Future Randomized Controlled Trials Research Articles

Depression is associated with worse health-related quality of life, lower physical activity levels, and inadequate sleep quality in a Greek elderly population

ABSTRACT The present study is a cross-sectional study that aimed to investigate the potential associations between depression status, health-related quality of life, physical activity levels and sleep quality in a representative Greek elderly population. Three thousand four hundred five (3405) men and women over 65 years old from 14 different Greek regions were enrolled. Geriatric Depression Scale (GDS) was used to assess depression status, Health-Related Quality of Life (HRQOL) was evaluated using Short Form Health Survey, physical activity levels were assessed via the International Physical Activity Questionnaire (IPAQ) and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). A high prevalence of depression and an increased incidence of poor quality of life, low physical activity levels and inadequate sleep quality among the elderly population were recorded. Depression status was independently associated with worse quality of life, poor physical activity, inadequate sleep quality, female gender, BMI and living alone after adjustment for potential confounding factors. Elderly age, low muscle mass, educational and financial status were also identified as indicators of depression; however, their impact on depression status was considerably attenuated after adjusting for confounding factors. In conclusion, depression was associated with worse health-related quality of life, poor physical activity and inadequate sleep quality in a Greek elderly population. Future randomized control trials should be performed to confirm the findings of this cross-sectional study.

A Review: Applications of Chemicals on the Health Aspects of Seborrheic Dermatitis in Coastal Tropical Region

Background: Knee osteoarthritis (KOA) is one of the most common degenerative diseases that can lead to disability and pain. The degenerative nature of this condition cannot be reversed or healed by any currently available treatments. Recently, there has been an upcoming interest in treating degenerative tissue disorders with minimally invasive autologous blood products. Autologous blood was preconditioned with gold particles to encourage the production of various proteins in patients’ blood. This current study investigated the safety and efficacy of pre-conditioning autologous blood with gold particles (GOLDIC®) in patients with severe knee osteoarthritis (KOA). Case presentation We report a case in which four intra-articular GOLDIC® injections were used to treat knee osteoarthritis. After a week, physiotherapy was recommended. Before and three weeks after the injections, she was assessed for her weight, the Visual Analog Scale (VAS), and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score. GOLDIC® treatment resulted in significant weight, VAS, and WOMAC score improvements without serious side effects. Conclusion Due to the one-time blood harvesting and only four injections, the initial results demonstrated that the treatment plan is safe, less expensive, patient-friendly, and more successful at achieving compliance. This GOLDIC® treatment can significantly decrease pain and improve knee capability with overall satisfaction over a significant period. To fully validate the real potential of GOLDIC® in heterogeneous patient populations and to compare these promising results to other blood-based platforms, future randomized-controlled trials with long-term follow-up are required, despite the promising early clinical results.

SPRINT INTERVAL TRAINING IN HYPOXIA AND EXERCISE PERFORMANCE – A SHORT REVIEW

Hypoxia is often used during training to augment metabolic load and heighten physiological adaptations with the aim of exercise performance improvements. The recently established altitude training method »sprint interval training in hypoxia« (SIH) requires individuals to perform multiple 30 s Wingate sprints under hypoxia, interspersed with 3–5 min recovery periods. As the execution of repeated supramaximal efforts in hypoxia does not seem to be compromised, it was hypothesized that SIH might further augment exercise performance compared to sprint interval training in normoxia (SIT). To elucidate the usefulness of hypoxia during sprint interval training for exercise performance a systematic review of the available literature was conducted. The PubMed, SportDiscusTM, and Web of Science online databases were searched for original articles – published up to March 2023 – assessing changes in exercise performance following SIH and SIT. Six studies (randomized controlled trials (RCTs)) were identified, evaluating SIH interventions lasting 2–6 weeks. Currently, the available scientific literature does not suggest that SIH additively augments exercise performance in comparison to SIT. The potential changes in anaerobic thresholds after SIH, but not after SIT require further investigation to fully elucidate the subsequent effects on exercise performance. Nevertheless, there is evidence to support beneficial peripheral adaptations known to increase the oxidative and glycolytic capacity, especially in type II, fast-twitch fibers, following SIH, but not SIT. These local adaptations could potentially enable superior improvement in exercise performance after long enough SIH training protocols. Future RCTs on SIH and, particularly, on the performance-related underlying mechanisms seem warranted.

