Gut-brain neuromodulators might be efficacious for irritable bowel syndrome (IBS), but there has been no synthesis of evidence from randomised controlled trials (RCTs) of some drug classes, and whether they have pain-modifying properties in IBS is unclear. We updated a previous systematic review and meta-analysis of RCTs examining these questions.

We searched MEDLINE (from Jan 1, 1946, to Jan 1, 2025), Embase and Embase Classic (from Jan 1, 1947, to Jan 1, 2025), and the Cochrane Central Register of Controlled Trials (from database inception to Jan 1, 2025). Trials recruiting adults with IBS and that compared gut-brain neuromodulators versus placebo over at least 4 weeks of treatment were eligible. Dichotomous symptom data were pooled using a random effects model to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.

The search strategy identified 3625 citations. 28 RCTs were eligible containing 2475 patients. Ten RCTs were identified since our previous meta-analysis, containing 1348 patients. The RR of global IBS symptoms not improving with gut-brain neuromodulators versus placebo in 22 RCTs (2222 patients) was 0·77 (95% CI 0·69-0·87). The best evidence in terms of persistence of global IBS symptoms was for tricyclic antidepressants (TCAs) in 11 trials (1144 patients; RR 0·70, 0·62-0·80). The RR of abdominal pain not improving with gut-brain neuromodulators versus placebo in 19 RCTs (1792 patients) was 0·72 (95% CI 0·62-0·83). The best evidence was for TCAs in seven trials (708 patients; RR 0·69, 0·54-0·87), but there was also a benefit of selective serotonin reuptake inhibitors in seven RCTs (324 patients; RR 0·74, 0·56-0·99), and serotonin and norepinephrine reuptake inhibitors in two trials (94 patients; RR 0·22, 0·08-0·59). Adverse events were not significantly more common with gut-brain neuromodulators, although rates of withdrawal due to adverse events were significantly higher. The certainty in the evidence for tricyclic antidepressants for global IBS symptoms was moderate, but it was low to very low for all other endpoints and drug classes studied.

Some gut-brain neuromodulators are efficacious in reducing global symptoms and abdominal pain in IBS. The findings support guidelines that recommend use of tricyclic antidepressants for ongoing global symptoms or abdominal pain but also highlight a potential for SSRIs to be modestly effective for abdominal pain. More data for SNRIs, azapirones, and tetracyclic antidepressants in IBS are required.

None.

Patients with irritable bowel syndrome (IBS) are often interested in dietary interventions as a means of managing their symptoms. However, the relative efficacy of available diets for the management of IBS is unclear. We aimed to examine the relative efficacy of various dietary interventions in IBS.

For this systematic review and network meta-analysis we searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials from database inception to Feb 7, 2025, to identify randomised controlled trials comparing an active dietary intervention requiring changes to the intake of more than one food in IBS with either a control intervention, such as a habitual diet, sham diet, a high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, or alternative miscellaneous dietary advice, or any other active dietary intervention requiring changes to the intake of more than one food. We assessed efficacy using dichotomous assessments of improvement in global IBS symptoms or improvement in individual IBS symptoms, including abdominal pain, abdominal bloating or distension, and bowel habit. We pooled data using a random-effects model, with the efficacy of each intervention reported as pooled relative risks (RRs) with 95% CIs. We ranked interventions according to their P-score, which measures the mean extent of certainty that one intervention is better than another, averaged over all competing interventions.

We identified 28 eligible randomised controlled trials (comprising 2338 patients) of 11 different dietary interventions compared with four control interventions, of which six (low FODMAP diet, British Dietetic Association/National Institute for Health and Care Excellence [BDA/NICE] diet, lactose-reduced diet, starch-reduced and sucrose-reduced diet, a personalised diet, and a Mediterranean diet) were studied in more than one trial. For global IBS symptoms, assessed in 28 randomised controlled trials and when considering only the dietary interventions studied in more than one trial, a starch-reduced and sucrose-reduced diet ranked first (RR of global IBS symptoms not improving 0·41 [95% CI 0·26-0·67]; P-score 0·84; two trials), a low FODMAP diet ranked fourth (0·51 [0·37-0·70]; P-score 0·71; 24 trials), and a BDA/NICE diet ranked tenth (0·62 [0·43-0·90]; P-score 0·44; eight trials), versus a habitual diet. For abdominal pain, assessed in 26 trials and when considering only the dietary interventions studied in more than one randomised controlled trial, a starch-reduced and sucrose-reduced diet ranked second (RR of abdominal pain not improving 0·54 [95% CI 0·33-0·90]; P-score 0·73; two trials), and a low FODMAP diet ranked fifth (0·61 [0·42-0·89]; P-score 0·64; 23 trials), versus a habitual diet. For abdominal bloating or distension, assessed in 26 trials and when considering only the dietary interventions studied in more than one randomised trial, only a low FODMAP diet (RR of abdominal bloating or distension not improving 0·55 [95% CI 0·37-0·80]; P-score 0·64; 23 trials) was superior to a habitual diet and ranked fourth. For bowel habit, assessed in 23 randomised trials, none of the dietary interventions was superior to any of the control interventions, but a low FODMAP diet was superior to a BDA/NICE diet (RR of bowel habit not improving 0·79 [95% CI 0·63-0·99]). All comparisons across the network were rated as low or very low confidence, except for direct comparisons between a low FODMAP diet or a starch-reduced and sucrose-reduced diet and habitual diet, both of which were rated as moderate confidence.

In terms of dietary interventions for IBS, the most evidence exists for a low FODMAP diet, but other promising therapies are emerging and should be the subject of further study.

None.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of sedative, analgesic, and anaesthetic drugs on neurological outcomes in adults with moderate-to-severe traumatic brain injury.

Autism Spectrum Disorder (ASD) has been associated with disruptions in one-carbon metabolism and vitamin D pathways. Nutritional exposures-particularly vitamin D, vitamin B12, and homocysteine-may influence neurodevelopmental outcomes. However, a comprehensive, lifespan-spanning synthesis of these modifiable nutritional biomarkers has not been conducted. This systematic review and stratified meta-analysis critically synthesized data on vitamin D, vitamin B12, and homocysteine to elucidate their relationships with ASD risk and symptomatology. Our central question was: How do levels of vitamin D, vitamin B12, and homocysteine-measured before and after birth-affect the risk, severity, and potential treatment outcomes for ASD? We conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) compliant systematic review and stratified meta-analysis (2015-2025) of 35 studies (11 randomized controlled trials, 24 observational), examining prenatal, neonatal, and postnatal biomarker levels. Eligibility criteria were defined using the PICOS (Population, Intervention, Comparator, Outcome, and Study Design) framework to ensure scientific rigor and clinical relevance, including studies involving human participants aged 0-18 years with a formal Autism Spectrum Disorder (ASD) diagnosis or prenatal exposures potentially linked to later ASD onset, while excluding animal studies, adult-only ASD populations, and studies lacking ASD cohorts or biomarker data. The search strategy, developed according to PRISMA, and Cochrane best practices, encompassed five major databases (PubMed/MEDLINE, Cochrane Library, Google Scholar, ClinicalTrials.gov, and ProQuest) alongside manual searches of key references, grey literature, and clinical trial registries to ensure comprehensive retrieval of both published and unpublished studies. Study quality was assessed using version 2 of the Cochrane risk-of-bias tool for RCTs (RoB2) and the Newcastle-Ottawa Scale (NOS) for observational studies; certainty of evidence was graded via GRADE (Grading of Recommendations Assessment, Development and Evaluation). Random-effects meta-analyses were stratified by biomarker and study design. Heterogeneity, small-study effects, and publication bias were evaluated using Cochran's Q, I2, Egger's test, and trim-and-fill. Prenatal vitamin D deficiency was associated with approximately two-fold increased odds of Autism Spectrum Disorder (ASD) in offspring (pooled OR ≈ 2.0; p < 0.05), while excessively elevated maternal B12 concentrations, often co-occurring with folate excess, were similarly linked to increased ASD risk. Meta-analytic comparisons revealed significantly lower circulating vitamin D (SMD ≈ -1.0; p < 0.001) and B12 levels (SMD ≈ -0.7; p < 0.001), alongside elevated homocysteine (SMD ≈ 0.7; p < 0.001), in children with ASD versus neurotypical controls. Early-life vitamin D/B12 insufficiency and elevated homocysteine are important, modifiable correlates of ASD risk and severity. Adequate maternal and child nutritional status could have risk-reducing and symptom-mitigating effects, although causality remains to be confirmed. This evidence supports tailored nutritional interventions as a component of ASD risk reduction and management strategies, within the bounds of overall developmental healthcare. The article processing charges (APC) were supported by "Dunărea de Jos" University of Galati, Romania. No external funding was received for the execution of the research. The review was not prospectively registered in PROSPERO or any other systematic review registry.

