gentamicin ointment to the exit sites of PD patients (GRADE 2C). CQ4: Which surgical approach is more desirable when a PD catheter is placed, open surgery or laparoscopic surgery? No recommendation. CQ5: Which administration route of antibiotics is better in PD patients with peritonitis, intravenous or intraperitoneal? Recommendation: We suggest intraperitoneal administration of antibiotics in PD patients with peritonitis (GRADE 2C). Note: The National Insurance does not currently cover intraperitoneal administration. CQ6: Is peritoneal dialysis or hemodialysis better as the first renal replacement therapy in diabetic patients? No recommendation. Conclusions In the future, we suggest that society members construct their own evidence to answer CQs not brought up in this guideline, and thereby show the achievements of Japan worldwide.

Abstract Background Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. Methods This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants’ scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. Results Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. Conclusions We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. Trial registration UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

Abstract Background Pelvic fractures are common among blunt trauma patients, and timely and accurate diagnosis can improve patient outcomes. However, it remains unclear whether physical examinations are sufficient in this context. This study aims to perform a systematic review and meta-analysis of studies on the diagnostic accuracy and clinical utility of physical examination for pelvic fracture among blunt trauma patients. Methods Studies were identified using the MEDLINE, EMBASE, and CENTRAL databases starting from the creation of the database to January 2020. A total of 20 studies (49,043 patients with 8300 cases [16.9%] of pelvic fracture) were included in the quality assessment and meta-analysis. Two investigators extracted the data and evaluated the risk of bias in each study. The meta-analysis involved a hierarchical summary receiver operating curve (ROC) model to calculate the diagnostic accuracy of the physical exam. Subgroup analysis assessed the extent of between-study heterogeneity. Clinical utility was assessed using decision curve analysis. Results The median prevalence of pelvic fracture was 10.5% (interquartile range, 5.1–16.5). The pooled sensitivity (and corresponding 95% confidence interval) of the hierarchical summary ROC parameters was 0.859 (0.761–0.952) at a given specificity of 0.920, which was the median value among the included studies. Subgroup analysis revealed that the pooled sensitivity among patients with a Glasgow Coma Scale score ≥ 13 was 0.933 (0.847–0.998) at a given specificity of 0.920. The corresponding value for patients with scores ≤ 13 was 0.761 (0.560–0.932). For threshold probability

Abstract Background While conducting systemic reviews, searching for ongoing or unpublished trials is critical to address publication bias. As of April 2019, records of ongoing or unpublished randomized and/or quasi-randomized controlled trials registered in the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov are available in the Cochrane Central Register of Controlled Trials (CENTRAL). These records registered in CENTRAL include studies published since the inception of ICTRP and ClinicalTrials.gov . Whether systematic reviewers can search CENTRAL to identify ongoing or unpublished trials instead of ICTRP and ClinicalTrials.gov is unknown. Methods This was a cross-sectional study. A consecutive sample of ongoing or unpublished studies published from June 1, 2019 to December 27, 2019 was selected from the Cochrane Reviews. The sensitivity and the number needed to read (NNR) were assessed from among the studies selected from CENTRAL instead of ICTRP and ClinicalTrials.gov and also assessed the characteristics of studies not identified by searching CENTRAL. Results In total, 247 records from 50 Cochrane reviews were included; of these, 200 were identified by searching CENTRAL, whereas the remaining 47 records were not. The sensitivity of searching CENTRAL was 0.81 (95% confidence interval [CI]: 0.76, 0.85). The NNR was 115 (95% CI: 101, 133). The 47 unidentified studies were registered through ClinicalTrials.gov or ICTRP. Sixteen unidentified studies were not indexed in CENTRAL. Conclusions For systematic reviewers, searching CENTRAL could not substitute for searching ClinicalTrials.gov and/or ICTRP. Systematic reviewers should not only search CENTRAL but also ICTRP and ClinicalTrials.gov to identify unpublished trials. Trial registration A pre-specified protocol was applied to conduct this study. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). Trial registration number: UMIN000038981 .