Calcium Carbonate as a Potential Intervention to Prevent Labor Dystocia: Narrative Review of the Literature.

Anecdotally, there are attestations from clinicians of calcium carbonate being used successfully for laboring people experiencing labor dystocia. The goal of this narrative review was to provide a synopsis of pertinent literature on calcium use in obstetrics to explore the potential benefit of calcium carbonate as a simple and low-cost intervention for prevention or treatment of labor dystocia. To answer how calcium and carbonate physiologically contribute to myometrium contractility, we conducted a literature search of English-language peer-reviewed articles, with no year limitation, consisting of the keywords "calcium," "calcium carbonate," "calcium gluconate," "pregnancy," "hemorrhage," and variations of "smooth muscle contractility" and "uterine contractions." Though no overt evidence on calcium carbonate's ability to prevent labor dystocia was identified; relevant information was found regarding smooth muscle contractility, calcium's influence on uterine muscle contractility, and carbonate's potential impact on reducing amniotic fluid lactate levels to restore uterine contractility during labor. Studies reporting the potential effectiveness of calcium gluconate and sodium bicarbonate in preventing labor dystocia offer background, safety information, and rationale for a future randomized control trial to evaluate the ability of calcium carbonate to prevent labor dystocia and reduce rates of cesarean section.

Outcome of Biological Therapies and Small Molecules in Ulcerative Proctitis: A Belgian Multicenter Cohort Study

Several advanced therapies (biologic therapies and small molecules) have been approved for the treatment of moderate-to-severe ulcerative colitis. The registration trials for these agents typically excluded patients with isolated proctitis, leaving an evidence gap. We evaluated efficacy and safety of advanced therapies in patients with ulcerative proctitis (UP). This multicenter retrospective cohort study included consecutive patients with active UP (Mayo endoscopy subscore of ≥2, rectal inflammation up to 15 cm) initiating advanced therapy, after failing conventional therapy. The primary end point was short-term steroid-free clinical remission (total Mayo score ≤2 with no individual subscore >1). In addition, drug persistence and relapse-free and colectomy-free survival were assessed. Both binary logistic and Cox regression analyses were performed. In total, 167 consecutive patients (52.0% female; median age 41.0 years; 82.0% bionaive) underwent 223 courses of therapy for UP (38 adalimumab, 14 golimumab, 54 infliximab, 9 ustekinumab, 99 vedolizumab, 9 tofacitinib). The primary end point was achieved with 36.3% of the treatment courses, and based on multivariate analysis, more commonly attained in bionaive patients (P= .001), patients treated with vedolizumab (P= .001), patients with moderate endoscopic disease activity (P= .002), and a body mass index <25 kg/m2 (P= .018). Drug persistence was significantly higher in patients treated with vedolizumab (P < .001) and patients with a shorter disease duration (P= .006). No new safety signals were observed. Advanced therapies are also efficacious and safe in patients with ulcerative colitis limited to the rectum. Therefore, the inclusion of patients with UP in future randomized-controlled trials should be considered.

Pilot Randomized, Double-Blind, Placebo-Controlled Crossover Trial Evaluating the Feasibility of an Intranasal Oxytocin in Improving Social Cognition in Individuals Living with Alzheimer's Disease.

