Multicenter Randomized Controlled Trials Research Articles

The effectiveness of dry needling for plantar fasciitis: a systematic review and meta-analysis

ObjectiveTo evaluate the effectiveness of dry needling (DN) on pain and functional outcomes in patients with plantar fasciitis (PF).MethodsPubMed, Embase, the Cochrane Library, EBSCO, web of science, physiotherapy Evidence Database (PEDro) were searched for randomized control trials (RCTs) evaluating the effectiveness of dry needling on plantar fasciitis. Article screening, data extraction and risk-of-bias evaluation were independently performed by two reviewers. Meta-analysis was conducted based on different control methods and assessment time using RevMan 5.3 software.ResultsA total of 12 RCTs involving 781 patients were included in the systemic review and meta-analysis. The comparison of DN + routine treatments vs. routine treatments alone demonstrated that PF patients receiving DN have significantly lower scores in Visual Analog Scale / Numerical Pain Rating Scale (VAS/NPRS) [95%CI (−2.12, −1.76), p < 0.0001], and the scores of Foot Function Index (FFI) [95%CI (−12.57, −3.58), p = 0.004]. In the comparison of DN vs. other treatments, results showed that DN significantly lowered the scores of FFI [95%CI (−6.55, −1.09), p = 0.006]. However, there was no significant difference in pain improvement between DN and other treatments [95%CI (−0.66, 0.06), p = 0.10]. In the meta-analysis based on different assessment time, results showed that there was significant difference in the scores of VAS/NPRS within 1 month, at 1 month and at over 1 month. But there was no significant difference in the scores of FFI within 1 month, while at 1 month and at over 1 month, the scores of FFI were lowered in patients receiving DN, and the difference were statistically significant.ConclusionDry needling is effective in relieving pain and restoring function in patients with plantar fasciitis. Furthermore, dry needling may take at least 1 month to take effects in patients with plantar fasciitis. More multi-center RCTs with high-quality, large sample size are needed to further conform our conclusion.

The role of healthcare professionals’ communication in trial participation decisions: a qualitative investigation of recruitment consultations and patient interviews across three RCTs

BackgroundAlthough the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients’ participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions.MethodsThree pragmatic UK-based multicentre RCTs were purposively sampled to provide contrasting clinical specialities. Data collection was integrated into each RCT, including audio-recordings of patient recruitment consultations and interviews with patients. Where possible, consultation audio-recordings were linked to interviews to explore how information communicated by recruiters was interpreted and used by patients during their decision-making. Data were analysed thematically, using the constant comparison approach.ResultsTwenty audio-recorded recruitment consultations were obtained across the 3 RCTs, combined with 42 interviews with patients who had consented to or declined RCT participation. Consultation and interview data were ‘linked’ for 17 individual patients. Throughout the patient’s clinical pathway, HCPs (both those involved in the RCT and not) influenced patients’ perceptions of treatment need and benefit by indicating that they preferred a particular treatment option for the patient as an individual. Whilst patients valued and were influenced by information conveyed by HCPs, they also drew on support from other sources and ultimately framed RCT participation decisions as their own. Patients’ willingness to be randomised hinged on perceptions of whether they stood to benefit from a particular treatment and the availability of those treatments outside of the trial.ConclusionThis study supports the need for training and support for healthcare professionals involved throughout the clinical pathway of patients eligible for RCTs, as all healthcare professionals who interact with patients have the potential to influence their perceptions of treatments being compared in the trial.Trial registrationOPTIMA ISRCTN42400492. Prospectively registered on 26 June 2012.Prepare for Kidney Care ISRCTN17133653. Prospectively registered on 31 May 2017.MARS 2 ISRCTN44351742. Retrospectively registered on 5 September 2018.

Acupuncture for atopic dermatitis: a systematic review and meta-analysis

ObjectivesAtopic dermatitis is a chronic, relapsing, inflammatory skin disease that impacts patients’ quality of life and imposes substantial economic burdens on their families. Acupuncture holds promise as a viable treatment...

