Efficacy and safety of alcohol reduction pharmacotherapy according to treatment duration in patients with alcohol dependence or alcohol use disorder: A systematic review and network meta-analysis.

BACKGROUND AND AIMS: Relapse is common in alcohol dependence (AD) and alcohol use disorder (AUD), so alcohol reduction therapy should be measured over as long a period as possible; however, existing reviews do not consider the duration of treatment and therefore alcohol reduction therapy may not have been appropriately evaluated. This review evaluated the efficacy and safety of alcohol reduction pharmacotherapy in patients with AD or AUD according to the duration of treatment. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) that assessed 15 pharmacological agents. MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov and the International Clinical Trials Registry Platform were searched for eligible trials through to May 2021. Outcomes were heavy drinking days (HDD), total alcohol consumption (TAC), any adverse event and days without drinking. RESULTS: Fifty-five RCTs (n = 8891) were included. Nalmefene was superior to placebo for reducing HDD (standard mean difference [SMD] -0.28, 95% confidence interval [CI] -0.37, -0.18) and TAC (SMD -0.25, 95% CI -0.35, -0.16) in the long-term, but not in the short-term. Topiramate was superior to placebo for reducing HDD (SMD -0.35, 95% CI -0.59, -0.12) and days without drinking (SMD 0.46, 95% CI 0.11, 0.82), and baclofen was superior for reducing TAC (SMD -0.70, 95% CI -1.29, -0.11), in the short-term. The frequency of adverse events was higher with nalmefene and topiramate than with placebo. CONCLUSION: Nalmefene, topiramate and baclofen may be effective as alcohol reduction pharmacotherapy; however, only nalmefene has demonstrated long-term efficacy, and nalmefene and topiramate have a significantly higher frequency of adverse events compared with placebo.

An open competition involving thousands of competitors failed to construct useful abstract classifiers for new diagnostic test accuracy systematic reviews.

There are currently no abstract classifiers, which can be used for new diagnostic test accuracy (DTA) systematic reviews to select primary DTA study abstracts from database searches. Our goal was to develop machine-learning-based abstract classifiers for new DTA systematic reviews through an open competition. We prepared a dataset of abstracts obtained through database searches from 11 reviews in different clinical areas. As the reference standard, we used the abstract lists that required manual full-text review. We randomly splitted the datasets into a train set, a public test set, and a private test set. Competition participants used the training set to develop classifiers and validated their classifiers using the public test set. The classifiers were refined based on the performance of the public test set. They could submit as many times as they wanted during the competition. Finally, we used the private test set to rank the submitted classifiers. To reduce false exclusions, we used the Fbeta measure with a beta set to seven for evaluating classifiers. After the competition, we conducted the external validation using a dataset from a cardiology DTA review. We received 13,774 submissions from 1429 teams or persons over 4 months. The top-honored classifier achieved a Fbeta score of 0.4036 and a recall of 0.2352 in the external validation. In conclusion, we were unable to develop an abstract classifier with sufficient recall for immediate application to new DTA systematic reviews. Further studies are needed to update and validate classifiers with datasets from other clinical areas.

Prediction Models for Intravenous Immunoglobulin Resistance in Kawasaki Disease: A Meta-analysis.

CONTEXT: Approximately 10% to 20% of patients with Kawasaki disease (KD) are refractory to initial intravenous immunoglobulin (IVIG) therapy. KD is mainly associated with coronary artery abnormalities. OBJECTIVES: To identify and evaluate all developed prediction models for IVIG resistance in patients with KD and synthesize evidence from external validation studies that evaluated their predictive performances. DATA SOURCES: PubMed Medline, Dialog Embase, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from inception until October 5, 2021. STUDY SELECTION: All cohort studies that reported patients diagnosed with KD who underwent an initial IVIG of 2 g/kg were selected. DATA EXTRACTION: Study and patient characteristics and model performance measures. Two authors independently extracted data from the studies. RESULTS: The Kobayashi, Egami, Sano, Formosa, and Harada scores were the only prediction models with 3 or more external validation of the161 model analyses in 48 studies. The summary C-statistics were 0.65 (95% confidence interval [CI]: 0.57-0.73), 0.63 (95% CI: 0.55-0.71), 0.58 (95% CI: 0.55-0.60), 0.50 (95% CI: 0.36-0.63), and 0.63 (95% CI: 0.44-0.78) for the Kobayashi, Egami, Sano, Formosa, and Harada models, respectively. All 5 models showed low positive predictive values (0.14-0.39) and high negative predictive values (0.85-0.92). LIMITATIONS: Potential differences in the characteristics of the target population among studies and lack of assessment of calibrations. CONCLUSIONS: None of the 5 prediction models with external validation accurately distinguished between patients with and without IVIG resistance.