Individuals living with Alzheimer's disease (AD) demonstrate extensive deficits in social cognition. To date, no studies have investigated the feasibility of an intranasal oxytocin (INOT) treatment to improve social cognition in individuals living with AD. We conducted a pilot trial to determine recruitment feasibility, enrolment acceptability, and adherence to an INOT treatment to inform on the subsequent design of a future randomized controlled trial (RCT). We also estimated the effect sizes of potential social cognitive function outcome measures related to participants and their caregivers. Four individuals with AD were enrolled in a single-center, randomized, double-blind, placebo-controlled crossover trial involving a one-week treatment period with both INOT (72 IU twice daily) and placebo. All participants reported no treatment-causative or serious adverse events following repeated INOT administration. While enrolment acceptability (100%) and INOT adherence (placebo, 95%; INOT, 98%) were excellent, feasibility of recruitment was not acceptable (i.e., n = 4/58 individuals screened met inclusion criteria). However, positive/large effects were associated with secondary outcomes of self-reported health and wellbeing, caregiver 'burden', intimacy and interpersonal-bonding, following repeated INOT administration. No positive effects were associated with participant outcomes of social cognition. This pilot RCT provides first evidence that INOT administration in individuals living with AD is safe and well-tolerated. Despite limitations in sample size, moderate-to-large effect size improvements were identified in participant health outcomes as well as core social cognitive functions and 'burden' as reported by a caregiver. This suggests potential broad-ranging beneficial effects of INOT which should be assessed in future RCTs.

A Rapid Systematic Review of Pharmacologic Sleep Promotion Modalities in the Intensive Care Unit.

Background: The Society of Critical Care Medicine Clinical Practice Guidelines for Management of Pain, Agitation, Delirium, Immobility, and Sleep recommend protocolized non-pharmacologic sleep improvement. Pharmacologic interventions are frequently initiated to promote sleep but the evidence supporting these strategies remains controversial. Purpose: To systematically search and synthesize evidence evaluating pharmacologic sleep promotion modalities in critically ill adults. Methods: A rapid systematic review protocol was used to search Medline, Cochrane Library, and Embase for reports published through October 2022. We included randomized controlled trials (RCTs) and before-and-after cohort studies evaluating pharmacologic modalities intended to improve sleep in adult intensive care unit (ICU) patients. Sleep-related endpoints were the primary outcome of interest. Study and patient characteristics and relevant safety and non-sleep outcome data were also collected. The Cochrane Collaboration Risk of Bias or Risk of Bias in Non-Randomized Studies of Interventions were used to assess the risk of bias for all included studies. Results: Sixteen studies (75% RCTs) enrolling 2573 patients were included; 1207 patients were allocated to the pharmacologic sleep intervention. Most studies utilized dexmedetomidine (7/16; total n = 505 patients) or a melatonin agonist (6/16; total n = 592 patients). Only half of the studies incorporated a sleep promotion protocol as standard of care. Most (11/16, 68.8%) studies demonstrated a significant improvement in ≥1 sleep endpoint (n = 5 dexmedetomidine, n = 3 melatonin agonists, n = 2 propofol/benzodiazepines). Risk of bias was generally low for RCTs and moderate-severe for cohort studies. Conclusions: Dexmedetomidine and melatonin agonists are the most studied pharmacologic sleep promotion modalities, but current evidence does not support their routine administration in the ICU to improve sleep. Future RCTs evaluating pharmacologic modalities for ICU sleep should consider patients' baseline and ICU risks for disrupted sleep, incorporate a non-pharmacologic sleep improvement protocol, and evaluate the effect of these medication interventions on circadian rhythm, physiologic sleep, patient-perceived sleep quality, and delirium.

Trauma-specific mindfulness-based cognitive therapy for women with post-traumatic stress disorder and a history of domestic abuse: intervention refinement and a randomised feasibility trial (coMforT study)

