BACKGROUND: Dengue fever continues to pose significant health challenges globally, with recent outbreaks in Bihar, India, prompting a search for effective therapeutic interventions. This study assesses the effectiveness of Montelukast, traditionally used for asthma, in mitigating the severity of dengue fever symptoms and its progression to dengue shock syndrome (DSS).
OBJECTIVE: To evaluate the impact of Montelukast on the prevalence of dengue warning signs and the incidence of DSS in adult patients.
METHODS: A prospective observational study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India, from August 2022 to October 2023, enrolling 500 patients diagnosed with dengue fever. Participants were divided into two groups. About 250 were treated with Montelukast and 250 received standard care. Outcomes measured included the incidence of warning signs, DSS, length of hospital stay, and 30-day mortality.
RESULTS: The Montelukast group exhibited a 24% lower prevalence of dengue warning signs compared to the control group, with 90 out of 250 patients (36%) in the Montelukast group versus 150 out of 250 patients (60%) in the control group (p < 0.001). The incidence of DSS was significantly reduced in the Montelukast group, with 4 out of 250 patients (1.6%) compared to 21 out of 250 patients (8.4%) in the control group (odds ratio: 0.178, p < 0.001). Furthermore, Montelukast users experienced shorter hospital stays (average 4.52 days vs. 6.54 days, T-statistic: -7.59, p = 1.58×10-13) and a reduced 30-day mortality rate, with 5 out of 250 patients (2%) in the Montelukast group versus 12 out of 250 patients (5%) in the control group (p < 0.03).
CONCLUSIONS: Montelukast significantly lowers the incidence of dengue warning signs and DSS, shortens hospital stays, and decreases mortality rates among dengue patients, supporting its potential integration into existing dengue treatment protocols. This study highlights the need for further clinical trials to confirm these findings and fully understand the therapeutic mechanisms of Montelukast in dengue management.

BACKGROUND: The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence.
METHODS: A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated.
RESULTS: Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73-3.32) with a mean absolute risk difference of 8.7% (- 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79-3.71) with a mean absolute risk difference of 10.8% (95%CrI - 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively.
CONCLUSIONS: The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials.
BACKGROUND: INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060 ).

OBJECTIVE: To evaluate the efficacy and safety of intra-articular injections of a novel aggrecan mimetic, SB-061, in subjects with knee OA.
METHODS: This was a randomized, placebo-controlled, double-blind phase II study comparing intra-articular injections of SB-061 with placebo (isotonic saline) for 52 weeks, administered at baseline, Wk 16, and Wk 32. Eligible subjects had a KL grade of 2 or 3 on X-ray of the target knee and a WOMAC pain score ≥20 out of 50 at screening and baseline visits. Subjects having any other knee condition were excluded. Use of analgesics was prohibited, except for rescue medication. The primary endpoint was change from baseline (CFB) in WOMAC pain at Week 8. Secondary endpoints were CFB in WOMAC function and total, ICOAP, PGA, and 20-meter walk test. Exploratory endpoints included structural CFB in MRI entities.
RESULTS: 288 subjects were randomized to SB-061 (n=145) or placebo (n=143), and 252 (87.5%) completed injections. The groups were comparable at baseline. The primary endpoint was not met, as no significant difference in the CFB of the WOMAC pain score at Week 8 between groups was observed, nor at any other time point during the study. Similarly, neither of the secondary or exploratory endpoints indicated any significant difference between groups. The frequency and type of adverse events was similar between groups. SB-061 was well-tolerated.
CONCLUSIONS: Intra-articular injections of SB-061 administered at baseline, Wk 16, and Wk 32, over one year in subjects with knee OA was safe but did not show any statistically significant effect on knee pain nor on other symptomatic or structural entities compared to placebo.
UNASSIGNED: 2019-004515-31.

