Risk Of Bias In Randomized Controlled Trials Research Articles

Sexual side effects of antipsychotic drugs in schizophrenia: Protocol for a systematic review with single-arm, pairwise and network meta-analysis of randomized controlled trials and non-randomized studies

Introduction Sexual dysfunctions are common yet underreported side effects of antipsychotics for schizophrenia, affecting 30-80% of treated individuals. These side effects can severely impact social interactions and treatment adherence for individuals with schizophrenia, but comprehensive comparative evidence assessing the risk profiles of different antipsychotics is lacking. This study aims to address this gap using network meta-analysis that integrates data from both randomized-controlled trials (RCTs) and non-randomized studies (NRS). Protocol This systematic review will include both RCTs and NRS focusing on participants with schizophrenia or schizophrenia-like psychoses, without restrictions on symptoms, gender, ethnicity, age, or setting. For interventions, all second-generation antipsychotics will be included. The primary outcome will be the occurrence of at least one sexual adverse event of any kind. Secondary outcomes will be the occurrence of any sexual adverse event evaluated in men and women separately, and any adverse event related to the three phases of sexual response cycle separately: desire (e.g. libido, sexual thoughts), arousal (e.g. erection, lubrication) and orgasm (e.g. ejaculation, anorgasmia), and any adverse effect related to breast dysfunction and menstruation irregularities. Study selection and data extraction will be performed independently by two reviewers. The Cochrane Risk of Bias tool 1 and ROBINS-I will be employed to evaluate the risk of bias for RCTs and NRS, respectively. Single-arm meta-analysis of proportions will synthesize the average frequency of sexual adverse events in treated participants. Pairwise and network meta-analysis of RCTs and NRS will be used to evaluate comparative tolerability. Subgroup and sensitivity analyses will explore possible heterogeneity in results and validate the findings’ robustness. The quality of the evidence will be evaluated using GRADE. Discussion This study will provide vital insights into the sexual side effects of antipsychotics by combining evidence from clinical trials and real-world practice, facilitating better decision-making in choosing the optimal antipsychotic for individuals.

P-405 Effects of intrauterine perfusion of autologous platelet-rich plasma on recurrent implantation failure in frozen-thawed embryo transfer: a meta-analysis of randomized controlled trials

Abstract Study question We aimed to evaluate the effect of the platelet-rich plasma （PRP) on pregnancy outcomes in patients with RIF undergoing frozen-thawed embryo transfer (FET). Summary answer Intrauterine infusion of PRP might have more beneficial effects on pregnancy outcomes in RIF patients undergoing FET. What is known already Immunological therapies are of great interest to specialists in reproductive medicine. The immune therapies use intrauterine infusion (i.e., PRP, PBMC, G-CSF, and hCG) for endometrial immunomodulation. Despite the limited number of publications available, the results are encouraging. In the network meta-analysis, PRP, PBMC, C-GCSF, and hCG administration all significantly increased embryo implantation and clinical pregnancy compared to controls. Additionally, PRP administration resulted in a higher live birth rate than the control. This year, more research has focused on PRP as an innovative method to treat RIF. Study design, size, duration Medline, Embase, and Cochrane Controlled Register of Trials (CENTRAL) were searched from inception to July 29, 2023. The randomized controlled trials (RCTs) reporting on pregnancy outcomes of women with RIF who were administered PRP undergoing FET were included. We conducted a meta-analysis where possible using a fixed effects model. The Cochrane Handbook was used to assess the risk of bias for RCTs. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Participants/materials, setting, methods Seven RCTs were included with 1,014 RIF women. The final number of women analyzed was 508 with intrauterine infusion PRP and 506 without it. Main results and the role of chance Meta-analysis showed that compared to the controls, the women who received PRP had a significantly higher embryo implantation rate (n = 2, risk ratio (RR) 2.34, 95% CI 1.65 to 3.32; P < 0.00001, I2 = 0%), biochemical pregnancy rate (n = 5, RR 1.94, 95% CI 1.60 to 2.36; P < 0.00001, I2 = 0%), clinical pregnancy rate (n = 7, RR 2.31, 95% CI 1.89 to 2.82; P < 0.00001, I2 = 0%), ongoing pregnancy rate (n = 3, RR 2.70, 95% CI 1.79 to 4.05, P = 0.0004, I2 = 31%), and multiple pregnancy rate (n = 3, RR 2.67, 95% CI 1.07 to 6.68, P = 0.04, I2 = 0%). However, PRP was not attributable to reduce the miscarriage rate (n = 3, RR 1.15, 95% CI 0.40 to 3.35; P = 0.80, I2 = 0%). Limitations, reasons for caution The proportion of small-sample studies included has to some extent affected the validity of the results. There were some variations regarding the PRP preparation process, which may result in a variable composition and concentrations of its different contents. Wider implications of the findings Intrauterine infusion PRP in patients with RIF who underwent FET may improve the pregnancy outcomes assessed in RCTs, including clinical pregnancy and ongoing pregnancy. Therefore, we suggest that PRP be included in endometrial preparation protocols. Trial registration number not applicable

