Randomized Controlled Trials Research Articles

A systematic review of techniques and clinical evidence to adopt virtual reality in post-stroke upper limb rehabilitation

AbstractRecognizing the limitations of traditional therapy can be tedious and demotivating, we explore VR’s dynamic and immersive environment to potentially improve patient engagement and motivation. This approach promises accelerated recovery by integrating real-time feedback and progress monitoring. This study aims to compare various VR training techniques employed for upper limb rehabilitation in stroke survivors. We have followed the PRISMA guidelines for systematic reviews. Articles were filtered with title words such as “virtual reality rehabilitation”, “rehabilitation”, “upper limb”, “lower limb”, “interactive gaming system”, and “VR based games” were searched in databases (LILACS, PUBMED, IEEE, WoS, and Scopus). Articles published between 2005 and 2021 were analyzed. There were 820 articles found, but only the most relevant 96 papers were analyzed. Most of the studies were randomised controlled trials (RCTs) that were submitted in 2014 or beyond. The sample size ranged from 5 to 96 persons with chronic stroke, or adults and seniors. There were no samples analyzed for those under the age of 18. Nintendo Wii® and Microsoft’s Kinect were the most popular video gaming systems. In most of the publications, the intervention took place 2–3 sessions per week, for about 2–12 weeks, with each session lasting 30 to 60 min. The most assessed outcomes were body steadiness, upper extremity motor capabilities, daily tasks, and quality of life. The Fugl–Meyer Assessment was one the commonly used tool for measuring outcomes. After VR therapy, the research found that quality of life, dynamic steadiness, and upper extremity movement function improved. To achieve dynamic equilibrium, VR proved more beneficial than traditional treatments. The most important outcomes, the researchers focused, were day-to-day activity and physical movements of the patients. Some studies investigated the early consequences of VR on daily activities and social involvement.

Perioperative administration of sub-anesthetic ketamine/esketamine for preventing postpartum depression symptoms: A trial sequential meta-analysis

Objective Postpartum depression (PPD) is a major mental health issue affecting 10%–15% of women globally. This meta-analysis synthesized updated evidence on sub-anesthetic ketamine/esketamine’s efficacy in preventing PPD. Methods Randomized controlled trials (RCTs) comparing ketamine/esketamine to a placebo for PPD prevention were searched without language restriction. Primary outcomes were PPD risk at 1- and 4–6-week postpartum. Secondary outcomes included the difference in depression scores and risk of adverse events. Trial sequential analysis (TSA) was conducted to validate the reliability. Results A meta-analysis of 22 RCTs (n = 3,463) showed that ketamine/esketamine significantly decreased PPD risk at 1- (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.3–0.57) and 4–6-week (RR, 0.47; 95%CI, 0.35–0.63) follow-ups. Consistently, participants receiving ketamine/esketamine had lower depression-related scores at 1- (standardized mean difference [SMD], −0.94; 95%CI, −1.26 to −0.62) and 4–6-week (SMD, −0.89; 95%CI, −1.25 to −0.53) follow-ups. Despite potential publication bias, TSA confirmed the evidence’s reliability. Subgroup analysis showed that ketamine/esketamine’s preventive effect on 1-week PPD was consistent, regardless of administration timing, type of agents, or total dosage (<0.5 vs. ≥0.5 mg/kg). For the 4–6-week period, PPD risk was favorably reduced only with postoperative administration or the use of esketamine, with the total dosage having no observed influence. Participants on ketamine/esketamine experienced more frequency of hallucinations (RR, 4.77; 95%CI, 1.39–16.44) and dizziness (RR, 1.36; 95%CI, 1.02–1.81). Conclusion Our findings advocate for the postoperative administration of low-dose ketamine/esketamine to avert PPD, which needed additional research for confirmation.

Meta-analysis of longitudinal comparison of transcatheter versus surgical aortic valve replacement in patients at low to intermediate surgical risk