This review evaluates randomized controlled trials (RCTs) intervening on adult state anxiety (fear and emotional distress during dental treatment), chronic dental (trait) anxiety or dental phobia (disproportionately high trait anxiety; meeting diagnostic criteria for specific phobia). Seven online databases were systematically searched. 173 RCTs met inclusion criteria, of which 67 qualified for 14 pooled analyses. To alleviate state anxiety during oral surgery, moderate-certainty evidence supports employing hypnosis (SMD=-0.31, 95 %CI[-0.56,-0.05]), and low-certainty evidence supports prescribing benzodiazepines (SMD=-0.43, [-0.74,-0.12]). Evidence for reducing state anxiety is inconclusive regarding psychotherapy, and does not support virtual reality exposure therapy (VRET), virtual reality distraction, music, aromatherapy, video information and acupuncture. To reduce trait anxiety, moderate-certainty evidence supports using Cognitive Behavioral Therapy (CBT; SMD=-0.65, [-1.06, -0.24]). Regarding dental phobia, evidence with low-to-moderate certainty supports employing psychotherapy (SMD=-0.48, [-0.72,-0.24]), and CBT specifically (SMD=-0.43, [-0.68,-0.17]), but not VRET. These results show that dental anxieties are manageable and treatable. Clinicians should ensure that interventions match their purpose-managing acute emotions during treatment, or alleviating chronic anxiety and avoidance tendencies. Existing research gaps underscore the necessity for future trials to minimize bias and follow CONSORT reporting guidelines.

BACKGROUND: Immunotherapy in combination with chemotherapy has been approved as an initial treatment strategy for unresectable advanced gastric cancer (GC). However, the efficacy of adding immunotherapy to perioperative chemotherapy in locally advanced resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) remains uncertain. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to compare the effectiveness of perioperative immune checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy alone in patients with locally advanced resectable GC/GEJC.
METHODS: A comprehensive search of online databases was conducted to identify RCTs published until November 30, 2023. Odds ratios (ORs) with 95% confidence interval (CI) were calculated for primary outcomes, including R0 resection rate, D2 lymphadenectomy, pathologic complete response (pCR), and treatment-related adverse events (TRAEs).
RESULTS: A total of 2718 patients from five RCTs (six reports) were included in the analysis. The pooled ORs of R0 resection rate and D2 lymphadenectomy demonstrated that combination therapy with ICIs showed no significant difference compared to chemotherapy alone. However, the addition of ICIs significantly improved pCR rates (OR = 3.43, 95 % CI 2.61-4.50, p < 0.0001). There were no significant differences observed in the incidence of any grade TRAEs and grade 3-4 TRAEs. However, ICIs combination therapy was associated with significantly higher incidences of any grade irAEs (OR = 4.03, 95 % CI: 2.70-6.00, p < 0.0001), as well as grade 3-4 irAEs (OR = 4.51, 95 % CI: 2.27-8.97, p < 0.0001).
CONCLUSIONS: This study represents the first meta-analysis to demonstrate that perioperative combination therapy with ICIs yields superior pCR rates for patients with locally advanced GC/GEJC compared to chemotherapy.