Comparative efficacy of Chinese tonic medicines for treating sepsis or septic shock: A systematic review and Bayesian network meta-analysis of randomized controlled trials

BackgroundSepsis or septic shock is a life-threatening medical emergency with a poor prognosis and a high economic burden for both individuals and healthcare resources. Evidence suggests that Chinese tonic medicines (CTMs), as adjuvant treatments, are effective in treating this disease. Nevertheless, the ongoing discourse regarding the optimal CTMs persists. This study was conducted to further explore the comparative effectiveness of CTMs for patients with sepsis or septic shock. MethodsWe systematically searched Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP database from inception to November 15, 2023. Primary outcomes encompassed the delta Sequential Organ Failure Assessment (ΔSOFA) score at day 7 after interventions and 28-day mortality. Secondary outcomes included delta serum lactate (ΔLac) and delta mean arterial pressure (ΔMAP) levels at day 7 after interventions, as well as the duration of vasoactive drug administration. The safety outcome was adverse drug reactions or adverse drug events (ADRs/ADEs). The risk ratio (RR) and mean difference (MD) with a 95 % confidence interval (95 %CI) were selected as effect measures. The Bayesian network meta-analysis was conducted by R version 4.2.2 software. The surface under the cumulative ranking curve (SUCRA) values were used to rank each treatment. The Cochrane Risk of Bias V.2.0 tool was employed to assess the within-study risk of bias. The CINeMA (Confidence in Network Meta-Analysis) web application was utilized to assess the quality of evidence. This protocol was prospectively registered in PROSPERO (CRD4202348572). ResultsA total of 45 randomized controlled trials (RCTs) involving 3433 patients were identified in this study. Seven CTMs including Shenfu injection (SF), Shenmai injection (SM), Sini decoction (SN), Shenfu and Shengmai granules (SF+SGM), Shengmai injection (SGM), Yiqifumai injection (YQFM), and Shenqifuzheng injection (SQFZ) were involved. Regarding the ΔSOFA score, interventions combining SM with Western medicine (WM) (MD, −2.77; 95 %CI, −3.28 to −2.27), YQFM+WM (MD, −1.76; 95 %CI, −2.73 to −0.79), SGM+WM (MD, −1.11; 95 %CI, −1.88 to −0.34), and SF+WM (MD, −0.98; 95 %CI, −1.17 to −0.78) demonstrated superiority over WM alone. According to the SUCRA values, SM+WM (99.28 %) achieved the highest ranking for the ΔSOFA score. Concerning 28-day mortality, SM+WM (RR, 0.51; 95 %CI, 0.35 to 0.72) and SF+WM (RR, 0.73; 95 %CI, 0.65 to 0.83) exhibited a superior effect in reducing 28-day mortality. Based on the SUCRA values, SM+WM (82.49 %) secured the top ranking for 28-day mortality. Among the secondary outcomes, SM+WM (MD, −2.50; 95 %CI, −4.15 to −0.83; SUCRA, 94.27 %) emerged as the most favorable in reducing serum lactate levels. SF+WM (MD, 10.78; 95 %CI, 3.11 to 18.71; SCURA, 78.3 %) exhibited superior effectiveness compared to other treatments in improving mean arterial pressure (MAP). The certainty of evidence for these outcomes was assessed as low. ConclusionCTMs combined with WM led to a significant improvement in ΔSOFA score and MAP, as well as a reduction in 28-day mortality and serum lactate levels. SM+WM emerged as the optimal treatment regimen for enhancing ΔSOFA, reducing 28-day mortality, and lowering serum lactate levels. Additionally, SF+WM exhibited superiority in improving MAP. Nevertheless, there is a need for large-scale, multicenter, and direct comparative RCTs to generate higher-quality evidence.

Electroacupuncture versus 5-HT4 receptor agonist for functional constipation: A systematic review and meta-analysis of randomized controlled trials.