Supratentorial function-eloquent brain tumour surgeries challenge the balance between maximal tumour resection and preservation of neurological function. This study aims to evaluate the efficacy of preoperative and intraoperative mapping techniques on resection outcomes and post-operative deficits.

This systematic review and meta-analysis examined literature up to March 2023, sourced from PubMed, Embase, and Medline. Criteria for inclusion were studies on patients undergoing surgery for supratentorial brain tumours, comparing preoperative mapping only (POM), intraoperative neuromonitoring and mapping (IONM), and combined techniques (POM&IONM), excluding non-randomized controlled trials. Data extraction focused on rates of gross total resection (GTR) and focal neurological deficits (FNDs). The main outcomes, assessed through a random-effects model and Cochran's Q-test for subgroup analysis. The study protocol is published on PROSPERO CRD42024512306.

19 studies involving 992 patients were included. Systematic review with meta-analysis revealed a non-significantly higher average GTR rates for POM&IONM (49.13%) and POM (50.79%) compared to IONM alone (41.23%). Highest rates of GTR were achieved with tractography-guided resection in POM group (66.59% versus fMRI-20.00%, p = 0.0004), multimodal stimulation in IONM group (54.16% versus low frequency stimulation (LFS)-13.29%, p < 0.0001) and in POM&IONM group (65.88% versus LFS-37.77%, p = 0.0036). Within the same tumour histology-metastasis, high grade and low grade glioma-there are no differences in the GTR rates achieved in the different groups (p > 0.05). In language-eloquent tumours and in awake craniotomy techniques regardless of tumour functional eloquence, POM&IONM group had higher GTR when compared to IONM groups (language eloquent tumours-POM&IONM 43.31% versus IONM-15.09%, p = 0.022; awake craniotomy technique-POM&IONM-41.22% versus IONM-12.08%, p = 0.0006). Permanent FNDs were higher in the IONM group (IONM-73.0%; POM-29.6%; POM&IONM-33.7% of immediate postoperative deficits, p = 0.0010).

A combined POM&IONM approach is responsible for higher rates of GTR in patients with language eloquent tumours and in both awake and asleep craniotomy techniques regardless of the tumour functional eloquence. The tumour histology is not relevant for differences in GTR rates among different mapping and monitoring strategies. Permanent postoperative FNDs are more likely with standalone utilization of IONM.

Not applicable.

Guidelines for randomised controlled trials (RCTs) recommend reporting relative and absolute measures of effect for binary outcomes while adjusting for covariates. There are a number of different ways covariate-adjusted relative risks and risk differences can be estimated.

Our goal was to identify methods used to estimate covariate-adjusted relative risk and risk differences in RCTs published in high-impact journals with binary outcomes. Other secondary objectives included the identification of how covariates are chosen for adjustment and whether covariate adjustment results in an increase in statistical precision in practice.

We included two-arm parallel RCTs published in JAMA, NEJM, Lancet, or the BMJ between January 1, 2018, and March 11, 2023, reporting relative risks or risk differences as a summary measure for a binary primary outcome. The search was conducted in Ovid-MEDLINE.

Of the 308 RCTs identified, around half (49%; 95% CI: 43-54%) reported a covariate-adjusted relative risk or risk difference. Of these, 82 reported an adjusted relative risk. When the reporting was clear (n = 65, 79%), the log-binomial model (used in 65% of studies; 95% CI: 52-76%) and modified Poisson (29%; 95% CI: 19-42%) were most commonly used. Of the 92 studies that reported an adjusted risk difference, when the reporting was clear (n = 56, 61%), the binomial model (used in 48% of studies; 95% CI: 35-62%) and marginal standardisation (21%; 95% CI: 12-35%) were the common approaches used.

Approximately half of the RCTs report either a covariate-adjusted relative risk or risk difference. Many RCTs lack adequate details on the methods used to estimate covariate-adjusted effects. Of those that do report the approaches used, the binomial model, modified Poisson and to a lesser extent marginal standardisation are the approaches used.

The current guidelines and canonical norms of diagnosis or treatment for Post-traumatic stress disorder (PTSD) with sleep disorder are still conflicting and have not yet reached a consensus. This study aimed to unravel the most effective countermeasures between two categories (psychotherapy and pharmacotherapy) put forward by the National Institute for Health and Clinical Excellence (NICE) and World Federation of Societies of Biological Psychiatry (WFSBP) respectively to treat PTSD individuals co-exist with sleep disorders.

Four databases, including PubMed, EMBASE, Cochrane Library, and APA PsyNet, were searched from inception to February 02, 2023.

Twenty articles with 24 Randomized controlled trials (RCTs) and a total number of 1,647 participants were included. As demonstrated in the network meta-analysis comparison results, CBT-I (standardized mean differences (SMD) = -1.51,95% confidence interval (CI):-2.55 to -0.47), CBT-I plus IRT (SMD = -1.71, 95%CI:-3.39, -0.03), prazosin (SMD = -0.87,95%CI:-1.59 to -0.16) and hydroxyzine (SMD = -1.06, 95%CI: -1.94 to -0.19) significantly reduced PTSD symptoms compared with placebo. In contrast to placebo, CBT-I (SMD = -5.61,95%CI:-8.82 to -2.40) significantly improved sleep quality. For nightmare severity, IRT (SMD =-0.65, 95%CI:-1.00 to -0.31), prazosin (SMD = -1.20,95%CI:-1.72 to -0.67) and hydroxyzine (SMD = -0.98,95%CI:-1.58 to -0.37) significantly reduced nightmare severity in comparison with placebo.

This study suggested that under most circumstances, psychotherapy namely CBT-I had a favorable profile, but pharmacotherapy with prazosin was effective in managing nightmare severity. The sole avail of CBT-I was recommended to improving sleep quality while CBT-I and CBT-I plus IRT showed excellent management of PTSD symptom severity. Exposure to CBT-I isrecommended for depression. The relevant clinical guidelines for the management of individuals with PTSD and sleep disorders may regard this as a reference.

CRD42023415240.

The application of network meta-analysis is becoming increasingly widespread, and for a successful implementation, it requires that the direct comparison result and the indirect comparison result should be consistent. Because of this, a proper detection of inconsistency is often a key issue in network meta-analysis as whether the results can be reliably used as a clinical guidance. Among the existing methods for detecting inconsistency, two commonly used models are the design-by-treatment interaction model and the side-splitting models. While the original side-splitting model was initially estimated using a Bayesian approach, in this context, we employ the frequentist approach. In this paper, we review these two types of models comprehensively as well as explore their relationship by treating the data structure of network meta-analysis as missing data and parameterizing the potential complete data for each model. Through both analytical and numerical studies, we verify that the side-splitting models are specific instances of the design-by-treatment interaction model, incorporating additional assumptions or under certain data structure. Moreover, the design-by-treatment interaction model exhibits robust performance across different data structures on inconsistency detection compared to the side-splitting models. Finally, as a practical guidance for inconsistency detection, we recommend utilizing the design-by-treatment interaction model when there is a lack of information about the potential location of inconsistency. By contrast, the side-splitting models can serve as a supplementary method especially when the number of studies in each design is small, enabling a comprehensive assessment of inconsistency from both global and local perspectives.