BackgroundWomen who have experienced domestic violence and abuse (DVA) are at increased risk of developing post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). In 2014–2015, we developed a prototype trauma-specific mindfulness-based cognitive therapy curriculum (TS-MBCT) for the treatment of PTSD in a DVA population. This study aimed to refine the prototype TS-MBCT and evaluate the feasibility of conducting a randomised controlled trial (RCT) testing its effectiveness and cost-effectiveness.MethodsIntervention refinement phase was informed by evidence synthesis from a literature review, qualitative interviews with professionals and DVA survivors, and a consensus exercise with experts in trauma and mindfulness. We tested the refined TS-MBCT intervention in an individually randomised parallel group feasibility trial with pre-specified progression criteria, a traffic light system, and embedded process and health economics evaluations.ResultsThe TS-MBCT intervention consisted of eight group sessions and home practice. We screened 109 women in a DVA agency and recruited 20 (15 TS-MBCT, 5 self-referral to National Health Service (NHS) psychological treatment), with 80% follow-up at 6 months. Our TS-MBCT intervention had 73% uptake, 100% retention, and high acceptability. Participants suggested recruitment via multiple agencies, and additional safety measures. Randomisation into the NHS control arm did not work due to long waiting lists and previous negative experiences. Three self-administered PTSD/CPTSD questionnaires produced differing outcomes thus a clinician administered measure might work better. We met six out of nine feasibility progression criteria at green and three at amber targets demonstrating that it is possible to conduct a full-size RCT of the TS-MBCT intervention after making minor amendments to recruitment and randomisation procedures, the control intervention, primary outcomes measures, and intervention content. At 6 months, none of the PTSD/CPTSD outcomes ruled out a clinically important difference between trial arms indicating that it is reasonable to proceed to a full-size RCT to estimate these outcomes with greater precision.ConclusionsA future RCT of the coMforT TS-MBCT intervention should have an internal pilot, recruit from multiple DVA agencies, NHS and non-NHS settings, have an active control psychological treatment, use robust randomisation and safety procedures, and clinician-administered measures for PTSD/CPTSD.Trial registrationISRCTN64458065 11/01/2019.

Statistical Fragility of Randomized Controlled Trials Evaluating Rehabilitation After Arthroscopic Rotator Cuff Repair.

Clinical decision-making often relies on evidence-based medicine, derived from objective data with conventional and rigorous statistical tests to evaluate significance. The literature surrounding rehabilitation after rotator cuff repair (RCR) is conflicting, with no defined standard of practice. To determine the fragility index (FI) and the fragility quotient (FQ) of randomized controlled trials (RCTs) evaluating rehabilitation protocols after RCR. Systematic review. A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching the PubMed, Cochrane Library, and Embase databases for RCTs evaluating rehabilitation protocols after arthroscopic RCRs from 2000 to June 1, 2022. The FI was determined by manipulating the dichotomous outcome events from each article until a reversal of significance with 2 × 2 contingency tables was achieved. The FQ was determined by dividing the FI by the sample size. Fourteen RCTs with 48 dichotomous outcomes were ultimately included for analysis. The mean FI for the included dichotomous outcomes was 4 (interquartile range, 3-6), suggesting that the reversal of 4 events is required to change study significance. The mean FQ was 0.048. Of the RCTs that reported data regarding loss to follow-up, most studies (58.5%) indicated that >4 patients had been lost to follow-up. The results of RCT studies of RCR rehabilitation protocols are moderately fragile, something clinicians should be aware of when implementing study results into practice. We recommend the inclusion of FI and FQ in addition to standard P values when reporting statistical results in future RCTs with dichotomous outcome variables on this topic.

Gold-Induced Cytokine (Goldic®) – A Promising Treatment in Patients with Grade 4 Knee Osteoarthritis: A Case Study

Background: Knee osteoarthritis (KOA) is one of the most common degenerative diseases that can lead to disability and pain. The degenerative nature of this condition cannot be reversed or healed by any currently available treatments. Recently, there has been an upcoming interest in treating degenerative tissue disorders with minimally invasive autologous blood products. Autologous blood was preconditioned with gold particles to encourage the production of various proteins in patients’ blood. This current study investigated the safety and efficacy of pre-conditioning autologous blood with gold particles (GOLDIC®) in patients with severe knee osteoarthritis (KOA). Case presentation We report a case in which four intra-articular GOLDIC® injections were used to treat knee osteoarthritis. After a week, physiotherapy was recommended. Before and three weeks after the injections, she was assessed for her weight, the Visual Analog Scale (VAS), and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score. GOLDIC® treatment resulted in significant weight, VAS, and WOMAC score improvements without serious side effects. Conclusion Due to the one-time blood harvesting and only four injections, the initial results demonstrated that the treatment plan is safe, less expensive, patient-friendly, and more successful at achieving compliance. This GOLDIC® treatment can significantly decrease pain and improve knee capability with overall satisfaction over a significant period. To fully validate the real potential of GOLDIC® in heterogeneous patient populations and to compare these promising results to other blood-based platforms, future randomized-controlled trials with long-term follow-up are required, despite the promising early clinical results.