Abstract Background Peritonitis is a common and clinically important complication in patients receiving peritoneal dialysis (PD). Antibiotic administration is essential for PD-related peritonitis, but routes of administration have not been established enough. Here, we performed a systematic review to assess the efficacy and safety of intraperitoneal (IP) antibiotic administration compared to intravenous (IV) antibiotic administration in patients with PD-related peritonitis. Methods Cochrane CENTRAL, MEDLINE, and Ichushi-Web were searched in June 2017. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and articles were screened by four independent reviewers. Results Two randomized controlled trials (113 patients) were identified. IP antibiotic administration was more effective than IV antibiotic administration. The pooled risk difference between IP and IV was 0.13 (95% CI − 0.17 to 0.43). Safety assessment indicated less frequency of side effects in patients receiving IP antibiotic administration. The pooled risk ratios of IV to IP regarding adverse drug reaction-related and administration route-related side effects were 5.13 (0.63 to 41.59) and 3.00 (0.14 to 65.90), respectively. Conclusion The systematic review and meta-analysis suggested that IP antibiotic administration is more effective and safer in patients with PD-related peritonitis compared to IV antibiotic administration.

Abstract Background The International Society for Peritoneal Dialysis guidelines recommends the topical application of antibiotics on the exit site for the prevention of peritoneal dialysis (PD)-related infections. However, the recommendation is based on meta-analyses on applying nasal mupirocin ointment or observational or retrospective studies. Here, we evaluated the efficacy of topical application of mupirocin on the exit site for the prevention of PD-related infections. Methods We searched the databases, MEDLINE and CENTRAL, documenting the topical application of antibiotics on the exit site in PD patients in April 2017. We included only randomized controlled trials (RCTs) with adult patients wherein the effects of mupirocin were examined. Exit site infection (ESI), peritonitis, and technical failure were assessed as the main outcomes. Results Overall, six RCTs were included in this study. It was uncertain whether the application of mupirocin ointment prevents ESI (rate ratio (RR), 0.36; 95% CI, 0.13–1.05), peritonitis (RR 0.78, 95% CI 0.50–1.21), and technical failure (RR, 1.35; 95% CI, 0.25–7.21). Moreover, a comparison between mupirocin and gentamicin showed no difference in the incidence of ESI (RR, 1.14; 95% CI, 0.27–4.81), peritonitis (RR, 0.85; 95% CI, 0.32–2.26), and technical failure (RR, 0.58; 95% CI, 0.28–1.20). Conclusions It remains unclear whether topical application of mupirocin on the exit site has any significant effects on PD-related infection or technical failure. Large-scale RCTs with high methodological quality are required to confirm the efficacy of topical application of antibiotics on the exit site. Trial registration UMINR000039267

Abstract Background Icodextrin enhances peritoneal filtration for patients on peritoneal dialysis (PD). However, clinically important outcomes have not yet been analyzed using authentic, objective statistical methods. The present systematic review aimed to determine the risks and benefits of icodextrin compared with a glucose-based solution with respect to clinically important and patient-centered outcomes. Methods We systematically investigated only randomized controlled trials (RCTs) by adopting the Cochrane Database of Systematic Review (2014) and searched the CENTRAL, MEDLINE, and EMBASE databases for eligible studies reported in the literature. The quality of the evidence was assessed using the GRADE approach. Results We finally evaluated important outcomes in 13 RCTs. Icodextrin significantly decreased the number of reported episodes of uncontrolled fluid overload in four RCTs that involved 236 patients (relative risk [RR], 0.31; 95% confidence interval [CI], 0.12 to 0.82; moderate certainty evidence). However, the inclusion of icodextrin for peritoneal ultrafiltration did not significantly differ in six RCTs involving 252 patients (mean difference [MD], 186.76 mL; 95% CI, − 47.08 to 420.59; low certainty evidence). Regarding other clinically important outcomes, all-cause mortality in 10 RCTs involving 1106 patients (RR, 0.75; 95% CI, 0.33 to 1.71; low certainty evidence) and technical survival in five RCTs involving 470 patients (RR, 0.57; 95%CI, 0.29 to 1.12; low certainty evidence) were not significant. Urine volume in four RCTs involving 136 patients, residual renal function in five RCTs involving 181 patients and peritoneal function measured as the ratio of solute concentration in dialysate and plasma (D/P ratio) in two RCTs involving 105 patients were not specifically affected by icodextrin, and the results for adverse events were similar between icodextrin and glucose PD solutions. Conclusion Icodextrin could relieve uncontrolled fluid overload without adding risk. However, a significant effect on clinically relevant outcomes such as technical survival and overall patient survival was not suggested. More trials are required to increase the statistical power and to verify the value of icodextrin in clinical practice. Trial registration PROSPERO, CRD42018104360