Although recreational cannabis use and abuse are expressive worldwide, the comparison of worldwide used psychotherapies, such as cognitive behavior therapy, with contingency management in the treatment of cannabis use disorder remains inconclusive.

We screened all articles published on MEDLINE (via PubMed) published until October 2023 and conducted a systematic review with meta-analysis.

Sixteen studies were included, and contingency management intervention likely promotes abstinence outcomes and more negative urinalyses for adults or adolescents with cannabis use disorder.

This review provides moderate- to high-quality evidence that contingency management can be used to treat cannabis use disorder. However, further trials need to be developed to analyze the quantity of substance use, personal achievements, and operational improvements after treatment.

People with schizophrenia often experience long-term psychosocial disabilities and frequent relapse. Family plays a key role in caring for ill relatives, which in turn probably contributes to high levels of distress and burdens for the family. Family-based interventions have been developed and applied to family members and their relatives with schizophrenia to improve their outcomes. This is an update of a Cochrane review that was last updated in 2011, which has been split into this review, one on group- versus individual-based family interventions and one on family-based cognitive versus behavioural management interventions.

To assess the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families compared with standard care.

We searched the following electronic databases from inception until April 2023: CENTRAL, Medline, Embase, PsycInfo, CINAHL, WHO International Clinical Trials Registry Platform (ICTRP), Clinicaltrials.gov, SinoMed, China Network Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific Journals Database (VIP). We also searched the reference lists of included studies and accessible reviews for additional references.

We included randomised controlled trials (RCTs) that compared the effects of family-based interventions for people with schizophrenia or schizophrenia-like disorders and their families and reported at least one patient's and one family member's outcomes. In this update, we only investigated standard care as the comparator.

We used standard Cochrane methods. The review authors independently screened studies, extracted data, and assessed risk of bias for each study using the Cochrane risk of bias tool for RCTs. We pooled data and estimated effects with the mean difference (MD), standardised mean difference (SMD), or risk ratio (RR) with 95% confidence interval (CI). We judged the certainty of evidence using GRADEpro GDT. We divided the outcomes into short-term (≤ 1 month postintervention), medium-term (> 1 to 6 months postintervention), and long-term follow-up (> 6 months postintervention), if available.

We identified 26 RCTs in this review, with 1985 people with schizophrenia or schizophrenia-like disorders, and 2056 family members. Most family-based interventions were conducted on a weekly or biweekly basis, with duration ranging from five weeks to two years. We had substantial concerns regarding the methodological quality of the included studies given that we judged all studies at high risk of performance bias and several studies at high risk of detection, attrition or reporting bias. Low-certainty evidence indicated that family-based interventions may reduce patients' relapse at one month or less postintervention (RR 0.66, 95% CI 0.49 to 0.89; 4 RCTs, 229 participants). We downgraded the evidence by two levels due to imprecision (small number of participants) and high risk of performance, detection and attrition bias. Compared to standard care, family-based interventions probably reduce caregiver burden at one month or less postintervention (MD -5.84, 95% CI -6.77 to -4.92; 8 RCTs, 563 participants; moderate-certainty evidence) and may result in more family members shifting from high to low expressed emotion (RR 3.90, 95% CI 1.11 to 13.71; 2 RCTs, 72 participants; low-certainty evidence). Family interventions may result in little to no difference in patients' death (RR 0.48, 95% CI 0.18 to 1.32; 6 RCTs, 304 participants; low-certainty evidence) and hospital admission (≤ 1 month postintervention; RR 0.81, 95% CI 0.51 to 1.29; 2 RCTs, 153 participants; low-certainty evidence) in comparison with standard care. Due to the heterogeneous measures and various follow-up periods, we were unable to provide pooled effect estimates for patients' compliance with medication and quality of life. We were very uncertain whether family interventions resulted in enhanced compliance with medication and improved quality of life for patients. We downgraded the evidence to very low certainty due to high risk of bias across studies, inconsistency (different directions of effects across studies), and imprecision (small number of participants or CIs of most studies including the possibility of no effect).

This review synthesised the latest evidence on family interventions versus standard care for people with schizophrenia or schizophrenia-like disorders and their families. This review suggests that family interventions might improve patients' outcomes (e.g. relapse) and families' outcomes (e.g. caregiver burden and expressed emotion), with little to no difference in patients' hospital admission and adverse effects in terms of death. However, evidence on patients' compliance with medication and quality of life was very uncertain. Overall, the evidence was of moderate to very low certainty. Future large and well-designed RCTs are needed to provide more reliable evaluation of effects of family interventions in people with schizophrenia or schizophrenia-like disorders and their families.

Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete reporting of adverse events (AEs) in published clinical studies is frequently encountered, especially if the observed number of AEs is below a pre-specified study-dependent threshold. Ignoring the censored AE information, often found in lower frequency, can significantly bias the estimated incidence rate of AEs. Despite its importance, this prevalent issue in meta-analysis has received little statistical or analytic attention in the literature. To address this challenge, we propose a Bayesian approach to accommodating the censored and possibly rare AEs for meta-analysis of safety data. Through simulation studies, we demonstrate that the proposed method can improve accuracy in point and interval estimation of incidence probabilities, particularly in the presence of censored data. Overall, the proposed method provides a practical solution that can facilitate better-informed decisions regarding drug safety.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness, safety, and side effects associated with the usage of different treatments for unscheduled vaginal bleeding in premenopausal women using progestin-only pills.

We respond to discussant comments on our paper "Twenty years of network meta-analysis: Continuing controversies and recent developments" (https://doi.org/10.1002/jrsm.1700) and raise some additional points for consideration, including: the way in which methodological guidance is generated; integration of the estimand framework with evidence synthesis; and implications of the European Joint Clinical Assessment. We ask: what properties are required of population adjustment methods to enable transparent and consistent decision-making? We also ask why individual patient data is not routinely made available to re-imbursement authorities and clinical guideline developers.

Due to the challenges of conducting randomised controlled trials (randomised trials) of dietary interventions, evidence in nutrition often comes from non-randomised (observational) studies of nutritional exposures-called nutritional epidemiology studies. When using systematic reviews of such studies to advise patients or populations on optimal dietary habits, users of the evidence (eg, healthcare professionals such as clinicians, health service and policy workers) should first evaluate the rigour (validity) and utility (applicability) of the systematic review. Issues in making this judgement include whether the review addressed a sensible question; included an exhaustive literature search; was scrupulous in the selection of studies and the collection of data; and presented results in a useful manner. For sufficiently rigorous and useful reviews, evidence users must subsequently evaluate the certainty of the findings, which depends on assessments of risk of bias, inconsistency, imprecision, indirectness, effect size, dose-response and the likelihood of publication bias. Given the challenges of nutritional epidemiology, evidence users need to be diligent in assessing whether studies provide evidence of sufficient certainty to allow confident recommendations for patients regarding nutrition and dietary interventions.

