In mechanically ventilated adult patients in the intensive care unit (ICU), selective decontamination of the digestive tract (SDD) has been shown to reduce the risk of infections and improve survival. While the benefits of SDD have been documented in this population, it remains unclear whether burn patients, who are at increased risk of infection and have distinct clinical characteristics, may experience similar benefits. In this systematic review we aimed to assess the desirable and undesirable patient-important effects of administering SDD to burn patients.

We conducted a systematic review with meta-analysis of randomized clinical trials (RCTs) assessing the effects of SDD versus placebo or no SDD in burn patients. The primary outcome was 30-day mortality. Secondary outcomes included serious adverse events, antimicrobial resistance, pneumonia, blood stream infections, ICU- and hospital-free days, and 90-day mortality. We searched all major databases and followed the recommendations provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The certainty of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation approach.

We identified four RCTs with a total of 457 burn patients. All trials were assessed as having either 'some concerns' or 'high risk' of bias. The evidence was found to be very uncertain across all outcomes assessed. For mortality, the relative risk (RR) was 0.62 (95 % confidence interval (CI) 0.22-1.78, I2 = 75 %, random-effects model (REM), very low certainty evidence). For pneumonia, the RR was 0.75 (95 % CI 0.48-1.19, I2 = 0 %, fixed-effect model, very low certainty evidence). For bloodstream infections, the RR was 1.10 (95 % CI 0.71-1.69, I2 = 0 %, REM, very low certainty evidence). For hospital length of stay, the mean difference was -2.03 days (95 % CI -9.64-5.59, I2 = 51 %, REM, very low certainty evidence). We did not perform meta-analyses for the remaining secondary outcomes due to limited or no data. Trial sequential analysis could not be performed due to insufficient number of total participants and events in the included trials.

We found that the certainty of evidence is very low about the effects of SDD on patient-important outcomes in burn patients. Extrapolating from the evidence on mechanically ventilated adult ICU patients may be reasonable until more data from RCTs in burn patients emerge.

Daratumumab (Dara)-based regimens have been investigated in randomized controlled trials (RCTs) involving patients with newly diagnosed and previously untreated multiple myeloma (NDMM), but the optimal daratumumab-based regimen remains unclear. This study compares the efficacy of daratumumab-containing regimens for NDMM patients and explores optimal combinations.

Databases were searched from inception until February 29, 2024. Trials comparing regimens with and without daratumumab, as well as their mutual comparisons, were included. Random effects models for serious adverse events (SAEs) and fixed effects models for other outcomes were utilized in both network meta-analysis (NMA) and component NMA (CNMA), with pooled effects estimated. The efficacy of all possible combinations of daratumumab with other drugs was assessed.

A total of 17 trials were included, enrolling 7261 patients, of whom 2083 were treated with daratumumab. The optimal regimens for different outcomes were identified as follows: Dara-bortezomib (V)-melphalan (M)-corticosteroids (D) (Dara-VMD) showed the best results for both overall response rate (ORR) [RR = 1.97; 95% CI: 1.42 to 2.75; I2 = 0.00%; 16 trials; 7136 participants; P = 0.00] and ≥ very good partial response (≥ VGPR) [RR = 7.46; 95% CI: 4.10 to 13.46; I2 = 23.96%; 16 trials; 7118 participants; P = 0.00]; Dara-V-thalidomide (T)-D (Dara-VTD) was optimal for achieving ≥ complete response (≥ CR) [RR = 14.15; 95% CI: 3.74 to 53.52; I2 = 0.00%; 17 trials; 7261 participants; P = 0.00]. The individual effects of daratumumab were calculated as follows: [ORR: RR = 1.14; 95% CI: 1.08 to 1.21; I2 = 0.00%; 16 trials; 7136 participants; P = 0.00; ≥ VGPR: RR = 1.46; 95% CI: 1.36 to 1.58; I2 = 23.96%; 16 trials; 7118 participants; P = 0.00; ≥ CR: RR = 1.77; 95% CI: 1.55 to 1.99; I2 = 0.00; 17 trials; 7261 participants; P = 0.00; progression-free survival (PFS): hazard ratio (HR) = 0.53; 95% CI: 0.43 to 0.65; I2 = 0.00%; 13 trials; 5977 participants; P = 0.00; overall survival (OS): HR = 0.68; 95% CI: 0.58 to 0.79; I2 = 28.97%; 12 trials; 5977 participants; P = 0.00]. Additionally, the optimal regimens for PFS and OS were Dara-lenalidomide (R)-D [HR = 0.37; 95% CI: 0.23 to 0.61; I2 = 0.00%; 13 trials; 5977 participants; P = 0.00] and Dara-VRD [HR = 0.40; 95% CI: 0.19 to 0.85; I2 = 28.97%; 12 trials; 5977 participants; P = 0.02], respectively. Finally, CNMA indicated that Dara-VRD, Dara-carfilzomib (K)-RD, Dara-RD, and Dara-cyclophosphamide (C)-RD were four regimens, which could improve remission rate, and reduce death or progression during induction and prolong lifetime.

Dara-VRD, Dara-KRD, Dara-RD, and Dara-CRD are optimal daratumumab-based regimens for patients with newly diagnosed and previously untreated multiple myeloma.

This fourth article in a seven part series presents the Core GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to addressing risk of bias, publication bias, and rating up certainty. In Core GRADE, randomised controlled trials begin as high certainty evidence and non-randomised studies of interventions (NRSI) as low certainty. To assess certainty of evidence for risk of bias, Core GRADE users first classify individual studies as low or high risk of bias. Decisions regarding rating down for risk of bias will depend on the weights of high and low risk of bias studies and similarities or differences between the results of high and low risk of bias studies. For publication bias, a body of evidence comprising small studies funded by industry should raise suspicion. Core GRADE users appraising results from well conducted NSRI can consider rating up certainty of evidence when risk ratios from pooled estimates suggest large or very large effects.

Evidence that smoking cessation benefits physical and mental health has led to recommendations to support quitting. Unsuccessful quit attempts are common and associated with guilt and frustration; however, their impact on mental health is unclear. This review investigated the association between the success/failure of smoking cessation attempts and changes in symptoms of depression and anxiety.

Systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines.

Inclusion and exclusion lists of two previous reviews, plus update searches of Embase, Medline and PsycINFO (January 2020-January 2025).

Trials and longitudinal observational studies measuring symptoms of anxiety or depression before and after a smoking cessation attempt, beyond the withdrawal period (6 weeks), in adults who successfully quit and made an unsuccessful attempt.

Standardised methods were used for screening and data extraction. Two independent reviewers screened a minimum of 25% and extracted data for 100% of studies. Meta-analyses were conducted using random effects models, and narrative synthesis was used when necessary. Study quality, heterogeneity and publication bias were assessed using the adapted Newcastle-Ottawa Scale, I 2 and funnel plots, respectively.

62 studies were included, representing 36 150 participants. Most featured behavioural smoking cessation interventions and defined successful cessation attempts by self-reported or biologically verified abstinence. Follow-up ranged from 6 weeks to 4 years. Overall, successfully quitting smoking was associated with reduced symptoms of depression (standardised mean difference (SMD)=-0.21, 95% CI -0.27 to -0.16) and anxiety (SMD=-0.22, 95% CI -0.33 to -0.12) compared with unsuccessful quit attempts. Heterogeneity was substantial (I 2=50-69%).

Most studies indicated a positive trend in alleviating symptoms of anxiety and depression during a quit attempt. Successful quitters experienced more substantial reductions in these symptoms compared with those who were unsuccessful. Importantly, those who made an unsuccessful quit attempt did not experience worse mental health.

CRD42022314728.

The majority of studies in our review indicated a positive trend in alleviating symptoms of anxiety and depression when individuals attempt to quit smoking. Successful quitters experienced more substantial reductions in these symptoms compared with those who were unsuccessful. Importantly, those who attempted to quit but failed did not experience worse mental health. These findings are relevant to people who smoke tobacco and the health professionals who support them as they may hold some apprehensions about quitting smoking or the anticipated emotional consequences of failing to quit. The current review contributes to clinical practice by adding to the information on which risk-benefit decisions are made regarding smoking cessation.

High discontinuation rates compromise the effectiveness of treatment regimens for schizophrenia, because consistent medication adherence is essential for the efficacy of antipsychotics. Understanding the relationship between antipsychotic doses and discontinuation rates is important. This study explores this relationship to identify doses that maximize treatment adherence and minimize discontinuation.

We systematically searched multiple electronic databases for fixed-dose RCTs assessing 20 antipsychotics in patients with acute exacerbation of schizophrenia and related disorders. We analyzed dose-response relationships using a one-stage dose-response meta-analysis within a frequentist framework, employing restricted cubic splines to model the relationships. The primary outcome was discontinuation for any reason, and secondary outcomes were discontinuation due to inefficacy and side effects.

