Randomized Controlled Trials Trials Research Articles

Efficacy and safety of neuroendoscopy surgery versus craniotomy for supratentorial intracerebral hemorrhage: an updated meta-analysis of randomized controlled trials.

Neuroendoscopy (NE) surgery emerged as a promising technique for the treatment of spontaneous intracerebral hemorrhage (ICH). A previous meta-analysis of randomized controlled trials (RCTs) analyzed the efficacy and safety of NE compared to craniotomy, but NE did not present a significant improvement in functional outcomes. However, a new study provided an opportunity to update the current knowledge. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCTs reporting NE evacuation of spontaneous supratentorial ICH compared to craniotomy. The efficacy outcomes of interest were favorable functional outcome, functional disability, hematoma evacuation rate, and residual hematoma volume. The safety outcomes of interest were rebleeding, infection, and mortality. Seven RCTs were included containing 879 patients. The NE approach presented a significantly higher rate of favorable functional outcome compared with craniotomy (RR: 1.42; 95% CI 1.17, 1.73; p < 0.001). The evacuation rate was higher in patients who underwent the NE approach (MD: -8.36; 95% CI -12.66, -4.07; p < 0.001). NE did not show a benefit in improving the mortality rate (RR: 0.81, 95% CI 0.54, 1.22; p = 0.32). NE was associated with more favorable functional outcomes and lower rates of functional disabilities compared to craniotomy. Also, NE was superior regarding evacuation rate, while presenting a reduction in residual hematoma volume. NE might be associated with lower infection rates. Mortality was not improved by NE surgery. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy and safety of NE compared to craniotomy.

Efficacy of mitral valve repair in combination with coronary revascularization for moderate ischaemic mitral regurgitation: a systematic review and meta-analysis of randomized controlled trials.

The efficacy of mitral valve repair (MVR) in combination with coronary artery bypass grafting (CABG) for moderate ischaemic mitral regurgitation (IMR) remains unclear. To evaluate whether MVR + CABG is superior to CABG alone, the authors conducted a systematic review and meta-analysis of existing randomized controlled trials (RCTs). The authors searched PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for eligible RCTs from the date of their inception to October 2023. The primary outcomes were operative (in-hospital or within 30 days) and long-term (≥ 1 year) mortality. The secondary outcomes were postoperative stroke, worsening renal function (WRF), and reoperation for bleeding or tamponade. The authors performed random-effects meta-analyses and reported the results as risk ratios (RRs) with 95% CIs. Six RCTs were eligible for inclusion. Compared with CABG alone, MVR + CABG did not increase the risk of operative mortality (RR, 1.244; 95% CI, 0.514-3.014); however, it was also not associated with a lower risk of long-term mortality (RR, 0.676; 95% CI, 0.417-1.097). Meanwhile, there was no difference between the two groups in terms of postoperative stroke (RR, 2.425; 95% CI, 0.743-7.915), WRF (RR, 1.257; 95% CI, 0.533-2.964), and reoperation for bleeding or tamponade (RR, 1.667; 95% CI, 0.527-5.270). The findings of this meta-analysis suggest that MVR + CABG fails to improve the clinical outcomes of patients with moderate IMR compared to CABG alone.

Evaluation of quality and quantity of randomized controlled trials in hepatobiliary surgery: A scoping/mapping review.

To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.

The effect of negative pressure wound therapy on the outcome of diabetic foot ulcers: A meta-analysis.