Despite the efficacy of onabotulinumtoxinA, its safety profile remains a concern. This meta-analysis reviewed the major adverse events (AEs) associated with intravesical onabotulinumtoxinA treatment in patients with neurogenic detrusor overactivity (NDO) and idiopathic overactive bladder (iOAB). Randomized controlled trials (RCTs) conducted between January 2000 and December 2022 were searched for adult patients administered different onabotulinumtoxinA dosages or onabotulinumtoxinA vs. placebo. Quality assessment was performed using the Cochrane Collaboration tool, and statistical analysis was performed using Review Manager version 5.3. A total of 26 RCTs were included in the analysis, including 8 on NDO and 18 on iOAB. OnabotulinumtoxinA vs. placebo significantly increased the urinary tract infection (UTI) incidence in patients with NDO (relative risk, or RR, 1.54) and iOAB (RR, 2.53). No difference in the RR with different onabotulinumtoxinA dosages was noted. Urinary retention was frequent with onabotulinumtoxinA use in the NDO (RR, 6.56) and iOAB (RR, 7.32) groups. Similar observations were made regarding the risks of de novo clean intermittent catheterization (CIC). The risk of voiding difficulty increased with onabotulinumtoxinA use in patients with iOAB. Systemic AEs of onabotulinumtoxinA, including muscle weakness (RR, 2.79) and nausea (RR, 3.15), were noted in patients with NDO; most systemic AEs had a low incidence and were sporadic.

The optimal fluid management strategy for patients undergoing cardiac surgery was controversial regarding fluid volume and intraoperative fluid types. This study aimed to assess the correlation between colloids and crystalloids used for perioperative fluid therapy in cardiac surgery patients and postoperative prognosis.

The Ovid MEDLINE(R) ALL, Embase, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies on fluid management strategies using colloids and crystalloids for cardiac surgery patients published before August 25th, 2023.

Ten randomized controlled trials met the eligibility criteria. Compared to the use of crystalloids, the use of colloids, including hydroxyethyl starch (HES), albumin, and gelatine, did not show any differences in mortality, transfusion, acute kidney injury, and atrial fibrillation rates, postoperative blood loss, the length of hospital stay, or the length of intensive care unit (ICU) stay. The results of this meta-analysis showed that the crystalloid group had significantly reduced postoperative chest tube output compared to the colloid group. In the subgroup analysis, the amount of fresh frozen plasma (FFP) infused was significantly lower when using fluid management in the ICU and when using isotonic crystalloids compared to the colloids. In addition, when using fluid management in the ICU, patients in the colloid group had a significant increase in urine volume 24 h after surgery. However, other related factors, including the type of crystalloid solution, type of colloidal solution, and timing of liquid management, did not affect most outcomes.

Both colloids and crystalloids could be used as alternatives for perioperative fluid management after cardiac surgery. The use of crystalloids significantly reduced the postoperative chest tube output, and the need for FFP infusion decreased significantly with the use of isotonic crystalloids or fluid management during the ICU stay. ICU patients in the colloid group had higher urine output 24 h after surgery. In addition, although the infusion method was not related to most outcomes, the rates of red blood cell and FFP transfusion and postoperative blood loss in the crystalloid group seemed to be lower, which needed to be further studied in high-quality and large-sample RCTs.

PROSPERO, CRD42023415234.

Acute traumatic stress symptoms may develop in people who have been exposed to a traumatic event. Although they are usually self-limiting in time, some people develop post-traumatic stress disorder (PTSD), a severe and debilitating condition. Pharmacological interventions have been proposed for acute symptoms to act as an indicated prevention measure for PTSD development. As many individuals will spontaneously remit, these interventions should balance efficacy and tolerability.

To assess the efficacy and acceptability of early pharmacological interventions for prevention of PTSD in adults experiencing acute traumatic stress symptoms.

We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase and two other databases. We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 23 January 2023.

We included randomised controlled trials on adults exposed to any kind of traumatic event and presenting acute traumatic stress symptoms, without restriction on their severity. We considered comparisons of any medication with placebo, or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy.

We used standard Cochrane methodological procedures. Using a random-effects model, we analysed dichotomous data as risk ratios (RR) and calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). Our primary outcomes were PTSD severity and dropouts due to adverse events. Secondary outcomes included PTSD rate, functional disability and quality of life.

We included eight studies that considered four interventions (escitalopram, hydrocortisone, intranasal oxytocin, temazepam) and involved a total of 779 participants. The largest trial contributed 353 participants and the next largest, 120 and 118 participants respectively. The trials enrolled participants admitted to trauma centres or emergency departments. The risk of bias in the included studies was generally low except for attrition rate, which we rated as high-risk. We could meta-analyse data for two comparisons: escitalopram versus placebo (but limited to secondary outcomes) and hydrocortisone versus placebo. One study compared escitalopram to placebo at our primary time point of three months after the traumatic event. There was inconclusive evidence of any difference in terms of PTSD severity (mean difference (MD) on the Clinician-Administered PTSD Scale (CAPS, score range 0 to 136) -11.35, 95% confidence interval (CI) -24.56 to 1.86; 1 study, 23 participants; very low-certainty evidence), dropouts due to adverse events (no participant left the study early due to adverse events; 1 study, 31 participants; very low-certainty evidence) and PTSD rates (RR 0.59, 95% CI 0.03 to 13.08; NNTB 37, 95% CI NNTB 15 to NNTH 1; 1 study, 23 participants; very low-certainty evidence). The study did not assess functional disability or quality of life. Three studies compared hydrocortisone to placebo at our primary time point of three months after the traumatic event. We found inconclusive evidence on whether hydrocortisone was more effective in reducing the severity of PTSD symptoms compared to placebo (MD on CAPS -7.53, 95% CI -25.20 to 10.13; I2 = 85%; 3 studies, 136 participants; very low-certainty evidence) and whether it reduced the risk of developing PTSD (RR 0.47, 95% CI 0.09 to 2.38; NNTB 14, 95% CI NNTB 8 to NNTH 5; I2 = 36%; 3 studies, 136 participants; very low-certainty evidence). Evidence on the risk of dropping out due to adverse events is inconclusive (RR 3.19, 95% CI 0.13 to 75.43; 2 studies, 182 participants; low-certainty evidence) and it is unclear whether hydrocortisone might improve quality of life (MD on the SF-36 (score range 0 to 136, higher is better) 19.70, 95% CI -1.10 to 40.50; 1 study, 43 participants; very low-certainty evidence). No study assessed functional disability.

This review provides uncertain evidence regarding the use of escitalopram, hydrocortisone, intranasal oxytocin and temazepam for people with acute stress symptoms. It is therefore unclear whether these pharmacological interventions exert a positive or negative effect in this population. It is important to note that acute traumatic stress symptoms are often limited in time, and that the lack of data prevents the careful assessment of expected benefits against side effects that is therefore required. To yield stronger conclusions regarding both positive and negative outcomes, larger sample sizes are required. A common operational framework of criteria for inclusion and baseline assessment might help in better understanding who, if anyone, benefits from an intervention. As symptom severity alone does not provide the full picture of the impact of exposure to trauma, assessment of quality of life and functional impairment would provide a more comprehensive picture of the effects of the interventions. The assessment and reporting of side effects may facilitate a more comprehensive understanding of tolerability.

The efficacy of botulinum toxin injection for the treatment of third, fourth, and sixth nerve palsy was evaluated. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar databases were searched. Data about the duration of palsy (acute vs chronic), cause of the palsy, type of toxin used, mean dose, and other background characteristics were collected. Outcome variables were success rate (defined by alleviation of diplopia or reduction in eye deviation) and standardized mean difference of prism diopter and abduction deficit before and after injection. The Joanna Briggs Institute checklist was implemented for the risk of bias assessment. The analysis included 38 articles, comprising 643 patients. The overall treatment success rate in acute and chronic nerve palsy was 79% and 33%, respectively. The success rate was not significantly different between different subgroups of age, type of botulinum toxin, pre-injection prism diopter, etiology of the palsy, duration of follow-up, and mean dose of botulinum toxin injection. However, in both acute and chronic palsy, diabetes etiology was accompanied by the highest success rate. Overall symptomatic response to botulinum injection was 84% (95% CI: 67% to 96%), whereas functional response was observed in 64% (95% CI: 47% to 79%) of the patients. The odds ratio for the success rate of treatment of palsies with botulinum toxin versus expectant management was 2.67 (95% CI: 1.12 to 6.36) for acute palsy and 0.87 (95% CI: 0.17 to 4.42) for chronic palsy. Botulinum toxin can be used for the treatment of acute third, fourth, and sixth nerve palsy, especially in patients with acute palsy and more severe tropia. [J Pediatr Ophthalmol Strabismus. 2024;61(3):160-171.].

Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making.

A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score.

Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety.

Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

A 2×2 factorial design evaluates two interventions (A versus control and B versus control) by randomising to control, A-only, B-only or both A and B together. Extended factorial designs are also possible (e.g. 3×3 or 2×2×2). Factorial designs often require fewer resources and participants than alternative randomised controlled trials, but they are not widely used. We identified several issues that investigators considering this design need to address, before they use it in a late-phase setting.

We surveyed journal articles published in 2000-2022 relating to designing factorial randomised controlled trials. We identified issues to consider based on these and our personal experiences.

We identified clinical, practical, statistical and external issues that make factorial randomised controlled trials more desirable. Clinical issues are (1) interventions can be easily co-administered; (2) risk of safety issues from co-administration above individual risks of the separate interventions is low; (3) safety or efficacy data are wanted on the combination intervention; (4) potential for interaction (e.g. effect of A differing when B administered) is low; (5) it is important to compare interventions with other interventions balanced, rather than allowing randomised interventions to affect the choice of other interventions; (6) eligibility criteria for different interventions are similar. Practical issues are (7) recruitment is not harmed by testing many interventions; (8) each intervention and associated toxicities is unlikely to reduce either adherence to the other intervention or overall follow-up; (9) blinding is easy to implement or not required. Statistical issues are (10) a suitable scale of analysis can be identified; (11) adjustment for multiplicity is not required; (12) early stopping for efficacy or lack of benefit can be done effectively. External issues are (13) adequate funding is available and (14) the trial is not intended for licensing purposes. An overarching issue (15) is that factorial design should give a lower sample size requirement than alternative designs. Across designs with varying non-adherence, retention, intervention effects and interaction effects, 2×2 factorial designs require lower sample size than a three-arm alternative when one intervention effect is reduced by no more than 24%-48% in the presence of the other intervention compared with in the absence of the other intervention.

Factorial designs are not widely used and should be considered more often using our issues to consider. Low potential for at most small to modest interaction is key, for example, where the interventions have different mechanisms of action or target different aspects of the disease being studied.

Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS.

We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs).

We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials.

Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.

This systematic review is aimed to evaluate in fixed prosthodontics treated teeth, the effect of the BOPT on periodontal health compared to the horizontal preparation technique using a chamfer finishing line or to the baseline.

The electronic databases Cochrane Central Library, PubMed, Scopus, and ScienceDirect were searched based on specific MeSH keywords. The Randomized controlled clinical trials (RCTs) and prospective clinical trials on BOPT printed in English up to July 2022 were selected. Screening, selection, and data extraction were done. The studies were assessed for risk of bias, and descriptive and meta-analyses were performed.

Eight studies were included in the systematic review and only three RCTs were involved in the meta-analysis. Two RCTs were assessed as low risk while one has some concerns. were grouped as good, fair, and poor based on NOS. Three of the prospective studies were considered to be of good quality and one study was fair. The meta-analysis revealed no statistically significant difference in the effect of BOPT and chamfer preparation on periodontal health status and success rate (P > 0.05).

Considering the limitation of this review, the BOPT is comparable to chamfer preparation and it resulted in an acceptable effect to maintain periodontal health with a high success rate. However, more evidence is required to support these findings.

Considering the worldwide mortality and morbidity of cardiovascular diseases (CVDs), the necessity of using multiple pills due to the chronicity of this condition, and the importance of medication adherence in these patients, we conducted this systematic review and meta-analysis to assess the polypill effect on adherence in patients with established CVD and at high risk. To accomplish this review, we searched various databases to access grey literature and several electronic databases to find randomized controlled trials (RCTs) assessing polypills compared to individual pills from January 2000 to October 2022. The outcomes were primarily medication adherence, secondarily systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C) serum level, and serious adverse events (SAEs). Ultimately, 2820 studies were detected and narrowed to 8 RCTs based on the eligibility criteria. In this study, involving 7364 patients, there was a significant improvement in medication adherence in the polypill group compared to the individual pills group (Risk Ratio [RR] = 1.29; [95%CI: 1.10; 1.50]). Out of secondary outcomes, SBP was significantly decreased (Mean Difference [MD] = -1.72 mmHg; [95%CI: -2.40; 1.03]), but LDL-C serum level (MD = -0.65 mg/dl; [95%CI: -4.47; 3.16]) and SAE (RR = 1.08; [95%CI: f0.98; 1.20]) did not have a notable difference in polypill compared to individual pills.

Null hypothesis significance testing (NHST) in medical research is increasingly being supplemented by estimation statistics, focusing on effect sizes (ESs) and confidence intervals (CIs). This study evaluates the expression of ESs and CIs for binary outcomes. A utilitarian framework is proposed, emphasizing the number of beneficiaries and the impact level. To evaluate clinical significance, minimal clinically important risk difference (MCIRD) is proposed based on event magnitude (EM). Within this framework, risk difference (RD) is introduced as the primary measure. To assess the performance of RD, we compared its statistical power against other measures (risk ratio, RR; odds ratio, OR; Cohen's h) in individual study scenarios, and visual information conveyance in meta-analysis scenarios. RDs maintain statistical power in comparison to other measures in individual studies. They provide clarity on the true impact of clinical interventions without compromising statistical integrity. Meta-analytic results indicate that using RDs directly enhances transparency, uncovers heterogeneity, and addresses misaligned assumptions. This approach, by quantifying clinical effectiveness under a utilitarian perspective, facilitates the applicability of research to patient care and encourages shared decision-making. The study advocates for reporting baseline risks (BRs) with RDs and recommends a standardized presentation of these statistics. In a utilitarian perspective, adopting RD as the preferred ES can foster a transparent, patient-focused research ethos. This aids in accurately presenting the magnitude and variability of treatment effects, offering a new direction in methodology.

Breast cancer patients undergoing trastuzumab therapy have greater risk of cardiovascular disease. Risk factors for this effect have been proposed. However, the role of dyslipidemia is not completely understood. This systematic review aimed to explore the role of dyslipidemia in trastuzumab-induced cardiotoxicity.

The investigators searched MEDLINE, Scopus, and Web of Science up to October 25, 2020. A random-effects model was used to determine pooled estimates of the results. The primary endpoint was trastuzumab-induced cardiotoxicity in patients with and without dyslipidemia.

A total of 39 studies were selected for inclusion in our systematic review assessing 21079 patients. One study demonstrated a statistically significant association between dyslipidemia and cardiotoxicity (OR=2.28, 95% CI 1.22-4.26, p=0.01). In all other studies, no such association was observed. Twenty-one studies including 6135 patients were eligible for meta-analysis. In this meta-analysis of unadjusted data, dyslipidemia was significantly associated with cardiotoxicity (OR=1.25, 95% CI 1.01-1.53, p=0.04, I2=0%), however, a subgroup analysis of studies reporting adjusted measures did not demonstrate a significant association (OR=0.89, 95% CI 0.73-1.10, p=0.28, I2=0%).

This systematic review and meta-analysis did not demonstrate a significant association between dyslipidemia alone and the development of cardiotoxicity. In the absence of other relevant cardiovascular risk factors, review of lipid profile may not be obligatory, and management of patients could be performed without referral for cardio-oncology assessment. Further investigation of risk factors for trastuzumab-induced cardiotoxicity is required to confirm these results.