Functional constipation (FC) has been found as a chronic gastrointestinal disease that is commonly diagnosed in patients. However, patients have a low satisfaction level with the treatment of constipation drugs (e.g., 5-HT4 agonists). A meta-analysis was performed to compare the efficacy and safety between electroacupuncture and 5-HT4 agonists. The included study were randomized controlled trials (RCTs), in which EA was used in the experimental group and 5-HT4 receptor agonist was used in the control group. Four English databases (PubMed, Cochrane Library, Web of Science, Embase) and 4 Chinese databases (China National Knowledge Infrastructure, CBM, WanFang, VIP) were searched. Relevant studies retrieved were published before September 30, 2024. The risk of bias was assessed by tool of Cochrane and GRADEpro. The Review Manager 5.4 was used for analyzing Data analysis, and Endnote X9 for screening studies. In this paper, we included 12 studies, involving 1473 participants. We found that EA significantly improved patient assessment of cab quality of life questionnaire (PAC-QOL) (MD = -0.52, P = .03), self-rating anxiety scale (SAS) (MD = -3.00, P < .00001) and self-rating depression scale (SDS) (MD = -4.13, P < .00001) compared with 5-HT4 receptor agonists. In addition, we failed to identify any significant difference in Stool consistency, the number of weekly complete spontaneous bowel movements and weekly spontaneous bowel movements (SBMs) between the 2 groups. EA has been indicated to be better than 5-HT4 receptor agonists since it can more effectively improve FC patients' life quality and mental state without an increased risk of adverse even. However, the previous evidence is characterized by low quality and small sample size, which should be further confirmed by high-quality and large-sample multicenter RCTs.

Effects of aerobic exercise on hippocampal formation volume in people with schizophrenia – a systematic review and meta-analysis with original data from a randomized-controlled trial

Abstract Background The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications. Methods The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes. Results Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [−0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus. Conclusions Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.

Anorexia nervosa-specific home treatment in children and adolescents and their families (the HoT study): a study protocol of a randomized, controlled, multicenter, open-label, parallel group superiority trial

BackgroundNew treatment approaches are urgently needed to improve the prognosis of children and adolescents with anorexia nervosa (AN). Recently, the feasibility of multidisciplinary home treatment that strongly involves the patients’ parents/caregivers has been investigated. However, no RCT has yet been performed to test the efficacy and safety of this approach compared to standard treatment approaches, such as inpatient treatment.MethodsIn this multicenter randomized-controlled trial, home treatment for children and adolescents with AN aged 12 to 18 years is established at 5 major treatment centers for AN in Germany. Approximately 240 patients who are admitted to the hospital for AN will be included in the trial. After a short inpatient somatic stabilization phase (5–8 weeks), patients are randomized to receive either treatment as usual (TAU), in the form of continued inpatient or day patient treatment, or the newly developed home treatment (HoT) (n = 82/arm, n = 164 in total). There are three assessments throughout treatment (admission, randomization, and discharge), as well as follow-up assessments at 9 and 12 months after admission. The BMI at 12 months after admission (primary outcome) is compared between groups (adjusted for premorbid BMI and admission BMI); secondary outcomes include eating disorder and general psychopathology, the number and duration of psychiatric rehospitalizations, quality of life, motivation for treatment and treatment satisfaction. Other secondary outcomes include the primary caregivers’ burden and skills in handling the child’s illness and direct treatment costs. Statistical analysis will be based on intention-to-treat principles, using mixed models for repeated measures. (Serious) adverse events are assessed throughout treatment. In addition, the feasibility and implementation of HoT as well as the satisfaction and workload of the members of the multidisciplinary treatment teams in both arms will be assessed.DiscussionIn the case of a positive evaluation, HoT can be considered an effective treatment method to replace or complete established treatment methods, such as IP, for treating AN in children and adolescents. The home treatment setting might shorten inpatient stays in this patient group, increase treatment satisfaction, and help to reduce the risk of rehospitalization, which is associated with a better outcome in this vulnerable patient group. Trial registrationThe trial was registered with the German Clinical Trial Register (DRKS) under the ID DRKS00025925 on November 26, 2021 (prospectively registered): https://drks.de/search/de/trial/DRKS00025925.