Negative pressure injury is one of the auxiliary methods of treating diabetes foot ulcers. It has been shown to be superior to conventional techniques in randomized controlled trials (RCTs). Nevertheless, the results of observational research are still scarce. A systematic review of RCTs and observations was carried out to evaluate the effectiveness and security of negative pressure wound therapy (NPWT) treatment for diabetes foot ulcers. Three English e-databases have been found for NPWT research. The meta-analyses of the comparative studies provided point estimates of results. Intermediate results were given as median and binary values were given in the form of odds ratios (OR). Seventeen trials, 13 RCTs and four randomized, controlled trials were found in the survey. Of these, 831 were treated with NPWT, 834 were treated with standard therapy. A total of 14 studies have been conducted to investigate the influence of NPWT on the healing of diabetic foot ulcers(DFU). In the study, NPWT was shown to speed up the healing of the wound in DFU patients(OR, 2.57; 95% CI, 1.72, 3.85 p < 0.0001). A subgroup analysis showed that NPWT was associated with an acceleration of the wound healing rate in 10 RCT trials (OR, 2.48; 95% CI, 1.58, 3.89 p < 0.001). In the four nRCT trials, NPWT was also shown to speed up the healing of the wound(OR, 2.95; 95% CI, 1.03, 8.42 p = 0.04). In 11 studies, the influence of NPWT on amputations of diabetes mellitus (DM) foot ulcers was investigated. The results showed that NPWT was associated with a reduction in amputations (OR, 0.53; 95% CI, 0.37, 0.74 p = 0.0002).In a subgroup of RCT trials, nine RCT trials showed a reduction in amputations(OR, 0.61; 95% CI, 0.43, 0.87 p = 0.007). In both nRCT trials, NPWT also showed a reduction in amputations (OR, 0.03; 95% CI, 0.00, 0.24 p = 0.001). Generally speaking, NPWT can help to heal the wound and lower the risk of amputations in people with diabetes. The subgroup analysis showed similar results for the RCT and non-RCT trials. NPWT can be used to treat diabetes foot ulcers caused by diabetes.

Impact of minimally invasive surgical procedures for Male Lower Urinary Tract Symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review.

Surgical treatments for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are affected by potentially bothersome side effects on sexual, and, above all, ejaculatory function. Several minimally invasive techniques have been proposed in the last years in order to overcome these consequences. Our aim is to summarize and evaluate the efficacy on LUTS relieve and the impact on sexual/ejaculatory function of Rezum, prostate artery embolization (PAE), implantation of a prostatic urethral lift (PUL) and the temporary implantable nitinol device (TIND). A systematic review of the English-language literature was conducted using the MEDLINE, Embase, and Web of Science databases from January 2000 to October 2022, according to the PRISMA guidelines (PROSPERO ID: CRD42023466515). Randomized controlled trials(RCTs), prospective studies and non-comparative or comparative studies assessing the impact on functional and ejaculatory function after minimally invasive surgical therapies for Male LUTS were evaluated. Risk of bias assessment was performed according to the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for comparative studies, and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs. Overall, 47 studies were included (n = 4 for TIND; n = 9 for Rezum; n = 13 for PUL; n = 21 for PAE). Most studies relied on prospective patient cohorts and were rated as low risk of bias. Across studies assessing the efficacy of Rezum, a significant improvement in terms of IPSS (ranging from -47% to -56%) and Qmax (ranging from +39% to +87%) was reported. On the other hand, according to IIEF-5 score, Rezum had a minimal impact on sexual function (ranging from -1% to -3%). PUL showed a positive impact on IPSS (ranging from -35% to -58.2%) and Qmax (ranging from +49.9% to +114.7%) and sexual function. Finally, PAE showed encouraging functional results with IPSS score reducing from -12.8% to 63.3% and Qmax improving from +8% to 114.9% but the available evidence regarding the potential impact of PAE on sexual outcomes were limited. Rezum, PAE, PUL and TIND are safe and feasible techniques associated with a significant functional improvement. While available data suggest a minimal impact of Rezum and PUL on ejaculatory function, the evidence after PAE and TIND are still limited. Therefore, our review lays the foundation for further research aiming to identify the criteria to select best candidates for uMIST to tailor the management in light of specific patient- and disease- factors.

INTENTION TO TREAT ANALYSIS IN CLINICAL RESEARCH: BASIC CONCEPTS FOR CLINICIANS.

This review presents a comprehensive summary and critical evaluation of Intention to Treat (ITT) analysis, with a particular focus on its application to randomized controlled trials (RCTs) within the field of rehabilitation. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a methodological review that encompassed electronic and manual search strategies to identify relevant studies. Our selection process involved two independent reviewers who initially screened titles and abstracts and subsequently performed full-text screening based on established eligibility criteria. Additionally, we included studies from manual searches that were already cataloged within the first author's personal database. The findings are synthesized through a narrative approach, covering fundamental aspects of ITT, including its definition, common misconceptions, advantages, disadvantages, and key recommendations. Notably, the health literature offers a variety of definitions for ITT, which can lead to misinterpretations and inappropriate application when analyzing RCT results, potentially resulting in misleading findings with significant implications for healthcare decision-making. Authors should clearly report the specific ITT definition used in their analysis, provide details on participant dropouts, and explain upon their approach to managing missing data. Adherence to reporting guidelines, such as the Consolidated Standards of Reporting Trials (CONSORT) for RCTs, is essential to standardize ITT information, ensuring the delivery of accurate and informative results for healthcare decision-making.

Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

The prevalence of osteoporosis is increasing in the United States. To evaluate low bone mass and osteoporosis treatments to prevent fractures. Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare. American College of Physicians. (PROSPERO: CRD42021236220).

Evaluation and Treatment of Vulvodynia: State of the Science.

Vulvodynia affects 7% of American women, yet clinicians often lack awareness of its presentation. It is underdiagnosed and often misdiagnosed as vaginitis. The etiology of vulvodynia remains unknown, making it difficult to identify or develop effective treatment methods. The purpose of this article is to (1) review the presentation and evaluation of vulvodynia, (2) review the research on vulvodynia treatments, and (3) aid the clinician in the selection of vulvodynia treatment methods. The level of evidence to support vulvodynia treatment varies from case series to randomized controlled trials (RCTs). Oral desipramine with 5% lidocaine cream, intravaginal diazepam tablets with intravaginal transcutaneous electric nerve stimulation (TENS), botulinum toxin type A 50 units, enoxaparin sodium subcutaneous injections, intravaginal TENS (as a single therapy), multimodal physical therapy, overnight 5% lidocaine ointment, and acupuncture had the highest level of evidence with at least one RCT or comparative effectiveness trial. Pre to posttest reduction in vulvar pain and/or dyspareunia in non-RCT studies included studies of gabapentin cream, amitriptyline cream, amitriptyline with baclofen cream, up to 6 weeks' oral itraconazole therapy, multimodal physical therapy, vaginal dilators, electromyography biofeedback, hypnotherapy, cognitive behavioral therapy, cold knife vestibulectomy, and laser therapy. There is a lack of rigorous RCTs with large sample sizes for the treatment of vulvodynia, rendering it difficult to determine efficacy of most treatment methods. Clinicians will be guided in the selection of best treatments for vulvodynia that have the highest level of evidence and are least invasive.

Underreporting of patient-reported outcomes in cystic fibrosis randomized controlled trials using CONSORT-PRO and RoB 2.0

BackgroundPatient-reported outcomes (PROs) are increasingly used in randomized controlled trials (RCTs) to foster patient-centered healthcare. The aim of this investigation was to assess the completeness of reporting of PROs in RCTs pertaining to cystic fibrosis (CF). MethodsWe searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for RCTs concerning CF that included PROs as a primary or secondary outcome. The RCTs were assessed by 2 independent investigators using an adaptation of the Consolidated Standards of Reporting Trials for Patient-Reported Outcomes (CONSORT-PRO) and the Cochrane Risk of Bias (RoB) 2.0 assessment. We calculated the mean completion percentage of adherence to the CONSORT-PRO adaptation and used bivariate regression models to evaluate for associations with particular trial characteristics. ResultsOur systematic search returned 2302 potential studies. Fifty-nine eligible RCTs were included after full-text screening. The RCT mean completeness of reporting was 38.38% (SD = 12.74). We found the following associations between trial characteristics and completeness of PRO reporting: (1) significantly higher reporting completeness for RCTs published in journals requiring adherence to the CONSORT guideline (p-value = 0.049), (2) improved reporting completeness in studies with ‘some concerns’ of RoB versus ‘high’ RoB (p-value = 0.042), and (3) significantly better reporting completeness when the PRO is the primary outcome of a RCT (p-value = 0.006). ConclusionInadequate PRO reporting exists within RCTs focused on CF. Given that CF has substantial effects on quality of life, PROs are imperative to understand patients’ experiences. We believe greater adherence to CONSORT-PRO will promote the standardization of PRO reporting and will facilitate comprehension of PROs by stakeholders, patients, and clinicians.

Early coronary angiography in patients after out-of-hospital cardiac arrest without ST-segment elevation: Meta-analysis of randomized controlled trials.