To assess the absolute treatment effects of intravascular imaging guided versus angiography guided percutaneous coronary intervention in patients with coronary artery disease, considering their baseline risk.

Systematic review and meta-analysis.

PubMed/Medline, Embase, and Cochrane Library databases up to 31 August 2023.

Randomized controlled trials comparing intravascular imaging (intravascular ultrasonography or optical coherence tomography) guided versus coronary angiography guided percutaneous coronary intervention in adults with coronary artery disease.

Random effect meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) were used to assess certainty of evidence. Data included rate ratios and absolute risks per 1000 people for cardiac death, myocardial infarction, stent thrombosis, target vessel revascularization, and target lesion revascularization. Absolute risk differences were estimated using SYNTAX risk categories for baseline risks at five years, assuming constant rate ratios across different cardiovascular risk thresholds.

In 20 randomized controlled trials (n=11 698), intravascular imaging guided percutaneous coronary intervention was associated with a reduced risk of cardiac death (rate ratio 0.53, 95% confidence interval 0.39 to 0.72), myocardial infarction (0.81, 0.68 to 0.97), stent thrombosis (0.44, 0.27 to 0.72), target vessel revascularization (0.74, 0.61 to 0.89), and target lesion revascularization (0.71, 0.59 to 0.86) but not all cause death (0.81, 0.64 to 1.02). Using SYNTAX risk categories, high certainty evidence showed that from low risk to high risk, intravascular imaging was likely associated with 23 to 64 fewer cardiac deaths, 15 to 19 fewer myocardial infarctions, 9 to 13 fewer stent thrombosis events, 28 to 38 fewer target vessel revascularization events, and 35 to 48 fewer target lesion revascularization events per 1000 people.

Compared with coronary angiography guided percutaneous coronary intervention, intravascular imaging guided percutaneous coronary intervention was associated with significantly reduced cardiac death and cardiovascular outcomes in patients with coronary artery disease. The estimated absolute effects of intravascular imaging guided percutaneous coronary intervention showed a proportional relation with baseline risk, driven by the severity and complexity of coronary artery disease.

PROSPERO CRD42023433568.

There is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE.

We searched MEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials from inception to June 2023. We included randomised controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with active EoE. Results were reported as pooled relative risks with 95% CIs to summarise effect of each comparison tested, with drugs ranked according to P score RESULTS: Seventeen RCTs were eligible for systematic review. Of these, 15 studies containing 1813 subjects with EoE reported extractable data for the network meta-analysis. For histological remission defined as ≤6 eosinophils/high-power field (HPF), lirentelimab 1 mg/kg monthly ranked first. For histological remission defined as ≤15 eosinophils/HPF, budesonide orally disintegrating tablet (BOT) 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE Endoscopic Reference Score, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo.

Although this network meta-analysis supports the efficacy of most available drugs over placebo for EoE treatment, significant heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy.

Some probiotics may be beneficial in irritable bowel syndrome (IBS), but differences in species and strains used, as well as endpoints reported, have hampered attempts to make specific recommendations as to which should be preferred. We updated our previous meta-analysis examining this issue.

MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to March 2023). Randomized controlled trials (RCTs) recruiting adults with IBS, comparing probiotics with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk of global symptoms, abdominal pain, or abdominal bloating or distension persisting after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized mean difference with a 95% CI. Adverse events data were also pooled.

We identified 82 eligible trials, containing 10,332 patients. Only 24 RCTs were at low risk of bias across all domains. For global symptoms, there was moderate certainty in the evidence for a benefit of Escherichia strains, low certainty for Lactobacillus strains and Lactobacillus plantarum 299V, and very low certainty for combination probiotics, LacClean Gold S, Duolac 7s, and Bacillus strains. For abdominal pain, there was low certainty in the evidence for a benefit of Saccharomyces cerevisae I-3856 and Bifidobacterium strains, and very low certainty for combination probiotics, Lactobacillus, Saccharomyces, and Bacillus strains. For abdominal bloating or distension there was very low certainty in the evidence for a benefit of combination probiotics and Bacillus strains. The relative risk of experiencing any adverse event, in 55 trials, including more than 7000 patients, was not significantly higher with probiotics.

Some combinations of probiotics or strains may be beneficial in IBS. However, certainty in the evidence for efficacy by GRADE criteria was low to very low across almost all of our analyses.

The purpose of the systematic review was to evaluate the efficacy and safety of interleukin-6 receptor (IL-6) antagonists (tocilizumab, sarilumab) in adult patients with severe or critical COVID-19. A systematic review of the literature was conducted in Medline, Cochrane and Embase databases, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov from the inception dates to10 January 2023. Randomized clinical trials comparing IL-6 receptor antagonists (tocilizumab, sarilumab) with a placebo or usual care treatment for adult patients with severe or critical COVID-19 were identified. Two independent reviewers performed the assessment and selection of eligible studies, assessed study quality and extracted data. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) with random-effects models was performed in meta-analysis. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the quality of the evidence. The search retrieved a total of 11 RCTs involving 5028 participants were eligible for meta-analysis. Our findings suggest that as the new drug used in adult patients with severe or critical COVID-19, IL-6 antagonists (tocilizumab, sarilumab) may reduce the length of ICU stay and hospital stay. However, they did not significantly increase the risks of serious adverse events and did not reduce all-cause mortality (28-day, 14-day, and 7-day).

Hyaluronic acid is synthesised in plasma membranes and can be found in extracellular tissues. It has been suggested that the application of hyaluronic acid to chronic wounds may promote healing, and the mechanism may be due to its ability to maintain a moist wound environment which helps cell migration in the wound bed.

To evaluate the effects of hyaluronic acid (and its derivatives) on the healing of chronic wounds.

We used standard, extensive Cochrane search methods. The latest search date was February 2022.

We included randomised controlled trials that compared the effects of hyaluronic acid (as a dressing or topical agent) with other dressings on the healing of pressure, venous, arterial, or mixed-aetiology ulcers and foot ulcers in people with diabetes.

We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach.

We included 12 trials (13 articles) in a qualitative synthesis, and were able to combine data from four trials in a quantitative analysis. Overall, the included trials involved 1108 participants (mean age 69.60 years) presenting 178 pressure ulcers, 54 diabetic foot ulcers, and 896 leg ulcers. Sex was reported for 1022 participants (57.24% female). Pressure ulcers It is uncertain whether there is a difference in complete healing (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.58 to 2.35); change in ulcer size (mean difference (MD) 25.60, 95% CI 6.18 to 45.02); or adverse events (none reported) between platelet-rich growth factor (PRGF) + hyaluronic acid and PRGF because the certainty of evidence is very low (1 trial, 65 participants). It is also uncertain whether there is a difference in complete healing between lysine hyaluronate and sodium hyaluronate because the certainty of evidence is very low (RR 2.50, 95% CI 0.71 to 8.83; 1 trial, 14 ulcers from 10 participants). Foot ulcers in people with diabetes It is uncertain whether there is a difference in time to complete healing between hyaluronic acid and lyophilised collagen because the certainty of evidence is very low (MD 16.60, 95% CI 7.95 to 25.25; 1 study, 20 participants). It is uncertain whether there is a difference in complete ulcer healing (RR 2.20, 95% CI 0.97 to 4.97; 1 study, 34 participants) or change in ulcer size (MD -0.80, 95% CI -3.58 to 1.98; 1 study, 25 participants) between hyaluronic acid and conventional dressings because the certainty of evidence is very low. Leg ulcers We are uncertain whether there is a difference in complete wound healing (RR 0.98, 95% CI 0.26 to 3.76), percentage of adverse events (RR 0.79, 95% CI 0.22 to 2.80), pain (MD 2.10, 95% CI -5.81 to 10.01), or change in ulcer size (RR 2.11, 95% CI 0.92 to 4.82) between hyaluronic acid + hydrocolloid and hydrocolloid because the certainty of evidence is very low (1 study, 125 participants). It is uncertain whether there is a difference in change in ulcer size between hyaluronic acid and hydrocolloid because the certainty of evidence is very low (RR 1.02, 95% CI 0.84 to 1.25; 1 study, 143 participants). We are uncertain whether there is a difference in complete wound healing between hyaluronic acid and paraffin gauze because the certainty of evidence is very low (RR 2.00, 95% CI 0.21 to 19.23; 1 study, 24 ulcers from 17 participants). When compared with neutral vehicle, hyaluronic acid probably improves complete ulcer healing (RR 2.11, 95% CI 1.46 to 3.07; 4 studies, 526 participants; moderate-certainty evidence); may slightly increase the reduction in pain from baseline (MD -8.55, 95% CI -14.77 to -2.34; 3 studies, 337 participants); and may slightly increase change in ulcer size, measured as mean reduction from baseline to 45 days (MD 30.44%, 95% CI 15.57 to 45.31; 2 studies, 190 participants). It is uncertain if hyaluronic acid alters incidence of infection when compared with neutral vehicle (RR 0.89, 95% CI 0.53 to 1.49; 3 studies, 425 participants). We are uncertain whether there is a difference in change in ulcer size (cm2) between hyaluronic acid and dextranomer because the certainty of evidence is very low (MD 5.80, 95% CI -10.0 to 21.60; 1 study, 50 participants). We downgraded the certainty of evidence due to risk of bias or imprecision, or both, for all of the above comparisons. No trial reported health-related quality of life or wound recurrence. Measurement of change in ulcer size was not homogeneous among studies, and missing data precluded further analysis for some comparisons.