Long-term impact of home-based monitoring after an admission for acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials

Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration's tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger's test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p=0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p=0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p=0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p=0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p=0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p=0.308). In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. None.

The methodological quality of systematic reviews regarding the Core Outcome Set (COS) development

BackgroundThe Core Outcome Measures in Effectiveness Trials (COMET) working group proposed core outcome sets (COS) to address the heterogeneity in outcome measures in clinical studies. According to the recommendations of COMET, performing systematic reviews (SRs) usually was the first step for COS development. However, the SRs that serve as a basis for COS are not specifically appraised by organizations such as COMET regarding their quality. Here, we investigated the status of SRs related to development of COS and evaluated their methodological quality.MethodsWe conducted a search on PubMed to identify SRs related to COS development published from inception to May 2022. We qualitatively summarized the disease included in SR topics, and the studies included in the SRs. We evaluated the methodological quality of the SRs using AMSTAR 2.0 and compared the overall quality of SRs with and without protocols using the Mann-Whitney U test.ResultsWe included 175 SRs from 23 different countries or regions, and they mainly focused on five diseases: musculoskeletal system or connective tissue disease (n = 19, 10.86%), injury, poisoning, or certain other consequences of external causes (n = 18, 10.29%), digestive system disease (n = 16, 9.14%), nervous system disease (n = 15, 8.57%), and genitourinary system disease (n = 15, 8.57%). Although 88.00% of SRs included randomized controlled trials (RCTs), only a few SRs (23.38%) employed appropriate tools to assess the risk of bias in RCTs. The assessment results on the basis of AMSTAR 2.0 indicated that most SRs (93.71%) were rated as ‘’critically low’’ to ‘’low’’ in terms of overall confidence. The overall confidence of SRs with protocols was significantly higher than that without protocols (P <.001). Compared to the SRs with protocols on Core Outcome Measures in Effectiveness Trials (COMET), SRs with protocols on PROSPERO were of better overall confidence (P = .017).ConclusionThe overall quality of published SRs regarding COS development was poor. Our findings emphasize the need for researchers to carefully select the disease topic and strictly adhere to the requirements of optimal methodology when conducting a SR for the establishment of a COS.

Efficacy of adjuvant-associated COVID-19 vaccines against SARS-CoV-2 variants of concern in randomized controlled trials: A systematic review and meta-analysis.

Adjuvants may enhance the efficacy of vaccines. however, the efficacy of adjuvant-associated COVID-19 vaccines (ACVs) remains unclear since the emergence of the COVID-19 pandemic. This study aimed to address this gap by conducting a systematic review and meta-analysis of the efficacy of ACVs against Severe Acute Respiratory Syndrome Coronavirus 2 CoV (SARS-CoV-2) variants of concern (VOC). A systematic search was conducted of randomized controlled trials (RCTs) evaluating the vaccine efficacy (VE) of ACVs against VOC (alpha, beta, gamma, delta, or Omicron), up to May 27, 2023. The DerSimonian-Laird random-effects model was used to assess VE with 95% confidence intervals (CI) through meta-analysis. Cochrane Risk of Bias tools were used to assess the risk of bias in RCTs. Eight RCTs with 113,202 participants were included in the analysis, which incorporated 4 ACVs [Matrix-M (NVX-CoV2373), Alum (BBV152), CpG-1018/Alum (SCB-2019), and AS03 (CoVLP]). The pooled efficacy of full vaccination with ACVs against VOC was 88.0% (95% CI: 83.0-91.5). Full vaccination was effective against Alpha, Beta, Delta, and Gamma variants, with VE values of 93.66% (95% CI: 86.5-100.74), 64.70% (95% CI: 41.87-87.54), 75.95% (95% CI: 67.9-83.99), and 91.26% (95% CI: 84.35-98.17), respectively. Currently, there is a lack of RCT evidence regarding the efficacy of ACVs against the Omicron variant. In this meta-analysis, it should be that full vaccination with ACVs has high efficacy against Alpha or Gamma variants and moderate efficacy against Beta and Delta variants. Notably, with the exception of the aluminum-adjuvanted vaccine, the other ACVs had moderate to high efficacy against the SARS-CoV-2 variant. This raises concerns about the effectiveness of ACVs booster vaccinations against Omicron.