To compare early coronary angiography to a delayed or selective approach in out-of-hospital cardiac arrest (OHCA) without ST-segment elevation of possible cardiac cause by means of meta-analysis of available randomized controlled trials (RCTs). We searched MEDLINE and the Cochrane Central Register of Controlled Trials for RCTs comparing early with delayed or selective coronary angiography in OHCA patients of possible cardiac origin without ST-segment elevation. The primary endpoint was all-cause short-term mortality (PROSPERO CRD42021271484). The search strategy identified three RCTs enrolling a total of 1167 patients. An early invasive approach was not associated with improved short-term mortality (odds ratio 1.19, 95% confidence interval 0.94-1.52; p = 0.15). Further, no significant differences were shown with respect to the risk of severe neurological deficit, the composite of all-cause mortality or severe neurological deficit, need for renal replacement therapy due to acute renal failure, and significant bleeding at short-term follow-up. Early coronary angiography in OHCA without ST-segment elevation is not superior compared to a delayed/selective approach.

The Efficacy of Vitamin D Supplementation in the Treatment of Fibromyalgia Syndrome and Chronic Musculoskeletal Pain.

Fibromyalgia syndrome (FMS) and chronic widespread musculoskeletal pain (CMP) are diffuse suffering syndromes that interfere with normal activities. Controversy exists over the role of vitamin D in the treatment of these diseases. We carried out a systematic literature review of randomized controlled trials (RCT) to establish whether vitamin D (25OHD) deficiency is more prevalent in CMP patients and to assess the effects of vitamin D supplementation in pain management in these individuals. We searched PubMed, Physiotherapy Evidence Database (PEDro), and the Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published in English from 1 January 1990 to 10 July 2022. A total of 434 studies were accessed, of which 14 satisfied the eligibility criteria. In our review three studies, of which two had the best-quality evidence, a correlation between diffuse muscle pain and 25OHD deficiency was confirmed. Six studies, of which four had the best-quality evidence, demonstrated that appropriate supplementation may have beneficial effects in patients with established blood 25OHD deficiency. Eight studies, of which six had the best-quality evidence, demonstrated that 25OHD supplementation results in pain reduction. Our results suggest a possible role of vitamin D supplementation in alleviating the pain associated with FMS and CMP, especially in vitamin D-deficient individuals.

Routine vaginal examinations compared to other methods for assessing progress of labour to improve outcomes for women and babies at term.

Routine vaginal examinations compared to other methods for assessing progress of labour to improve outcomes for women and babies at term.

Does Certainty of Genuine Treatment Increase the Drug Response in Alzheimer's Disease Patients: A Meta-Analysis and Critical Discussion.

Non-specific treatment effects, such as expectations, contribute to the effectiveness of pharmacological treatments across diseases. However, the contribution of expectancy, i.e., certainty of receiving treatment, in patients with Alzheimer's disease (AD) is unknown. The aim is to investigate whether certainty of receiving a genuine treatment influences the response to active treatment in AD patients. The efficacy of active treatments in open-label trials, where patients are certain of receiving treatment (100%certainty), was compared to the same active treatments in randomized controlled trials (RCT), where patients are uncertain of receiving treatment or placebo (50%certainty). In the seven open-label trials, there was no significant difference between post- and pre-treatment scores (difference in means = 0.14, 95%CI [-0.51; 0.81], p = 0.66). In the eight RCT trials, there was a significant difference between post- and pre-treatment (difference in means = -0.91, 95%CI [-1.43; -0.41], p < 0.001). There was a statistically significant difference between open-label and RCT trials (difference = 1.06, 95%CI [0.23; 1.90], p = 0.001). Patients with AD did not benefit from certainty of receiving genuine treatment. This could be due to the nature/progression of the disease, but it could also be related to an order effect in the practice of running AD trials, where RCTs are conducted prior to open label. These findings have implications for the understanding of non-specific treatment effects in AD patients as well as for the design of clinical trials that test pharmacological treatments in AD.