Objectives This study aimed to investigate the efficacy of providing education on injection technique to patients with diabetes with lipohypertrophy (LH).Design We conducted a systematic review and meta-analysis.Methods We included patients with diabetes who use insulin and have LH, and excluded patients without LH. We performed a literature search on CENTRAL, MEDLINE, EMBASE, ICTRP and ClinicalTrials.gov in November 2021 for randomised controlled trials (RCTs). We used the revised Cochrane Risk of Bias 2 tool to evaluate the risk of bias in each outcome in each study. We then pooled the data using a random-effects model and evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.Outcome measures The primary endpoints were change in total daily dose (TDD) of insulin, change in HbA1c levels and prevalence of hypoglycaemia.Results We screened 580 records and included three RCTs (637 participants) in the meta-analysis. Education on injection technique may slightly increase the change of TDD of insulin (three studies, 637 participants: mean difference (MD) −6.26; 95% CI −9.42 to –3.10; p

The aim of this review is to investigate the diagnostic accuracy or performance of contrast‐enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for acute pelvic inflammatory disease (PID) in an emergency care setting. We searched for studies on the diagnostic test accuracy of contrast‐enhanced CT or MRI for women of reproductive age with acute abdominal pain using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov. The reference standard was gynecological examinations by gynecologists using standard diagnostic criteria with or without laparoscopy or transcervical endometrial biopsy. Two reviewers undertook screening of records, data extraction, and assessment of the risk of bias in each included study using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. A bivariate model was used for the meta‐analysis. Of 2,619 screened studies, three studies investigating contrast‐enhanced CT and one study investigating MRI were eligible, including a total 635 patients and with a median prevalence of acute PID of 29%. All of the included studies had a high risk of bias for a reference standard and had some applicability concerns. Contrast‐enhanced CT had a pooled sensitivity of 0.79 (95% confidence interval [CI], 0.52–0.93) and specificity of 0.99 (95% CI, 0.94–1.00). Magnetic resonance imaging had a sensitivity of 0.95 (95% CI, 0.76–1.00) and specificity of 0.89 (95% CI, 0.52–1.00). Contrast‐enhanced CT might serve as a practical alternative to gynecological examination in the diagnosis of acute PID in an emergency care setting, however, the evidence was uncertain. The evidence on MRI was also very uncertain.