Analysis of 136 trials involving 44,126 participants revealed various dose-response relationships for antipsychotics. For the primary outcome, all-cause discontinuation, amisulpride, cariprazine, olanzapine (Zyprexa), and quetiapine demonstrated U-shaped curves, indicating optimal dosing thresholds where further increases in dosage led to heightened discontinuation rates, possibly due to side effects. Aripiprazole, asenapine, brexpiprazole, clozapine, paliperidone, and risperidone (Risperdal) had plateaus, suggesting no additional benefit from increasing doses beyond specific points. For haloperidol, iloperidone, lumateperone, lurasidone, sertindole, and ziprasidone, the dose-response curves did not reach a plateau within the examined doses. Inefficacy discontinuation curves were similar to total discontinuation. Most discontinuation for side-effects curves showed sharp increases in side-effects associated with higher doses.

Dose discontinuation curves varied between the antipsychotics and included U-shaped, monotonic, and hyperbolic patterns. Future studies should consistently present disease-related and side-effect-related dropouts due to adverse events separately.

Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in people living with HIV (PWH) who have low CD4 counts. Despite its side effects, trimethoprim-sulfamethoxazole (TMP-SMX) is currently considered the primary treatment for PCP.

The objectives of this study are to compare the efficacy (treatment failure and mortality) and tolerability (treatment change) of PCP treatment regimens with a frequentist network meta-analysis.

Data sources include Embase, Medline, and CENTRAL from inception to 3 February 2024.

Study eligibility criteria include comparative randomized controlled trials (RCTs) of at least two PCP treatment regimens.

Participants include PWH.

Interventions include treatment regimens for PCP compared head-to-head.

Assessment of risk of bias includes Cochrane Risk-of-bias tool for RCTs (Cochrane Risk-of-Bias 2).

Title, abstract, and full-text screening, along with data extraction, were conducted by two independent reviewers. Data on PCP treatment failure, all-cause mortality, and discontinuation because of toxicity were pooled and ranked.

Fourteen RCTs conducted between 1983 and 1996 included 1788 participants across 27 treatment arms. No regimen showed statistically significant superiority over TMP-SMX in direct comparison. In the network meta-analysis, clindamycin/primaquine was ranked the best (surface under the cumulative ranking curve, 0.8), followed by intravenous pentamidine (0.8) and TMP-SMX (0.8) regarding treatment failure. Regarding all-cause mortality, TMP-SMX was superior to atovaquone in direct comparison, but no treatment was superior in the full network analysis. Dapsone-TMP (0.7) and intravenous pentamidine (0.8) were ranked the highest for mortality reduction. For safety and tolerability, comparator drugs consistently outperformed TMP-SMX, with significant reductions in toxicity observed for dapsone-TMP, inhaled pentamidine, and atovaquone. Inhaled pentamidine (0.9) was the best tolerated, followed by trimetrexate (0.8) and atovaquone (0.8).

We conclude that TMP-SMX should be reassessed as the standalone first-line therapy for PCP in PWH, given the better tolerability and comparable efficacy of other treatments. In places with access to alternative drugs for PCP treatment, our analysis suggests that alternative regimens may offer comparable effectiveness, providing flexibility to use alternative treatments when comorbidities necessitate it.

The prevalence of anxiety disorders among the adult population in Latin America (LATAM) and its association with development indicators is insufficiently characterised. We estimated pooled regional, country, and sex-specific prevalence rates of anxiety disorders in LATAM based on International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Additionally, we examined the association between its prevalence and four country-level development indicators: Human Development Index (HDI), income inequality (Gini coefficient), Gender Inequality Index (GII), and Intentional Homicide Rate (IHR).

We conducted a systematic review and meta-analysis of population-based studies on the prevalence of ICD/DSM anxiety disorders in LATAM from 1990 to 2024, irrespective of language. We searched PubMed, PsycINFO, Cochrane Library, SciELO, LILACS, and grey literature. Study quality was assessed using JBI's critical appraisal tools. Pooled estimates were generated using random-effects meta-analysis, and heterogeneity was evaluated using the I-squared (I 2) statistic. Meta-regression analyses were performed to examine the ecological association between anxiety disorders prevalence and four development indicators. The study was registered with PROSPERO (CRD42020190238).

Using data from 36 studies in LATAM, we calculated the lifetime, 12-month, and current prevalence of ICD/DSM anxiety disorders at 14.55% (95% Confidence Interval 12.32%-17.11%; I 2 = 97.9%); 6.61% (5.20-8.37; I 2 = 98.1%), and 3.27% (2.34-4.56; I 2 = 97.5%), respectively. Heterogeneity was high across prevalence periods, sexes, and countries (all I 2 ≥ 91.4%), warranting caution in interpreting pooled estimates. Elevated 12-month and current prevalence rates of anxiety disorders were associated with higher Gini coefficients (p ≤ 0.0013). Additionally, higher current prevalence was associated with lower HDI (p = 0.0103) and higher GII (p = 0.0023), while elevated 12-month prevalence was associated with higher IHR (p = 0.011).

This study shows that approximately one in seven people in LATAM experience anxiety disorders at some point in their lives. These findings highlight the need to strengthen mental health systems in the region, and evidence the association between prevalence of anxiety disorders and development indicators. Our results can serve as a baseline for tracking anxiety disorders and for informed decision-making at the national and regional levels. The substantial heterogeneity between studies and the underrepresentation of some countries underscore the imperative for enhancing regional mental health capacities.

Pfizer Independent Medical Education Grant (69879319).

18F-fluoroestradiol (18F-FES) PET/CT has been investigated as a potential biomarker to predict response to endocrine therapies in patients with estrogen receptor (ER)-positive breast cancer. Although previous findings were promising, most had limited statistical significance because of small individual sample sizes. Therefore, we performed a systematic review and metaanalysis of the 18F-FES PET/CT literature to increase our power to evaluate the utility of 18F-FES PET/CT as a biomarker for prediction of clinical benefit from endocrine therapy in patients with ER-positive breast cancer. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, MEDLINE via OVID, Embase, Web of Science, Emcare, and the Cochrane Central Register of Controlled Trials through November 1, 2024, for studies that included patients with ER-positive breast cancer who received an 18F-FES PET/CT at baseline and received subsequent endocrine therapy. For each eligible study, data were extracted using a predesigned data extraction form. Random effects models were used to estimate the likelihood of clinical benefit from endocrine therapy after a positive 18F-FES PET scan, the likelihood of clinical benefit from endocrine therapy after a negative 18F-FES PET scan, and the risk ratio of clinical benefit from endocrine therapy comparing those who were 18F-FES-positive to those who were 18F-FES-negative. Results: From 1,105 database records retrieved, 12 studies were included in the metaanalysis (n = 308 participants with data on 18F-FES PET results and response to endocrine therapy). The likelihood of clinical benefit after a positive 18F-FES PET scan was 66% (95% CI, 51%-79%; I 2 = 76.6%; n = 227 participants) and the likelihood after a negative 18F-FES PET scan was 11% (95% CI, 3.5%-22%; I 2 = 0.0%; n = 81 participants). The risk ratio of response that compared those who were 18F-FES-positive with those who were 18F-FES-negative was 3.21 (95% CI, 1.96-5.25; I 2 = 0.0%; P < 0.0001). Conclusion: 18F-FES PET is a successful biomarker for predicting the likelihood of success of endocrine therapy in patients with ER-positive breast cancer. There is strong evidence that patients with 18F-FES-negative disease are unlikely to derive clinical benefit from endocrine therapies, despite the presence of ER-positive disease on pathology. This supports a role for 18F-FES PET in identifying patients for whom endocrine therapy may or may not be an appropriate treatment option.

Atherosclerosis, a chronic vascular disease, impacts various arterial systems, such as the coronary, carotid, cerebral, renal, and peripheral arteries. Dietary factors, especially alcohol consumption, significantly contribute to the progression of atherosclerosis. However, systematic evaluations of alcohol's impact on atherosclerosis are still limited. This study investigates the impact of alcohol consumption on atherosclerosis via meta-analysis and assesses the moderating effects of drinking frequency, gender, and other factors.

By December 2024, a comprehensive literature search was conducted across PubMed, Embase, Cochrane, and Web of Science databases. Studies evaluating the relationship between alcohol consumption and atherosclerosis were rigorously selected and assessed for quality. The study protocol was registered with the INPLASY database. Data extraction and statistical analysis were conducted using STATA 18.0 software. A total of 26 studies involving 326,513 patients across 10 countries were included. Considering that different biological mechanisms may regulate atherosclerosis in different arterial locations, we conducted subgroup analyses to explore differences in country, study type, arterial site, diagnostic criteria, type of alcohol, and gender.