Abstract 4113561: Efficacy and Outcomes of Empagliflozin in Acute Coronary Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated mortality benefits in patients with heart failure (HF). Since acute coronary syndrome (ACS) is an increasingly prevalent cardiovascular condition that often leads to HF, SGLT2i might play a role in reducing mortality in these patients. Previous randomized controlled trials (RCTs) have demonstrated inconsistent efficacy of Empagliflozin, an SGLT2i, in patients with ACS. Methods: A comprehensive systematic literature search was conducted spanning the major bibliographic databases to retrieve RCTs comparing Empagliflozin to placebo in patients with ACS. Odds ratios (OR) and mean differences (MD) with 95% confidence intervals were pooled using the DerSimonian and Laird random-effects model with statistical significance set at p&lt;0.05. Results: 5 RCTs were included with 7229 ACS patients (3608 in the Empagliflozin group and 3621 in the placebo group). Empagliflozin treatment was not associated with a statistically significant difference in all-cause mortality [OR: 0.94; 95% CI: 0.76, 1.17; p=0.60], cardiovascular death [OR: 1.00; 95% CI: 0.79, 1.28; p=0.99], hospitalization for heart failure [OR: 0.86; 95% CI: 0.42, 1.74; p=0.67], serious adverse events [OR: 1.85; 95% CI: 0.29, 11.87; p=0.51], LVEF on follow-up [MD: 4.35; 95% CI: -4.52, 13.23; p=0.34], NT-ProBNP [MD: -126.02; 95% CI: -279.37, 27.32; p=0.11], estimated glomerular filtration rate [MD: 1.59; 95% CI: -1.35, 4.52; p=0.29], and HbA1c [MD: -0.17; 95% CI: -0.53, 0.20; p=0.38] compared to placebo. Conclusion: This study concludes no statistical difference in all-cause mortality, cardiovascular death, and hospitalization for heart failure with empagliflozin therapy in ACS patients compared to placebo, however, the largest study (EMPACT-MI) had a statistically significant difference in hospitalizations for HF. Further large multicentric RCTs are warranted to validate these findings.

Morbidity and quality of life of totally laparoscopic versus laparoscopy-assisted distal gastrectomy for early gastric cancer: a multi-center prospective randomized controlled trial (CKLASS01).

There is a paucity of confirmatory randomized controlled trials (RCTs) comparing the effectiveness of totally laparoscopic distal gastrectomy (TLDG) vs laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer (EGC). A phase III, prospective, multi-center RCT was conducted, wherein patients (n = 442) with clinical stage I gastric cancer eligible for laparoscopic distal gastrectomy were randomized 1:1 to the TLDG or the LADG group. Postoperative morbidity and quality of life (QoL) were compared. In total, 422 patients were assessed (TLDG, 216; LADG, 206) in the modified intention-to-treat (mITT) analysis. The morbidity rate did not differ significantly between the two groups (TLDG, 6.0%; LADG, 5.8%; P = 0.93). The 90-day mortality rate was comparable between the groups (TLDG, 0.5%; LADG, 0.0%; P > 0.99). TLDG was significantly associated with a lower pain score compared with LADG in patients with a BMI of ≥ 25 kg/m2 (P = 0.002) at 24 h postoperatively. Moreover, TLDG significantly improved QoL in terms of C30 social functioning at 3 and 6 months (P = 0.03 and P = 0.04), C30 global health status at 3 months (P = 0.02), and STO22 body image at 3 months (P = 0.01), with differences dissipating at 12 months. TLDG is not superior to LADG in terms of postoperative morbidity and mortality, but it provides better C30 social functioning at 3 and 6 months, C30 global health status and STO22 body image at 3 months, and reduces early postoperative pain for patients with a BMI of ≥ 25 kg/m2. ClinicalTrials.gov: NCT03393182.