Background: Surgical aortic valve replacement (SAVR) is the commonly used approach for aortic valve replacement (AVR) in patients with aortic stenosis at low or intermediate surgical risk. However, transcatheter aortic valve replacement (TAVR) has emerged as an alternative to SAVR for AVR. This meta-analysis aims to assess the comparative efficacy and safety of TAVR versus SAVR in low-to-intermediate surgical risk patients by analyzing temporal trends in the outcomes of TAVR and SAVR at various follow-up intervals, providing a more detailed understanding. Methods: A thorough literature search was performed across PubMed/MEDLINE, Embase, and the Cochrane Library from their inception up to May 2024 to identify eligible randomized controlled trials (RCTs). Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95% confidence intervals (CIs). Results: A total of 17 studies reporting data at different follow-ups for 9 trials were included (n=9,092). No statistically significant difference was observed between TAVR and SAVR for reducing all-cause death at 30 days, 1 year, and 2 years but significantly increased risk with TAVR at 5 years or longer follow-up (RR=1.13, 95% CI: 1.03 to 1.23). However, TAVR was associated with a significantly decreased risk for cardiac death at 1-year follow-up (RR=0.79, 95% CI: 0.64 to 0.96) and comparable risk for cardiac death at 30 days, 2 years, and 5 years or longer follow-up when compared with SAVR. No statistically significant difference was observed between TAVR and SAVR for reducing the risk of myocardial infarction (MI) at 30 days, 1 year, 2 years, and 5 years or longer follow-up. TAVR was associated with a significantly lower risk of major bleeding events at 30 days (RR=0.38, 95% CI: 0.21 to 0.67); lower risk of acute kidney injury (AKI) at 30 days (RR=0.38, 95% CI: 0.26 to 0.54) and 1 year (RR=0.58, 95% CI: 0.41 to 0.82) and lower risk of new onset or worsening atrial fibrillation (AF) at 30 days (RR=0.25, 95% CI: 0.18 to 0.34), 1 year (RR=0.26, 95% CI: 0.16 to 0.41) and 2 years (RR=0.32, 95% CI: 0.20 to 0.49) when compared with SAVR. However, TAVR was associated with a significantly increased risk of permanent pacemaker implantation (PPI) at 30 days (RR: 2.62, 95% CI: 1.40 to 4.91), at 1 year (RR: 2.19, 95% CI: 1.24 to 3.87), at 2 years (RR: 2.74, 95% CI: 1.31 to 5.71), and beyond 5 years (RR: 1.95, 95% CI: 1.20 to 3.15). TAVR was also associated with a significantly increased risk of prosthetic valve thrombosis at 2 years (RR=2.70, 95% CI: 1.08 to 6.71), though no significant association was observed at 30 days, 1 year, or 5 years. Similarly, no significant differences were observed in aortic-valve reintervention rates at 30 days, 2 years, or 5 years, but TAVR showed a significantly increased risk at 1 year (RR=1.98, 95% CI: 1.21 to 3.24). TAVR was associated with a significantly increased risk of major vascular complications at 30 days (RR=2.37, 95% CI: 1.38 to 4.04) and a significantly increased risk of TIA at 2 years (RR: 1.43, 95% CI: 1.02 to 2.00, I2=0%). The risk of hospitalizations was comparable between the groups. Conclusion: TAVR and SAVR demonstrated comparable rates of all-cause death up to 2 years of follow-up. However, at 5 years or longer follow-up, TAVR was associated with a higher risk of all-cause death. While TAVR showed certain procedural advantages, such as a lower risk of major bleeding, AKI, and new-onset or worsening AF, the choice between TAVR and SAVR in patients with low or intermediate surgical risk should consider long-term outcomes, with SAVR potentially being more favorable due to better survival observed on longer follow-up durations.

The effect of ischemic preconditioning on the cardiac autonomic nervous system after exercise: A systematic review and meta-analysis

Aims: The objective of this study is to comprehensively evaluate the influence of ischemic preconditioning intervention on the autonomic control nerves of athletes during the post-exercise period. Methods: Randomized controlled trials (RCTs) were sourced from PubMed, Web of Science, Embase, Wipo, CNKI, and Cochrane databases, covering the period from inception to December 2023. The quality of the included RCTs was evaluated using the Cochrane Risk Assessment Tool, and a systematic assessment was conducted using RevMan 5.3. Results: Seven randomized controlled trials (RCTs) involving 88 subjects were included in the analysis. The meta-analysis indicated that ischemic preconditioning significantly improved heart rate during both short-term recoveries (mean difference [MD] = -3.99, 95% confidence interval [CI]: -5.93 to -2.05, p < 0.00001) and long-term recovery post-exercise (MD = -9.73, 95% CI: -12.74 to -6.73, p < 0.00001). However, there was no significant effect observed on resting state heart rate variability (HRV) or peak heart rate (HR peak) at the end of exercise (MD = -0.16, 95% CI: -2.46 to 2.14, p = 0.89). Conclusion: Ischemic preconditioning facilitates the prompt reactivation of cardiac parasympathetic nerves following exercise and enhances both short-term and long-term heart rate recovery. The extent of this recovery effect may be influenced by factors such as the dosage of the intervention, the individual’s training level, and the intensity of the exercise performed. Limitation: Given the limited number of included studies, the small sample size, and the unclear definition of some experimental procedures, it is essential to design more rigorous and comprehensive high-quality randomized controlled trials (RCTs) in the future to investigate the effects of ischemic preconditioning on cardiac autonomic control nerves following exercise. Registration: INPLASY202440069

