Ongoing Randomised Controlled Trials Research Articles

Which Intravenous Isotonic Fluid Offers Better Outcomes for Patients with a Brain Injury?

Administering intravenous fluids is a common therapy for critically ill patients. Isotonic crystalloid solutions, such as saline or balanced solutions, are frequently used for intravenous fluid therapy. The choice between saline or a balanced crystalloid has been a significant question in critical care medicine. Recent large randomized controlled trials (RCTs) have investigated whether balanced crystalloids yield better outcomes in general or specific critical care populations, and many of them have confirmed this hypothesis. Although the broad eligibility criteria of these RCTs suggest applicability to neurocritical care patients, it is important to discuss whether using balanced crystalloids, as opposed to saline, would benefit patients who primarily have neurological disorders or diseases. This review considers the relevance of this question, weighs the pros and cons of the two fluid types, examines available data, and anticipates results from ongoing RCTs to guide clinicians in selecting the optimal fluid for patients with brain injury.

Caregiver Wellness after Traumatic Brain Injury (CG-Well): Protocol for a randomized clinical trial

IntroductionAfter injury, survivors of moderate to severe traumatic brain injury (msTBI) depend on informal family caregivers. Upwards of 77% of family caregivers experience poor outcomes, such as adverse life changes, poor health-related quality of life, and increased depressive symptoms. Caregivers frequently report minimal support or training to prepare them for their new role. The majority of previously developed caregiver and caregiver/survivor dyad interventions after msTBI focus on providing information to either survivors only, or to long-term caregivers, rather than to the new caregiver. This manuscript describes the protocol of an ongoing randomized control trial, Caregiver Wellness after TBI (CG-Well), developed to provide education, support, and skill-building to caregivers of adults with msTBI, beginning when the survivor is early in the clinical course. MethodsWithin two weeks of admission to the ICU, participants are randomized to CG-Well online modules (intervention group, n = 50 dyads) or information, support, and referral (ISR) e-bulletins that exist in the public domain (control group, n = 50 dyads) over the first six months after their family member’s msTBI. Both groups receive regular phone calls. The primary outcome is intervention satisfaction at six months. ResultsEnrollment began in March, 2022 and is projected to complete October 2024. We have enrolled approximately 70% of participants at this time. Primary analysis completion is anticipated April, 2025. DiscussionThis RCT is designed to evaluate caregiver satisfaction by addressing the need for tailored supportive care for caregivers of msTBI beginning during the ICU admission. Trial RegistrationClinicaltrials.gov Registration Number: NCT05307640

Unravelling the complexity of ventilator-associated pneumonia: a systematic methodological literature review of diagnostic criteria and definitions used in clinical research

BackgroundVentilator-associated pneumonia (VAP) is a prevalent and grave hospital-acquired infection that affects mechanically ventilated patients. Diverse diagnostic criteria can significantly affect VAP research by complicating the identification and management of the condition, which may also impact clinical management.ObjectivesWe conducted this review to assess the diagnostic criteria and the definitions of the term “ventilator-associated” used in randomised controlled trials (RCTs) of VAP management.Search methodsBased on the protocol (PROSPERO 2019 CRD42019147411), we conducted a systematic search on MEDLINE/PubMed and Cochrane CENTRAL for RCTs, published or registered between 2010 and 2024.Selection criteriaWe included completed and ongoing RCTs that assessed pharmacological or non-pharmacological interventions in adults with VAP.Data collection and synthesisData were collected using a tested extraction sheet, as endorsed by the Cochrane Collaboration. After cross-checking, data were summarised in a narrative and tabular form.ResultsIn total, 7,173 records were identified through the literature search. Following the exclusion of records that did not meet the eligibility criteria, 119 studies were included. Diagnostic criteria were provided in 51.2% of studies, and the term “ventilator-associated” was defined in 52.1% of studies. The most frequently included diagnostic criteria were pulmonary infiltrates (96.7%), fever (86.9%), hypothermia (49.1%), sputum (70.5%), and hypoxia (32.8%). The different criteria were used in 38 combinations across studies. The term “ventilator-associated” was defined in nine different ways.ConclusionsWhen provided, diagnostic criteria and definitions of VAP in RCTs display notable variability. Continuous efforts to harmonise VAP diagnostic criteria in future clinical trials are crucial to improve quality of care, enable accurate epidemiological assessments, and guide effective antimicrobial stewardship.