Meta-analyses examining dichotomous outcomes often include single-zero studies, where no events occur in intervention or control groups. These pose challenges, and several methods have been proposed to address them. A fixed continuity correction method has been shown to bias estimates, but it is frequently used because sometimes software (e.g., RevMan software in Cochrane reviews) uses it as a default. We aimed to empirically compare results using the continuity correction with those using alternative models that do not require correction. To this aim, we reanalyzed the original data from 885 meta-analyses in Cochrane reviews using the following methods: (i) Mantel-Haenszel model with a fixed continuity correction, (ii) random effects inverse variance model with a fixed continuity correction, (iii) Peto method (the three models available in RevMan), (iv) random effects inverse variance model with the treatment arm continuity correction, (v) Mantel-Haenszel model without correction, (vi) logistic regression, and (vii) a Bayesian random effects model with binominal likelihood. For each meta-analysis we calculated ratios of odds ratios between all methods, to assess how the choice of method may impact results. Ratios of odds ratios <0.8 or <1.25 were seen in [approximately]30% of the existing meta-analyses when comparing results between Mantel-Haenszel model with a fixed continuity correction and either Mantel-Haenszel model without correction or logistic regression. We concluded that injudicious use of the fixed continuity correction in existing Cochrane reviews may have substantially influenced effect estimates in some cases. Future updates of RevMan should incorporate less biased statistical methods.

Abstract Background Diabetes has become the most common cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) in most countries around the world. Peritoneal dialysis (PD) is valuable for patients newly requiring RRT because of the preservation of residual renal function (RRF), higher quality of life, and hemodynamic stability in comparison with hemodialysis (HD). A previous systematic review produced conflicting results regarding patient survival. As several advances have been made in therapy for diabetic patients receiving PD, we conducted a systematic review of studies published after 2014 to determine whether incident PD or HD is advantageous for the survival of patients with diabetes. Methods For this systematic review, the MEDLINE, EMBASE, and CENTRAL databases were searched to identify articles published between February 2014 and August 2017. The quality of studies was assessed using the GRADE approach. Outcomes of interest were all-cause mortality; RRF; major morbid events, including cardiovascular disease (CVD) and infectious disease; and glycemic control. This review was performed using a predefined protocol published in PROSPERO (CRD42018104258). Results Sixteen studies were included in this review. All were retrospective observational studies, and the risk of bias, especially failure to adequately control confounding factors, was high. Among them, 15 studies investigated all-cause mortality in diabetic patients initiating PD and HD. Differences favoring HD were observed in nine studies, whereas those favoring PD were observed in two studies. Two studies investigated effects on CVD, and both demonstrated the superiority of incident HD. No study investigated the effect of any other outcome. Conclusions In the present systematic review, the risk of death tended to be higher among diabetic patients with ESRD newly initiating RRT with incident PD in comparison with incident HD. However, we could not obtain definitive results reflecting the superiority of PD or HD with regard to patient outcomes because of the severe risk of bias and the heterogeneity of management strategies for diabetic patients receiving dialysis. Further studies are needed to clarify the advantages of PD and HD as RRT for diabetic patients with ESRD.

Abstract Background The low data publication rate for Food and Drug Administration (FDA)-approved drugs, and discrepancies between FDA-submitted versus published data, remain a concern. We investigated the publication statuses of sponsor-submitted clinical trials supporting recent anticancer drugs approved by the FDA, with a focus on immune checkpoint inhibitors (ICPis). Methods We identified all ICPis approved between 2011 and 2014, thereby obtaining 3 years of follow-up data. We assessed the clinical trials performed for each drug indication and matched each trial with publications in the literature. The primary benchmark was the publication status 2 years post-approval. We examined the association between time to publication and drug type using a multilevel Cox regression model that was adjusted for clustering within drug indications and individual covariates. Results Between 2011 and 2014, 36 anticancer drugs including 3 ICPis were newly approved by the FDA. Of 19 trials investigating the 3 ICPis, 11 (58%) were published within 2 years post-approval. We randomly selected 10 of the 33 remaining anticancer drugs; 68 of 101 trials investigating these drugs (67%) were published. Overall, the publication rate was 66% at 2 years post-approval with a median time to publication of 2.3 years. There was no significant difference in the time to trial publication between ICPis and other anticancer drugs (adjusted hazard ratio [HR], 1.1; 95% confidence interval [CI], 0.8–1.7; P = 0.55). However, findings related to non-ICPis investigated specifically in randomized phase 2 or phase 3 trials were significantly more likely to be published earlier than those related to ICPis (adjusted HR, 7.4; 95% CI, 1.8–29.5; P = 0.005). Conclusion One in 3 sponsor-submitted trials of the most recently approved anticancer drugs remained unpublished 2 years post-FDA approval. We found no evidence that the drug type was associated with the time to overall trial publication.