There is currently insufficient evidence to determine the effectiveness of hyaluronic acid dressings in the healing of pressure ulcers or foot ulcers in people with diabetes. We found evidence that hyaluronic acid probably improves complete ulcer healing and may slightly decrease pain and increase change in ulcer size when compared with neutral vehicle. Future research into the effects of hyaluronic acid in the healing of chronic wounds should consider higher sample size and blinding to minimise bias and improve the quality of evidence.

Considering the conceptual migration from vocal load and vocal loading to vocal demand and vocal demand response, this review of literature aimed to identify physiological explanations, reported measurements, and associated factors (vocal demands) reported in the literature when considering the phonatory response to a vocal demand.

A systematic review of literature, following the PRISMA Statement, was conducted using Web of Science, PubMed, Scopus, and ScienceDirect. Data were analyzed and presented in two parts. First, a bibliometric analysis, co-occurrence analysis, and content analysis were performed. Three criteria that got article inclusion were defined: (1) written in English, Spanish, and Portuguese; (2) published between 2009 and 2021; and (3) focused on vocal load and loading, vocal demand response, and voice assessment parameters. A total of 54 publications met the criteria and were included in this review. The second part included a conceptual framework based on the content analysis of three aspects of vocal demand response: (1) physiological explanations, (2) reported measurements, and (3) vocal demands.

As would be expected since vocal demand response is a relatively new term and not yet commonly used in literature when discussing way that the speakers respond to communicative scenarios, most of the studies reviewed (both historical and recent) still use the term of vocal load and vocal loading. Although there is a broad variety of literature discussing a wide range of vocal demands and voice parameters used to characterize the vocal demand response, results show that there is consistency across the studies. While vocal demand response is unique and intrinsic to the talker, associated factors that contribute to this response include both internal talker and external talker factors. Internal factors include muscle stiffness, viscosity in the phonatory system, vocal fold tissue damage, elevated sound pressure levels during occupational voice demands, extended periods of voice use, suboptimal body posture, difficulties in breathing technique, and sleep disturbances. Associated external factors include the working environment (noise, acoustics, temperature, humidity). In conclusion, although vocal demand response is intrinsic to the speaker, the speaker's response is affected by external vocal demands. However, due to the wide methods to evaluate vocal demand response, it has been difficult to establish its contribution to voice disorders in the general population and, specifically, among occupational voice users. This literature review identified commonly reported parameters and factors that may help clinicians and researchers define vocal demand response.

Cochran's Q statistic is routinely used for testing heterogeneity in meta-analysis. Its expected value (under an incorrect null distribution) is part of several popular estimators of the between-study variance, [Formula: see text]. Those applications generally do not account for use of the studies' estimated variances in the inverse-variance weights that define Q (more explicitly, [Formula: see text]). Importantly, those weights make approximating the distribution of [Formula: see text] rather complicated.

As an alternative, we are investigating a Q statistic, [Formula: see text], whose constant weights use only the studies' arm-level sample sizes. For log-odds-ratio (LOR), log-relative-risk (LRR), and risk difference (RD) as the measures of effect, we study, by simulation, approximations to distributions of [Formula: see text] and [Formula: see text], as the basis for tests of heterogeneity.

The results show that: for LOR and LRR, a two-moment gamma approximation to the distribution of [Formula: see text] works well for small sample sizes, and an approximation based on an algorithm of Farebrother is recommended for larger sample sizes. For RD, the Farebrother approximation works very well, even for small sample sizes. For [Formula: see text], the standard chi-square approximation provides levels that are much too low for LOR and LRR and too high for RD. The Kulinskaya et al. (Res Synth Methods 2:254-70, 2011) approximation for RD and the Kulinskaya and Dollinger (BMC Med Res Methodol 15:49, 2015) approximation for LOR work well for [Formula: see text] but have some convergence issues for very small sample sizes combined with small probabilities.

The performance of the standard [Formula: see text] approximation is inadequate for all three binary effect measures. Instead, we recommend a test of heterogeneity based on [Formula: see text] and provide practical guidelines for choosing an appropriate test at the .05 level for all three effect measures.

The safety and utility of endotracheal intubation by paramedics in the United Kingdom is a matter of debate. Considering the controversy surrounding the safety of paramedic-performed endotracheal intubation, any interventions that enhance patient safety should be evaluated for implementation based on solid evidence of their effectiveness. A systematic review performed by Hansel and colleagues (2022) sought to assess compare video laryngoscopes against direct laryngoscopes in clinical practice. This commentary aims to critically appraise the methods used within the review by Hansel et al (2022) and expand upon the findings in the context of clinical practice.

In clinical settings, the absolute risk reduction due to treatment that can be expected in a particular patient is of key interest. However, logistic regression, the default regression model for trials with a binary outcome, produces estimates of the effect of treatment measured as a difference in log odds. We explored options to estimate treatment effects directly as a difference in risk, specifically in the network meta-analysis setting. We propose a novel Bayesian (meta-)regression model for binary outcomes on the additive risk scale. The model allows treatment effects, covariate effects, interactions and variance parameters to be estimated directly on the linear scale of clinical interest. We compared effect estimates from this model to (1) a previously proposed additive risk model by Warn, Thompson and Spiegelhalter ("WTS model") and (2) backtransforming the predictions from a logistic model to the natural scale after regression. The models were compared in a network meta-analysis of 20 hepatitis C trials, as well as in the analysis of simulated single trial settings. The resulting estimates diverged, in particular for small sample sizes or true risks close to 0% or 100%. Researchers should be aware that modelling untransformed risk can yield very different results from default logistic models. The treatment effect in participants with such extreme predicted risks weighed more heavily on the overall treatment effect estimate from our proposed model compared to the WTS model. In our network meta-analysis, this sensitivity of our proposed model was needed to detect all information in the data.

Acceptable, effective and feasible support strategies (interventions) for parents experiencing complex post-traumatic stress disorder (CPTSD) symptoms or with a history of childhood maltreatment may offer an opportunity to support parental recovery, reduce the risk of intergenerational transmission of trauma and improve life-course trajectories for children and future generations. However, evidence relating to the effect of interventions has not been synthesised to provide a comprehensive review of available support strategies. This evidence synthesis is critical to inform further research, practice and policy approaches in this emerging area.