Community-Based Assessment and Treatment of Hepatitis C Virus-Related Liver Disease, Injecting Drug and Alcohol Use Amongst People Who Are Homeless: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug use (IDU) and alcohol use amongst people who are homeless (PWAH). Using systematic review methodology, databases were searched (MEDLINE/EMBASE/CINAHL) for studies combining PWAH, HCV-related liver disease and community assessment until December 2019. Studies with a sample size ≥ 30, with PWAH constituting at least 30% of the cohort were included and a quality assessment performed. Pooled estimates of key indicators were analysed using meta-analysis. We identified 39 studies (n=13,918), 37 categorised as poor quality (Newcastle-Ottawa Scale). Prevalence of homelessness ranged between 30%-100% (37 studies). Eight studies provided all of the following: HCV screening, alcohol/substance use/liver fibrosis assessment and HCV treatment. No study provided interventions for alcohol use, with two providing opioid substitution treatment. Alcohol use prevalence (24 studies) was 4%-97%, being 59% (95% CI 20%-92%) in four studies that included only PWAH. Recent IDU prevalence (16 studies) was 7%-73%, being 21% (95% CI 17%-26%) in four studies that included only PWAH. HCV seroprevalence (25 studies) was 2.5% - 58%; in 13 studies that included only PWAH, this was 20% (95% CI 12%-30%). Prevalence of F4 fibrosis (nine studies) was 6%-28%, being 7% and 16% in two studies that included only PWAH. Direct acting antiviral-based intention-to-treat sustained virological response (SVR) rates (five studies) were 82%-92%, being 92% in the one study that included only PWAH. In the only two randomised controlled trials (RCT) identified, community-based interventions (mental health/peer mentor) significantly increased linkage to care (p=0.04), HCV treatment (p=0.005) and SVR rates (p=0.018). The burden from alcohol/IDU and HCV, and consequently liver disease in PWAH needs addressing. RCT trials assessing community-based interventions to improve liver health in PWAH are needed.

Effectiveness and safety of dual antiplatelet therapy in coronary aneurysms caused by Kawasaki disease in children: study protocol for a multicenter randomized clinical trial.

BackgroundMedium or large coronary artery aneurysm (CAA) is a serious complication of Kawasaki disease (KD) and may cause thrombosis, coronary artery stenosis, and even myocardial infarction at different stages of the disease. Dual antiplatelet therapy (aspirin plus clopidogrel) is considered for prophylaxis of coronary thrombosis in KD presenting with more than medium CAAs based on adult coronary artery disease experience and expert consensus. This paper describes the study protocol for a randomized controlled trial that measures the clinical effectiveness and safety of dual antiplatelet therapy in the thromboprophylactic treatment of KD.MethodsThe present study is a multicenter, open-label, randomized controlled trial (RCT) with a 12-month follow-up. KD patients with medium or large CAAs (Z-value ≥5), evaluated by echocardiogram and clinicians before treatment, are randomized in a 1:1 ratio and assigned to aspirin therapy alone (Control group), or dual antiplatelet (aspirin plus clopidogrel) therapy (Experimental group). Antiplatelet therapy is given to the KD patients from the time of diagnosis until the coronary artery returns to normal. Weekly or monthly follow-up visits are conducted to record compliance, recovery, and biochemical indicators and continue for one year. The primary outcome is the incidence of thrombus throughout the disease and the effective of dual antiplatelet. The secondary outcomes are the safety of dual antiplatelet drugs, platelet-related indicators, inflammatory indicators, biochemical indexes and drug-related indicators during the study period. Patients who do not meet the inclusion criteria of the RCT trial or those unwilling to provide informed consent enter the registration trial.DiscussionThis is the first study to evaluate the effectiveness and safety of dual antiplatelet therapy in coronary aneurysms caused by Kawasaki disease in children. It is hoped that this study will play an important and significant role in improving the prognosis and long-term quality of life for children with KD complicated by CAAs.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019181. Registered on Oct 30, 2018.

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data Sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. Study Selection: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. Data Extraction: Mortality was assessed using Mantel-Haenszel models, and I² was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I². Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. Data Synthesis: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; p < 0.001; I² = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], p < 0.001; I² = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; p = 0.02; I² = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], p = 0.99; I² = 64%), CPFA (OR 0.50 [0.10–2.47]; p = 0.40; I² = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; p = 0.69; I² = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. Conclusion: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials

Thrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52-0.85, p = 0.001), cardiovascular mortality (OR 0.44, 95% CI 0.22-0.89, p = 0.02), and MI (OR 0.70, 95% CI 0.51-0.96, p = 0.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45-1.35, p = 0.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24-0.81, p = 0.008), including DVT (OR 0.41, 95% CI 0.26-0.65, p < 0.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40-2.15, p = 0.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47-2.74, p = 0.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.