Abstract Success in peritoneal dialysis (PD) requires a well-functioning catheter, and catheter placement at PD initiation is extremely important for long-term PD. Although several randomized, controlled trials (RCTs) have compared open surgery with laparoscopic surgery, there is controversy regarding which surgical approach is desirable. The present systematic review and meta-analysis was performed to clarify which surgical approach is superior. A systematic literature search for RCTs was performed using the Cochrane Central Register of Controlled Trials and the MEDLINE database, and a meta-analysis was performed using Review Manager Version 5.3.5 (Cochrane Collaboration, Oxford, UK). Catheter survival was the primary outcome, and leakage, hernia, requirement for reoperation, catheter-related infection, postoperative pain, hospitalization period associated with catheter placement, and catheter migration were the secondary outcomes. After screening 913 references, seven RCTs were analyzed. Laparoscopic surgery was found to have no favorable effect on catheter survival (5 trials, 424 patients; risk ratio [RR] 1.02; 95% confidence interval [CI] 0.92–1.13; p = 0.68; low-quality evidence]. The incidence of catheter migration was significantly lower with laparoscopic surgery (6 trials, 526 patients; RR 0.42; 95% CI 0.18–0.96; p = 0.04; moderate-quality evidence). However, the significance decreased on limiting the analysis to RCTs involving laparoscopic surgery without secured suture of the PD catheter (4 trials, 431 patients; RR 0.58; 95% CI 0.27–1.25; p = 0.17; moderate-quality evidence). Other outcomes were similar between open surgery and laparoscopic surgery. The present findings indicate that laparoscopic surgery has a limited advantage over open surgery with respect to PD patients’ outcomes.

Abstract Background Renin-angiotensin system inhibitors (RASIs), either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are widely used in patients with non-dialysis chronic kidney disease, as a renin-angiotensin system (RAS) blockade has renoprotective effects. Several studies show that preserving residual renal function is important for a better prognosis in peritoneal dialysis (PD) patients. Here, we systematically reviewed the beneficial or harmful effects of RAS blockade in PD patients. Methods PubMed, the Cochrane Library, Embase, the Ichushi web databases, and other resources were selected to search clinical guidelines, systematic reviews, and randomized controlled trials (RCT) published before April 14, 2017, using “peritoneal dialysis,” “angiotensin-converting enzyme inhibitors,” “angiotensin II type 1 receptor blockers,” and “randomized controlled trial” as keywords. Desired results were total mortality, technical survival, urine volume, residual renal function calculated by glomerular filtration rate (GFR), cardiovascular events, and anuria progression rate. The study protocol is registered in PROSPERO (International Prospective Register of Systematic Reviews) under the registration number CRD42018104106. Results Of a total of 339 studies, eight were identified as suitable for the analysis. Only one study was blinded, whereas the other seven studies were open-label. RASI appeared to preserve residual renal function, GFR (4 studies, 163 participants, mean difference [MD] 0.97 mL/min/1.73 m2, 95% confidence interval [CI] 0.49–1.44), and urine volume (6 studies, 194 participants, MD 142.56 mL 95% CI 25.42–259.69), although there were no beneficial effects of RASI on total mortality, technical survival, cardiovascular events, and anuria rate. Conclusions Our analysis found that RASIs contribute to preserving GFR and urine volume in PD patients. As the number of study participants is small, further studies with a larger sample size are required.