Cognitive behavioural therapy for insomnia (CBT-I) in schizophrenia and schizoaffective disorder: protocol for a randomised controlled trial

IntroductionInsomnia is a common symptom among patients with schizophrenia and schizoaffective disorder, negatively impacting symptom severity, functioning and well-being; however, it is rarely the direct focus of treatment. The main...

Workplace interventions to reduce the risk of SARS-CoV-2 infection outside of healthcare settings.

Workplace interventions to reduce the risk of SARS-CoV-2 infection outside of healthcare settings.

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from ameta-analysis of randomized controlled trials.

COVID-19 induces a pro-coagulant state with thrombotic events. This meta-analysis explores the efficacy and safety of antiplatelet-based therapy in COVID-19 patients through randomized controlled trials (RCTs). A systematic literature search until March 10, 2023, identified 7 RCTs involving 23,415 inpatients. Of these, 11,891 received antiplatelet-based treatment, and 11,524 received placebo/other drugs. Statistical analysis was performed using Review Manager 5.4. The included trials involved patients with a mean age ranging from 54.3 to 62.0 years and a prevalence of hypertension ranging from 10.9 to 65.0% and coronary artery disease ranging from 3.2 to 32.7%. The pooled analysis showed no significant difference in overall mortality between groups (RR 1.0, 95% CI 0.99-1.01, p=0.76). However, antiplatelet therapy significantly reduced major thrombotic events (RR 0.86, 95% CI 0.75-0.99, p=0.04). Conversely, it increased major bleeding risks (RR 1.62, 95% CI 1.24-2.12, p=0.0005). There was no significant difference in the incidence of invasive mechanical ventilation and respiratory death. Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.

Do one-stage indications predict success following two-stage arthroplasty for chronic periprosthetic joint infection?

Introduction: The 2018 International Consensus Meeting (ICM) proposed criteria for one-stage exchange arthroplasty in treating periprosthetic joint infection (PJI). Our study aimed to determine what proportion of PJI patients met the 2018 ICM criteria and how this affected infection-free survivorship for patients. Methods: All chronic PJI patients treated with two-stage exchange within our institution between 2017-2020 were retrospectively reviewed. Included cases met 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI and had a 2-year minimum follow-up. Treatment success was defined as Tier 1A in the 2019 MSIS working group definition. ICM one-stage criteria included non-immunocompromised host, absence of sepsis, adequate soft tissue for closure, known preoperative pathogen, and susceptibility. Immunocompromised host was analyzed as two separate definitions. Kaplan-Meier survivorship, Cox regression, and univariate analyses were performed. Results: A total of 293 chronic PJI patients were included. Overall, treatment failure occurred in (21.8 %) patients. Only 13 % () met ICM criteria definition no.1 for one-stage exchange; 12 % () met definition no.2. In both definitions, infection-free survivorship at 2years did not differ between patients who met and did not meet criteria (). Cox proportional hazard regression analyses demonstrated that the only variable predicting treatment failure was knee joint involvement (). Conclusions: We found that a very limited number of chronic PJI patients were suitable for a one-stage exchange. Furthermore, the supposition that healthier hosts with known pathogens (the basis of the ICM criteria) yield better PJI treatment outcomes was not observed. These results justify the ongoing multicenter randomized control trial comparing one-stage versus two-stage treatment for chronic PJI.

Role of Preoperative Radiation Therapy for Resectable Gastric Cancer.

While surgery is the primary curative treatment for resectable gastric and gastroesophagealjunction (GEJ) cancer, rates of locoregional and distant recurrence remain high with surgery alone,especially in more advanced disease. Multimodal approaches with perioperative therapy includingchemotherapy and/or radiation therapy (RT) have thus evolved as ways to reduce the rates of diseaserecurrence and improve survival outcomes. This review article provides a comprehensive literaturereview on the role of preoperative RT for resectable gastric and GEJ cancer. A literature review on the role of preoperative RT for resectable gastric and GEJ cancer wasconducted. Preoperative RT has the potential to facilitate tumor downstaging and improved R0 resection,allowing for better locoregional control and thereby survival. For resectable locally advanced GEJ cancer,preoperative chemoradiotherapy (CRT) is currently a standard of care option along with perioperativechemotherapy, based on evidence from randomized trials. In resectable gastric cancer, however, therole of preoperative CRT is less defined with no randomized data to date, although phase II single-armstudies have shown promising results. Current standard of care for gastric cancer remains perioperativechemotherapy, with consideration for preoperative CRT in select cases. Results from ongoing and future randomized controlled trials are expected to help definethe role of preoperative CRT compared to perioperative chemotherapy alone as well as postoperativeCRT for gastric and GEJ cancer.