The results show that the overall analysis did not show a significant promoting effect of alcohol consumption on the development of atherosclerosis (OR = 0.91, 95% CI 0.79-1.05). Subgroup analyses revealed several important trends. Alcohol consumption may increase the risk of atherosclerosis in specific countries (Japan, South Korea, Brazil, and Denmark), types of studies (cohort and case-control studies), arterial locations (coronary arteries), and diagnostic criteria (clinical diagnosis and computed tomography). Interestingly, we found that alcohol consumption may increase the risk of atherosclerosis in women. Furthermore, varying levels of alcohol consumption appear to result in differing risks of the disease.

The impact of alcohol consumption on atherosclerosis is not singular and may interact with multiple factors, including environmental factors, lesion location, and individual characteristics.

https://inplasy.com/inplasy-2025-1-0031/, INPLASY202510031.

The bidirectional relationship between autoimmune diseases and malignancy has been widely discussed. And the relationship between autoimmune diseases and the risk of malignancy varies. Here, we categorized and re-analyzed the evidence of the association between six autoimmune diseases and malignancy risk, in order to provide ideas for the prevention of malignancy in the long-term individualized management of patients with autoimmune diseases.

We systematically searched the relevant literatures in PubMed, Web of Science and Cochrane Library to identify and re-analyze studies methodically on the association between six autoimmune diseases and their malignancy risk. Our results showed that.

We included 34 meta-analyses including systematic lupus erythematosus, rheumatoid arthritis, psoriasis, ankylosing spondylitis, primary Sjogren's syndrome, multiple sclerosis, totalling 742 studies. Our results showed that the remaining five AIDs, with the exception of MS, were positively associated with the risk of overall malignancy. Among them, patients with SLE had the highest risk of developing lymphomas, oropharyngeal cancer and non-Hodgkin's lymphoma, and the lowest risk of developing uterine cancer, melanoma and endometrial cancer. The RA patients had the highest risk of developing lymphomas, Hodgkin's lymphoma and non-Hodgkin's and the lowest risk of colon cancer. pSS patients had the highest risk of lymphoma. MS patients had the highest risk of lung cancer and the lowest risk of testicular cancer. AS patients had the highest risk of lymphoblastic leukemia. PsO patients had the highest risk of keratinocyte cancer.

Patients with systematic lupus erythematosus, rheumatoid arthritis, psoriasis, ankylosing spondylitis and primary Sjogren's syndrome lead to an increased risk of overall malignancy, whereas patients with MS lead to a decreased risk of overall malignancy. However, the risk relationship between the same AIDs and different malignancies varied.

Cardiovascular diseases remain the leading cause of mortality worldwide. Tirzepatide is approved for the treatment of type 2 diabetes mellitus and overweight and is increasingly used. The adverse effects with tirzepatide may not be disease-specific and have not been assessed previously.

We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S)) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in January 2025. Two review authors will independently extract data and perform risk of bias assessments. We will include randomised clinical trials comparing tirzepatide versus placebo or no intervention in all patient groups with an increased risk of cardiovascular events. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and Trial Sequential Analysis, risk of bias will be assessed with the Cochrane Risk of Bias tool-version 2. We will systematically assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.

This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.

CRD42024599035.

There is no current consensus on the presence of viral infections in acute apical abscesses; therefore, this protocol for a systematic review and meta-analysis is designed to detail the procedures required to investigate the prevalence of viral infections in acute apical abscesses, a common dental condition characterized by pus accumulation due to bacterial infection. Viral infections in oral tissues have been linked to systemic health risks, including chronic inflammation and oncogenesis, which further emphasize the importance of understanding their role in acute apical abscesses.

We adopted a systematic review and meta-analysis protocol design followed by PRISMA guidelines. A priori protocol was registered in PROSPERO with registry number: CRD42023468287. Inclusion criteria will be established according to the PICO framework; hence, we will include original articles with no restriction on publication date or population group. The selective screening of information will be conducted by peers, starting with titles, abstracts, and keywords, and finally reviewing the full text. The risk of bias will be assessed using the ROBINS tool, and the certainty of the evidence will be evaluated following the GRADE guidelines. We will perform a random-effects meta-analysis, utilizing the Freeman-Tukey double arcsine transformation, to estimate the pooled prevalence of viral infections in acute apical abscesses, assess heterogeneity using the Q-test and I² statistic, evaluate potential publication bias with funnel plots and Egger's test, and conduct sensitivity analyses to ensure robust results.

At present, no consensus exists regarding the prevalence of viral infections in acute apical abscesses that could inform clinical dental practice. Moreover, the existing body of knowledge on this subject is notably limited. This approach is intended to provide data that will facilitate the improvement of clinical practice and serve as a methodological framework for studying various pathologies. By elucidating the prevalence of viral infections, the findings of this study could enhance diagnostic accuracy and inform more targeted and effective treatment strategies, ultimately improving patient outcomes.

Patients with obstructive sleep apnea (OSA) may be at increased risk for adverse events during procedural sedation, however, there remains a gap in the literature quantifying these risks. This systematic review and meta-analysis aimed to evaluate the risk of peri-procedural adverse events in OSA patients undergoing procedural sedation in ambulatory settings, compared to those without OSA.

Four databases were systematically searched for studies published from January 1, 2011 to January 4, 2024. The inclusion criteria were: adult patients with OSA undergoing procedural sedation in ambulatory settings, peri-procedural adverse events reported, and control group included. The primary outcome was the incidence of peri-procedural adverse events amongst patients with vs without OSA.

Nineteen studies (27,973 patients) were included. The odds of respiratory adverse events were significantly increased for patients with OSA (OR 1.65, 95 % CI 1.03-2.66, P = 0.04). Furthermore, the odds of requiring an airway maneuver/intervention were significantly greater for patients with OSA (OR 3.28, 95 % CI 1.43-7.51, P = 0.005). The odds of cardiovascular adverse events were not significantly increased for patients with OSA.

Patients with OSA undergoing procedural sedation in ambulatory settings had 1.7-fold greater odds of respiratory adverse events and 3.3-fold greater odds of requiring airway maneuvers/interventions.

Midazolam and propofol are frequently used for procedural sedation. Remimazolam may provide a more controllable sedation with fewer adverse effects.

To assess the sedation success rate and respiratory and cardiovascular complications of remimazolam versus placebo and other sedatives in adults undergoing procedural sedation.

A systematic review of randomised controlled trials (RCTs) with meta-analyses, trial sequential analyses (TSA), and GRADE evaluations of the certainty of evidence.

We searched Medline, Embase, CENTRAL, BIOSIS, CINAHL, and Web of Science Core Collection from their inception to 22 June 2024.

RCTs allocating participants undergoing procedural sedation to remimazolam versus placebo or any active comparator.

We included 63 trials randomising 13 953 participants. All included trial results were judged to be at high risk of bias. The sedation success rate was similar with remimazolam versus active comparators, relative risk (RR) 1.04, [97.5% confidence interval (CI), 0.96 to 1.14; TSA-adjusted CI, 0.95 to 1.18], P   =  0.26, GRADE: very low. Subgroup analyses indicated that remimazolam versus midazolam increased sedation success rate, while the risks were similar with remimazolam versus comparators. Remimazolam versus active comparators decreased the risk of respiratory complications, RR 0.47, (97.5% CI, 0.36 to 0.61; TSA-adjusted CI, 0.35 to 0.61), P  < 0.01; and cardiovascular complications, RR 0.46, (97.5% CI, 0.37 to 0.56; TSA-adjusted CI, 0.38 to 0.57), P  < 0.01. Subgroup analyses indicated that remimazolam versus propofol reduced respiratory and cardiovascular complications, while the risks were similar versus midazolam.

Remimazolam seems to provide a similar sedation success rate as other active comparators (propofol, ciprofol, midazolam, dexmedetomidine, etomidate), although subgroup analyses indicated that remimazolam increased sedation success rate compared to midazolam. Remimazolam compared to propofol may decrease the risk of respiratory and cardiovascular complications. The certainty of the evidence was very low to low, and firm conclusions could not be drawn.

Several pharmacologic options exist for the management of acute pediatric pain; however, their comparative effectiveness remains uncertain.

To assess the relative benefits and harms of pharmacotherapy for acute pediatric pain through a network meta-analysis of randomized clinical trials.

Cochrane Database of Systematic Reviews, Medline, Embase, CINAHL, Web of Science, and Scopus to October 2023.

Trials that enrolled children (aged <18 years) with acute pain and randomized them to receive a pharmacologic analgesic vs an alternate analgesic or placebo were included.

Pairs of reviewers independently reviewed abstracts, extracted data, and assessed risk of bias of eligible trials. A frequentist random-effects model was used for all meta-analyses, and the certainty of evidence was assessed for treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation approach.