Different minimally invasive surgical methods to hysterectomy for benign gynecological disease: A systematic review and network meta-analysis.

This network meta-analysis aimed to compare the perioperative efficacy of various minimally invasive hysterectomy procedures for treating benign gynecological diseases and to assess whether vaginal natural orifice transluminal endoscopic hysterectomy (VNOTEH), a recently emerging procedure, is inferior to traditional laparoscopy. We searched PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), Wanfang Data, and China VIP Database from inception to August 2022 and updated in June 2023. We included randomized controlled trials (RCTs) comparing different minimally invasive hysterectomy techniques in patients with benign gynecological conditions. The intervention measures included nine minimally invasive hysterectomies. The two researchers used the Cochrane risk-of-bias assessment tool for study appraisal. All statistical analyses and drawings were performed using STATA 17.0 and R 4.4.1. A network meta-analysis (NMA) was conducted to compare the effectiveness of minimally invasive hysterectomy and rank its relative impact probabilistically. A total of 78 RCTs involving 7640 patients and nine minimally invasive hysterectomy methods with 16 intervention combinations were included in this study. Among these, 2, 63, and 13 studies were deemed to have a low, medium, and high risk of bias, respectively. Based on the Surface Under the Cumulative Ranking (SUCRA) probability ranking results of NMA, laparoendoscopic single-site surgery-laparoscopic-assisted vaginal hysterectomy (LESS-LAVH) demonstrated superior outcomes in terms of complications, infections, and 24-h postoperative pain scores. LAVH exhibited better performance in injuries and hospital stays, total laparoscopic hysterectomy showed the least blood loss, and vaginal hysterectomy had the shortest operation time. LESS-LAVH and LAVH are recommended options, if feasible. Meanwhile, VNOTEH can achieve comparable results to traditional laparoscopy but requires careful attention to the risk of injury and infection. Future research should aim to broaden the search scope by including high-quality, large-scale, multicenter RCTs.

From the INVICTUS Trial to Current Considerations: It's Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies-e.g., osocimab, anti-sense oligonucleotides-e.g., fesomersen, and small molecule inhibitors-e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

The impact of exercise training in Fontan procedure patients: a systematic review and meta-analysis

Abstract Background Patients undergoing the Fontan procedure experience long-term complications related to decreased exercise capacity. Exercise training(ET) has emerged as a non-pharmacological solution for increasing cardiorespiratory fitness. However, the effect and safety of exercise training in patients following the Fontan procedure are still unclear. Objectives We aimed to perform a meta-analysis comparing ET versus no exercise intervention for patients following Fontan operation in efficacy and safety outcomes. Methods We systematically searched PubMed, Embase, and Cochrane databases on November 23, 2023, for randomized controlled trials (RCTs) comparing ET, including aerobic, endurance, or inspiratory muscle training, versus no exercise intervention in patients following Fontan operation. We computed mean differences (MD) with a 95% confidence interval (CI) for continuous endpoints. The primary endpoint was (1) peak O2 consumption. Our study also included the secondary endpoints of: (2) maximum workload; (3) peak heart rate(HR); and (4) peak saturation of O2. We performed a subgroup analysis between different exercise therapies. Results This meta-analysis included five RCTs and 154 patients. Follow-up ranged from 3 to 6 months. Regarding ET, two studies used aerobics, one used endurance, and three used inspiratory muscle therapy as exercise therapy for patients with Fontan operations. Our findings on the maximum workload endpoint were more significant for exercise therapy (MD 20.98W; 95% CI 5.32 to 36.65; p&amp;lt;0.01; Fig. 1A) compared to no intervention group. However, there was no significant difference in peak oxygen (MD 2.03 ml/kg/min; 95% CI -0.29 to 4.35; p=0.095; Fig. 1B), peak HR (MD 1.10 bpm; 95% CI -4.07 to 6.27; p=0.68); and peak saturation of O2 (MD 0.39%; 95% CI -1.93 to 2.72; p=0.74). A subgroup analysis between different ET types (aerobic vs. endurance vs. inspiratory muscle training) showed no significant subgroup interaction(p=0.91; Fig. 1B). Conclusion In this meta-analysis, ET is associated with a slight increase in maximum workload in patients following the Fontan procedure. Further multicenter RCTs are warranted to assess the efficacy of comparing different types of ET and their impact on peak oxygen consumption.