Effectiveness of exercise for improving physical and renal function in older adults with pre-dialysis chronic kidney disease: A systematic review and meta-analysis

Purpose : Exercise may prevent the worsening of chronic kidney disease (CKD) and progression of cardiovascular diseases in patients with CKD. This review aims to identify the best type of exercise modality and summarizes the beneficial effects of exercise on physical and renal function among older adults with pre-dialysis CKD.Methods : A systematic search of PubMed, Embase, CINAHL, Cochrane Library, Web of Science, SCOPUS, and domestic database was performed for randomized controlled trials (RCTs) assessing the effect of exercise intervention on older adults with pre-dialysis CKD published until February 2023. A random-effects metaanalysis was conducted. The risk of bias was assessed using a Cochrane tool for assessing the risk of bias in RCTs (RoB 2.0).Results : The systematic review included 11 RCTs (n = 591, average age 60.2–76), of which 8 could be included for meta-analysis. Exercise was significant in increasing peak oxygen consumption and knee muscle strength among physical functions, and also in improving glomerular filtration rate among kidney functions.Conclusion : Exercise has beneficial effects on physical and renal function among older adults with pre-dialysis CKD. In the future, it is necessary to verify the effectiveness of exercise by subdividing it by type, intensity, duration, and delivery.

The impact of Pilates exercise for depression symptoms in female patients: A systematic review and meta-analysis.

The Pilates exercise has recently become an increasingly popular way of exercise in female patients since it is an attractive and low-cost physical exercise modality. Pilates may be a beneficial method of exercise for female patients with depression and anxiety symptoms. However, to date, there has been no attempt to collate this literature. This review aims to systematically assess and meta-analyze the efficacy of Pilates exercise for female patients with depression and anxiety symptoms and inform evidence-based guidelines for exercise prescription. Five electronic databases (Scopus, MEDLINE/PubMed, Embase, Web of Science, and the Cochrane Library) were systematically searched up to January 2023 to examine randomized controlled trials (RCTs) focused on the effects of Pilates exercise for female patients with depressive disorders and individuals with elevated levels of depression were included. The primary outcomes were the severity of depression, and the secondary outcomes were anxiety. Statistical analyses were performed using Stata version 15.1 software with a 95% confidence interval (Registration number: CRD42023426522), and the PEDRO Scale was used to evaluate the risk of bias for RCT. 18 RCTs with 827 female patients were included. The methodological quality of the RCTs was considered an A level in 4 studies, B level in 13, studies, and C level in 1 study investigation. The meta-analysis showed that there was moderate evidence for the Pilates exercise significantly improved the severity of depression symptoms (SMD = -0.73; 95% CI -0.86 to -0.59; P < .01) and anxiety symptoms (SMD = -0.62; 95% CI -0.79 to -0.46; P < .01). Pilates exercise could reduce levels of depression and anxiety in female patients with depression and anxiety symptoms. Pilates exercise can be used as a potential ancillary program to improve depression and anxiety symptoms for female patients.

Quality evaluation of the literature on randomized controlled clinical trials of traditional Chinese medicine for treatment of gastric precancerous lesions in last 20 years.