The primary outcomes were pain severity (range, 0-10 cm using a visual analog scale; minimally important difference [MID], 1 cm), need for rescue medication, symptom relief, and adverse drug events.

A total of 41 trials involving 4935 children were included. High- to moderate-certainty evidence found that compared with placebo, nonsteroidal anti-inflammatory drugs (NSAIDs) (weighted mean difference [WMD], -1.29; 95% CI, -1.89 to -0.70; modeled risk difference [RD] for achieving the MID, 16%), ketamine (WMD, -1.12; 95% CI, -2.09 to -0.14; modeled RD for achieving the MID, 14%), and mid-high potency opioids (WMD, -1.19; 95% CI, -1.83 to -0.55; modeled RD for achieving the MID, 15%) reduced pain. Only NSAIDs reduced the need for rescue medication (relative risk [RR], 0.31; 95% CI, 0.14 to 0.68; modeled RD, 16% fewer patients). Neither NSAIDs (RR, 0.69; 95% CI, 0.31 to 1.55) nor acetaminophen (RR, 0.63; 95% CI, 0.21 to 1.87) increased the risk of short-term gastrointestinal adverse events. All other comparisons showed moderate-certainty evidence of little to no difference from placebo or were supported by low/very low-certainty evidence.

Compared with placebo, NSAIDs, ketamine, and mid- to high-potency opioids are effective in reducing acute pediatric pain. NSAIDs provide the greatest benefits and least harm, suggesting that they should be the first-line therapy for acute painful conditions in children.

Background: About 15 million people suffer a stroke each year, of which 10-15% occur in people under 50 years of age. The clinical management of neurological disorders depends on reliable diagnostic tools to identify impairments and aid in the early and accurate detection of disease. The objective of this study is to present a systematic review protocol for identifying the scientific evidence on the use of tele-assessment compared with in-person assessment delivery by physiotherapists for stroke patients. This protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42024613552). Methods: Original studies of any design in which physiotherapy tele-assessment using videoconferencing compared with face-to-face assessment for patients with stroke conditions will be included. The research will be carried out in PubMed/Medline, Cochrane Library, PEDro (Physiotherapy Evidence Database), and NICE. The risk of bias will be assessed using the Quality Appraisal Tool for studies of diagnostic Reliability (QAREL) and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Results: The screening, selection, and analysis process will be conducted by two independent researchers and reviewed by a third evaluator to resolve any potential disagreements. The feasibility of conducting a meta-analysis for quantitative data will be evaluated based on the homogeneity analysis of the selected studies. Conclusions: We hope that this systematic review protocol will provide scientific evidence for tele-assessment as a physiotherapeutic assessment strategy for stroke patients and that it will be available as a complementary tool to face-to-face physiotherapeutic assessments for specific situations.

Postoperative atrial fibrillation (PAF) is a common complication after lung resection, since surgical stress may act as a trigger. The VATS approach reduces surgical stress and alleviates inflammation and oxidative stress commonly associated with open lung surgery. However, only a few studies have investigated the possible impact of the surgical approach on the incidence of PAF. A literature review was performed through PubMed, EMBASE, and Google Scholar in March 2024, to identify any study published since 2000 evaluating the role of the VATS vs the open approach to perform lung resections as a risk factor for postoperative atrial fibrillation. Pooled odds ratio (OR) estimates with 95% confidence intervals (CIs) were calculated. Twenty-one studies, including 59,101 patients, met the criteria for inclusion. Both propensity-matched and non-matched data showed that VATS was associated with a significant reduction in PAF compared to open thoracotomy (OT) (OR 0.73; 95% CI 0.58-0.91; I2 = 10.1%, p = 0.349). A meta-regression was conducted to explore contributing factors, showing the geographic regions in which the studies were conducted may be a significant source of heterogeneity. Subgroup analyses revealed less heterogeneity in studies conducted in Europe and on those focused solely on lobectomy. Postoperative atrial fibrillation risk following VATS is significantly lower than OT. Further prospective randomized controlled trials with large sample sizes are needed to confirm these findings.

Frailty is a significant predictor of adverse outcomes in patients with acute coronary syndrome (ACS). However, its impact on short-term clinical outcomes remains unclear. We conducted a systematic review and meta-analysis to investigate the associations between frailty and adverse clinical outcomes in patients with ACS.

We systematically searched the Embase, MEDLINE, and CENTRAL databases from inception to 1 August 2023 for observational cohort studies, cross-sectional studies, or clinical trials involving hospitalised adults with ACS. Studies utilising validated frailty screening tools and examining the associations between frailty and clinical endpoints, such as in-hospital mortality, length of hospital stay, major bleeding, and stroke, were included. The meta-analysis was performed via random effects models and meta-regression analyses.

Among the 4,458 records identified, 42 were deemed eligible, and data from 14 studies were included in the analysis. Frailty was significantly associated with increased in-hospital all-cause mortality (relative risk [RR] 2.89; 95% confidence interval [CI] 2.49-3.34) and prolonged length of hospitalisation (standardised mean difference [SMD] 2.01; 95% CI 1.48-2.46), with frail patients with ACS spending an average of 3.5 more days in the hospital. Furthermore, frail patients with ACS presented a significantly greater risk of adverse outcomes than non-frail patients with ACS did (RR 1.86; 95% CI 1. 41-2.46). Subgroup analysis revealed a significant increase in major bleeding events (RR 2.03; 95% CI 1.51-2.73) among frail patients with ACS, whereas the incidence of stroke showed a nonsignificant trend towards elevation (RR 1.23; 95% CI 0.56-2.72).

Frailty is strongly associated with in-hospital all-cause mortality, prolonged length of hospitalisation, and adverse clinical outcomes such as major bleeding in patients with ACS.

Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces mortality. Nevertheless, in high tuberculosis-burden countries (HTBC), there are concerns about high false-positive rates due to persistent lung lesions from prior tuberculosis (TB) infections. This study aims to evaluate the screen-positive rate (SPR) of LDCT screening in HTBC.

We conducted a systematic review and meta-analysis to identify studies utilizing LDCT for LCS in HTBC and reported SPR from inception to December 6, 2023. The primary outcome was the SPR, and the secondary outcome was the lung cancer detection rate (LCDR). The summary data was pooled using a random-effects model, and factors influencing the SPR were analyzed using multivariable meta-regression analysis.

A total of 44 studies with 477,424 individuals (59.3% men) were included in the systematic review. Lung Imaging Reporting and Data System (Lung-RADS) (31%, 14 studies) and National Lung Screening Trial (NLST) criteria (non-calcified nodule ≥ 4 mm; 10 studies) were the most common criteria used for assessing SPR. The pooled SPR and LCDR were 18.36% (95% confidence interval [CI]: 14.6-22.1) and 0.94% (95% confidence interval: 0.75-1.15), respectively. Although SPR was significantly higher with NLST criteria than Lung-RADS criteria (25.6% versus 10.4%, p < 0.0001), the LCDR remained similar (0.91% versus 0.95%, p = 0.92). Studies using NLST criteria had a higher SPR in multivariable meta-regression analysis. Nevertheless, the analysis is limited by significant statistical heterogeneity and publication bias.

Lung cancer screening by LDCT in HTBC demonstrates comparable SPR and LCDR to regions with lower TB incidence rates. Lung-RADS criteria are preferable to NLST criteria for LCS in HTBC to mitigate false-positive rates.

Bronchoscopy-guided percutaneous dilatational tracheostomy (BPDT) and ultrasound-guided percutaneous dilatational tracheostomy (USPDT) are widely employed techniques. However, USPDT provides better vascular mapping and reduces bleeding risk, while BPDT offers better tracheal entry and fewer airway complications. Their comparative efficacy and safety were systematically evaluated, with special consideration for high-risk patients, including obese and critically ill individuals with complex airway anatomy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an in-depth literature search was conducted in Embase, PubMed, Scopus, and Cochrane Library, focusing on adult patients undergoing percutaneous tracheostomy with USPDT, BPDT, or both. Quality assessment indicated that most studies exhibited a low risk of bias, though concerns regarding randomization and selective reporting were noted in some cases. A meta-analysis was conducted using pooled effect sizes, procedural success rates, complication rates, and heterogeneity (I²), applying a random-effects model. Ten studies involving 1,069 patients were analyzed. The pooled analysis demonstrated a moderate positive association between USPDT and BPDT in improving procedural success and reducing complications (CI: 0.41 to 0.55, standardized mean difference = 0.48, 95%, p < 0.05). However, significant heterogeneity (I² = 72.95%) was observed, likely due to variations in study design and patient populations. USPDT and BPDT are both practical and safe for percutaneous tracheostomy, with unique advantages for different clinical scenarios. The findings support a hybrid approach integrating both modalities to enhance procedural safety and efficiency, particularly in high-risk populations. Future large-scale trials should focus on reducing heterogeneity, assessing long-term outcomes, and improving cost-effectiveness to establish best-practice guidelines for broader clinical implementation.