Does acupuncture combined with MOTOmed movement therapy have a better rehabilitation effect on post-stroke hemiplegia patients? A systematic review and meta-analysis

ABSTRACT Background Combinations of rehabilitation therapies are widely used in patients with post-stroke hemiplegia. A combination of acupuncture and MOTOmed had been shown to promote the recovery of post-stroke hemiplegia patients. We conducted a systematic review of evidence from studies that investigated the use of acupuncture combined with MOTOmed for rehabilitation of patients with post-stroke hemiplegia. Objective To estimate the rehabilitation effect of acupuncture combined with MOTOmed movement therapy in patients with post-stroke hemiplegia. Methods Randomized controlled trials (RCTs) of acupuncture combined with MOTOmed movement therapy in patients with post-stroke hemiplegia were retrieved from nine databases. Risk-of-bias assessments were conducted using the Cochrane Risk-of-bias Tool. Meta-analysis of outcome measures was performed using RevMan 5.4 software. And we followed the PRISMA 2020 guidelines. Results Eighteen studies involving 1637 participants were included. Compared with conventional rehabilitation, acupuncture, or MOTOmed movement therapy alone, acupuncture combined with MOTOmed movement therapy increased the scores of Fugl-Meyer Assessment Scale-lower extremity (FMA-LE), Berg Balance Scale (BBS), Functional Ambulation Categories scale (FAC), Maximal Walking Speed test (MWS), gait parameters of 3D gait analysis, Barthel Index (BI), Modified Barthel Index (MBI), total effective rate, and the levels of neurotrophic factors (NGF, BDNF and NT-3) in serum, while reduced the scores of Clinic Spasticity Index (CSI) and National Institutes of Health Stroke Scale-Lower Extremity (NIHSS-LE) (p < 0.05 for all). Conclusion Acupuncture combined with MOTOmed movement therapy has better efficacy than conventional rehabilitation, acupuncture, or MOTOmed alone in patients with post-stroke hemiplegia. This combination therapy can promote the rehabilitation of these patients.

An Overview of Randomized Controlled Trials Examining Prescription and Nonprescription Pharmacological Interventions for Moderate to Severe Traumatic Brain Injury

Objective: To characterize randomized controlled trials (RCTs) of pharmacological interventions (prescription medications, nonprescription medications, and supplements) for the management of moderate to severe traumatic brain injury (MSTBI). Data sources: Systematic searches were conducted in MEDLINE, PubMed, Scopus, CINAHL, EMBASE, and PsycINFO for RCTs up to December 2022 inclusive in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study selection and data extraction: Inclusion criteria were RCT study design; participants’ mean age ≥ 18 years and ≥ 50% had MSTBI; examined ≥ 1 pharmacological intervention(s), either alone or in combination with other interventions. Two independent reviewers conducted Cochrane risk of bias assessment. Data synthesis: Three hundred thirteen RCTs (1978-2022) met inclusion criteria. A total of 146 unique pharmacotherapies and supplements were studied. The most frequently studied intervention was mannitol ( n = 20 RCTs). Mean sample size was 230.4 (4-12 737) and 195 studies (62.3%) were conducted in the acute phase post-MSTBI. Four hundred thirty-five unique outcome measures (OMs) were studied; the most common OMs used were Glasgow Outcome Scale (GOS) (29.4%), mortality (25.2%), and intracranial pressure (25.2%), Glasgow Coma Scale (GCS) (19.5%), and mean arterial pressure (17.3%), and heart rate (10%). Of the included studies, only 7% ( n = 22) had low risk of bias. Conclusion: The paucity of high-quality studies, variability in RCT methodology, sample sizes, and OMs utilization, as well as the low number of RCTs conducted in the subacute- and chronic-phase after injury pose a challenge for conducting meta-analyses to provide strong recommendations for informed decision-making in clinical practice.

A Network Meta-Analysis of Vasodilator Therapies in Pulmonary Hypertension Patients Undergoing Mitral Valve Replacement Surgery: Insights for Optimizing Hemodynamics.