BACKGROUND: Artificial intelligence (AI) medical devices have the potential to transform existing clinical workflows and ultimately improve patient outcomes. AI medical devices have shown potential for a range of clinical tasks such as diagnostics, prognostics, and therapeutic decision-making such as drug dosing. There is, however, an urgent need to ensure that these technologies remain safe for all populations. Recent literature demonstrates the need for rigorous performance error analysis to identify issues such as algorithmic encoding of spurious correlations (eg, protected characteristics) or specific failure modes that may lead to patient harm. Guidelines for reporting on studies that evaluate AI medical devices require the mention of performance error analysis; however, there is still a lack of understanding around how performance errors should be analyzed in clinical studies, and what harms authors should aim to detect and report.
OBJECTIVE: This systematic review will assess the frequency and severity of AI errors and adverse events (AEs) in randomized controlled trials (RCTs) investigating AI medical devices as interventions in clinical settings. The review will also explore how performance errors are analyzed including whether the analysis includes the investigation of subgroup-level outcomes.
METHODS: This systematic review will identify and select RCTs assessing AI medical devices. Search strategies will be deployed in MEDLINE (Ovid), Embase (Ovid), Cochrane CENTRAL, and clinical trial registries to identify relevant papers. RCTs identified in bibliographic databases will be cross-referenced with clinical trial registries. The primary outcomes of interest are the frequency and severity of AI errors, patient harms, and reported AEs. Quality assessment of RCTs will be based on version 2 of the Cochrane risk-of-bias tool (RoB2). Data analysis will include a comparison of error rates and patient harms between study arms, and a meta-analysis of the rates of patient harm in control versus intervention arms will be conducted if appropriate.
RESULTS: The project was registered on PROSPERO in February 2023. Preliminary searches have been completed and the search strategy has been designed in consultation with an information specialist and methodologist. Title and abstract screening started in September 2023. Full-text screening is ongoing and data collection and analysis began in April 2024.
CONCLUSIONS: Evaluations of AI medical devices have shown promising results; however, reporting of studies has been variable. Detection, analysis, and reporting of performance errors and patient harms is vital to robustly assess the safety of AI medical devices in RCTs. Scoping searches have illustrated that the reporting of harms is variable, often with no mention of AEs. The findings of this systematic review will identify the frequency and severity of AI performance errors and patient harms and generate insights into how errors should be analyzed to account for both overall and subgroup performance.
BACKGROUND: PROSPERO CRD42023387747; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387747.
UNASSIGNED: PRR1-10.2196/51614.

UNASSIGNED: Females are historically underenrolled in heart failure (HF) randomized controlled trials (RCTs) relative to disease prevalence. Sex differences in trial flow, including withdrawals and losses to follow up, may further limit the generalizability of results.
UNASSIGNED: This study aimed to assess the frequency of sex-specific reporting of trial flow, treatment efficacy, and adverse events in HF RCTs.
UNASSIGNED: We systematically searched MEDLINE, Embase, and CINAHL for HF RCTs published between 2000 and 2020 in journals with an impact factor ≥10. We assessed whether trial flow, treatment effect, and adverse events were disaggregated by sex. We used multivariable regression to assess associations between trial characteristics and sex subgroup analysis. We analyzed temporal trends in sex-specific reporting.
UNASSIGNED: We included 224 RCTs with 228,801 total participants (28.2% female). No RCT reported sex-disaggregated screening, consent, or withdrawal rates; and 2 (0.9%) reported sex-disaggregated losses to follow-up. Seventy-five RCTs (33.4%) presented sex subgroup analysis, and 63 (28.3%) reported sex-treatment interaction. No RCT reported sex-specific adverse events. Large trial size (odds ratio: 13.16, 95% CI: 5.67-30.52; P < 0.001) and device/procedure interventions (odds ratio: 5.13, 95% CI: 1.55-16.95; P < 0.007) were independently associated with sex subgroup analysis. Over the study period, there was an increase in sex subgroup analysis (P < 0.001) and testing for sex-treatment interaction (P < 0.001).
UNASSIGNED: HF RCTs rarely reported sex differences in trial flow or adverse events and uncommonly performed sex subgroup analysis. Improved sex-disaggregated reporting could highlight the causes and extent of sex differences in trial participation and facilitate appropriate inferences about treatment effect.