Video-assisted thoracoscopic surgery (VATS) is widely used in lung cancer surgery, as this technique causes less pain and faster recovery than open thoracotomy. However, significant postoperative pain persists in a number of patients, often leading to increased opioid use and opioid-related adverse events in addition to prolonged admission times. Perioperatively administered glucocorticoids have been demonstrated effective in reducing pain after other types of surgeries, but the effect in VATS remains unclear.

This systematic review will assess the impact of glucocorticoids on postoperative pain in adult patients undergoing VATS. We will include randomised trials comparing higher doses of glucocorticoids to lower doses, placebo or no treatment. The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement and Cochrane methodology. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation system. The primary outcome is standardised dynamic pain scores within 24 h. Secondary outcomes are opioid use, time to first mobilisation, length of hospital stay and numeric rating score >3 at any point within the first 24 h following surgery. Exploratory outcomes are opioid-related adverse effects and glucocorticoid-related adverse effects classified in major and minor events. Data will be meta-analysed with sensitivity and subgroup analyses and trial sequential analyses. Furthermore, we will assess the risk of reporting bias and heterogeneity.

This systematic review and meta-analysis will provide an overview of the current evidence of how glucocorticoids affect postoperative pain and recovery in adult patients undergoing VATS.

The optimal antiviral drug for treatment of nonsevere influenza remains unclear.

To compare effects of antiviral drugs for treating nonsevere influenza.

MEDLINE, Embase, CENTRAL, CINAHL, Global Health, Epistemonikos, and ClinicalTrials.gov were searched from database inception to September 20, 2023.

Randomized clinical trials comparing direct-acting influenza antiviral drugs to placebo, standard care, or another antiviral drug for treating people with nonsevere influenza.

Paired reviewers independently performed data extraction and risk of bias assessment. A frequentist network meta-analysis was performed to summarize the evidence and the certainty of evidence was evaluated using the GRADE approach.

Mortality, admission to hospital, admission to the intensive care unit, duration of hospitalization, time to alleviation of symptoms, emergence of resistance, and adverse events.

Overall, 73 trials with 34 332 participants proved eligible. Compared with standard care or placebo, all antiviral drugs had little or no effect on mortality for low-risk patients and high-risk patients (all high certainty). All antiviral drugs (no data for peramivir and amantadine) had little or no effect on hospital admission for low-risk patients (high certainty). For hospital admission in high-risk patients, oseltamivir (risk difference [RD], -0.4%; 95% CI, -1.0 to 0.4; high certainty) had little or no effect and baloxavir may have reduced risk (RD, -1.6%; 95% CI, -2.0 to 0.4; low certainty); all other drugs may have had little or uncertain effect. For time to alleviation of symptoms, baloxavir probably reduced symptom duration (mean difference [MD], -1.02 days; 95% CI, -1.41 to -0.63; moderate certainty); umifenovir may have reduced symptom duration (MD, -1.10 days; 95% CI, -1.57 to -0.63; low certainty); oseltamivir probably had no important effect (MD, -0.75 days; 95% CI, -0.93 to -0.57; moderate certainty). For adverse events related to treatment, baloxavir (RD, -3.2%; 95% CI, -5.2 to -0.6; high certainty) had few or no adverse events; oseltamivir (RD, 2.8%; 95% CI, 1.2 to 4.8; moderate certainty) probably increased adverse events.

This systematic review and meta-analysis found that baloxavir probably reduced risk of hospital admission for high-risk patients and may reduce time to alleviation of symptoms, without increasing adverse events related to treatment in patients with nonsevere influenza. All other antiviral drugs either probably have little or no effect, or uncertain effects on patient-important outcomes.

To evaluate the impact of pancreatic duct stent outcomes on the prognosis of postoperative pancreatic fistula in patients with high-risk anastomoses.

Randomized controlled trials were identified through comprehensive searches in Cochrane Library, Web of Science, Embase, and PubMed databases. Cochrane Collaboration's tool RoB2 was used to evaluate study quality. The presence of non-dilated main pancreatic duct and soft gland texture were used to identify high risk anastomoses. The primary outcome measured was clinically relevant postoperative pancreatic fistula rate. The heterogeneity and sensitivity analyses were performed.

Six studies (n = 476) were included. The pooled data showed no significant difference in the clinically relevant postoperative pancreatic fistula rate between stented and nonstented groups for at least one high-risk factor out of two factors selected (p = 0.234). Patients with non-dilated main pancreatic duct who received stent placement had a lower clinically relevant postoperative pancreatic fistula rate (RR = 0.582, 95%CI = 0.383-0.883, p = 0.011). In contrast, patients with soft pancreatic texture showed no significant difference between two groups (p = 0.879). After removing the study identified by sensitivity analysis as the origin of heterogeneity from general cohorts, the stented group had a lower clinically relevant postoperative pancreatic fistula rate (RR = 0.608, 95%CI = 0.413-0.895, p = 0.012).

There is a lack of robust evidence to support pancreatic duct stent placement for high-risk anastomoses. Nevertheless, stent implantation may be beneficial for patients with non-dilated pancreatic duct or external stent drainage.

The protocol was registered in advance with PROSPERO (CRD42023471943).

To address the comparative effectiveness of common interventional procedures for chronic non-cancer (axial or radicular) spine pain.

Systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs).

Medline, Embase, CINAHL, CENTRAL, and Web of Science from inception to 24 January 2023.

RCTs that enrolled patients with chronic non-cancer spine pain, randomised to receive a commonly used interventional procedure versus sham procedure, usual care, or another interventional procedure.

Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence.

Of 132 eligible studies, 81 trials with 7977 patients that explored 13 interventional procedures or combinations of procedures were included in meta-analyses. All subsequent effects refer to comparisons with sham procedures. For chronic axial spine pain, the following probably provide little to no difference in pain relief (moderate certainty evidence): epidural injection of local anaesthetic (weighted mean difference (WMD) 0.28 cm on a 10 cm visual analogue scale (95% CI -1.18 to 1.75)), epidural injection of local anaesthetic and steroids (WMD 0.20 (-1.11 to 1.51)), and joint-targeted steroid injection (WMD 0.83 (-0.26 to 1.93)). Intramuscular injection of local anaesthetic (WMD -0.53 (-1.97 to 0.92)), epidural steroid injection (WMD 0.39 (-0.94 to 1.71)), joint-targeted injection of local anaesthetic (WMD 0.63 (-0.57 to 1.83)), and joint-targeted injection of local anaesthetic with steroids (WMD 0.22 (-0.42 to 0.87)) may provide little to no difference in pain relief (low certainty evidence); intramuscular injection of local anaesthetic with steroids may increase pain (WMD 1.82 (-0.29 to 3.93)) (low certainty evidence). Evidence for joint radiofrequency ablation proved of very low certainty.For chronic radicular spine pain, epidural injection of local anaesthetic and steroids (WMD -0.49 (-1.54 to 0.55)) and radiofrequency of dorsal root ganglion (WMD 0.15 (-0.98 to 1.28)) probably provide little to no difference in pain relief (moderate certainty evidence). Epidural injection of local anaesthetic (WMD -0.26 (-1.37 to 0.84)) and epidural injection of steroids (WMD -0.56 (-1.30 to 0.17)) may result in little to no difference in pain relief (low certainty evidence).

Our NMA of randomised trials provides low to moderate certainty evidence that, compared with sham procedures, commonly performed interventional procedures for axial or radicular chronic non-cancer spine pain may provide little to no pain relief.

PROSPERO (CRD42020170667).

Trauma is a major cause of mortality in the elderly population. Hyponatremia is the most common electrolyte imbalance in geriatric patients and has been demonstrated to be a risk factor for altered cognition, low bone density, falls, and death. We systematically and critically reviewed the literature to ascertain the association between hyponatremia and geriatric trauma outcomes.

We searched seven databases for articles published from inception to October 2023. Studies included reported on geriatric trauma, hyponatremia, and clinical outcomes. Two investigators independently reviewed 6535 abstracts, 235 full-text articles, and critically appraised each study. Study details, patient characteristics, and outcomes were independently extracted by two reviewers. Data quality assessment was performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Publication bias was assessed using funnel plot-based methods. A meta-analysis of risk ratios (RR) was performed using the random effects method.

Four retrospective cohort studies involving 11 894 geriatric patients were included. Among these, 492 (21.4%) were classified as trauma patients due to a fall and 1806 (78.6%) were classified as a trauma patient due to the presence of a fracture. In total, 2298 (19.3%) patients were classified as hyponatremic (125-135 mmol/L) while 9596 (80.7%) were classified as normonatremic. The pooled RR for in-hospital mortality for hyponatremic patients was 2.23 (95% CI 1.51 to 3.74) with high heterogeneity across the studies (I2=82.17%).