Pulmonary hypertension (PH) is a progressive hemodynamic condition associated with significant morbidity and mortality, especially in patients undergoing cardiac surgery. Therefore, the objective of this network meta-analysis (NMA) is to compare the efficacy of various pulmonary vasodilators in perioperative control of PH among patients undergoing mitral valve replacement surgery (MVRS), aiming to address the existing knowledge gap and improve perioperative outcomes. Electronic databases including PubMed, Cochrane Central Registry of Controlled Trials, Scopus, Embase, and Web of Science (WOS) from inception to 17 September 2024. Only randomized controlled trials (RCTs) evaluating vasodilators in PH patients undergoing MVRS were included. We used netmeta package in RStudio to analyze the outcome data with their corresponding mean difference (MD) and confidence intervals (CI). Seventeen RCTs including 862 patients were analyzed. Prostacyclin, nitric oxide (NO), and sodium nitroprusside (SN) significantly reduced mean pulmonary arterial pressure with effect sizes [MD, 95% confidence interval (CI)] of (11.77, -18.78; -4.76; -8.3, -15.9; -0.6; -11.02, -20.1; -3.8, respectively). While no treatment showed significant efficacy on pulmonary capillary wedge pressure, systolic pulmonary arterial pressure, or heart rate, nitroglycerin, NO, and prostacyclin, showed significant increases in cardiac index with effect sizes (MD, 95% CI) of (1, 0.3; 1.7; 1.2 0.8; 1.6; 1.2 0.8; 1.6, respectively). Additionally, NO, prostacyclin, SN, and nitroglycerin demonstrated significant reductions in systemic vascular resistance (SVR), with effect sizes of. (-0.54, -0.82; -0.26, -0.37, -0.65; -0.09; -0.47, -0.77; -0.16; -0.14, -0.24; -0.03, respectively). This NMA highlights prostacyclin, nitroglycerin, NO, and SN as consistently effective in improving hemodynamics for patients with PH undergoing MVRS, and provides valuable insights for surgeons to choose the suitable vasodilator for these surgeries. However, limitations and the need for further RCTs are acknowledged.

Efficacy and safety of Piclidenoson in the treatment of plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials.

Psoriasis, an autoimmune inflammatory disease characterized by hyperproliferation of keratinocytes, affects 0.2-4.8% of the global population. The disease manifests primarily as plaque psoriasis, causing chronic physical and psychological burdens. Although numerous treatments exist, there is ongoing exploration for novel therapies due to concerns about the toxicity, efficacy, and costs of current options. An A3 adenosine receptor (A3AR) agonist called Piclidenoson has been shown to reduce inflammation and could be used to treat moderate to severe psoriasis. This meta-analysis evaluates the safety and efficacy of Piclidenoson in psoriasis treatment. This meta-analysis was conducted accordance with the PRISMA guidelines and has been registered on PROSPERO (CRD42024566459). A comprehensive search on Cochrane CENTRAL, PubMed/MEDLINE, and Google Scholar was conducted up to July 2024. Included studies were randomized controlled trials (RCTs) involving Piclidenoson. Efficacy outcomes included PASI 75 and PGA 0 or 1, while safety outcomes included adverse events. Pooled outcomes were presented as odds ratio (OR) with 95% confidence intervals (CI). Statistical analysis employed the Mantel-Haenszel random-effects model, and heterogeneity was assessed using the I2 and X2index. Three RCTs with 574 patients (313 Piclidenoson, 261 placebo) met the inclusion criteria. The pooled analysis showed no significant difference in achieving PASI 75 between Piclidenoson and placebo (OR: 1.62, 95% CI 0.70-3.75, P = 0.26, I2 = 12%). However, Piclidenoson significantly improved PGA scores (OR: 2.74, 95% CI 1.22-6.16, P = 0.01, I²=0%). Safety assessment revealed no significant differences in adverse events, including nervous system, gastrointestinal, musculoskeletal, renal, and infections, compared to placebo. Piclidenoson demonstrates a significant improvement in PGA scores and a favorable safety profile, suggesting it could be a valuable addition to plaque-like psoriasis treatment. Further research with larger, longer-term RCTs is needed to confirm its efficacy and optimize clinical use.

Machine learning approach for detection of MACE events within clinical trial data.

Randomized controlled trials (RCTs) are the gold standard for clinical research but may not accurately reflect the impact of medicines in real-world settings. Supplementing RCTs with insights from real-world data (RWD) can address known limitations by including more diverse patient populations, additional types of sites-of-care, and practices more representative of the care most people receive. One current challenge in using RWD is the lack of an algorithmic approach to identifying outcomes. To address this, machine learning models for identifying a frequently used outcome, Major Adverse Cardiovascular Events (MACE), were developed in Clinical Trial Data (CTD). Anonymized CTD sourced from the Medidata Enterprise Data Store were used to develop model features on the condition that they would be useful for labelling MACE events and that they could also be found in RWD. These features were used to train three random forest models to identify each component of 3-point MACE in a patient's clinical trial journey. Performance metrics for the models are presented (recall = 0.72 [0.07], precision = 0.68 [0.12] - mean, [SD]) along with the top contributing features. We show that the models can be tuned specifically to replicate the adjudication panels' results and present a cost-benefit analysis for deploying such models in clinical trial settings. We demonstrate the viability of using advanced algorithms for identifying clinical outcomes in prospective clinical trials. Deployment of such models could reduce the resources required to conduct RCTs. Extending such models to RWD would facilitate approval of pragmatic clinical trials for regulatory submissions.