Abstract Objective PROSPERO, an international prospective register of systematic reviews, was launched in February 2011 to reduce publication bias of systematic reviews (SRs). A questionnaire survey of SR researchers conducted in 2005 indicated the existence of unpublished SRs and the potential influence of lack of funding as a reason for non-publication. Here, we investigated the publication status of registered SRs in the 1st year that PROSPERO launched and assessed the association between publication and the existence of funding or conflicts of interest (COIs). Results We identified 326 SRs registered in PROSPERO from February 2011 through February 2012. Among them, 85 SRs (26%) remained unpublished at least 65 months after registration. We found 241 published reports, including four conference abstracts and one poster presentation. Median time to publication from protocol registration was 16.3 months. Funding for SRs was associated with publication [odds ratio (OR) = 2.10; 95% confidence interval (CI) = 1.26 to 3.50]. We found no significant association of author-reported COIs with publication (OR = 2.35; 95% CI = 0.67 to 8.20). Twenty SRs were not published despite the authors reporting completion of the reviews in PROSPERO.

Objectives To accumulate evidence that obstacle avoidance training alone is effective in improving the locomotor ability of individuals with stroke.Design Systematic review and meta-analysis.Setting MEDLINE, EMBASE, CENTRAL, ICTRP and PEDro were searched for related information until December 2018. Two independent reviewers extracted data. Outcome measurement data were subjected to meta-analyses using random-effects models. Data syntheses were conducted using RevMan V.5.3, and the certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach.Participants Participants with various types and phases of stroke were included.Intervention The usual gait training including obstacle avoidance training (interventions of any type, intensity, duration and frequency).Primary and secondary outcome measures Primary outcomes were gait speed, composite gait ability and objective balance ability. Secondary outcomes were subjective balance ability, gait endurance and fall incidence.Results Two randomised controlled trials with a total of 49 participants were used as data sources for this study. The obstacle avoidance training (training) group had lower gait speed than the control group (mean difference (MD) 0.03, 95% CI −0.11 to 0.16, p=0.51). Further, the certainty of evidence was very low. The subjective balance ability (Activities-specific Balance Confidence scale) was not significantly different between the training and control groups (MD 6.65, 95% CI −7.59 to 20.89, p=0.36), and it showed very low certainty of evidence.Conclusions Obstacle avoidance training may have little or no effect on individuals with stroke. The failure to find the effectiveness of obstacle avoidance training alone is possibly attributable to the insufficient amount of training in the intervention and the lack of well-designed studies that measured relevant outcomes.PROSPERO registration number CRD42017060691.

Introduction Vasoplegia is common and associated with a poor prognosis in patients with sepsis and septic shock. Vitamin C therapy in combination with vitamin B1 and glucocorticoid, as well as monotherapy in various doses, has been investigated as a treatment for the vasoplegic state in sepsis, through targeting the inflammatory cascade. However, the combination effect and the relative contribution of each drug have not been well evaluated. Furthermore, the best combination between the three agents is currently unknown. We are planning a systematic review (SR) with network meta-analysis (NMA) to compare the different treatments and identify the combination with the most favourable effect on survival.Methods and analysis We will include all randomised controlled trials comparing any intervention using intravenous vitamin C, vitamin B1 and/or glucocorticoid with another or with placebo in the treatment of sepsis. We are interested in comparing the following active interventions. Very high-dose vitamin C (≥12 g/day), high-dose vitamin C (≥6 g/day), vitamin C (

[This corrects the article DOI: 10.1371/journal.pone.0201292.].