Geriatric trauma patients presenting with hyponatremia appear to have an increased risk of in-hospital mortality. Given this association, national trauma registries should consider collecting serum sodium values for geriatric patients and providers should work to address hyponatremia as a possible contribution to falls. Given the paucity of published literature on this topic, there is a need for prospective studies evaluating the association between hyponatremia and geriatric trauma outcomes.

Level III, systematic review with meta-analysis.

Postpartum haemorrhage (PPH) is commonly defined as blood loss of 500 mL or greater within 24 hours after birth. Intravenous transfusions of whole blood, red blood cells (RBC), or other blood components collected from a donor may be administered to manage PPH. Key questions remain regarding optimal timing for initiating blood and blood product transfusion in managing PPH and whether the use of fractionated blood products, either as replacement for or in addition to whole blood transfusion, could improve maternal outcomes. No systematic review has examined appropriate transfusion strategies for managing PPH.

To assess the benefits and harms of transfusion of whole blood or other blood products for preventing morbidity and mortality among women with PPH.

We searched CENTRAL, MEDLINE, Embase, and two trials registers, together with reference checking, citation searching, and contact with study authors to identify studies for inclusion in the review. The latest search was 18 July 2024.

We considered randomised controlled trials (RCTs), cluster-randomised trials, or controlled non-randomised studies of interventions (NRSI) evaluating the efficacy and safety of blood transfusion for managing PPH, regardless of the mode of birth.

Our critical outcomes were maternal death, severe maternal morbidity, and adverse effects.

We assessed risk of bias in included studies using the Cochrane RoB 2 tool and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool.

We synthesised results for each outcome within each comparison using meta-analysis where possible, and used GRADE to assess the certainty of evidence for each outcome.

We included 12 studies with 17,868 participants. We excluded five NRSIs from outcome analyses due to critical risk of bias related to confounding.

One threshold for initiating transfusion versus another threshold for initiating transfusion None of the studies assessed this comparison. One- to two-unit RBCs versus no transfusion Among women with moderate blood loss, low-certainty evidence from one NRSI found that transfusing 1 to 2 units of RBCs to treat PPH may increase severe maternal morbidity - composite excluding intensive care unit (ICU) admission (risk ratio (RR) 7.00, 95% confidence interval (CI) 2.75 to 17.80; 2130 women) and severe maternal morbidity - ICU admission (RR 2.12, 95% CI 1.20 to 3.75; 2130 women), though we have substantial concerns about the potential bias due to confounding as the volume of blood lost was not controlled for in the analysis. The study did not report maternal death or adverse effects. Packed RBCs versus whole blood versus combination of blood products One NRSI assessed this comparison but had critical risk of bias and was subsequently excluded from analysis. Fresh frozen plasma (FFP)/RBCs with fibrinogen concentrate versus FFP/RBCs alone One NRSI assessed this comparison but had critical risk of bias and was subsequently excluded from analysis. Fibrinogen concentrate versus placebo or no fibrinogen concentrate The evidence is very uncertain about the effect of fibrinogen concentrate on maternal death (0 events; 2 studies, 674 women; very low-certainty evidence). Fibrinogen concentrate probably results in little to no difference in severe maternal morbidity - ICU admission (RR 1.09,0 95% CI 0.80 to 1.49; 2 studies, 485 women; moderate-certainty evidence). The evidence is very uncertain about the effect of fibrinogen concentrate on severe maternal morbidity - arterial embolisation (1 study, 430 women; very low-certainty evidence). One RCT (430 women) and one NRSI (730 women) reported severe maternal morbidity - hysterectomy, each of which reported different directions of effect with low-certainty evidence. Fibrinogen concentrate may result in little to no difference in adverse effect - thromboembolic events (RR 0.19, 95% CI 0.01 to 3.95; 2 studies, 674 women; low-certainty evidence). The evidence is very uncertain about the effects of fibrinogen concentrate on additional adverse effects, such as shivering or fever (1 study, 244 women; very low-certainty evidence). Cryoprecipitate versus no cryoprecipitate The evidence is very uncertain about the effect of cryoprecipitate on maternal death. One RCT (0 deaths; 180 women; very low-certainty evidence) and one NRSI (0 deaths; 157 women; very low-certainty evidence) reported this outcomes. The evidence is also very uncertain about the effects of cryoprecipitate on severe maternal morbidity - ICU admission, severe maternal morbidity - any organ failure, severe maternal morbidity - laparotomy, or severe maternal morbidity - uterine artery embolisation (1 study, 180 women; very low-certainty evidence). One RCT (180 women; very low-certainty evidence) and one NRSI (157 women; very low-certainty evidence) reported severe maternal morbidity - hysterectomy and the evidence is very uncertain. The evidence is also very uncertain about the effects of cryoprecipitate on adverse effects, such as thromboembolic events or transfusion-related reactions (1 study, 180 women; very low-certainty evidence). Massive transfusion protocol versus no massive transfusion protocol Two NRSIs assessed this comparison but had critical risk of bias and were subsequently excluded from analysis.

Overall, available evidence for the effects of blood and blood product transfusion on priority maternal outcomes is largely uncertain. Low-certainty evidence suggests that 1 to 2 units of RBC transfusion may increase the risk of severe maternal morbidity; however, we urge caution when interpreting this finding as the effect estimates are at serious risk of bias due to possible confounding. We are unable to comment on the effects of larger blood transfusion amounts on severe maternal morbidity.

This review received no dedicated funding.

This protocol for this Cochrane review is registered with PROSPERO. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024599608.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effectiveness of education and training interventions on improving knowledge and skills for managing sexual harassment, and to assess their impact on the incidence of sexual harassment towards healthcare workers in healthcare settings. We will include all forms of sexual harassment committed by patients, visitors, and co-workers.

This head-to-head comparative meta-analysis aimed to evaluate the comparative diagnostic efficacy of [18F]FDG PET/CT and dynamic contrast-enhanced CT(DCE-CT) for the differentiation between malignant and benign pulmonary nodules.

An extensive search was conducted in the PubMed, Embase, and Web of Science to identify available publications up to March 23, 2024. Studies were included if they evaluated the diagnostic efficacy of [18F]FDG PET/CT and DCE-CT for the characterization of pulmonary nodules. Sensitivity and specificity were assessed using the inverse variance method, followed by transformation via the Freeman-Tukey double inverse sine transformation. The quality of the included studies utilizing the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.

Seven articles involving 1,183 patients were included in the meta-analysis. The sensitivity of [18F]FDG PET/CT was comparable to that of DCE-CT (0.88 vs. 0.87, P = 0.95). Similarly, the specificity of [18F]FDG PET/CT was not significantly different from that of DCE-CT (0.63 vs. 0.54, P = 0.47). No significant publication bias was detected for any outcome (Egger's test: all P > 0.05). For DCE-CT, meta-regression analysis identified the mean lesion size of pulmonary nodules (<20 mm vs. ≥ 20 mm, P = 0.01) as a potential source of heterogeneity. Meanwhile, the number of patients (<100 vs. ≥ 100, P < 0.01) for PET/CT may also contribute to the heterogeneity.

Our meta-analysis indicates that [18F]FDG PET/CT demonstrates similar sensitivity and specificity to DCE-CT for the diagnosis of pulmonary nodules. However, the number of the head-to-head studies were relatively small, further larger sample prospective research is required to confirm these findings.

Background: Minimally invasive surgery is the preferred method for treating colorectal disease. Laparoscopic suturing is complex, and barbed sutures (BS) can improve the process by eliminating the need for surgical knots and constant traction on the suture line. This study compares intraoperative and postoperative outcomes in patients undergoing laparoscopic-assisted colorectal surgery (LCS) with anastomosis using BS and conventional sutures (CS). Methods: PubMed, Scopus and Cochrane Library were systematically searched for studies comparing BS to CS in patients undergoing LCS. Continuous outcomes were compared using mean differences (MDs), and odds ratios (ORs) were computed for binary endpoints with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics. Statistical analysis was performed using Software R, version 4.2.3. Results: A total of four studies comprising 285 patients were included, of whom 143 patients (50.17%) underwent BS. Compared with CS, BS significantly reduced the total operative time (MD -16.25 minutes; 95% CI: -25.94, -6.56; P < .01; I2 = 0%). However, there were no significant differences between groups in the occurrence of intraoperative complications (OR .74; 95% CI: .26-2.12; P = .58; I2=0%), anastomotic leakage (OR 1.00; 95% CI: .14-7.26; P = 1.00), and Clavien-Dindo ≥III complications (OR 1.80; 95% CI: .41-7.95; P = .44, I2 = 0%). Conclusion: In this meta-analysis, BS significantly reduced the operative time in the anastomotic closure compared to CS in LCS. Furthermore, there were no significant differences between the groups in anastomotic leakage, intraoperative complications, and severe postoperative complications.