Therapeutic efficacy and pharmacological mechanism of Bailing capsule on chronic obstructive pulmonary disease: a meta-analysis and network pharmacology

Context Bailing capsule, derived from Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae), has shown potential in the treatment of chronic obstructive pulmonary disease (COPD), a prevalent respiratory disorder. Objective This study elucidates the efficacy and mechanism of action of the use of Bailing capsules in the treatment of COPD using meta-analysis and network pharmacology. Materials and methods A meta-analysis of randomized controlled trials (RCTs) was performed. The treatment group received Bailing capsules alongside standard therapy, while the control group received standard therapy or in combination with other traditional Chinese medicines. Efficacy outcomes included lung function, exercise tolerance, acute exacerbation risk, and quality of life. Network pharmacology and molecular docking identified key targets of Bailing capsules. Results The meta-analysis of 27 RCTs showed significant improvements in the treatment group for forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and the 6-min walk test (6MWT). Additionally, there was a marked reduction in acute COPD attacks and an improvement in quality of life. Meanwhile, network pharmacological analysis identified SRC, HIF1A, NFKB1, HDAC2, and PRKACA, as the potential core targets for Bailing capsules in the treatment of COPD. Discussion and conclusion Bailing capsules have shown promising results in the treatment of stable COPD. Future studies should focus on large-scale, multicenter RCTs to confirm the long-term benefits and safety of Bailing capsules.

Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.

The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. Adult patients presenting to the emergency department with severe sepsis or septic shock. EGDT vs. usual care. A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

Efficacy and safety of benralizumab in eosinophilic granulomatosis with polyangiitis: A meta-analysis of eight studies.

Eosinophilic granulomatous polyangiitis (EGPA) is a rare autoimmune disease characterized by multisystemic inflammation, with eosinophils playing a central role in its pathogenesis. Traditional management relies heavily on corticosteroids and immunosuppressants, which are associated with significant side effects. The emergence of biologic agents, such as benralizumab, offers targeted therapeutic options by inhibiting the interleukin-5 receptor α, thereby reducing eosinophilic inflammation. This systematic review and meta-analysis comprehensively evaluate the efficacy and safety of benralizumab in EGPA patients, focusing on its ability to reduce oral corticosteroid (OCS) use, facilitate remission and spare immunosuppressants. We searched MEDLINE, LILACS and ISI Web of Science databases for relevant studies up to July 2024. Eight studies, including both randomized controlled trials (RCTs) and observational studies, were included in the meta-analysis, involving a total of 396 EGPA patients. The pooled analysis demonstrated a significant reduction in OCS dose, with an overall estimated effect of -8.25 mg/day (95% CI, -9.39 to -7.10). Complete remission was achieved in 56.8% of patients, and immunosuppressants were reduced or discontinued in 28.1% of cases. Adverse events (AEs) were reported in 21.9% of patients, with only one discontinuation due to an AE. These findings provide robust evidence supporting the use of benralizumab as an effective and well-tolerated treatment option for EGPA, significantly reducing OCS requirements and offering promising remission rates. Future research should focus on larger, multicentre RCTs to confirm these findings and further elucidate the long-term benefits and safety profile of benralizumab in EGPA.