Effect of an abdominal binder on postoperative outcomes after ventral hernia repair: a systematic review and meta-analysis of randomized controlled trials.

Abdominal binders consist of a wide compression belt that encircles the abdomen, theoretically supporting the abdominal wall. However, their use after ventral hernia repair is debated. Therefore, this meta-analysis evaluates their efficacy. We searched PubMed, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing the effects of abdominal binders after ventral hernia repair. Outcomes included postoperative pain using the visual analog scale (VAS), surgical site infection (SSI), seroma formation and size, general well-being, activity limitation, forced expiratory volume in the first second (FEV1), and a 6-min walk test. Statistical analysis was performed with Review Manager 5.4.1 using a random-effects model. We included five RCTs encompassing 297 patients. Overall analysis showed decreased SSI rates (RR 0.21; 95% CI 0.07 to 0.59; p = 0.003; I2 = 0%) and reduced pain two weeks after surgery (MD -0.89; 95% CI -1.41 to -0.37; p = 0.0008; I2 = 0%) using abdominal binders. For patients undergoing open ventral hernia repair, it also demonstrated reduced SSI, pain four weeks after surgery (MD -0.60; 95% CI -0.88 to -0.32; p < 0.0001; I2 = 66%) and increased 6-min walk test performance four weeks after the procedure (MD 32.78m; 95% CI 15.28 to 50.29m; p = 0.0002; I2 = 0%). Abdominal binders may decrease SSI, postoperative pain, and increase physical condition, particularly in open ventral hernia repair. Further studies are still required to evaluate the role of abdominal binders in minimally invasive techniques.

Enhanced Recovery After Surgery (ERAS) Protocol for Craniotomy Patients: A Systematic Review

Context: The enhanced recovery after surgery (ERAS) protocol is a multidisciplinary approach aimed at improving surgical outcomes, reducing complications, minimizing hospital stays, and lowering healthcare costs. Objectives: This study assesses the impact of the ERAS protocol on elective craniotomies, a routine procedure in neurosurgery. Methods: A comprehensive search across PubMed, Embase, Scopus, and Web of Science identified 562 articles. Following strict screening criteria, 54 studies were reviewed, and ultimately 10 studies meeting the inclusion criteria were selected for detailed analysis. Results: The review encompassed ten studies [one prospective, one systematic review, and eight randomized controlled trials (RCTs)] published between 2016 and 2023. Key components of the ERAS protocol included preoperative counseling, high-protein intestinal nutrition, preoperative fasting while avoiding carbohydrate intake within 2 hours of surgery, standardized anesthetic and analgesic regimens, and early postoperative initiation of enteral feeding. Postoperative outcomes showed fewer complications, early mobilization, and notably shorter hospital stays, all of which contributed to improved patient recovery. Conclusions: This review demonstrates that the ERAS protocol, when applied to elective craniotomies, is effective in enhancing postoperative recovery, improving functional outcomes, and reducing hospitalization duration.

Effect of different training modalities on lipid metabolism in patients with type ii diabetes mellitus: a network meta-analysis.

This study to evaluate the effects of different training modalities on blood lipids in type II diabetic patients by Network Meta-analysis, and provide a relevant basis for patients to develop exercise prescriptions to regulate blood lipids. Randomized controlled trials (RCTs) were retrieved from Zhiwang, Wanfang, Wipu, PubMed, EBSCO, Cochrane Library, and Web of Science that were published from the establishment to February 2023. Relevant statistical analyses were performed using Stata 17.0 software and Revman 5.4. A total of 35 randomized controlled trials with 2771 patients with type II diabetes were finally included. The results of Network Meta-analysis showed that, compared with the control group, Chinese traditional fitness exercise (CTF), resistance training (RT), and aerobic training (AT) could reduce total cholesterol (TC) levels; CTF, RT, whole body vibration training (WBV), and AT could reduce triacylglycerol (TG) levels; CTF, WBV and AT could increase High-density lipoprotein cholesterol (HDL) levels; CTF, RT and AT could reduce Low-density lipoprotein cholesterol (LDL) levels. SUCRA probability ranking results showed that CTF was the most effective in reducing TC[SMD= -0.57, 95% CI (-0.83, -0.31), p < 0.001], TG[SMD= -0.24, 95% CI (-0.36, -0.12), p < 0.001], LDL[SMD= -0.52, 95% CI (-0.70, -0.35), p < 0.001]; RT was the most effective in increasing HDL[SMD = 0.14, 95% CI (0.03, 0.26), p < 0.05]. CTF is more effective in improving TC, TG and LDL levels, while RT is most effective in improving HDL levels.