The objective of this systematic review was to compare the effectiveness of prophylactic angioembolization with observation as primary management strategies for patients with high-grade (grades 3-5) blunt trauma splenic injury.

The spleen is commonly injured in abdominal trauma. Historical management practices involved splenectomy, but more recent evidence suggests an increased risk of severe infections and sepsis associated with this approach. Accordingly, nonoperative management strategies, including prophylactic splenic artery embolization and clinical observation, have gained prominence. This systematic review with meta-analysis directly compared angioembolization with clinical observation for high-grade splenic injuries only, aiming to provide clarity on this matter amid ongoing debates and variations in clinical practice.

This review included adult patients aged 15 years or older with high-grade splenic injuries (grades 3-5) due to blunt trauma. Outcomes of interest include the need for further intervention (failure of management), mortality, complications, red blood cell transfusion requirements, hospital length of stay, and intensive care unit length of stay.

A comprehensive search of PubMed, Embase, and CINAHL (EBSCOhost) was performed, with no restrictions on language or publication date. Gray literature was searched, including trial registries and relevant conference proceedings. After deduplication, 2 reviewers independently assessed titles and abstracts, and, subsequently, full-text articles for eligibility. Methodological quality of the included studies was assessed using standardized instruments from JBI. Data were extracted using predefined templates, and statistical meta-analysis was performed, where possible, using a random-effects model. Heterogeneity was assessed using statistical methods, and potential publication bias was tested with a funnel plot. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence.

Sixteen studies were included in this review. Methodological quality assessment indicated some risk of bias in most studies, with concerns primarily related to differences in injury severity and potential confounding factors. Meta-analysis revealed that prophylactic angioembolization significantly reduced risk of management failure by 57% (OR 0.43, 95% CI 0.28-0.68, I2 =53%, 15 studies) and decreased patient mortality by 37% (OR 0.63, 95% CI 0.43-0.93, I2 =0%, 9 studies) compared with clinical observation alone. There was a 47% reduction in risk of complications associated with prophylactic embolization compared with clinical observation (OR 0.53, 95% CI 0.29-0.95, I2 =0%, 4 studies). Some statistical heterogeneity was observed, with I2 ranging from 0% to 53%. No significant differences were observed between the 2 management strategies for red blood cell transfusion requirements or hospital length of stay.

The results of this review support the use of prophylactic embolization for high-grade blunt trauma splenic injuries, indicated by lower rates of management failure, reduced need for additional interventions, lower mortality, and fewer complications.

PROSPERO CRD42023420220.

Whether in utero exposure to pregestational (type 2 [T2D] and type 1 diabetes [T1D]) and gestational diabetes (GDM) are contributing factors in the rise of neurodevelopmental alterations such as autism is yet unclear. Therefore, we summarized the evidence from studies that assessed such association.

A systematic review with meta-analyses was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines; eligible studies were identified in PubMed, Web of Science, and EBSCO up to April 3rd, 2023. We estimated pooled OR of autism from random effects meta-analyses for each type of maternal diabetes.

26 publications were selected (18 cohorts and 8 case-controls); 17 had data for the meta-analysis. We observed an increased risk of autism in the offspring exposed in utero to T2D (pooled OR = 1.48; 95%CI: 1.31, 1.68; n = 3,141,255), T1D (pooled OR = 1.73; 95%CI: 1.05, 2.87; n = 2,791,607), and GDM (pooled OR = 1.31; 95% CI: 1.16, 1.47; n = 3,259,557) compared to those unexposed. No evidence of heterogeneity (I2 = 0.0%) was observed for T2D, whereas for T1D the heterogeneity was substantial (I2 = 64.7%) and for GDM was moderate (I2 = 53.1%). The evidence was stronger for in utero exposure to GDM, followed by T2D and T1D.

Our results support the hypothesis that in utero exposure to maternal T2D or GDM moderately increased the offspring's risk of developing autism later in life. Prospectively conducted studies are still warranted to better estimate the size of the effect of maternal diabetes on autism risk.

This meta-analysis elucidates the efficacy of the Transradial Band Device (TR Band) in minimizing complications like radial artery occlusion and hematoma, preserving heart health, and enhancing blood flow post-transradial catheterization.

A comprehensive literature search across databases including PubMed, Cochrane, and Embase examined the impact of radial artery compression techniques and decompression times on complications. Data from 13 studies were analyzed using R 4.1.2 with fixed-effects and random-effects models. The Newcastle-Ottawa Scale assessed the risk of bias in observational cohort studies.

In our meta-analysis, we evaluated data from various studies encompassing different air volumes in transradial band devices across several outcomes including bleeding, hematoma, radial artery occlusion (RAO), Visual Analog Scale (VAS) scores, and compression time. The collective analysis integrated findings from 11 studies, totaling 4,679 patients. No significant difference in bleeding risk (OR 1.04, 95% CI 0.60-1.82, p > 0.05, I 2 = 78%), hematoma incidence (OR 0.96, 95% CI 0.78-1.19, p > 0.05, I 2 = 0%), or RAO incidence (OR 0.96, 95% CI 0.78-1.19, p > 0.05, I 2 = 0%) was observed between the "Less air" and "15 ml air" groups. However, the "Less air" group reported significantly higher VAS scores indicating increased pain or discomfort (Mean Difference 0.25, 95% CI 0.09-0.41, p < 0.05, I 2 = 0%). Compression time analyses showed no significant difference between groups (Mean Difference -17.73, 95% CI -54.65-19.20, p > 0.05, I 2 = 99%). Sensitivity analyses confirmed the stability of these findings, and Egger's test indicated no significant publication bias across the outcomes. This synthesis highlights the nuanced impact of air volume adjustments in transradial bands on patient outcomes, emphasizing the necessity for further research and standardized protocols to optimize patient safety and comfort post-intervention.

The TR Band, when utilized with optimized air volume/pressure, maintains an essential balance between ensuring hemostasis and enhancing patient comfort without elevating the risk of radial artery complications. These findings support the careful selection of TR Band settings to optimize clinical outcomes in patients undergoing transradial cardiac procedures. Further research is warranted to establish standardized guidelines for the most effective use of TR Band in various clinical scenarios.

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock.

Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched.

Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate.

Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials.

Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence.

While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

Stenosis in arteriovenous fistulas (AVF) due to neointimal hyperplasia is one of the most common causes of hemodialysis vascular access dysfunction. Treating patients with dysfunctional AVF with drug-coated balloon (DCB) angioplasty may potentially improve outcomes.

This systematic review aimed to compare the effectiveness and safety of DCB angioplasty versus conventional balloon angioplasty by pooling evidence from the most recent randomized controlled trials.

We conducted a comprehensive literature search in the Web of Science, Embase, and Cochrane central databases. Two independent researchers screened the article, extracted interest, and evaluated included studies for risk of bias. Pooled estimation was conducted in terms of 6-month target-lesion primary patency (TLPP) and target-lesion reintervention (TLR), as well as other outcomes.

Results were expressed with odds ratio (OR) and 95% confidence interval (CI). A total of five RCTs were identified and included in the meta-analyses, with 1107 participants. DCB has a trend of a higher rate of TLPP (OR 1.79, 95% CI 0.66-4.90, p = 0.181) and a significantly lower rate of TLR (0.52, 95% CI 0.29-0.92, p = 0.034), as compared to conventional balloon angioplasty. No difference in the 6-month access circuit primary patency and reinvention was observed between the two groups.

DCB may be an alternative treatment of dysfunctional AVF given a trend of a higher rate of TLPP and a significantly lower rate of TLR than conventional balloon angioplasty within 6 months after the indexed procedure. Moreover, DCB was non-inferior to conventional balloon angioplasty in terms of safety. Considering variations in the DCB technique, further studies are warranted for a standardized process.

Patients with clinical tendinopathy often demonstrate significant abnormalities with ultrasound (US) imaging. Tendon abnormalities likely precede pain in these patients. The purpose of this review was to systematically evaluate the available literature regarding the utility of US imaging as a method to predict Achilles and patellar tendon pain.

Systematic review and meta-analysis. Inclusion criteria were as follows: prospective studies of Achilles and patellar tendon pain development with baseline US measurements, follow-up clinical measurements, and English-language studies published after 2000. Exclusion criteria were prior rupture or surgery and presence of rheumatologic disorder.

N/A.

Athletes without Achilles or patellar tendon pain at baseline.

N/A.

Risk ratios (RRs) were identified for the development of pain in those with Achilles or patellar tendon sonographic abnormalities.