Forced randomization: the what, why, and how

BackgroundWhen running a randomized controlled trial (RCT), a clinical site may face a situation when an eligible trial participant is to be randomized to the treatment that is not available at the site. In this case, there are two options: not to enroll the participant, or, without disclosing to the site, allocate the participant to a treatment arm with drug available at the site using a built-in feature of the interactive response technology (IRT). In the latter case, one has employed a “forced randomization” (FR). There seems to be an industry-wide consensus that using FR can be acceptable in confirmatory trials provided there are “not too many” instances of forcing. A better understanding of statistical properties of FR is warranted.MethodsWe described four different IRT configurations with or without FR and illustrated them using a simple example. We discussed potential merits of FR and outlined some relevant theoretical risks and risk mitigation strategies. We performed a search using Cortellis Regulatory Intelligence database (IDRAC) (www.cortellis.com) to understand the prevalence of FR in clinical trial practice. We also proposed a structured template for development and evaluation of randomization designs featuring FR and showcased an application of this template for a hypothetical multi-center 1:1 RCT under three experimental settings (“base case”, “slower recruitment”, and “faster recruitment”) to explore the effect of four different IRT configurations in combination with three different drug supply/re-supply strategies on some important operating characteristics of the trial. We also supplied the Julia code that can be used to reproduce our simulation results and generate additional results under user-specified experimental scenarios.ResultsFR can eliminate refusals to randomize patients, which can cause frustration for patients and study site personnel, improve the study logistics, drug supply management, cost-efficiency, and recruitment time. Nevertheless, FR carries some potential risks that should be reviewed at the study planning stage and, ideally, prospectively addressed through risk mitigation planning. The Cortellis search identified only 9 submissions that have reported the use of FR; typically, the FR option was documented in IRT specifications. Our simulation evidence showed that under the considered realistic experimental settings, the percentage of FR is expected to be low. When FR with backfilling was used in combination with high re-supply strategy, the final treatment imbalance was negligibly small, the proportion of patients not randomized due to the lack of drug supply was close to zero, and the time to complete recruitment was shortened compared to the case when FR was not allowed. The drug overage was primarily determined by the intensity of the re-supply strategy and to a smaller extent by the presence or absence of the FR feature in IRT.ConclusionFR with a carefully chosen drug supply/re-supply strategy can result in quantifiable improvements in the patients’ and site personnel experience, trial logistics and efficiency while preventing an undesirable refusal to randomize a patient and a consequential unblinding at the site. FR is a useful design feature of multi-center RCTs provided it is properly planned for and carefully implemented.

Anticoagulation Therapy Timing in patients with Atrial Fibrillation after Acute and Chronic Subdural Haematoma (ATTAACH): a pilot randomised controlled trial

IntroductionSubdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding...

Non-invasive remote ischemic preconditioning for patients with heart failure undergoing cardiac catheterization: a network meta-analysis of randomized controlled trials

ObjectiveThis study aimed to evaluate the efficacy of six non-invasive remote ischemic preconditioning (RIPC) interventions during the nursing care of patients with heart failure (HF) prior to cardiac catheterization.MethodsA comprehensive search of nine Chinese and English online databases was conducted from the date of their inception to June 2023 to identify randomized controlled trials (RCTs) investigating RIPC in patients with HF prior to cardiac catheterization. Two independent investigators screened the articles, extracted data, and assessed their quality. The risk of bias was evaluated using the Cochrane risk-of-bias tool, and a network meta-analysis was conducted using R software.ResultsFour trials involving 511 patients with a low risk of bias were included in the analysis. Six non-invasive RIPC interventions were identified, all demonstrating effectiveness in reducing the incidence of contrast-induced acute kidney injury (CI-AKI). Among these, Intervention F (applying up to 50 mmHg above the resting systolic pressure for 5 min to the dominant leg or upper limb, repeated three times with an 18-minute interval) was deemed optimal, although the timing of the procedure was not specified. Intervention D (applying up to 200 mmHg pressure to the upper limb for 5 min, repeated four times with 5-minute intervals, within 45 min prior to cardiac catheterization, ) was considered suboptimal.ConclusionAlthough Intervention D was recommended as the preferred option, none of the four trials examined its impact on the cardiac function of patients with HF. Large-scale, multi-center RCTs are required, with outcome indicators including cardiac function and the occurrence of CI-AKI, to better understand the therapeutic effects of RIPC on HF and reduce the incidence of CI-AKI. This will provide a more robust foundation for clinical practice.

