Multicenter Randomized Controlled Trials Research Articles

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<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<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.

When 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. We 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. FR 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. FR 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.

Equal Treatment, Unequal Outcomes? Debunking the Racial Disparity in Renin Angiotensin Aldosterone System Inhibitor Associated Reduction in Heart Failure Hospitalizations

BackgroundRenin angiotensin aldosterone system inhibitors (RAASi) are a mainstay treatment in patients with heart failure with reduced ejection fraction (HFrEF) in part to prevent hospitalizations. However, whether RAAS inhibitors reduce the risk of hospitalization in Black patients is not entirely clear because enrollment of Black patients in previous clinical trials was low, and a previous meta-analysis showed a significant racial disparity: reduction in hospitalizations with an RAAS inhibitor in White patients but not Black patients. Previous studies relied on the use of self-identified race instead of genomic ancestry. Therefore, this study aimed to investigate the role of self-identified race and genomic ancestry in the racial disparity in RAAS inhibitor associated reductions in HFrEF hospitalizations. MethodsThe primary outcome was time to first heart failure hospitalization. A (de-identified) heart failure patient registry and data from the GUIDE-IT multi-center randomized control trial were analyzed with Cox proportional hazards models un/adjusted for clinical risk factors, death as a competing risk, and time-varying RAAS inhibitor exposure. The proportion of Yoruba African ancestry was quantified.. Analysis of self – identified race were performed in both the registry and GUIDE-IT. Analysis of genomic ancestry was only performed in the registry since this information was not available in GUIDE-IT. A fixed effect meta-analysis combined results of both the registry and GUIDE-IT for race. ResultsThe registry had 1010 total HFrEF patients (Black = 509 and White = 501) with 852 having ancestry quantification (>80% Yoruba African Ancestry = 381 and <5% Yoruba African Ancestry = 471). GUIDE-IT had 810 HFrEF patients (Black = 322 and White = 488). There was no significant difference in the association of RAAS inhibitor exposure with heart failure hospitalization by race (meta-analysis p-value for race*RAAS inhibitor exposure interaction = 0.49; Black patients HR [95% CI] for RAAS inhibitor exposure = 0.89 [0.64-1.23)] P = 0.47; White patients = 1.20 (0.83-1.75) P = 0.34). Results were similar when analyzed by ancestry (p-value for ancestry*RAAS inhibitor exposure interaction = 0.57; >80% Yoruba African Ancestry = 0.93 [0.51-1.69] P = 0.80; <5% Yoruba African Ancestry = 1.29 [0.57-2.92] P = 0.54). ConclusionsIn contrast to a previous meta-analysis, this more contemporary analysis of 2 HFrEF patient datasets demonstrates the absence of a racial disparity in RAAS inhibitor associated reductions in heart failure hospitalizations. The difference in this racial disparity over time may be due to improvements in background heart failure therapies, racial differences in healthcare usage, and the use of more advanced statistical approaches.

Frailty as a sequela of burn injury: a post hoc analysis of the “RE-ENERGIZE” multicenter randomized-controlled trial and the National Health Interview Survey

BackgroundWith advancements in burn treatment and intensive care leading to decreased mortality rates, a growing cohort of burn survivors is emerging. These individuals may be susceptible to frailty, characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging, which significantly complicates their recovery process. To date, no study has investigated burns as a potential risk factor for frailty. This study aimed to determine the short-term prevalence of frailty among burn survivors’ months after injury and compare it with that of the general population.MethodsA post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury (RE-ENERGIZE) trial, an international randomized-controlled trial involving 1200 burn injury patients with partial- or full-thickness burns. Participants who did not complete the 36-Item Short Form Health Survey (SF-36) questionnaire were excluded. Data for the general population were obtained from the 2022 National Health Interview Survey (NHIS). Frailty was assessed using the FRAIL (Fatigue, Resistance, Ambulation, Illness, Loss of weight) scale. Due to lack of data on loss of weight, for the purposes of this study, malnutrition was used as the fifth variable. Illness and malnutrition were based on admission data, while fatigue, resistance, and ambulation were determined from post-discharge responses to the SF-36. The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status. Within the burn group, patients were divided into different subgroups based on their frailty status, and the differences in their (instrumental) activities of daily living (iADL and ADL) were compared. A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.ResultsOut of the 1200 burn patients involved in the study, 600 completed the required questionnaires [follow-up time: (5.5 ± 2.3) months] and were matched to 1200 adults from the general population in the U.S. In comparison to the general population, burn patients exhibited a significantly higher likelihood of being pre-frail (42.3% vs. 19.8%, P < 0.0001), or frail (13.0% vs. 1.0%, P < 0.0001). When focusing on specific components, burn patients were more prone to experiencing fatigue (25.8% vs. 13.5%, P < 0.0001), limited resistance (34.0% vs. 2.7%, P < 0.0001), and restricted ambulation (41.8% vs. 3.8%, P < 0.0001). Conversely, the incidence rate of illness was observed to be higher in the general population (1.2% vs. 2.8%, P = 0.03), while no significant difference was detected regarding malnutrition (2.3% vs. 2.6%, P = 0.75). Furthermore, in comparison with robust burn patients, it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL. The frail cohort reported the most pronounced limitation.ConclusionsOur findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury. Burn survivors experience compromised fatigue, resistance, and ambulation, while rates of illness and malnutrition were lower or unchanged, respectively. These results underscore the critical need for early identification of frailty after a burn injury, with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists, community physicians, physiotherapists, nutritionists, and social workers. This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.