Comparative Effects of Different Nutritional Supplements on Inflammation, Nutritional Status, and Clinical Outcomes in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis.

Nutritional supplements have been widely used in colorectal cancer (CRC) patients. The aim of this network meta-analysis (NMA) was to compare the effects of different nutritional supplements on inflammation, nutritional status, and clinical outcomes in CRC patients. Four electronic databases were searched until December 2022. Randomized controlled trials (RCTs) comparing nutritional supplements of omega-3 fatty acids (omega-3), arginine, vitamin D, glutamine, probiotics, or their combinations with placebo or standard treatment were selected. The outcomes were inflammatory indicators, nutritional indicators, and clinical outcomes. A random-effects Bayesian NMA was performed to rank the effect of each supplement. In total, 34 studies involving 2841 participants were included. Glutamine was superior in decreasing tumor necrosis factor-α (MD -25.2; 95% CrI [-32.62, -17.95]), whereas combined omega-3 and arginine supplementation was more effective in decreasing interleukin-6 (MD -61.41; 95% CrI [-97.85, -24.85]). No nutritional supplements significantly maintained nutritional indicators in CRC patients. Regarding clinical outcomes, glutamine ranked highest in reducing the length of hospital stay (MD -3.71; 95% CrI [-5.89, -1.72]) and the incidence of wound infections (RR 0.12; 95% CrI [0, 0.85]), and probiotics were rated as best in reducing the incidence of pneumonia (RR 0.38; 95% CrI [0.15, 0.81]). Future well-designed RCTs are needed to further confirm these findings.

The role of music in promoting health and wellbeing: a systematic review and meta-analysis.

The higher disease burden and related costs due to an increasing aging population have placed tremendous pressure on the healthcare systems worldwide. Given that music, both listened and actively performed, promotes and maintains good health and wellbeing among the population, we sought to perform a systematic review that would assess its biopsychosocial effects on a population over 40 years of age. A comprehensive search of peer-reviewed articles up to April 2021 was conducted on six electronic databases (i.e. Cochrane, MEDLINE, PubMed, PsycINFO, Web of Science and Scopus). Our study population only included healthy adults of 40 years and older. A total of 11 randomized controlled trials (RCTs) matched the inclusion criteria and were therefore analyzed. Despite the heterogeneity of the methodologies used in the selected studies, our findings suggest that active musical participation can lead to beneficial effects on both cognitive and psychosocial functioning, whereas the positive impact of listening to music seems to be predominantly restricted to the cognitive domain. Although our results are consistent with both active and passive music activities favouring health and wellbeing in individuals 40 years old and over, future prospective RCTs, employing more uniformed and sensitive measurements, should allow us to better gauge the role of music participation in healthy aging and longevity, especially in countries with a high population density of elderly people.

Alone, together: On the benefits of Bayesian borrowing in a meta-analytic setting.

It is common practice to use hierarchical Bayesian model for the informing of a pediatric randomized controlled trial (RCT) by adult data, using a prespecified borrowing fraction parameter (BFP). This implicitly assumes that the BFP is intuitive and corresponds to the degree of similarity between the populations. Generalizing this model to any historical studies, naturally leads to empirical Bayes meta-analysis. In this paper we calculate the Bayesian BFPs and study the factors that drive them. We prove that simultaneous mean squared error reduction relative to an uninformed model is always achievable through application of this model. Power and sample size calculations for a future RCT, designed to be informed by multiple external RCTs, are also provided. Potential applications include inference on treatment efficacy from independent trials involving either heterogeneous patient populations or different therapies from a common class.