To evaluate the methodological quality of randomized controlled trials (RCTs) of traditional Chinese medicines for the treatment of gastric precancerous lesions in the past 20 years. The studies of RCTs on traditional Chinese medicines for gastric precancerous lesions were searched from the Chinese full-text journal database, Wanfang database, VIP database, PubMed, and Embase from January 2001 to December 2021. The retrieved articles were screened, extracted and evaluated based on the 2010 edition of CONSORT statement, Cochrane Risk of Bias Assessment Scale and additional indicators. A total of 840 papers were included. According to the Cochrane Risk of Bias Assessment Scale, the high risk of bias in the application of randomized methods was 5.95%; the concealed risk of uncertainty in the allocation scheme was 98.93%; the low risk of bias for blinding of patients or testers was 1.30%; the risk of bias for blinding of the outcome assessor was 100.00%; the risk of bias for completeness of the outcome data was 2.86%; and the risk of uncertainty for selective reporting was 98.44%. The CONSORT statement evaluating the quality of reporting showed that 100.00% of the RCT articles reported the 8 entries of introduction, objectives and interventions; 36.79% of the literature mentioned the method of randomized sequence generation, but only 27.62% of the literature implemented a randomized program, 1.07% of the literature hid the randomized program and 1.31% of the literature was blinded; 36.67% of the literature reported adverse reactions; no literature reported sample size prediction methods; additional evaluation indicators showed that 17.02% of the studies had ethical approval; 43.81% of the literature specified Chinese medicine evidence; 16.55% of the studies excluded severe heterotrophic hyperplasia; 7.26% of the studies conducted follow-up; and 65.12% of the literature used composite efficacy indicators; 46.67% of the literature applied pathological histological evaluation; 2.62% of the literature applied quality of life evaluation, etc. The overall risk of bias in RCTs of traditional Chinese medicines for gastric precancerous lesions is high, and the quality of most of the study reports needs to be improved. In the future, it is necessary to strengthen the study design of RCTs and refer to appropriate traditional Chinese medicines evidence grading standards, select study protocols according to different purposes, provide objective and strong evidence of clinical studies on traditional Chinese medicines, and carry out clinical study design and result reporting suitable for traditional Chinese medicines according to the CONSORT principle.

Comparative safety of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma: a systematic review and network meta-analysis.

Objective: This study aimed to compare the safety profile of tyrosine kinase inhibitors (TKIs) approved for use as monotherapy or combination therapy for the first-line treatment of adult patients with metastatic clear cell renal cell carcinoma (RCC). Methods: A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials (RCTs) investigating the use of: cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib, cabozantinib + nivolumab, lenvatinib + pembrolizumab, axitinib + avelumab, and axitinib + pembrolizumab in previously untreated adult patients with metastatic clear cell RCC. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The risk of bias for RCTs was assessed using the Cochrane Collaboration tool. The P score was used to determine the treatment ranking. The mean probability of an event along with the relative measures of the NMA was considered with the treatment rankings. Results: A total of 13 RCTs were included in the systematic review and NMA. Sorafenib and tivozanib used as monotherapy were the best treatment options. Sorafenib achieved the highest P score for treatment discontinuation due to adverse events (AEs), fatigue, nausea, vomiting of any grade, and hypertension of any grade or grade ≥3. Tivozanib achieved the highest P score for AEs, grade ≥3 AEs, dose modifications due to AEs, and grade ≥3 diarrhea. Sunitinib was the best treatment option in terms of diarrhea and dysphonia of any grade, while cabozantinib, pazopanib, and axitinib + pembrolizumab-in terms of grade ≥3 fatigue, nausea, and vomiting. TKIs used in combination were shown to have a poorer safety profile than those used as monotherapy. Lenvatinib + pembrolizumab was considered the worst option in terms of any AEs, grade ≥3 AEs, treatment discontinuation due to AEs, dose modifications due to AEs, fatigue of any grade, nausea, vomiting, and grade ≥3 nausea. Axitinib + avelumab was the worst treatment option in terms of dysphonia, grade ≥3 diarrhea, and hypertension, while cabozantinib + nivolumab was the worst option in terms of grade ≥3 vomiting. Interestingly, among the other safety endpoints, cabozantinib monotherapy had the lowest P score for diarrhea and hypertension of any grade. Conclusion: The general safety profile, including common AEs, is better when TKIs are used as monotherapy vs. in combination with immunological agents. To confirm these findings, further research is needed, including large RCTs.

Duplex ultrasound for surveillance of lower limb revascularisation.

Duplex ultrasound for surveillance of lower limb revascularisation.

Peripheral Nerve Block and Peri-operative Neurocognitive Disorders in Older Patients With Hip Fractures: A Systematic Review With Meta-analysis.