Patient profiles in randomised controlled trials versus a real-world study, in psoriatic arthritis: scoping review and meta-analysis.

Patients with psoriatic arthritis (PsA) in randomised controlled trials (RCTs) may not reflect patients in clinical practice. The objective was to perform a meta-analysis of PsA patients' characteristics in RCTs of biologic disease-modifying antirheumatic drugs (bDMARDs), and to compare them to patient profiles in a real-world study. Data sources: (a) Scoping literature review of phase III RCTs of bDMARDs in PsA published 2015-2020; (b) International observational study of PsA patients starting a bDMARD enrolled in 2015-2018 (PsABio: NCT02627768). Data collected at baseline included swollen and tender joint counts (SJC/TJC), enthesitis, skin involvement (body surface area -BSA-), C-reactive protein (CRP), physician global assessment (PhGA) and patient-reported outcomes (HAQ, pain). Univariate random-effects meta-analysis was conducted to calculate pooled means and proportions. Overall, 5654 patients from 10 RCTs were compared to 930 PsABio patients. Demographic data were similar. SJC/TJC were higher in RCTs than in PsABio (pooled means, 11.8/21.5 vs 5.7/11.9 respectively); enthesitis was more frequent in RCTs (64.7% vs 48.2%); as were patients with a BSA≥3% (62.2% vs 54.0%). PhGA was higher in RCTs (59.7mm vs 54.1mm). In contrast, patient-reported outcomes were similar, while CRP was significantly higher in PsABio (1.1 vs 1.4mg/dl). PsA patients starting a bDMARD in RCTs had highly active disease and a high patient-reported disease burden. In contrast, PsABio real-world patients starting a bDMARD had lower joint counts, skin disease and PhGA, but presented with similar patient-reported disease burden. The extrapolation of RCT data in clinical practice should take these elements into account.

Management of Muscle Cramps in Patients With Cirrhosis: A Systematic Review of Randomised Controlled Trials.

Muscle cramps are common in patients with cirrhosis. Despite their prevalence and impact on health-related quality of life, there are no widely used clinical practice guidelines for management of muscle cramps in cirrhosis. The aim of this review was to critically evaluate current evidence regarding treatment of muscle cramps in cirrhosis. A systematic review using PubMed, MEDLINE (Ovid), Embase, and Scopus databases was performed on 30 June by two independent reviewers to identify randomised controlled trials (RCTs) reporting interventions for muscle cramps in cirrhotic patients. Twelve RCTs evaluating 13 distinct interventions were identified. Baclofen, methocarbamol, orphenadrine, and taurine supplementation reduced cramp frequency, severity, and duration when compared to placebo. Human albumin, pregabalin, and quinidine reduced cramp frequency compared to placebo. Pickle juice reduced cramp severity compared to placebo. BCAA supplementation and calcium carbonate were found to reduce cramp frequency compared to baseline. Stretching demonstrated a signal towards reducing cramp severity and frequency, and meditation had a signal towards reducing severity only when compared to baseline. Electro-acupuncture was the only intervention which demonstrated no therapeutic effect. Pregabalin was the only agent associated with significant side effects that limited its use. Methocarbamol, orphenadrine, and taurine supplementation were found in placebo-controlled RCTs to be effective in reducing cramp frequency, severity, and duration in cirrhotic patients. All other interventions reported aside from electro-acupuncture demonstrated a positive impact on cramps. High-quality RCTs are needed to further investigate the use of these treatments in terms of comparative efficacy and safety.

Comparative Analysis of Cellulite Treatment Modalities: A Systematic Review.