Randomized Controlled Feasibility Trial of Robot-assisted Versus Conventional Open Partial Nephrectomy: The ROBOCOP II Study

BackgroundThere is no evidence from randomized controlled trials (RCTs) comparing robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN). ObjectiveTo assess the feasibility of trial recruitment and to compare surgical outcomes between RAPN and OPN. Design, setting, and participantsROBOCOP II was designed as single-center, open-label, feasibility RCT. Patients with suspected localized renal cell carcinoma referred for PN were randomized at a 1:1 ratio to either RAPN or OPN. Outcome measurements and statistical analysisThe primary outcome was the feasibility of recruitment, assessed as the accrual rate. Secondary outcomes included perioperative and postoperative data. Data were analyzed descriptively in a modified intention-to-treat population consisting of randomized patients who underwent surgery. Results and limitationsA total of 50 patients underwent RAPN or OPN (accrual rate 65%). In comparison to OPN, RAPN had lower blood loss (OPN 361 ml, standard deviation [SD] 238; RAPN 149 ml, SD 122; difference 212 ml, 95% confidence interval [CI] 105–320; p < 0.001), less need for opioids (OPN 46%; RAPN 16%; difference 30%, 95% CI 5–54; p = 0.024), and fewer complications according to the mean Comprehensive Complication Index (OPN 14, SD 16; RAPN 5, SD 15; difference 9, 95% CI 0–18; p = 0.008). OPN has a shorter operative time (OPN 112 min, SD 29; RAPN 130 min, SD 32; difference −18 min, 95% CI −35 to −1; p = 0.046) and warm ischemia time (OPN 8.7 min, SD 7.1; RAPN 15.4 min, SD 7.0; difference 6.7 min, 95% CI −10.7 to −2.7; p = 0.001). There were no differences between RAPN and OPN regarding postoperative kidney function. ConclusionsThis first RCT comparing OPN and RAPN met the primary outcome of the feasibility of recruitment; however, the window for future RCTs is closing. Each approach has advantages over the other, and both remain safe and effective options. Patient summaryFor patients with a kidney tumor, open surgery and robot-assisted keyhole surgery are both feasible and safe approaches for partial removal of the affected kidney. Each approach has known advantages. Long-term follow-up will explore differences in quality of life and cancer control outcomes.

THE HIPHOP STUDY: A FEASIBILITY STUDY FOR A RANDOMIZED CONTROLLED TRIAL OF HYBRID VERSUS CEMENTED TOTAL HIP ARTHROPLASTY

Studies have shown that 10–30% patients do not achieve optimal function outcomes after total hip replacement (THR). High quality randomised controlled trials (RCTs) evaluating the clinical and cost-effectiveness of techniques to improve functional outcomes after THR are lacking. We performed this study to evaluate the feasibility of a RCT comparing patient-reported functional outcomes after hybrid or fully cemented THR (ISRCTN11097021).Patients were recruited from two centres and randomised to receive either a fully cemented or hybrid THR. Data collection included Patient Reported Outcome Measures (PROMs), non-serious adverse events of special interest (AESI), serious adverse device effects (SADE) and NHS resource use. Qualitative interviews were undertaken to understand a) patient experiences of study processes and their reasons for taking part or not, and b) to understand surgeons’ perceptions of the study, factors affecting willingness to participate, and barriers to implementation of the future RCT findings.The target of 40 patients were successfully recruited for the feasibility RCT; the ratio of successful recruitment to eligible patients was 0.61 across both sites. Treatment crossovers occurred in four patients, all related to bone quality. Four patients were withdrawn due to not undergoing surgery within the study window because of the pandemic. Follow-up was 100% and PROMs were completed by all patients at all time points. The feasibility of conducting a within-trial cost-utility analysis was demonstrated. Interviews were conducted with 27 patients and 16 surgeons. Patients and surgeons generally found the study procedures acceptable and workable. Some declined participation because they did not want treatment allocated at random, or because blinding was off-putting. Surgeons’ perceptions of equipoise varied, and implementation of findings from the future RCT would need to recognise the ‘craft’ nature of surgery and the issue of training.We conclude that a full RCT with economic analysis will be both feasible and practicable, although mechanisms to safely implement potential changes to practice because of RCT findings may need consideration by the wider arthroplasty community.