Somatosensory and dynamic balance improvement in older adults with diabetic peripheral neuropathy through sensorimotor exercise: A multisite randomized controlled trial

PurposeTo examine the effect of the Feldenkrais method on lower legs and foot somatosensory postural control-related function, dynamic balance, fear of falling and quality of life in adults with diabetic polyneuropathy in the short and mid-term. MethodsA single-blinded, parallel, multicentric randomized control trial was conducted in two health hospitals. Subjects with diabetic polyneuropathy and older than 55 years with a history of falls or dynamic balance dysfunction were recruited from the hospital databases and randomly allocated to the experimental or control group. The experimental group received 16 sessions of sensorimotor training based on the Feldenkrais method. Both groups received diabetic foot care instructions. The results were measured at the 3 and 6-month follow-up periods. ResultsThe mean age was 70 ± 8. A total of 44 participants were enrolled in the study, and 27 completed the process. No adverse events were reported. After the intervention, significant somatosensory results were obtained (p < 0.001). The results of the Up and Go and POMA tests were significant after the intervention (p < 0.001) and during the 3-month follow-up period for POMA (p = 0.018). The fear of falling showed significant results at the 3-month follow-up period (p = 0.03), and the quality of life in all measurements. ConclusionsSignificant short-term effects were obtained on somatosensory postural control-related function, dynamic balance, and fear of falling. Significant short and mid-term effects were achieved on quality of life. Older adults with diabetic polyneuropathy, dynamic balance impairment, or a history of falls can improve their abilities through the Feldenkrais method. Trial registrationClinicaltrials.gov: NCT05262946.

A multicenter randomized control trial: Point-of-care syndromic assessment versus standard testing in urgent care center patients with acute respiratory illness.

Syndromic assessment with multiplex polymerase chain reaction (mPCR) testing in patients with acute respiratory illness (ARI) allows for simultaneous identification of multiple possible infectious etiologies. Point-of-care (POC) syndromic assessment can be conducted in a clinical setting, such as an urgent care center (UCC), without requiring certified laboratories. The primary objective of this study was to determine whether POC syndromic assessment improved patient satisfaction for patients seen at an UCC with ARI; secondary objectives included whether syndromic assessment reduced self-isolation time, increased diagnostic confidence, and reduced overall antibiotic utilization. We conducted an unblinded multicenter randomized controlled trial on UCC patients with an ARI. Patients were randomized to either SC (defined as standard UCC testing for ARI) or syndromic assessment with POC mPCR. Patients were surveyed for patient satisfaction, self-isolation plans, diagnostic confidence, and overall antibiotic utilization. Among the 360 patients enrolled, those in the syndromic assessment group were more satisfied with the time required to communicate the results (98.4%vs. 42.4%, p<0.001) on day of treatment, more likely to resume normal activities sooner (83.3%vs. 69.4%, p=0.039), and more confident in their illness cause (60.7%vs. 29.6%, p<0.001); however, the rate of antibiotic utilization did not differ (33.5%vs. 26%, p=1.0). In conclusion, our study provides evidence supporting the use of syndromic assessment in UCCs for ARI diagnosis, including patient-centered outcomes such as greater confidence in diagnosis and more efficient isolation strategies. This study did not show a difference in more clinically oriented outcomes, such as a change in antibiotic utilization. Future studies should identify clinical care pathways to improve antibiotic stewardship for likely viral syndromes and whether the increased initial cost of syndromic assessment is offset by the clinical benefits and subsequent cost savings.