Effect of Acupuncture Intervention and Manipulation Types on Poststroke Dysarthria: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the effect of acupuncture intervention and manipulation types on poststroke dysarthria. Electronic database, including PubMed, CENTRAL, Scopus, RISS, and CNKI, were searched for randomized controlled trials (RCT), treating dysarthria using acupuncture, speech-language therapy (SLT), and general management (GM), published before April 2019. The number, distribution, intensity, depth, and repetition of acupuncture and bleeding therapy on the sublingual veins were considered as manipulation types. Risk of bias of the included trials was evaluated, and their efficacy was assessed using risk ratio (RR) and the standard mean differences in the Frenchay Dysarthria Assessment and Speech Function Grading, with 95% confidence intervals (CIs).Fifteen RCT trials involving 1453 patients were isolated. Electroacupuncture plus SLT and manual acupuncture plus SLT were more effective than SLT only, respectively (RR = 1.520, 95% CI [1.183–1.952], RR = 1.380, 95% CI [1.281–1.488]). The clinical efficacy of acupuncture plus GM was higher than that of GM alone (RR = 1.165, 95% CI [1.050–1.293]). Meta-ANOVA showed that none of the manipulation types increased the clinical efficacy of acupuncture on dysarthria. The methodological quality was low. In conclusion, our study suggests that the effect of acupuncture on poststroke dysarthria may be maximized when manual acupuncture or electroacupuncture is combined with SLT, irrespective of manipulation types.

Comparative Analysis of 9 COVID-19 Convalescent Plasma Protocols Registered by Cochrane Central Register of Controlled Trials

Context: Coronavirus disease 2019 (COVID-19) has progressed into a public health emergency of international concern. Passive immunotherapy has been successfully used for the treatment of infectious diseases since the 1890s. It is necessary and constructive to compare and analyze COVID-19 convalescent plasma (CCP) randomized controlled trials (RCTs) to help clinicians to have a potential option for COVID-19. Evidence Acquisition: In this study, eight databases were searched on May 1, 2020, such as China National Knowledge Infrastructure, PubMed, and Cochrane Library, with the search fields of "Title Abstract Keyword" of "Convalescent plasma AND COVID-19" or " Convalescent plasma AND SARS-CoV-2". The outcome of interest was clinical RCTs for COVID-19. Results: The search retrieved nine relevant CCP protocols for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All nine trials were randomized, parallel assignment, interventional, clinical treatment studies with NCT04344535, NCT04345289, and NCT04323800 masking and the rest open-label. The estimated enrollment is within the range of 40-1,500 subjects, and five trials will be finished in 2020 as opposed to two in 2021 and two in 2022. Except for NCT04323800 on the prevention of COVID-19, other eight trials will test and verify the effectiveness and safety of CCP for the treatment of COVID-19. The used dosage of CCP is within the range of 200-600 mL. NCT04344535, NCT04323800, and NCT04346446 use standard donor plasma in controlled groups in comparison to NCT04348656, NCT04342182, NCT04333251, and NCT04345523 without any positive drug in controlled groups. NCT04332835 adds hydroxychloroquine to both groups, and only NCT04345289 is a six-armed placebo-controlled trial. Primary and secondary outcome measures are differently expressed in the nine trials. Nevertheless, they can be summarized as ㈠ changes in time, day, and number of a 7-point ordinal scale. There are ㈡ changes in SARS-CoV-2 ribonucleic acid (i.e., viral load), anti-SARS-CoV-2 antibody titers (i.e., immunoglobulin M and immunoglobulin G), C-reactive protein, lymphocyte count, lactate dehydrogenase, and interleukin 6 on a specified day or during a specific period. Conclusion: The nine well-designed RCT trials will establish the efficacy of CCP for the treatment of SARS-CoV-2 from the perspective of evidence-based medicine.

Differences in patient characteristics and external validity of randomized clinical trials on pain management following total hip and knee arthroplasty: a systematic review

BackgroundThe external validity of randomized controlled trials (RCTs) is critical for the relevance of trial results in a clinical setting. We aimed to assess the external validity of RCTs investigating...