A Comprehensive Review on the Surgical Landscape in Breast Cancer Management

Purpose: The purpose of this narrative review is to examine the literature on the topic of breast surgery and its benefits for women with metastatic breast cancer. Breast surgery can involve either a mastectomy, which involves removing the entire breast along with lymph nodes, nipple, and areola, or a lumpectomy, which involves removing breast tissue and tumour but leaving the nipple and areola intact.
 Methodology: We included any English-language study published between 2000 and 2021 that looked at the effects of breast surgery on survival or quality of life for women with metastatic breast cancer, whether it was an interventional study or an observational study. We utilised a combination of keywords like "Breast surgery," "mastectomy," "lumpectomy," "metastatic disease," "survival," "observational studies," "intervention studies," and "quality of life" to scour sources like PubMed and Embase. We considered randomised controlled trials that contrasted hormonal therapy, radiation, chemotherapy, biologic therapy, and supportive care with breast surgery alone or in combination with systemic therapy. A variety of outcomes were considered, including overall survival, quality of life, toxicity from local treatment as measured by one-month mortality, survival without progression, and survival specific to breast cancer.
 Findings: The evidence from randomised controlled trials is limited and not conclusive, while observational studies do suggest that breast surgery may benefit with metastatic breast cancer. Since observational studies are prone to problems like selection bias and unmeasured confounding, it is difficult to draw any conclusions regarding the advantages of breast surgery without solid proof from RCTs.
 Implications to Theory, Practice and Policy: Each woman diagnosed with metastatic breast cancer should be considered individually when deciding whether or not to undergo surgery. This should be done until results from big ongoing RCTs are available. When considering treatment options, the patient and doctor must weigh the pros and cons of each, as well as the associated costs. The current lack of strong evidence calls for more randomised controlled trials (RCTs) in both developing and developed nations, with bigger sample sizes.

Education, incentive, and engineering-based interventions to promote the use of seat belts.

Education, incentive, and engineering-based interventions to promote the use of seat belts.

Robotic radical hysterectomy for cervical cancer: current trends and controversies.

Minimally invasive radical hysterectomy (MIRH) is widely performed as a treatment for early-stage cervical cancer. However, in 2018, a randomized controlled trial (RCT) called the Laparoscopic Approach to Cervical Cancer (LACC) trial showed that MIRH had poorer oncologic outcomes compared to laparotomy. Since then, several clinical studies have supported this finding, and most surgeons now perform MIRH with limited surgical indications. However, most of the reported studies evaluated laparoscopic radical hysterectomy rather than robotic radical hysterectomy (RRH). Robotic surgery has advantages for complex surgical procedures in the deep and narrow pelvic cavity in cervical cancer, making it necessary to evaluate the benefits and potential harms of RRH individually. Based on this systematic review, RRH is a safe and effective alternative to abdominal approach for early-stage cervical cancer. RRH offers significant perioperative benefits, including reduced blood loss, shorter hospital stays, and fewer complications, without compromising oncologic outcomes such as overall survival and progression-free survival. Additionally, surgeons should aim to minimize tumor cell spillage into the peritoneal cavity by eliminating the use of uterine manipulators or vaginal colpotomy. Ongoing RCTs will reveal whether we can perform RRH without oncologic compromise in cervical cancer.

Stroke in Patients with Atrial Fibrillation: Epidemiology, Screening, and Prognosis.