SP1.2 - Laparoscopic versus Robotic ventral hernia repair: a systematic review and meta-analysis comparing the perioperative outcomes randomised controlled trials

Abstract Objective The objective of this meta-analysis is to compare the perioperative surgical outcomes and cost-effectiveness of robotic incisional/ventral hernia repair (RIVHR) versus laparoscopic incisional/ventral hernia repair (LIVHR). Methods Randomised control trials (RCTs) reporting perioperative outcomes and costs in patients undergoing RIVHR versus LIVHR were selected from medical electronic databases and meta-analysis was conducted under the guidelines of the Cochrane Collaboration using statistical software RevMan version 5. Results Four RCTs on 337 patients reporting perioperative outcomes and cost comparison were included. In the random effect model analysis, the duration of operation [standardized mean difference (SMD) -48.07, 95%, CI (-78.06, -18.07), z = 3.14, p = 0.002] was shorter and cost was lower [SMD 0.82, 95%, CI (-1.48, -0.16), z = 2.45, p = 0.01] in the LIVHR group but with significant statistical heterogeneity. However, the variables of hernia recurrence [risk ratio (RR) 2.29, 95%, CI (0.73, 7.12), z = 1.43, p = 0.15] and surgical site complications [RR 0.85, 95%, CI (0.48, 1.50), z = 0.55, p = 0.58] were statistically similar in both groups without any statistical heterogeneity among the included studies. Conclusion The RIVHR does not offer any superiority over LIVHR in all perioperative variables and it is not cost effective. Due to the paucity of the RCTs, a major multi-centre RCT is needed to validate these findings.

SP4.6 - Endoscopic versus laparoscopic management of pancreatic pseudocyst - A systematic review and meta-analysis

Abstract Objective The aim of this meta-analysis is to compare the postoperative surgical outcomes of endoscopic versus laparoscopic management of pancreatic pseudocyst. Methods Two randomised control trials (RCTs) and four comparative trials reporting postoperative outcomes for patients undergoing treatment with endoscopic transgastric or transduodenal drainage versus laparoscopic cyst-gastrectomy or cyst-jejunostomy for the pancreatic pseudocyst were selected from medical electronic databases and meta-analysis was conducted by the guidelines of the Cochrane Collaboration using statistical software RevMan version 5.4. Results Two RCTs and four comparative trials on 401 patients reporting postoperative outcomes were included. In the random effect model analysis, the overall success rate [odds ratio (OR) 0.81, 95%, CI (0.38, 1.72), Z = 0.54, P = 0.59] was comparable between the two groups with no heterogeneity among the included studies. Adverse events after the procedure was also comparable between the two groups [OR 0.72, 95%, CI (0.34, 1.50), Z = 0.89, P = 0.37] with no heterogeneity among the included studies. Hospital stay was shorter in the endoscopic group [Mean difference -2.71, 95%, CI (-4.14, -1.27), Z = 3.69, P = 0.0002] with high statistical heterogeneity among the included studies. Conclusion The patients managed with endoscopic procedures had shorter hospital stay, but the incidence of adverse post-procedure outcomes and overall success rate were comparable between the two groups. Due to the paucity of the RCTs, a major multi-centre RCT is needed to strengthen the findings of this systematic review.