Randomized controlled trials (RCTs) affect clinical decisions and their number is increasing. However, trends in international collaboration on RCTs and involvement of healthcare-related industries, the latter of which may contribute to bias, are not known. The objectives were to identify concerns surrounding RCTs, and to quantify changes in (1) the numbers of RCT articles in journals of high clinical importance, (2) international collaboration, and (3) commercial involvement in RCTs by authors in countries that contribute the most to the scientific literature. This was not a systematic review of the medical literature. It is a descriptive study of trends during the past two decades. We extracted RCT articles from MEDLINE data (1997-2019). When grouped by authors\' country, the analyses were limited to the 10 leading countries in the natural sciences, as defined by the Nature Index 2019 Annual Tables. The Core Clinical Journals (CCJ) filter in PubMed was used to identify journals that were likely to be highly relevant to clinical practice. RCT articles that included authors from multiple countries were used as examples of international collaboration, and RCTs in which at least one author\'s affiliation was corporate were considered to have commercial involvement. The annual number of RCT articles more than doubled (from 10,360 to 22,384), but the number published in the CCJ was essentially unchanged (from 2,245 to 2,346). The vast majority of RCT articles had US-based authors. International collaboration increased in nine of the 10 countries studied, and it was particularly common among researchers in Europe, Canada, and Australia. In contrast, international collaboration decreased in China. Regarding commercial involvement, between 1997 and 2019 the proportion of single-country RCTs with commercial involvement decreased (from 12.4% to 3.8% for the United States, and from 2.5% to 0.0% for Europe-Canada-Australia). In contrast, the proportion of international-collaborative RCTs with commercial involvement increased (from 9.2% to 17.6% for the United States, and from 17.9% to 21.3% for Europe-Canada-Australia). The largest change in commercial involvement was the 12-fold increase in Japan: from 3% to 36% (1997-2019). Japan was also noteworthy for its 28-percentage-point decrease in first-authorship of RCT articles from 2012 to 2019. In conclusion, recent increases in the number of RCT articles have occurred almost exclusively outside the CCJ. Thus, many newer RCT articles might have relatively low clinical relevance or impact. International collaboration has generally increased, along with commercial involvement. The latter has become particularly common in Japan, increasing the potential for sponsorship bias. The effects of ongoing attempts to reverse that trend should be evaluated.

暂无摘要。

UNASSIGNED: Handheld single-lead electrocardiographic (1L ECG) devices are increasingly used for atrial fibrillation (AF) screening, but their real-world performance is not well understood.
UNASSIGNED: The purpose of this study was to quantify the diagnostic test characteristics of 1L ECG automated interpretations for prospective AF screening.
UNASSIGNED: We calculated the diagnostic test characteristics of the AliveCor KardiaMobile 1L ECG (AliveCor, US) algorithm using unblinded cardiologist overread as the gold standard using single 30s tracings administered by medical assistants among individuals aged ≥65 years participating in the VITAL-AF trial (NCT03515057) of population-based AF screening embedded within routine primary care.
UNASSIGNED: A total of 14,230 individuals (mean age 74 ± 7 years, 60% women, 82% White) had 31,376 tracings reviewed by 13 cardiologists. A total of 24,906 (79.6%) tracings had an AliveCor interpretation of normal, 5,046 (16.1%) were unclassified, 797 (2.5%) were possible AF, and 573 (1.8%) were no analysis. Cardiologists read 808 (2.6%) tracings as AF. AliveCor possible AF had a PPV of 51.7% (95% CI: 47.8%-55.6%). AliveCor normal had an NPV of 99.8% (95% CI: 99.7%-99.8%). The AliveCor algorithm had an overall sensitivity of 51.0% (95% CI: 47.1%-54.9%) and a specificity of 98.7% (95% CI: 98.6%-98.9%). AliveCor tracings interpreted as unclassified (PPV 5.9%, 95% CI: 5.1%-6.7%) and no analysis (PPV 6.5%, 95% CI: 4.6%-8.9%) had low predictive values for AF and were increasingly prevalent at older ages (13.7% for age 65-69 years to 28.1% for age ≥85 years, P < 0.01).
UNASSIGNED: In an older primary care population undergoing AF screening with handheld 1L ECGs, automated algorithm interpretations were sufficiently accurate to exclude the presence of AF but not to establish an AF diagnosis.