Mindfulness-Based Interventions for the Reduction of Postoperative Pain in Hip and Knee Arthroplasty Patients: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis is to evaluate the effect of mindfulness-based interventions (MBIs) on post-surgical pain in patients undergoing a total hip replacement (THR) or total knee replacement (TKR). We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A search of multiple databases, including PubMed and EMBASE, was performed for studies from database inception through March 2nd, 2022. Data were extracted, and pooled estimates of standardized mean differences in pain scores were calculated using a random effects model and inverse probability weighting. Two randomized control trials were eligible for inclusion (299 patients). The average ages of participants in each study were similar at 65.5 and 64.8 years, and both studies were predominantly female at 72.4% and 61.9%. The mindfulness intervention ranged from an eight-week program to a 20-minute session. Both individual studies reported statistically significant reductions in postoperative pain for MBI groups. The pooled standardized mean difference in pain scores for the MBI groups compared to the control groups was -1.94 (-3.39; -0.48). There exists preliminary evidence for the beneficial effect of MBIs on reducing the postoperative pain experience in this patient population. Given the significant consequences of postoperative pain and the necessity for non-opioid forms of analgesia, this topic represents a promising area of research that warrants future randomized control trials to better understand the role of MBIs for postoperative analgesia.

Who Benefits More From IBMS or Qigong? Clinical Data-Mining RCT Data

Purpose: A recent three-arm randomized controlled trial (RCT) with depressed Hong Kong adults demonstrated the comparable effectiveness of integrative Body-Mind-Spirt (IBMS) and Qigong interventions in relieving sleep disturbance and depression, but not which is best for whom? Guided by concept and theory-based hypotheses, clinical data-mining (CDM), the RCT data answers the more clinically relevant question: who responds best to which intervention? Method: Paired-sample t-tests and Wilcoxon signed-ranked tests were adopted to compare the within-subgroup differences; linear mixed models for normally distributed outcomes and generalized linear mixed models for non-normally distributed outcomes were used to compare the between-subgroup differences. Results: Results indicate that IBMS is more efficacious for older, more educated females, suffering from physical pain and illness; whereas younger, less educated males, not in full-time employment benefit more from Qigong. Discussion: This productive joining together of RCT and CDM recommends itself to both past and future RCTs, further informing evidence-based practice decision making.

Outcomes of intravenous and subcutaneous cladribine administration in patients with hairy cell leukemia: A systematic review and meta-analysis.

e19546 Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Cladribine (2CdA) monotherapy is used as a first line treatment for HCL. 2CdA can be administered intravenously (IV) or subcutaneously (SC). The aim of our study is to compare the safety and efficacy of these two routes of administration of 2CdA as a first line treatment of HCL. Methods: We conducted a systematic literature search across multiple databases and Google up to February 2023. We included studies that reported outcomes for either intravenous (IV) or subcutaneous (SC) cladribine (2CdA) therapy, as well as those that directly compared the two routes. Our primary efficacy outcomes were overall response rate (ORR) and complete response rate (CRR), and our primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random effects model and conducted subgroup analysis for HCL type (classical vs classic and variant both). We calculated odds ratios (ORs) for studies involving a head-to-head comparison between the two routes and used the Higgins I2 statistic to assess heterogeneity. Results: We identified a total of 25 studies (15 trials, 10 cohorts) with a patient population of 2669. The median age of the patients was 53.5 years. The pooled ORR and CRR for IV and SC 2CdA therapy were 96%, 82%, 88% and 67% respectively. The incidence of neutropenia (82% vs 61%) and infections (13% vs 16%) was greater for SC 2CdA than IV 2CdA. Five studies provided a direct comparison between SC and IV routes but three were excluded from the analysis due to unavailability of desired outcomes. Studies involving a direct comparison between the 2 routes of administration showed that the odds of achieving CRR were 86.6% greater with IV than SC 2CdA but these results were not significant. The proportion of adverse events was comparable for IV and SC routes. Subgroup analysis for HCL type did not resolve heterogeneity for ORR and CRR. It did, however, result in greater ORR for classic (92%) and mixed (92%) HCL treated with SC 2CdA. Conclusions: Compared to SC 2CdA, IV 2CdA is safer and more effective as a first-line treatment of HCL. However, future high-power randomized control trials that directly compare IV and SC routes are needed to confirm this evidence. [Table: see text]

Does CGA Improve Health Outcomes in the Community? An Umbrella Review.