Poor pain control and opioid use are risk factors for perioperative neurocognitive disorders (PND). The peripheral nerve block (PNB) can reduce pain and opioid consumption. This systematic review aimed to investigate the effects of PNB on PND in older patients with hip fractures. The PubMed, Cochrane Central Registers of Controlled Trial, Embase and ClinicalTrials.gov databases were searched from inception until November 19, 2021 for all randomized controlled trials (RCTs) comparing PNB with analgesics. The quality of the selected studies was assessed according to Version 2 of the Cochrane tool for assessing the risk of bias in RCTs. The primary outcome was the incidence of PND. Secondary outcomes included pain intensity and the incidence of postoperative nausea and vomiting. Subgroup analyses were based on population characteristics, type and infusion method of local anesthetics, and type of PNB. Eight RCTs comprising 1015 older patients with hip fractures were included. Compared with analgesics, PNB did not reduce the incidence of PND in the elderly hip fracture population comprising patients with intact cognition and those with pre-existing dementia or cognitive impairment (risk ratio [RR] = .67; 95% confidence interval [CI] = .42 to 1.08; P = .10; I2 = 64%). However, PNB reduced the incidence of PND in older patients with intact cognition (RR = .61; 95% CI = .41 to .91; P = .02; I2 = 0%). Fascia iliaca compartment block, bupivacaine, and continuous infusion of local anesthetics were found to reduce the incidence of PND. PNB effectively reduced PND in older patients with hip fractures and intact cognition. When the study population included patients with intact cognition and those with pre-existing dementia or cognitive impairment, PNB showed no reduction in the incidence of PND. These conclusions should be confirmed with larger, higher-quality RCTs.

Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Zinc supplementation has been explored as a potential intervention to reduce the risk of malaria parasitaemia in randomised controlled trials (RCTs). However, inconsistent evidence has been obtained regarding the efficacy of zinc supplementation in the context of malaria prevention. This systematic review was implemented to survey the existing literature to determine the effects of the daily oral administration of zinc, either alone or in combination with other nutrient supplements, on the risk of malaria parasitaemia. The systematic review was prospectively registered in the PROSPERO database CRD42023424345 and followed PRISMA protocols. A comprehensive search was conducted across multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar, from their inception until 6 May 2023. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool 2 (RoB 2). The effect sizes, represented as risk ratios (RRs) with 95% confidence intervals (CIs), were standardised by transforming them into log RRs and then pooling them using a fixed-effects or random-effects model depending on the heterogeneity across studies. Comparisons were made between individuals who received zinc alone or zinc in combination with other micronutrient supplements and those who did not receive zinc. A total of 1339 articles were identified through the database searches, and after the screening and selection process, 10 studies were included in the final synthesis. The meta-analysis revealed that zinc supplementation alone did not significantly affect the risk of malaria parasitaemia compared with placebo (p = 0.30, log RR = 0.05, 95% CI: -0.05-0.15, I2 = 0.00%, with 566 malaria cases in the zinc intake group and 521 malaria cases in the placebo group). However, the analysis demonstrated a borderline significant effect of zinc supplementation in combination with other micronutrients on the risk of malaria parasitaemia compared with placebo (p = 0.05, log RR = 1.31, 95% CI: 0.03-2.59, I2 = 99.22%, with 8904 malaria cases in the zinc intake group and 522 malaria cases in the placebo group). The findings of this systematic review indicate that zinc supplementation, either alone or combined with the supplementation of other micronutrients such as vitamin A, iron, or multiple nutrients, does not significantly alter the risk of malaria parasitaemia. Further research with larger sample sizes is warranted to explore the potential effects of multi-nutrient supplementation and to identify more specific micronutrients and additional factors associated with the risk of malaria, rather than just zinc alone, among individuals in different malaria-endemic areas.

Efficacy of high dose tranexamic acid (TXA) for hemorrhage: A systematic review and meta-analysis

Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population. We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias usingthe Cochrane Risk of Bias for RCTs and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31ml less, 95% CI 135.53 to 48.90ml less, low certainty), and an uncertain effect on thromboembolic events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70, 95% CI 0.37 to 1.32, very low certainty). When compared to standard dose, high dose IV TXA probably reduces transfusion requirements with an uncertain effect on thromboembolic events and mortality. Systematic review and meta-analysis, level IV.

Efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients: a meta-analysis of randomized controlled trials

BackgroundIntranasal midazolam and ketamine have been widely used as sedative premedication in children. It is difficult to determine which one yields better sedative effects for clinical practice. We conducted the present meta-analysis by summarizing the evidences to evaluate the efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients.MethodsWe searched PubMed, Embase, and Cochrane Library from inception to April 2022. All randomized controlled trials (RCTs) used intranasal midazolam and ketamine as sedatives in children were enrolled. The risk of bias in RCTs was assessed by Cochrane risk of bias tool. Condition of parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as the outcomes in our study.ResultsA total of 16 studies with 1066 patients were enrolled. Compared with midazolam, administration of intranasal ketamine might be associated with severer changes in hemodynamics parameters including mean blood pressure (SMD = -0.53, with 95% CI [-0.93, -0.13]) and heart rate (HR) (SMD = -1.39, with 95% CI [-2.84, 0.06]). Meanwhile, administration of intranasal midazolam was associated with more satisfactory sedation level (61.76% vs 40.74%, RR = 1.53, with 95%CI [1.28, 1.83]), more rapid onset of sedation (SMD = -0.59, with 95%CI [-0.90, -0.28]) and more rapid recovery (SMD = -1.06, with 95%CI [-1.83, -0.28]). Current evidences also indicated that the differences of various adverse effects between two groups were not significant.ConclusionsGiven that administration of midazolam via intranasal route provides more satisfactory sedative level with less fluctuation of hemodynamics parameters and more rapid onset and recovery, it might be considered as the preferred sedative premedication for pediatric patients compared to ketamine. However, the widespread evidences with low or moderate quality indicated that superiority of intranasal midazolam in pediatric sedation needs to be confirmed by more studies with high quality and large sample size in future.Trial registrationThe protocol of present study was registered with PROSPERO (CRD42022321348).

The Efficacy and Safety of Tolvaptan in Heart Failure Patients with Congestive Signs: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective: The aim of this study was to investigate the efficacy and safety of tolvaptan, as well as the impact of its treatment dose and duration in heart failure patients with congestive signs. Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched to collect data from all randomized controlled trials (RCT) examining the efficacy and safety of tolvaptan in heart failure patients with congestive signs compared with placebo or blank control until March 4, 2021. Urine volume, change in body weight, improvement in dyspnea, and reduction of edema were evaluated as efficacy indicators. All-cause mortality, worsening heart failure, and adverse events were considered safety indicators. The quality of eligible publications was assessed using the Cochrane risk of bias for RCTs. Results: Ten RCTs with 5,980 patients were included in this analysis. Compared with control, tolvaptan significantly reduced weight in the short term (day 1, 7 RCTs, weighted mean difference (WMD): –1.09, 95% confidence interval (CI): –1.27 to –0.91; day 2, 2 RCTs, WMD: –1.67, 95% CI: –3.00 to –0.33; day 7, 4 RCTs, WMD: –0.95, 95% CI: –1.25 to –0.66), increased urine volume (WMD: 1,825.72, 95% CI: 1,438.38–2,213.07), and relieved dyspnea (risk ratio (RR): 1.12, 95% CI: 1.05–1.19) without increasing the mortality rate (RR: 0.96, 95% CI: 0.87–1.06). Furthermore, the weight loss and increase in urine volume were not dose-dependent effects, and prolonged medication did not lead to sustained weight loss. In addition, there seemed to be more adverse events (RR: 1.17, 95% CI: 1.03–1.32) after treatment with tolvaptan. Further analysis revealed that patients treated with tolvaptan were more likely to report thirst (RR: 6.09, 95% CI: 3.37–11.00) and dry mouth (RR: 6.36, 95% CI: 4.09–9.90), as well as develop hypernatremia (RR: 12.76, 95% CI: 3.52–46.32). Conclusions: The meta-analysis shows that tolvaptan can improve congestion with no increase in mortality rate, but should be used to guard against adverse events. Deserve to be mentioned, the number of RCTs included was limited, suggesting that the observed results should be interpreted with caution. Additional robust clinical studies are warranted to validate the present findings.

Network Meta-Analysis of Trials Testing If Home Exercise Programs Informed by Wearables Measuring Activity Improve Peripheral Artery Disease Related Walking Impairment.