This review of 16 studies included 810 Achilles and 1156 patellar tendons from a variety of sports and demonstrated that the RR for pain development from abnormal Patellar and Achilles tendons was 6.07 [95% confidence interval (CI), 2.88-12.81; P < 0.001] and 3.96 [95% CI, 2.21-7.09; P < 0.001], respectively. The positive and negative predictive values of an abnormal US finding were 27.2% and 92.0% for the Achilles tendon and 27.2% and 93.5% for the patellar tendon, respectively.

This systematic review and meta-analysis identified that the use of asymptomatic US scanning of the Achilles or patellar tendon has a low positive predictive value but a high negative predictive value for the future development of pain.

Endoscopic vacuum-assisted closure (EVAC) is a novel technique used to repair esophageal perforation and leaks. Varying data have been reported on the overall success rate of EVAC. We aimed to conduct a meta-analysis of the available data on the clinical success rate of EVAC.

Electronic databases were searched for publications addressing the efficacy of EVAC in esophageal luminal defects. Pooling was conducted using both fixed and random-effects models. The overall clinical success of EVAC therapy was considered the primary outcome, whereas, overall complication rates, need for adjunct therapy, and mortality were considered secondary outcomes.

In total, 366 patients were included in the study. On pooled analysis, the mean age was 66 years with 68.32% of patients being men. Overall pooled clinical success rate of EVAC therapy was 87.95%. Upon subgroup analysis, the pooled clinical success rate of postsurgical anastomotic leak and transmural esophageal perforation were found to be 86.57% and 88.89%, respectively. The all-cause hospital mortality was 14% and 4.2% in patients with esophageal perforation and EVAC, respectively.

This study demonstrates that EVAC therapy has a high overall clinical success rate, with low mortality. EVAC therapy seems to be a promising procedure with excellent outcomes in patients with luminal esophageal defects.

The anterior quadratus lumborum (QL) block may be used for postoperative pain management for intra-abdominal surgeries, but the evidence is uncertain. We aimed to investigate the benefit and harm of the anterior QL block compared to placebo/no block for intra-abdominal surgery.

We searched Medline, Embase, and CENTRAL for randomized controlled trials investigating anterior QL block for postoperative pain management for adult patients undergoing any intra-abdominal surgery. The two co-primary outcomes were cumulative 24-h opioid consumption and serious adverse events. We performed meta-analysis, trial sequential analysis (TSA), assessed the risk of bias, and present the certainty of evidence with the Grading of Recommendations, Assessment, Development and Evaluation approach.

Thirty-five trials randomizing 2418 patients were included in the meta-analyses. Anterior QL block may reduce cumulative 24-h intravenous opioid consumption compared to placebo/no block (MD -10.42 mg, 96.7% CI -14.83 to -6.01, TSA-adjusted CI -17.03 to -3.82, p < .01). Two trials reported on SAEs. Anterior QL block may have little to no effect on the number of serious adverse events compared to placebo (RR 1.49, 96.7% CI 0.19 to 11.47, p = .68), but the evidence is very uncertain. All trial results were assessed as being high risk of bias.

The anterior QL block may reduce cumulative 24-h opioid consumption. Reported serious adverse events were few and the anterior QL block may have little to no effect on the number of SAEs, but the evidence was very uncertain.

Isatuximab, an anti-CD38 monoclonal antibody, has been shown to induce apoptosis in multiple myeloma (MM) cells and is effective in both relapsed/refractory and newly diagnosed MM cases. This study aims to compare the safety profile of isatuximab by examining a broader range of adverse events (AEs) using data from the FDA Adverse Event Reporting System (FAERS) and a meta-analysis of randomized controlled trials (RCTs). The study analyzed FAERS data up to March 2024, identifying suspected AEs using Preferred Terms. Data extraction from FAERS was conducted using OpenVigil-2.1-MedDRA-v24. Disproportionality analysis was performed by calculating the proportional reporting ratio (PRR) with Chi-square value, and the reporting odds ratio (ROR) with a 95% confidence interval (CI). For the meta-analysis, safety outcomes of isatuximab in adult patients were reviewed from RCTs sourced from databases such as PubMed, EMBASE, and ClinicalTrials.gov, employing a random-effects meta-analysis to determine the risk ratio (RR) with 95% CI. The meta-analysis protocol was registered with PROSPERO (CRD42022379632). Based on the FAERS quarterly reports, a total of 2,325 AE reports were identified, with a higher incidence in men (n = 1156, 49.7%) compared to women (n = 960, 41.3%). AEs commonly observed with isatuximab therapy included neutropenia, pneumonia, infusion-related reactions, thrombocytopenia, acute kidney injury, and anemia. In our meta-analysis of three RCTs involving 1,258 patients, 659 (52.4%) in the isatuximab treatment group experienced 1,135 AEs, with 58% classified as grade three or higher. In comparison, 599 (47.6%) patients in the control group reported 906 AEs, with 59% categorized as grade three or higher. Notably, the isatuximab group showed a statistically significant increased risk of grade three or higher neutropenia (RR = 2.13, 95% CI: 1.12-4.03, p = 0.0207) and a 30% increased risk of grade 3 or higher thrombocytopenia (RR = 1.30, 95% CI: 1.03-1.64, p = 0.0244). Isatuximab therapy was generally well-tolerated and exhibited a manageable safety profile. Considering these findings, future research might benefit from longer follow-up periods to capture delayed and less frequent AEs.

The stent-assisted coiling (SAC) and flow-diverter stent (FDS) techniques are widely used in the endovascular treatment of paraclinoid aneurysms. This article compares the occlusion rate, periprocedural complications, and clinical outcomes of SAC and FDSs.

Between January 2010 and December 2020, a systematic search of electronic databases identified 2283 articles for screening. After the application of inclusion and exclusion criteria, data were extracted for a meta-analysis of the proportions.

Of 23 articles containing 4 comparative studies, 27 cohorts were included, and 1208 patients with 1328 aneurysms were analyzed: In 10 cohorts, 381 (28.7%) patients were treated with SAC, whereas in 17 cohorts, 947 (71.3%) patients were treated with FDSs. In the comparative studies, no significance was observed between the 2 treatments. In the pooled cohorts, complete occlusion was achieved in 85% of aneurysms after treatment with FDSs (95% CI: 0.81-0.88, I2=34.7%) and 76% after treatment with SAC (95% CI: 0.70-0.81, I2=16.6%); the subgroup analysis was statistically significant (P=0.003). New visual complications were observed in 5% of the FDS-treated group (95% CI: 0.02-0.09, I2=76.9%) and in 1% of the SAC-treated group (95% CI: 0.00-0.02, I2=0%); the subgroup analysis was statistically significant (P=0.018). Other observational indices, including total procedure-related complications; hemorrhagic, thrombotic, and ischemic complications; permanent morbidities, and favorable neurological outcomes, showed no statistical significance between the groups.

Compared with SAC, treatment with FDSs may have a higher complete occlusion rate at follow-up. The similarly low rates for procedure-related complications and permanent morbidities indicate that both treatments are safe. A higher rate of new visual complications was noted in the FDS-treated group. Further research is required for direct comparisons along with a complete ophthalmological examination.

Under which conditions antibiotic combination therapy decelerates rather than accelerates resistance evolution is not well understood. We examined the effect of combining antibiotics on within-patient resistance development across various bacterial pathogens and antibiotics.

We searched CENTRAL, EMBASE, and PubMed for (quasi)-randomised controlled trials (RCTs) published from database inception to 24 November 2022. Trials comparing antibiotic treatments with different numbers of antibiotics were included. Patients were considered to have acquired resistance if, at the follow-up culture, a resistant bacterium (as defined by the study authors) was detected that had not been present in the baseline culture. We combined results using a random effects model and performed meta-regression and stratified analyses. The trials' risk of bias was assessed with the Cochrane tool.

42 trials were eligible and 29, including 5054 patients, qualified for statistical analysis. In most trials, resistance development was not the primary outcome and studies lacked power. The combined odds ratio for the acquisition of resistance comparing the group with the higher number of antibiotics with the comparison group was 1.23 (95% CI 0.68-2.25), with substantial between-study heterogeneity (I2=77%). We identified tentative evidence for potential beneficial or detrimental effects of antibiotic combination therapy for specific pathogens or medical conditions.

The evidence for combining a higher number of antibiotics compared to fewer from RCTs is scarce and overall compatible with both benefit or harm. Trials powered to detect differences in resistance development or well-designed observational studies are required to clarify the impact of combination therapy on resistance.

Support from the Swiss National Science Foundation (grant 310030B_176401 (SB, BS, CW), grant 32FP30-174281 (ME), grant 324730_207957 (RDK)) and from the National Institute of Allergy and Infectious Diseases (NIAID, cooperative agreement AI069924 (ME)) is gratefully acknowledged.