Atrial fibrillation (AF) is the most common sustained arrythmia and one of the strongest risk factors and causal mechanisms of ischemic stroke (IS). Acute IS due to AF tends to be more severe than with other etiology of IS and patients with treated AF have reported to experience worse outcomes after endovascular treatment compared with patients without AF. As cardioembolism accounts for more than a fifth of ISs and the risk of future stroke can be mitigated with effective anticoagulation, which has been shown to be effective and safe in patients with paroxysmal or sustained AF, the screening of patients with cryptogenic IS (CIS) for AF is paramount. Embolic stroke of undetermined source (ESUS) is a subtype of CIS with a high likelihood of cardioembolism. The European Stroke Organization and European Society of Cardiology guidelines recommend at least 72 h of screening when AF is suspected. The longer the screening and the earlier the time point after acute IS, the more likely the AF paroxysm is found. Several methods are available for short-term screening of AF, including in-hospital monitoring and wearable electrocardiogram recorders for home monitoring. Implantable loop monitors provide an effective long-term method to screen patients with high risk of AF after IS and artificial intelligence and convolutional neural networks may enhance the efficacy of AF screening in the future. Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists in both primary and secondary prevention of IS in AF patients. Recent data from the randomized controlled trials (RCT) also suggest that early initiation of DOAC treatment after acute IS is safe compared to later initiation. Anticoagulation treatment may still predispose for intracranial bleeding, particularly among patients with prior cerebrovascular events. Left atrial appendix closure offers an optional treatment choice for patients with prior intracranial hemorrhage and may offer an alternative to oral anticoagulation even for patients with IS, but these indications await validation in ongoing RCTs. There are still controversies related to the association of found AF paroxysms in CIS patients with prolonged screening, pertaining to the optimal duration of screening and screening strategies with prolonged monitoring techniques in patients with ESUS. In this review, we summarize the current knowledge of epidemiology, screening, and prognosis in AF patients with stroke.

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Robotic pancreas surgery for pancreatic cancer.

Since the introduction of robotic pancreas surgery in the early 2000s, there has been significant increase in the adoption of the robot to perform complex pancreatic resections. However, utilization of the robot for pancreatic cancer has lagged behind due to concern for inferior oncologic outcomes. Furthermore, research in this field has previously been limited to small, single institution observational studies. Recent and ongoing randomized control trials in robotic distal pancreatectomy and robotic pancreatoduodenectomy have aimed to address concerns regarding the use of robotic techniques in pancreatic cancer. Together, these studies suggest similar, if not improved, outcomes with a robotic approach, including shorter hospital stays, expedited recovery with less post-operative complications, and equivalent resection rates, when compared to the standard open approaches. Additionally, surgical training in robotic pancreas surgery is of equal importance for patient safety. This review summarizes the available literature on the efficacy and safety of robotic pancreas surgery for pancreatic cancer, with specific focus on robotic distal pancreatectomy and robotic pancreatoduodenectomy.

Feasibility of DNA Methylation Age as a Biomarker of Symptoms and Resilience among Cancer Survivors with Multiple Chronic Conditions.

This study aims to examine the feasibility of DNA methylation age as a biomarker for symptoms and resilience in cancer survivors with multiple chronic conditions (MCCs). We included ten participants from our parent study, an ongoing randomized control trial study. Participants' symptoms and resilience were assessed, and peripheral blood was collected. DNA methylation age calculation was performed using DNAge® analysis. Data were analyzed using Spearman's correlation analysis and the Mann-Whitney U test. Participants in the intervention group tended to have a decrease in DNA methylation age and age acceleration after completing an exercise program (mean difference = -0.83 ± 1.26). The change in DNA methylation age was significantly correlated with the change in resilience score (r = -0.897, p = 0.015). The preliminary results suggest that DNA methylation age can be a potential biomarker for improving resilience in cancer survivors with multiple chronic conditions. This finding is limited by the small sample size, and a larger study is needed.

Cerebral embolic protection devices during transcatheter aortic valve implantation: a meta-analysis of randomised controlled trials