Clinical characterization of patients with schizophrenia and 16p13.11 duplication: A case series.

BACKGROUND: Chromosome 16p13.11 duplication is a well-known genetic risk factor for schizophrenia (SCZ) (odds ratio = 1.84). However, no case reports focusing on patients with SCZ and 16p13.11 duplication have been published. Therefore, here, we report the detailed clinical cases of four patients with SCZ and 16p13.11 duplication who were identified in our previous whole-genome copy number variant (CNV) study. CASE PRESENTATION: In the four patients with SCZ and 16p13.11 duplication detected by array comparative genomic hybridization, one patient was found to have treatment-resistant SCZ and an additional pathogenic rare CNV. Two of the four patients in this study had environmental risk factors that may have been involved in the development of SCZ. CONCLUSIONS: The results of this case series suggest that a genetic cohort study would be useful for evaluating which genetic and environmental risk factors could better explain the variable expressivity of 16p13.11 duplication. Furthermore, this work could be useful for elucidating the pathophysiology of SCZ.

Efficacy of intravenous dexamethasone on postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid: a systematic review and meta-analysis.

PURPOSE: Intravenous dexamethasone is recommended in elective caesarean delivery to decrease postoperative pain. However, the efficacy of spinal anaesthesia with an intrathecal long-acting opioid such as morphine or diamorphine for caesarean delivery has not been systematically investigated. METHODS: We searched all randomized controlled trials (RCTs) of pregnant women undergoing caesarean delivery under spinal anaesthesia with an intrathecal morphine or diamorphine via MEDLINE, CENTRAL, EMBASE, ICTRP, and ClinicalTrials.gov on May 18, 2022. Primary outcomes were time to first rescue analgesia, consumption of oral morphine equivalents, and incidence of drug-related adverse reactions. We evaluated the risk of bias for each outcome using the Risk of Bias 2. We conducted a meta-analysis using a random effects model. We evaluated the certainty of evidence with the GRADE approach. RESULTS: Five RCTs (455 patients) were included. The results of intravenous dexamethasone were as follows: time to first rescue analgesia (mean difference [MD] 0.99 h, 95% confidence interval [CI] - 0.86 to 2.84; very low certainty) and consumption of oral morphine equivalents (MD - 6.55 mg, 95% CI - 17.13 to 4.02; moderate certainty). No incidence of drug-related adverse reactions was reported (very low certainty). CONCLUSION: The evidence was very uncertain about the efficacy of intravenous dexamethasone on time to first rescue analgesia and the incidence of drug-related adverse reactions. Intravenous dexamethasone probably reduces the consumption of oral morphine equivalents. Anaesthesiologists might want to consider intravenous dexamethasone for postoperative pain after caesarean delivery under spinal anaesthesia with an intrathecal long-acting opioid.

Beta-lactam allergy and drug challenge test in children: a systematic review and meta-analysis.

BACKGROUND: Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test. METHODS: We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021. RESULTS: The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I2 = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I2 = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I2 = 38%) from 18 studies. CONCLUSIONS: The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare. IMPACT: Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.

Diagnostic accuracy of pelvic imaging for acute pelvic inflammatory disease in an emergency care setting: a systematic review and meta-analysis.

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.

Unclear Insomnia Concept in Randomized Controlled Trials and Systematic Reviews: A Meta-Epidemiological Study.

There are two possible ways to conceptualize the term "insomnia": insomnia disorder and insomnia symptoms, which are often poorly reported. The purpose of this study was to examine the proportion of randomized controlled trials (RCTs) and systematic reviews (SRs) that mention insomnia in their abstracts and cannot distinguish between insomnia disorder and insomnia symptoms from the abstract. We included RCT and SR articles that included the word "insomnia" in the methods or results sections of their structured abstracts, published after 2010. We searched PubMed using English language restrictions on 10 March 2022. From 1580 PubMed articles, we obtained 100 random samples each for eligible RCTs and SRs. The unclear insomnia concept accounted for 88% of the RCT abstracts and 94% of the SR abstracts. Among the RCT and SR abstracts with unclearness, the concept of insomnia was unclear in 27% of RCTs and 57% of SRs after investigating the full text. The concept of insomnia has been unclear in many RCTs and SRs abstracts. The authors of RCTs and SRs are recommended to state "insomnia disorder" or "insomnia symptoms" in the methods and results sections of their abstracts.