SP2.11 - Continuous versus interrupted closure of midline laparotomy wound with absorbable suture material - A systematic review and meta-analysis of randomised controlled trials

Abstract Objective The objective of this meta-analysis is to compare the postoperative surgical outcomes of continuous versus interrupted closure of the midline laparotomy wound with absorbable suture material. Methods Randomised control trials (RCTs) reporting postoperative outcomes for patients undergoing closure with continuous versus interrupted closure of midline laparotomy wound with absorbable suture material were selected from medical electronic databases and meta-analysis was conducted by the guidelines of the Cochrane Collaboration using statistical software RevMan version 5. Results Four RCTs on 2,198 patients reporting postoperative outcomes were included. In the random effect model analysis, the wound dehiscence [odds ratio (OR) 0.93, 95%, CI (0.52, 1.64), Z = 0.26, P = 0.79] was comparable between the two groups with no heterogeneity among the included studies. Incisional hernia was also comparable between the two groups [OR 0.82, 95%, CI (0.59, 1.14), Z = 1.19, P = 0.23] with mild heterogeneity among the included studies. Wound infection was also comparable between the two groups [OR 1.30, 95%, CI (0.78, 2.17), Z = 1.01, P = 0.31] with moderate statistical heterogeneity among the included studies. Conclusion The continuous suturing closure had no superiority over interrupted closure for the midline laparotomy wound on comparing wound dehiscence, incisional hernia and wound infection. Due to the paucity of the RCTs, a major multi-centre RCT is needed to validate these findings.

WP1.7 - A systematic review and a meta-analysis of randomised control trials of prophylactic ilioinguinal neurectomy versus ilioinguinal nerve preservation for open inguinal hernia repair

Abstract Objective The objective of this meta-analysis is to compare the outcomes of prophylactic ilioinguinal neurectomy versus ilioinguinal nerve preservation for open inguinal hernia repair. Methods Studies reporting the patient outcomes were selected from medical electronic databases and meta-analysis was conducted by following the guidelines of the Cochrane Collaboration using statistical software RevMan version 5. Results Seven studies on 1,333 patients reporting post-operative outcomes were included. In the random effect model analysis, the severe pain at the end of the follow-up period [odds ratio (OR) 0.45, 95%, CI (0.10, 2.08), Z = 1.03, p = 0.30] was similar in both the groups with high heterogeneity (Tau2 = 0.97; Chi2 = 4.45, df = 1 (P = 0.03; I2 = 78 %) among included studies. Hypoesthesia at 6-month follow-up period [odds ratio 1.00, 95%, CI (0.47, 2.15), Z = 0.00, p = 1.00] suggests comparable outcomes in both groups with no heterogeneity among the included studies. The absence of pain reported by patients at the 6-month follow-up period [odds ratio 0.96, 95%, CI (0.72, 1.27), Z = 0.28, P = 0.78] suggests comparable outcomes in both groups with no heterogeneity among the included studies. Conclusion Post-operative outcomes like chronic groin pain, hypoesthesia or no pain reported by patients were similar in both groups. There was a paucity of data, therefore a major multicentre randomised control trial is recommended to strengthen the findings of this meta-analysis.

ThP7.13 - A systematic review of the perioperative outcomes of surgical fixation versus conservative approach for severe rib fractures

Abstract Objective The objective of this meta-analysis is to compare the patient outcomes for severe rib fractures being managed by operative or non-operative treatment. Methods Studies reporting patient outcomes in patients undergoing surgical fixation or conservative approach were selected from medical electronic databases and meta-analysis was conducted by following the guidelines of the Cochrane Collaboration using statistical software RevMan version 5. Results Three studies on 258 patients reporting patient outcomes were included. In the random effect model analysis, the total hospital stay [mean difference -1.44, 95%, CI (-2.88, 0.00), Z = 1.96, p = 0.05] was comparable between the two groups with no heterogeneity among included studies. The intensive care stay [mean difference -2.36, 95%, CI (-5.92, 1.21), Z = 1.30, p = 0.20] and mortality [odds ratio 1.08, 95%, CI (0.11, 10.31), Z = 0.07, p = 0.94] was comparable between the two groups but with moderate heterogeneity among included studies. Pneumonia was more common in patients of the non-operative group [odds ratio 0.35, 95%, CI (0.15, 0.82), Z = 2.41, p = 0.02] with no heterogeneity among included studies. Conclusion Pneumonia was more common in patients in the patients managed with the conservative approach. Other patient outcomes were comparable between the two groups. Due to the paucity of data, multiple other crucial variables could not be assessed and a major multi-centre randomised control trial is needed to confirm the findings of this meta-analysis.