Abstract Background Stroke is a feared complication of transcatheter aortic valve implantation (TAVI), which may be mitigated by embolic protection devices (EPDs). Purpose We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) to test the effect of EPDs in TAVI. Methods All RCTs comparing EPDs with control during TAVI were systematically identified. Pre-specified primary endpoints were all stroke, disabling stroke, non-disabling stroke and all-cause mortality. Safety and neuroimaging parameters were assessed. Sensitivity analyses were stratified by EPD type. This study was prospectively registered. Results Eight trials randomising 4043 patients were included. There was no significant difference between EPDs and control for all stroke [RR 0.88, 95%CI 0.65–1.18, p=0.386, I2=0%], disabling stroke [RR 0.59, 95%CI 0.31–1.14, p=0.117, I2=0%], non-disabling stroke [RR 0.99, 95%CI 0.71–1.40, p=0.967, I2=0%] or all-cause mortality [RR 0.88, 95%CI 0.44–1.78, p=0.727, I2=0%]. There were no differences in safety endpoints of bleeding, vascular complications, or acute kidney injury. EPDs resulted in reduced cerebral lesion volume [SMD -0.55, 95%CI -0.91– -0.18, p=0.003, I2=63.6%], but no difference in number of patients with new lesions. The Sentinel EPD significantly reduced risk of disabling stroke [RR 0.42, 95%CI 0.20–0.88, p=0.022, I2=0%] but did not impact all stroke, non-disabling stroke or all-cause mortality. Conclusion The totality of randomised data for EPDs during TAVI demonstrated no safety concerns or significant differences in clinical endpoints, although total cerebral lesion volume was reduced. Analyses restricted to the Sentinel EPD demonstrated large, clinically meaningful reductions in disabling stroke. Ongoing RCTs may help validate these results.Effects of cerebral embolic protectionEffects of the Sentinel device

Abstract 12199: Mid-Term Survival of Low-Risk Patients Treated With Transcatheter versus Surgical Aortic Valve Replacement: Meta-Analysis of Reconstructed Time-to-Event Data

Background: We performed a meta-analysis of reconstructed time-to-event data from randomized controlled trials (RCTs) and propensity-score matched (PSM) studies comparing transcatheter versus surgical aortic valve replacement (TAVR versus SAVR) to evaluate mid-term outcomes in patients considered low risk for SAVR. Methods and Results: Study-level meta-analysis of Kaplan-Meier-derived time-to-event of RCTs and PSM studies published by December 31, 2022. Eight studies (3 RCTs; 5 PSM studies) met our eligibility criteria and included 5,444 patients (2,639 patients underwent TAVR and 2,805 patients underwent SAVR). TAVR showed a higher risk of all-cause mortality at 8 years of follow-up [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.03-1.43, P=0.018]. Up to 2 years of follow-up, TAVR was not inferior to SAVR (HR 1.08, 95%CI 0.89-1.31, P=0.448); however, we observed a statistically significant difference after 2 years with higher mortality with TAVR (HR 1.51; 95% CI 1.14-2.00; P=0.004). This difference was driven by PSM studies; our sensitivity analysis showed a statistically significant difference between TAVR and SAVR when we included only PSM studies (HR 1.41, 95%CI 1.16-1.72, P=0.001), but no statistically significant difference when we included only RCTs (HR 0.89, 95%CI 0.69-1.16, P=0.398). At 8 years of follow-up after the primary intervention, the treatment difference in restricted mean survival time (RMST) is statistically significant, resulting in a benefit of 187.2 days (95% CI, 85.1-289.2, P<0.001) in the SAVR arm. Conclusion: In comparison with TAVR, SAVR appeared to be associated with improved survival beyond 2 years in low-risk patients. However, the survival benefit of SAVR was only observed in PSM studies and not in RCTs. The addition of data from ongoing RCTs as well as longer follow-up in previous RCTs will help to confirm if there is a difference in mid- and long-term survival between TAVR vs. SAVR in low-risk population.

Midterm Survival of Low-Risk Patients Treated With Transcatheter Versus Surgical Aortic Valve Replacement: Meta-Analysis of Reconstructed Time-to-Event Data.