To assess the effects of interventions provided to support parents who were experiencing CPTSD symptoms or who had experienced childhood maltreatment (or both), on parenting capacity and parental psychological or socio-emotional wellbeing.

In October 2021 we searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, together with checking references and contacting experts to identify additional studies.

All variants of randomised controlled trials (RCTs) comparing any intervention delivered in the perinatal period designed to support parents experiencing CPTSD symptoms or with a history of childhood maltreatment (or both), to any active or inactive control. Primary outcomes were parental psychological or socio-emotional wellbeing and parenting capacity between pregnancy and up to two years postpartum.

Two review authors independently assessed the eligibility of trials for inclusion, extracted data using a pre-designed data extraction form, and assessed risk of bias and certainty of evidence. We contacted study authors for additional information as required. We analysed continuous data using mean difference (MD) for outcomes using a single measure, and standardised mean difference (SMD) for outcomes using multiple measures, and risk ratios (RR) for dichotomous data. All data are presented with 95% confidence intervals (CIs). We undertook meta-analyses using random-effects models.

We included evidence from 1925 participants in 15 RCTs that investigated the effect of 17 interventions. All included studies were published after 2005. Interventions included seven parenting interventions, eight psychological interventions and two service system approaches. The studies were funded by major research councils, government departments and philanthropic/charitable organisations. All evidence was of low or very low certainty. Parenting interventions Evidence was very uncertain from a study (33 participants) assessing the effects of a parenting intervention compared to attention control on trauma-related symptoms, and psychological wellbeing symptoms (postpartum depression), in mothers who had experienced childhood maltreatment and were experiencing current parenting risk factors. Evidence suggested that parenting interventions may improve parent-child relationships slightly compared to usual service provision (SMD 0.45, 95% CI -0.06 to 0.96; I2 = 60%; 2 studies, 153 participants; low-certainty evidence). There may be little or no difference between parenting interventions and usual perinatal service in parenting skills including nurturance, supportive presence and reciprocity (SMD 0.25, 95% CI -0.07 to 0.58; I2 = 0%; 4 studies, 149 participants; low-certainty evidence). No studies assessed the effects of parenting interventions on parents' substance use, relationship quality or self-harm. Psychological interventions Psychological interventions may result in little or no difference in trauma-related symptoms compared to usual care (SMD -0.05, 95% CI -0.40 to 0.31; I2 = 39%; 4 studies, 247 participants; low-certainty evidence). Psychological interventions may make little or no difference compared to usual care to depression symptom severity (8 studies, 507 participants, low-certainty evidence, SMD -0.34, 95% CI -0.66 to -0.03; I2 = 63%). An interpersonally focused cognitive behavioural analysis system of psychotherapy may slightly increase the number of pregnant women who quit smoking compared to usual smoking cessation therapy and prenatal care (189 participants, low-certainty evidence). A psychological intervention may slightly improve parents' relationship quality compared to usual care (1 study, 67 participants, low-certainty evidence). Benefits for parent-child relationships were very uncertain (26 participants, very low-certainty evidence), while there may be a slight improvement in parenting skills compared to usual care (66 participants, low-certainty evidence). No studies assessed the effects of psychological interventions on parents' self-harm. Service system approaches One service system approach assessed the effect of a financial empowerment education programme, with and without trauma-informed peer support, compared to usual care for parents with low incomes. The interventions increased depression slightly (52 participants, low-certainty evidence). No studies assessed the effects of service system interventions on parents' trauma-related symptoms, substance use, relationship quality, self-harm, parent-child relationships or parenting skills.

There is currently a lack of high-quality evidence regarding the effectiveness of interventions to improve parenting capacity or parental psychological or socio-emotional wellbeing in parents experiencing CPTSD symptoms or who have experienced childhood maltreatment (or both). This lack of methodological rigour and high risk of bias made it difficult to interpret the findings of this review. Overall, results suggest that parenting interventions may slightly improve parent-child relationships but have a small, unimportant effect on parenting skills. Psychological interventions may help some women stop smoking in pregnancy, and may have small benefits on parents' relationships and parenting skills. A financial empowerment programme may slightly worsen depression symptoms. While potential beneficial effects were small, the importance of a positive effect in a small number of parents must be considered when making treatment and care decisions. There is a need for further high-quality research into effective strategies for this population.

Although there have been multiple drugs tested in gastroparesis, their relative efficacy and safety are unknown. We evaluated this in a network meta-analysis of randomized controlled trials (RCTs).

We searched the literature to September 7, 2022. We judged the efficacy of drugs based on global symptoms of gastroparesis; individual symptoms, including nausea, vomiting, abdominal pain, bloating, or fullness; and safety according to total adverse events and adverse events leading to withdrawal. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of not improving with 95% confidence intervals (CIs), ranking drugs according to P-score.

We identified 29 RCTs (3772 patients). Based on global symptoms, clebopride ranked first for efficacy (RR, 0.30; 95% CI, 0.16-0.57; P-score = .99) followed by domperidone (RR, 0.68; 95% CI, 0.48-0.98; P-score = .76). No other drug was superior to placebo. Only 2 drug classes were efficacious: in rank order, oral dopamine antagonists (RR, 0.58; 95% CI, 0.44-0.77; P-score = .96) and tachykinin-1 antagonists (RR, 0.69; 95% CI, 0.52-0.93; P-score = .83). For individual symptoms, oral metoclopramide ranked first for nausea (RR 0.46; 95% CI, 0.21-1.00; P-score = .95), fullness (RR 0.67; 95% CI, 0.35-1.28; P-score = .86), and bloating (RR 0.53; 95% CI, 0.30-0.93; P-score = .97), based on only 1 small trial. Only prucalopride was more likely to be associated with adverse events than placebo.

In a network meta-analysis, oral dopamine antagonists and tachykinin-1 antagonists were more efficacious than placebo for gastroparesis, but confidence in the evidence was low to moderate for most comparisons. There is an unmet need for efficacious therapies for gastroparesis.

Studies included in a meta-analysis are often heterogeneous. The traditional random-effects models assume their true effects to follow a normal distribution, while it is unclear if this critical assumption is practical. Violations of this between-study normality assumption could lead to problematic meta-analytical conclusions. We aimed to empirically examine if this assumption is valid in published meta-analyses.

In this cross-sectional study, we collected meta-analyses available in the Cochrane Library with at least 10 studies and with between-study variance estimates > 0. For each extracted meta-analysis, we performed the Shapiro-Wilk (SW) test to quantitatively assess the between-study normality assumption. For binary outcomes, we assessed between-study normality for odds ratios (ORs), relative risks (RRs), and risk differences (RDs). Subgroup analyses based on sample sizes and event rates were used to rule out the potential confounders. In addition, we obtained the quantile-quantile (Q-Q) plot of study-specific standardized residuals for visually assessing between-study normality.

Based on 4234 eligible meta-analyses with binary outcomes and 3433 with non-binary outcomes, the proportion of meta-analyses that had statistically significant non-normality varied from 15.1 to 26.2%. RDs and non-binary outcomes led to more frequent non-normality issues than ORs and RRs. For binary outcomes, the between-study non-normality was more frequently found in meta-analyses with larger sample sizes and event rates away from 0 and 100%. The agreements of assessing the normality between two independent researchers based on Q-Q plots were fair or moderate.

The between-study normality assumption is commonly violated in Cochrane meta-analyses. This assumption should be routinely assessed when performing a meta-analysis. When it may not hold, alternative meta-analysis methods that do not make this assumption should be considered.

Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA).

Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022.

Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score.

The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.

Whether low-dose alteplase is similar to standard-dose bridging alteplase prior to endovascular mechanical thrombectomy in patients with acute ischemic stroke (AIS) remains uncertain.