Background: This study aimed to investigate whether home exercise programs informed by wearable activity monitors improved walking ability of patients with peripheral artery disease (PAD). Methods: A systematic literature search was performed to identify randomised controlled trials (RCT) testing home exercise that were or were not informed by wearable activity monitors. The primary outcome was the change in walking distance measured by a six-minute walking test or treadmill test over the course of the trial. Network meta-analysis (NMA) was performed using the gemtc R statistical package. The risk of bias was assessed using Cochrane tool for assessing risk of bias in RCTs (RoB 2.0). Results: A total of 14 RCTs involving 1544 participants were included. Nine trials used wearable activity monitors to inform the home exercise program tested, while five trials did not use wearable activity monitors to inform the home exercise program tested. Overall quality assessment showed 12 trials to be at low risk of bias and two trials at high risk of bias. Home exercise programs informed by wearable activity monitors significantly improved walking distance compared to non-exercise controls (Mean difference, MD: 32.8 m [95% credible interval, CrI: 6.1, 71.0]) but not compared to home exercise programs not informed by wearable activity monitors (MD: 4.7 m [95% CrI: −38.5, 55.4]). Conclusions: Home exercise informed by wearable activity monitors improve walking ability of patients with PAD. It is, however, unclear if activity monitoring informed exercise programs are more effective than exercise programs not using activity monitors.

Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BackgroundVinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn’t find conclusive evidence favoring its use, two more RCTs have also been completed.MethodsRelevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration’s tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson’s I2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger’s test. We used a random effect model when I2 was more than 50% and a fixed-effect model for other parameters.ResultsFour placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65–0.99 and relative risk 0.67, CI 0.48–0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03–0.95 and SMD 1.22, CI 0.23–2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02–1.82, p = 0.04).ConclusionsVinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12028-022-01499-y.

Anticoagulants for people hospitalised with COVID-19.

Anticoagulants for people hospitalised with COVID-19.

Comparing estrogen-based hormonal contraceptives and hormone therapy on bone mineral density in women with premature ovarian insufficiency: a systematic review.

Premature ovarian insufficiency (POI) is a condition associated with estrogen deficiency which leads to decreased bone mineral density and an increased risk of osteoporosis and fractures. Estrogen-based hormone therapy is an integral component of treatment; however, to date the ideal hormone formulation for optimizing bone health has not been established. To assess the effects of estrogen-based oral contraceptives (OCP) versus hormone therapy (HT) on bone mineral density (BMD) in women with POI. A systematic review of Ovid MEDLINE, EMBASE, Cochrane Library, and Web of Science databases was conducted from conception until December 2020. Randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. Risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale for cohort studies and the Cochrane Risk of Bias for RCTs. The study protocol was registered with the International Prospective Register of Systematic Reviews and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Our search yielded 1,227 studies; 3 RCTs and 2 observational cohort studies met inclusion criteria and were included in our study. The largest subpopulation was Turner Syndrome (n = 625), followed by idiopathic POI (n = 146). Of the four studies that assessed changes in BMD, two studies reported a significant increase in lumbar spine BMD with HT compared with OCP (+0.050 g/cm2, P < 0.025; +0.019 g/cm2, P < 0.01), one study found similar improvement in lumbar spine BMD across treatments (HT -0.003 g/cm2, P = 0.824), and one study did not directly compare treatments. Effects on bone turnover markers were inconsistent across three studies that evaluated this outcome. This is the first systematic review to include studies that directly compared OCP and HT on bone outcomes in POI. While two studies reported increased lumbar spine BMD with HT, this result was not consistently found across studies. There were important differences in POI etiology, treatment regimens and formulations, and risk of bias was high in many of the studies. These results indicate future, larger-scale trials are needed to further understand the optimal hormone therapy for bone density in POI.

Therapeutic Effects of the Pilates Method in Patients with Multiple Sclerosis: A Systematic Review.

The Pilates Method is a rehabilitation tool with verified benefits in pain management, physical function, and quality of life in many different physiotherapy areas. It could be beneficial for patients with multiple sclerosis (pwMS). The aim of the study was to summarize current evidence for the effectiveness of Pilates in pwMS. A comprehensive search of Cinahl, Scopus, Web of Science, PEDro, and PubMed (including PubMed Central and Medline) was conducted to examine randomized controlled trials (RCT) that included Pilates intervention in multiple sclerosis. The PEDro scale and the Cochrane risk-of-bias tool, RoB-2, were used to evaluate risk of bias for RCT. Twenty RCT (999 patients) were included. Ten were of good quality (PEDro), and seven had low risk of bias (RoB-2). Pilates improves balance, gait, physical-functional conditions (muscular strength, core stability, aerobic capacity, and body composition), and cognitive functions. Fatigue, quality of life, and psychological function did not show clear improvement. There was good adherence to Pilates intervention (average adherence ≥ 80%). Cumulative data suggest that Pilates can be a rehabilitation tool for pwMS. High adherence and few adverse effects were reported. Future research is needed to develop clinical protocols that could maximize therapeutic effects of Pilates for pwMS.