Background We performed a meta-analysis of reconstructed time-to-event data from randomized controlled trials (RCTs) and propensity-score matched (PSM) studies comparing transcatheter versus surgical aortic valve replacement (TAVR versus SAVR) to evaluate midterm outcomes in patients considered low risk for SAVR. Methods and Results Study-level meta-analysis of reconstructed time-to-event data from Kaplan-Meier curves of RCTs and PSM studies published by December 31, 2022 was conducted. Eight studies (3 RCTs, 5 PSM studies) met our eligibility criteria and included 5444 patients; 2639 patients underwent TAVR, and 2805 patients underwent SAVR. TAVR showed a higher risk of all-cause mortality at 8 years of follow-up (hazard ratio [HR] 1.22, [95% CI, 1.03-1.43], P=0.018). Up to 2 years of follow-up, TAVR was not inferior to SAVR (HR, 1.08 [95% CI, 0.89-1.31], P=0.448); however, we observed a statistically significant difference after 2 years with higher mortality with TAVR (HR, 1.51 [95% CI, 1.14-2.00]; P=0.004). This difference was driven by PSM studies; our sensitivity analysis showed a statistically significant difference between TAVR and SAVR when we included only PSM studies (HR, 1.41 [95% CI, 1.16-1.72], P=0.001) but no statistically significant difference when we included only RCTs (HR, 0.89 [95% CI, 0.69-1.16], P=0.398). Conclusions In comparison with TAVR, SAVR appeared to be associated with improved survival beyond 2 years in low-risk patients. However, the survival benefit of SAVR was observed only in PSM studies and not in RCTs. The addition of data from ongoing RCTs as well as longer follow-up in previous RCTs will help to confirm if there is a difference in mid- and long-term survival between TAVR versus SAVR in the low-risk population.

Cerebral Embolic Protection Devices During Transcatheter Aortic Valve Replacement: A Meta-analysis of Randomized Controlled Trials.

Stroke is a feared complication of transcatheter aortic valve replacement (TAVR), which embolic protection devices (EPDs) may mitigate. This systematic review and meta-analysis synthesized randomized controlled trials (RCTs) to evaluate the effect of EPDs in TAVR. All RCTs comparing EPDs with control during TAVR were systematically identified. Prespecified primary end points were all stroke, disabling stroke, nondisabling stroke, and all-cause mortality. Safety and neuroimaging parameters were assessed. Sensitivity analyses were stratified by EPD type. Study registration was a priori (CRD42022377939). Eight trials randomizing 4043 patients were included. There was no significant difference between EPDs and control for all stroke (relative risk [RR], 0.88; 95% CI, 0.65-1.18; P = .39; I2 = 0%), disabling stroke (RR, 0.67; 95% CI, 0.31-1.46; P = .32; I2 = 8.6%), nondisabling stroke (RR, 0.99; 95% CI, 0.71-1.40; P = .97; I2 = 0%), or all-cause mortality (RR, 0.87; 95% CI, 0.43-1.78; P = .71; I2 = 2.3%). There were no differences in safety end points of bleeding, vascular complications, or acute kidney injury. EPDs did not result in differences in total lesion volume or the number of new lesions. The Sentinel EPD significantly reduced the risk of disabling stroke (RR, 0.42; 95% CI, 0.20-0.88; P = .022; I2 = 0%) but did not affect all stroke, nondisabling stroke, or all-cause mortality. The totality of randomized data for EPDs during TAVR demonstrated no safety concerns or significant differences in clinical or neuroimaging end points. Analyses restricted to the Sentinel EPD demonstrated large, clinically meaningful reductions in disabling stroke. Ongoing RCTs may help validate these results.

Effectiveness of Osteopathic Manipulative Treatment in Adults with Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of the osteopathic manipulative treatment (OMT) in adults with irritable bowel syndrome (IBS). A literature resview was carried out on the following databases: PubMed, Embase, Cochrane, Cinahl, Scopus, PEDro and ClinicalTrials.gov. 350 articles were recovered. Eligibility criteria were evaluated by two independent reviewers, including randomized controlled trials (RCTs), quasi-RCTs, or ongoing RCTs with OMT compared to any kind of control in patients diagnosed with IBS. Six studies (five RCTs and one ongoing RCT) were considered eligible. Four RCTs were classified as some concerns and one as high risk of bias. In the meta-analysis, OMT compared to sham/no intervention showed statistically significant results for abdominal pain (effect size ES = -1.14 [-1.66, -0.62]; p < 0.0001) and constipation (ES = -0.66 [-1.12, -0.20]; p = 0.005). Instead, OMT was not superior to the control for the IBS symptoms measured with the IBS Severity Score and the Likert scale (ES = -0.34 [-0.83, 0.16]; p = 0.19), and diarrhea (ES = -1.20 [-2.84, 0.43]; p = 0.15). The quality of evidence was "low" for IBS symptoms in general for abdominal pain and constipation, while it was judged as "very low" for diarrhea. OMT turns out to be safe in the treatment of IBS without major adverse effects. OMT may be effective in IBS patients, however the results must be interpreted carefully due to the low methodological quality of the studies.