Efficacy of albumin with diuretics in mechanically ventilated patients with hypoalbuminemia: A systematic review and meta-analysis.

BACKGROUND: Hypoalbuminemia is associated with fluid overload, the development of acute respiratory distress syndrome, and mortality. The co-administration of albumin and diuretics for the treatment of patients with hypoalbuminemia is expected to increase urine output, without hemodynamic instability, and improve pulmonary function; however, these effects have not been systematically investigated. Here, we aimed to clarify the benefits of the co-administration of albumin and diuretics in mechanically ventilated patients. METHODS: We searched for randomized, placebo-controlled trials that investigated the effects of the co-administration of albumin and diuretics compared with placebo and diuretics, in mechanically ventilated patients with hypoalbuminemia. We searched these trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, and EMBASE databases. Primary outcomes were hypotensive events after the intervention, all-cause mortality, and the length of mechanical ventilation. Secondary outcomes were improvement in the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (P/F ratio) at 24 hours, total urine output (mL/d), and the clinical requirement of renal replacement therapy (RRT). RESULTS: From the 1574 records identified, we selected 3 studies for quantitative analysis. The results of albumin administration were as follows: hypotensive events (risk ratio [RR] -1.05 [95% confidence interval {CI}: 0.15-0.81]), all-cause mortality (RR 1.0 [95% CI: 0.45-2.23]), the length of mechanical ventilation in days (mean difference -1.05 [95% CI: -3.35 to 1.26]), and improvement in P/F ratio (RR 2.83 [95% CI: 1.42-5.67]). None of the randomized controlled trials reported the total urine output, and one reported that no participants required RRT. Adverse events were not reported during the trials. The certainty of evidence was low (in the hypotensive events after the intervention and all-cause mortality) to moderate (in the length of mechanical ventilation in days, improvement of P/F ratio, clinical requirement of RRT, and adverse events). CONCLUSIONS: Although this treatment combination reduced the number of days for which mechanical ventilation was required, it did not reduce the all-cause mortality at 30 days. In conclusion, the co-administration of albumin and diuretics may reduce hypotensive events and improve the P/F ratio at 24 hours.

Association of visceral adipose tissue with postoperative outcome in upper gastrointestinal cancer: a systematic review and meta-analysis.

BACKGROUND: There is no consensus on the relation between visceral fat mass and long-term postoperative prognosis in patients with upper gastrointestinal (GI) cancer. OBJECTIVES: The purpose of this study was to investigate the association of preoperative visceral fat mass with postoperative complications and overall survival (OS) in patients with upper GI cancer. METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE (Dialog), the WHO International Clinical Trials Platform Search Portal, and ClinicalTrials.gov and identified observational studies published from inception through 20 July 2022. We conducted a systematic review and random-effects meta-analysis of studies including patients who were surgically treated for upper GI cancer and whose visceral fat mass was assessed on the basis of body composition. We independently assessed the risk of bias and quality of evidence using the Quality In Prognosis Studies and the Grading of Recommendations, Assessment, Development, and Evaluation approach, respectively. The primary outcome was OS. HRs and 95% CIs for OS were pooled. RESULTS: Ninety-one studies (n = 20,583) were included. All studies used computed tomography (CT) to assess the body composition of patients. Twenty-four studies reported the relation between high visceral fat and postoperative outcomes, and their results were synthesized. Compared with low visceral adipose tissue, high visceral adipose tissue assessed by CT may improve OS (HR: 0.69; 95% CI: 0.55, 0.87; I2 = 65%; n = 3407). The risk of bias for OS in each study was moderate or high. The certainty of evidence for OS was very low because of inconsistency in the forest plot, the moderate or high risk of bias, and publication bias. CONCLUSIONS: High visceral fat may be associated with improved OS after radical resection in patients with upper GI cancer. Further studies are needed to confirm these findings and mitigate the risk.

Retracted randomized controlled trials were cited and not corrected in systematic reviews and clinical practice guidelines.