OBJECTIVES:Little is known about the physician characteristics associated with appraisal skills of research evidence, especially the assessment of the validity of study methodology. This study aims to explore physician characteristics associated with proper assessment of overstated conclusions in research abstracts. DESIGN:A secondary analysis of a randomized controlled trial. SETTING AND PARTICIPANTS:We recruited 567 volunteers from the Japan Primary Care Association. METHODS:Participants were randomly assigned to read the abstract of a research paper, with or without an overstatement, and to rate its validity. Our primary outcome was proper assessment of the validity of its conclusions. We investigated the association of physician characteristics and proper assessment using logistic regression models and evaluated the interaction between the associated characteristics and overstatement. RESULTS:We found significant associations between proper assessment and post-graduate year (odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.49 to 0.91, for every 10-year increase) and research experience as a primary investigator (PI; OR = 2.97, 95% CI 1.65 to 5.34). Post-graduate year and PI had significant interaction with overstatement (P = 0.015 and < 0.001, respectively). Among participants who read abstracts without an overstatement, post-graduate year was not associated with proper assessment (OR = 1.04, 95% CI 0.82 to 1.33), and PI experience was associated with lower scores of the validity (OR = 0.58, 95% CI 0.35 to 0.96). CONCLUSION:Physicians who have been in practice longer should be trained in distinguishing overstatements in abstract conclusions. Physicians with research experience might be informed that they tend to rate the validity of research lower regardless of the presence or absence of overstatements. TRIAL REGISTRATION:UMIN000026269.

Background Insomnia is common. However, no systematic reviews have examined the effect of exercise on patients with primary and secondary insomnia, defined as both sleep disruption and daytime impairment. This systematic review and meta-analysis aimed to examine the effectiveness/efficacy of exercise in patients with insomnia. Methods We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify all randomized controlled trials that examined the effects of exercise on various sleep parameters in patients with insomnia. All participants were diagnosed with insomnia, using standard diagnostic criteria or predetermined criteria and standard measures. Data on outcome measures were subjected to meta-analyses using random-effects models. The Cochrane Risk of Bias Tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of the individual studies and the body of evidence, respectively. Results We included nine studies with a total of 557 participants. According to the Pittsburgh Sleep Quality Index (mean difference [MD], 2.87 points lower in the intervention group; 95% confidence interval [CI], 3.95 points lower to 1.79 points lower; low-quality evidence) and the Insomnia Severity Index (MD, 3.22 points lower in the intervention group; 95% CI, 5.36 points lower to 1.07 points lower; very low-quality evidence), exercise was beneficial. However, exercise interventions were not associated with improved sleep efficiency (MD, 0.56% lower in the intervention group; 95% CI, 3.42% lower to 2.31% higher; moderate-quality evidence). Only four studies noted adverse effects. Most studies had a high or unclear risk of selection bias. Discussion Our findings suggest that exercise can improve sleep quality without notable adverse effects. Most trials had a high risk of selection bias. Higher quality research is needed.

The objective of this systematic review was to determine whether rehabilitation impacts clinically relevant outcomes among adult patients with sepsis. Randomized controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PEDro, and the World Health Organization International Clinical Trials Platform Search Portal, as well as conference proceedings and reference lists of relevant articles were collected. Two reviewers independently identified randomized controlled trials on the rehabilitation of patients with sepsis, and the two reviewers independently abstracted trial level data including population characteristics, interventions, comparisons, and clinical outcomes. Our primary outcomes were quality of life (QOL), activity of daily living (ADL), and mortality. Our secondary outcomes were length of stay, return to work, muscle strength, delirium, and all adverse events. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We included two trials enrolling 75 patients. The mean difference (95% confidence interval [CI]) of physical function and physical role in QOL measured by SF-36 were 21.10 (95% CI: 6.57-35.63) and 44.40 (95% CI: 22.55-66.05), respectively. Rehabilitation did not significantly decrease intensive care unit (ICU) mortality (risk ratio, 2.02 [95% CI: 0.46-8.91], I2 = 0%; n = 75). ICU length of stay and hospital length of stay and muscle strength were not statistically significantly different and no adverse events were reported in both studies. The certainty of the evidence for these outcomes was "very low." Data on ADL, return to work, and delirium were not available in any of the trials. Rehabilitation of patients with sepsis might not decrease ICU mortality, but might improve QOL. Further, well-designed trials measuring important outcomes will be needed to determine the benefit and harm of rehabilitation among patients with sepsis.