To perform an umbrella review of systematic reviews with meta-analyses (MAs) examining the effectiveness of comprehensive geriatric assessment (CGA) delivered within community settings to general populations of community-dwelling older people against various health outcomes. Umbrella review of MAs of randomized controlled trials (RCTs). Systematic reviews with MAs examining associations between CGA conducted within the community and any health outcome, where participants were community-dwelling older people with a minimum mean age of 60years or where at least 50% of study participants were aged ≥60years. Studies focusing on residential care, hospitals, post-hospital care, outpatient clinics, emergency department, or patients with specific conditions were excluded. We examined CGA effectiveness against 12 outcomes: not living at home, nursing home admission, activities of daily living (ADLs) and instrumental ADLs (IADLs), physical function, falls, self-reported health status, quality of life, frailty, mental health, hospital admission, and mortality, searching the MEDLINE/PubMed, Cochrane Library, CINAHL, Embase databases from January 1, 1999, to August 10, 2022. AMSTAR-2 was used to assess the quality of included systematic reviews, including risk of bias. We identified 10MAs. Only not living at home (combined mortality and nursing home admission) demonstrated concordance between effect direction, significance, and magnitude. Significant effects were more typically observed in earlier rather than later studies. Given the widespread adoption of CGA as a component of usual care within geriatric medicine, the lack of strong evidence demonstrating the protective effects of CGA may be indicative of a cohort effect. If so, future RCTs examining CGA effectiveness are unlikely to demonstrate significant findings. Future studies of CGA in the community should focus on implementation and adherence to key components. Study protocol registered in PROSPERO 2020 CRD42020169680.

Induction immunochemotherapy conversion rate and survival outcomes versus chemotherapy in initially unresectable esophageal squamous cell carcinoma.

e16077 Background: Currently, no comparative study has been reported to elucidate whether the addition of immunotherapy in the induction setting could improve treatment efficacy and prolong the overall survival of initially-unresectable locally advanced esophageal squamous cell carcinoma (iuESCC). This study aimed to compare surgical conversion rate and short-term overall survival in induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with iuESCC. Methods: In this multicenter retrospective cohort study, patients with the guideline-defined unresectable disease were included at four high-volume institutions. The primary endpoints were conversion surgical rate and overall survival (OS). Pathological complete response (pCR) was defined as the disappearance of tumor cells in the primary lesion site. Multivariate cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting (IPTW) was applied to confirm the survival comparison between iIC and iC cohorts. Results: A total of 309 patients (150 in iIC and 159 in iC cohort) were included. A significantly higher conversion surgical rate was observed in iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P &lt; 0.001). In terms of pathological response, the rates of pCR were 22.0% and 5.1% in the iIC and the iC cohort, respectively (P = 0.001). A significant difference in OS was observed between iIC (not reached) and iC cohorts (median [95% CI]: 36.3 [27.2 – 45.5] months). The stabilized IPTW yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI: 0.102 - 0.454, P &lt; 0.001) and operation (Yes vs. No, HR 0.262, 95% CI: 0.161 - 0.427, P &lt; 0.001) were the significant prognostic factors for OS. Further, subgroup analysis revealed that significantly higher OS was seen in iIC cohort than that in the iC cohort (P = 0.003) in patients who had non-pCR disease. Conclusions: Immunochemotherapy plus conversion surgery in the induction setting had higher pathological response rate and better OS in iuESCC patients. Moreover, this combined modality also contributed to improving OS in patients with residual tumor burden. This study provided evidence for future randomized control trial designs.