BACKGROUND AND OBJECTIVES: To investigate whether and when the correction is done in Systematic Reviews (SRs) and Clinical Practice Guidelines (CPGs) when included Randomized Controlled Trials (RCTs) have been retracted. METHODS: In this meta-epidemiological study, we included SRs and CPGs citing the retracted RCTs from the Retraction Watch Database. We investigated how often the retracted RCTs were cited in SRs and CPGs. We also investigated whether and when such SRs and CPGs corrected themselves. RESULTS: We identified 587 articles (525 SRs and 62 CPGs) citing retracted RCTs. Among the 587 articles, 252 (43%) were published after retraction, and 335 (57%) were published before retraction. Among 127 articles published citing already retracted RCTs in their evidence synthesis without caution, none corrected themselves after publication. Of 335 articles published before retraction, 239 included RCTs that were later retracted in their evidence synthesis. Among them, only 5% of SRs (9/196) and 5% of CPGs (2/43) corrected or retracted their results. CONCLUSION: Many SRs and CPGs included already or later retracted RCTs without caution. Most of them were never corrected. The scientific community, including publishers and researchers, should make systematic and concerted efforts to remove the impact of retracted RCTs.

Regarding "Stress management and In Vitro Fertilization (IVF): A pilot randomized controlled trial".

Koumparou et al.1 recently published a randomized controlled trial (RCT) on the effectiveness of psychological interventions (stress management training, SMT) for women planning in vitro fertilization (IVF). They concluded that while the effect of SMT was limited in terms of IVF outcome, it resulted in a significant reduction of stress levels in infertile patients. Since most women undergoing infertility treatment are exposed to high psychological stress,2 this study may be of great value in demonstrating the need for proactive SMT to maintain infertile women's mental health and motivation to continue treatment. However, we are concerned that the reliability of this RCT has been compromised in several ways. First, the registration of the RCT was not clearly stated. According to The CONsolidated Standards of Reporting Trials (CONSORT) 2010 guidelines, a prospective registration of the RCT is required, which prevents unnecessary concerns about the bias of results selection.3,4 Second, the lack of specific figures on the background of the participants in the case and control groups risks distorting the RCT results. The article states that there was no significant difference between the two groups. However, since aging and prolonged infertility treatment increase the psychological burden on infertile patients,5 detailed background information is necessary to interpret the results of an RCT accurately. Selection bias could not be determined, which weakened the validity of this RCT. Furthermore, the absence of any mention of case dropout makes the conclusions of this RCT uncertain; a discussion of cases demonstrating difficulty in completing an 8-week psychological program would clarify whether temporary SMT would show efficacy for patients. Finally, it is essential to note that the details of IVF have not been clarified. Since the timing of the SMT and IVF-ET cycles or details of the IVF-ET protocol were not shown, this RCT could not be used as a reference for IVF facilities to actually operate SMT. There is no doubt that psychological interventions are necessary for infertile patients exposed to high psychological stress, but this RCT has many details that have not been clarified, and the conclusions are attenuated. As details become clearer, this RCT will provide a foundation for the active use of SMT in infertility treatment settings.

Association of low birthweight and premature birth with hypertensive disorders in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that women born preterm or small have an increased risk of experiencing hypertensive disorders during pregnancy; however, a quantitative summary of the evidence on this issue is unavailable. OBJECTIVE: We aimed to systematically review the literature to describe the association between being born preterm, low birthweight (LBW), or small for gestational age (SGA), and future gestational hypertension, preeclampsia, or eclampsia. METHODS: We searched the MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and ICTRP databases. We included all cohort and case-control studies examining the association between LBW, preterm birth, or SGA and hypertensive disorders in pregnancy. We pooled the odds ratios and 95% confidence intervals using the DerSimonian and Laird random-effects model. We assessed the certainty of evidence for each outcome using the Grading of Recommendations, Assessment, Development, and Evaluation criteria. RESULTS: Eleven studies were identified, totalling 752 316 participants. Being born preterm, LBW, or SGA was associated with gestational hypertension [pooled odds ratio (OR), 1.31; 95% confidence interval (CI) 1.15-1.50; moderate certainty of evidence] and preeclampsia (pooled OR, 1.35; 95% CI 1.23-1.48; moderate certainty of evidence). No study measured eclampsia as an outcome. CONCLUSION: Women born preterm, LBW, or SGA have an increased risk of gestational hypertension and preeclampsia. The course of the mother's own birth might be used to identify women at risk of gestational hypertension and preeclampsia.