Cellulite is a highly prevalent and aesthetically distressing skin condition. Whilst there are a variety of treatment modalities, none are definitively established. This systematic review aims to assess invasive and noninvasive treatment modalities for cellulite management. The review protocol was published and registered a priori (PROSPERO CRD42022359334). A comprehensive electronic search for relevant randomised controlled trials, (RCTs) was performed in CENTRAL, MEDLINE, Embase and Web of Science databases. Study quality and risk of bias were assessed using Cochrane's risk of bias tool, respectively. Overall, 753 studies were initially identified, of which 24 randomised controlled trials (RCTs) satisfied the eligibility criteria with a total of 2084 patients with a mean follow-up of 3.33 ± 13.4weeks. Evaluated interventions included mechanical stimulation, topical therapy, shock wave therapy (SWT), laser and light-based devices, radiofrequency therapy, subcutaneous injectables, and ultrasound. SWT emerged as a standout intervention, demonstrating a consistent cellulite reduction score of 2.07 ± 0.39 across four studies. Radiofrequency therapy exhibited a statistically significant reduction of thigh circumference (- 2.09cm, p < 0.001) and subcutaneous tissue thickness (- 2.23cm, p < 0.001). Subcutaneous injectables, specifically collagenase Clostridium histolyticum-aaes, demonstrated a statistically significant improvement in the clinician-reported photonumeric cellulite severity scale (17.0%) and patient-reported photonumeric cellulite severity scale (25.7%) (p < 0.001). The overall quality of the studies using the grading of recommendations, assessment, development and evaluation approach was moderate. This is the first methodologically robust systematic review evaluating interventions for cellulite. SWT, radiofrequency therapy, and subcutaneous injectables have shown promising findings in cellulite treatment. The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266 .

Perioperative direct oral anticoagulant management during cardiac implantable electronic device surgery: an updated systematic review and meta-analysis.

Patients undergoing cardiovascular implantable electronic device (CIED) implantation are often on direct oral anticoagulation (DOAC). However, the evidence on whether to continue or temporarily discontinue DOAC therapy during the perioperative period in these patients is unclear. We conducted a comprehensive literature review using PubMed, Embase, and Cochrane databases through July 2024. We included studies comparing uninterrupted versus interrupted perioperative DOAC therapy in patients undergoing CIED procedure- primary implants, pulse generator replacement, and device upgrades. Primary outcomes were clinically significant device-pocket hematoma and thromboembolic events. Secondary outcomes included any device-pocket hematoma, all-cause mortality, major bleeding, and any bleeding. A total of 1,607 patients from 8 studies were included. The mean age was 73.2years, with atrial fibrillation as the indication for DOAC therapy in most patients. The mean CHA2DS2-VASc was 3.4. Among the included studies, 2 were randomized control trials (RCTs), while the others were observational cohort studies, including one that was propensity score matched. Our meta-analysis found both strategies to be similar in terms of clinically significant pocket hematoma (RR 1.70; 95%CI 0.84-3.45; p = 0.14; I2 = 0%), thromboembolic complications (RR 0.35; 95%CI 0.04-3.32; p = 0.36; I2 = 19%), any pocket hematoma, all-cause mortality and any bleeding with a higher risk of major bleeding with uninterrupted anticoagulation. This meta-analysis shows that uninterrupted DOAC therapy is comparable to interrupted therapy for CIED procedures, with a potential increase in major bleeding risk but low overall complication rates. Further research is needed to confirm the best approach of periprocedural anticoagulation in these patients.

Early Palliative Care in Advanced Non-Small Cell Lung Cancer Patients: A Meta-Analysis.

This study aims to assess the efficacy of Early Palliative Care (EPC) in non-small cell lung cancer (NSCLC) through a meta-analysis approach. A computerized search was conducted in databases such as PubMed, Cochrane Library, Scopus, Embase, and Web of Science for prospective randomized controlled trials (RCTs) investigating the application of EPC in advanced NSCLC. Outcome measures including Overall Survival (OS), quality of life, and psychological status were extracted and subjected to pooled analysis. After the computerized search, a total of 7 studies comprising 1185 participants were included, with 597 patients receiving EPC intervention and 588 patients receiving Standard Care (SC) intervention. Three studies reported OS after the intervention, demonstrating a significant improvement in OS for patients receiving EPC (pooled HR = 1.60, 95% CI: 1.22, 1.98). Five studies analyzed the Functional Assessment of Cancer Therapy (FACT) scores after the intervention, revealing a significant improvement in FACT scores for patients receiving EPC (pooled SMD = 1.18, 95% CI: 1.04, 1.31). No significant differences were found in anxiety and depression scores between the 2 interventions in the 5 studies. In advanced NSCLC, EPC provides benefits in terms of increased survival rates and improved quality of life. EPC should be considered as part of multidisciplinary treatment for patients with advanced NSCLC.

An Overview of Medical, Surgical, and Rehabilitation Outcome Measures Used in Randomized Controlled Trials of Moderate to Severe Traumatic Brain Injury

Abstract Optimal reporting of outcomes is critical for the interpretation of research findings. This review aimed to examine the utilization of outcome measures (OMs) in randomized controlled trials (RCTs) of moderate to severe TBI (MSTBI). Systematic searches were conducted up to December 2022 in MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RCTs were included if the population studied had ≥18 years and ≥ 50% had MSTBI. 662 met inclusion criteria. There was a total of 839 unique OMs across all included RCTs. Of these, only 195 (23.2%) were used in ≥4 RCTs. On average, RCTs included 1.26 OMs (range 1 to 23). A total of 495 (59%) of OMs were classified in the recovery and rehabilitation category, and 344 (41%) in the medical and surgical measures category. There was a more equal representation of OMs in high income countries (HICs) compared to low to middle income countries (LMICs), with the latter using fewer recovery and rehabilitation OMs. OMs used in RCTs of MSTBI have significant heterogeneity and variable clinical relevance, which limits the impact and generalizability of research in MSTBI, and the ability to compare across studies.

Criticism to the revascularization indications attained in the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease

Clinical practice guidelines are valuable tools that guide doctors' conduct in a series of diseases with high prevalence in the population. The 2023 guideline on chronic coronary disease (CCD), written by the American Heart Association and the American College of Cardiology in conjunction with other American entities is no exception to this rule and although it is designed for application in American medical practice, it gains relevance for use in care of patients affected by this disease worldwide 1. The guidelines help healthcare professionals the best decision-making, with the aim of offering the best possible care to patients, aligned with their expectations, needs and interests. Furthermore, they are important documents for governments, payers and healthcare providers by providing a set of recommendations that help and guide decisions about coverage of diagnostic and therapeutic procedures related to diseases with high prevalence in the population. In this 2023 guideline, the authors say that revascularization is an evolving topic and emphasize that recommendations are typically based on the results of larger randomized controlled trials (RCTs), meta-analyses, or both encompassing a wide range of knowledge on the subject. but they recognize that RCTs do not cover all the nuances involved with the topic, nor do they address all issues comprehensively. Based on this, they made a concentrated effort to stay within the strongest evidence to define these revascularization recommendations in patients with CCD. Within this principle, reviewing chapter 5 dedicated specifically to myocardial revascularization, we are concerned, among other things, with the recommendations resulting from the analysis of some studies that do not clearly reflect the reality of contemporary care provided to patients with CCD, in addition to events that do not reflect the primary outcomes of many of these studies. For this reason, we performed a careful review of the most relevant randomized controlled trials (RCTs), systematic reviews and meta-analyses used in the guideline for revascularization recommendations, which impact a significant number of patients affected by CCD worldwide.

Intravenous ketamine versus electroconvulsive therapy for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled trials.

Intravenous (IV) ketamine has been evaluated alongside electroconvulsive therapy (ECT) in addressing major depressive disorder (MDD) or bipolar depression (BD), though the comparative outcomes remain inconclusive. This meta-analysis aimed to provide a systematic assessment of the efficacy, safety, and tolerability of IV ketamine relative to ECT for treating MDD or BD. Randomized controlled trials (RCTs) comparing IV ketamine and ECT in terms of efficacy, safety, and tolerability for MDD or BD were identified and reviewed. Three independent investigators extracted relevant data, which was synthesized using RevMan 5.3 software under a random effects model. Five RCTs encompassing 664 patients diagnosed with MDD or BD were analyzed. At 24 h post-initial treatment, IV ketamine demonstrated a statistically greater reduction in depressive symptoms compared to ECT (standardized mean difference (SMD) = -0.53; 95 % CI = -1.03 to -0.04; P = 0.04; I2 = 80 %). However, no significant differences were observed between groups in terms of the study-defined response (risk ratio (RR) = 1.49; 95 % CI = 0.08 to 28.42; P = 0.79; I2 = 0 %) at 24 h. Similarly, no notable differences were found for depressive symptom improvement (SMD = -0.48; 95 % CI = -2.41 to 1.45; P = 0.63; I2 = 99 %), the study-defined response (RR: 0.96, 95 % CI: 0.70 to 1.31; P = 0.79; I2 = 75 %) or remission (RR: 0.91, 95 % CI: 0.45 to 1.82; P = 0.78; I2 = 90 %) at the end-of-treatment visit. Among the three RCTs (60 %) comparing the neurocognitive outcomes of IV ketamine and ECT through varying test batteries, results were inconsistent. IV ketamine was associated with marked increases in dissociation, blurred vision, dizziness, and diplopia, while ECT led to a significant rise in muscle pain (all Ps < 0.05). Discontinuation rates due to any cause were comparable between both groups (P > 0.05). IV ketamine demonstrates a faster onset of antidepressant effects compared to ECT, despite both treatments yielding comparable outcomes at the end-of-treatment visit for patients with MDD or BD. However, large-scale RCTs are required to thoroughly evaluate the long-term efficacy and safety of IV ketamine relative to ECT in these populations.