Future Randomized Controlled Trials Research Articles

Randomised, controlled, feasibility trial comparing vasopressor infusion administered via peripheral cannula versus central venous catheter for critically ill adults: A study protocol.

When clinicians need to administer a vasopressor infusion, they are faced with the choice of administration via either peripheral intravenous catheter (PIVC) or central venous catheter (CVC). Vasopressor infusions have traditionally been administered via central venous catheters (CVC) rather than Peripheral Intra Venous Catheters (PIVC), primarily due to concerns of extravasation and resultant tissue injury. This practice is not guided by contemporary randomised controlled trial (RCT) evidence. Observational data suggests safety of vasopressor infusion via PIVC. To address this evidence gap, we have designed the "Vasopressors Infused via Peripheral or Central Access" (VIPCA) RCT. The VIPCA trial is a single-centre, feasibility, parallel-group RCT. Eligible critically ill patients requiring a vasopressor infusion will be identified by emergency department (ED) or intensive care unit (ICU) staff and randomised to receive vasopressor infusion via either PIVC or CVC. Primary outcome is feasibility, a composite of recruitment rate, proportion of eligible patients randomised, protocol fidelity, retention and missing data. Primary clinical outcome is days alive and out of hospital up to day-30. Secondary outcomes will include safety and other clinical outcomes, and process and cost measures. Specific aspects of safety related to vasopressor infusions such as extravasation, leakage, device failure, tissue injury and infection will be assessed. VIPCA is a feasibility RCT whose outcomes will inform the feasibility and design of a multicentre Phase-3 trial comparing routes of vasopressor delivery. The exploratory economic analysis will provide input data for the full health economic analysis which will accompany any future Phase-3 RCT.

THE EFFECTS OF HYBRID FUNCTIONAL ELECTRICAL STIMULATION INTERVAL TRAINING ON AEROBIC FITNESS AND FATIGUE IN PEOPLE WITH ADVANCED MULTIPLE SCLEROSIS

INTRODUCTION & AIMS Improving aerobic fitness in people with multiple sclerosis (MS) can reduce fatigue, and lower the risk of cardiovascular disease. Aerobic training can be challenging due to paresis, access to suitable equipment and fatigue. The aim was to investigate whether functional electrical stimulation (FES) cycling combined with arm crank interval exercise (hybrid FES interval training) is feasible for people with advanced MS, and its effects on aerobic fitness and fatigue. METHODS Hybrid FES interval training was performed 2 d/wk for 12 weeks. Each session consisted of 40 minutes of continuous FES cycling with arm crank intervals of 30 seconds work/30 seconds rest added concurrently for 20 minutes. The intensity target was a minimum of 60% of arm crank power and ‘hard’ measured by rate of perceived exertion (RPE) on a scale of 6-20. Feasibility was measured by attendance, compliance to intensity and time targets, adverse events, and drop outs. Aerobic fitness was assessed by an arm crank maximal test. Fatigue was measured via the Modified Fatigue Impact Scale (MFIS). RESULTS Seven participants (6 female; age 57.1±7.8y; Expanded Disability Status Scale 7.1±0.8) with advanced MS attended 80±10.4% of the scheduled sessions and there were no adverse events or drop outs. Average RPE at the end of each training session was 15±2, representing vigorous intensity exercise. Aerobic fitness did not change pre- to post-intervention [14.2±5.7 to 14.78±6.0 mL/kg/min (p=0.43)]. There was a trend towards a reduction in the MFIS score pre- to post-intervention [31.0±10.4 to 21.7±11.4 (p=0.10)]. CONCLUSION Hybrid FES interval training is feasible for people with advanced MS who need exercise equipment appropriate for their condition, and can represent vigorous intensity exercise. The positive findings support the need for future randomized control trials that can assess the aerobic fitness changes and associated health benefits of hybrid FES interval training.

Systematic Review and Meta-Analysis: Pharmacological and Nonpharmacological Interventions for Disruptive Mood Dysregulation Disorder.

Objectives: Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnosis that comprises severe, nonepisodic irritability and recurrent outbursts of emotional instability in adolescents. This meta-analysis examined the efficacy of the available pharmacological and nonpharmacological interventions for DMDD. Methods: Literature searches were conducted in July 2023. To determine relevant articles, 330 abstracts were reviewed, and 39 articles were identified for full review. A random-effects model was used for the meta-analysis, and a subgroup analysis was performed to assess the effects of study design and intervention type. Results: Eleven studies were reviewed, including six pharmacological and five nonpharmacological. Despite high heterogeneity in effects (I2 = 85%), we showed statistically significant improvements in irritability symptoms following intervention. We showed statistically significant enhancements in symptoms of irritability following the intervention. The subgroup analysis revealed that, compared with randomized controlled trials (RCTs), open trials showed significant improvements in irritability. In addition, drug intervention significantly improved irritability compared to nondrug interventions. Atomoxetine (ATX), optimized stimulants, and stimulants combined with other drugs and behavioral therapy effectively improved irritability. Conclusions: With research indicating potential benefits for irritability from a combination of pharmacological interventions and therapy, including ATX, stimulants in conjunction with antipsychotic or antidepressant medications, and cognitive-behavioral techniques such as Dialectical Behavior Therapy for Children. Future large-scale RCTs are essential to further explore and refine these treatment approaches, especially focusing on the efficacy of combining pharmacological with effective nonpharmacological to improve irritability and overall outcomes in this population.

Digital health-based exposure therapies for patients with posttraumatic stress disorder: A systematic review of randomized controlled trials.

Although exposure therapies have established effects in treating posttraumatic stress disorder (PTSD), these therapies might be hindered by issues of cost, distance, time, and human resources, which are potentially alleviated by digital health. Despite the potential of digital health, there is currently no systematic review specifically evaluating digital health-based exposure therapies. We aimed to conduct a systematic literature review of randomized controlled trials (RCTs) examining the impact of digital health-based exposure therapies in treating patients with PTSD. A literature search was conducted from December 31, 2023, to February 22, 2024, using the PubMed, Web of Science, and PsycINFO databases. A total of 12 RCTs with 1,361 participants were included in the systematic review. These RCTs were conducted mainly in the United States and primarily enrolled military samples. Overall, the utility of digital health-based exposure therapies appeared plausible and comparable to that of in-person therapies. The dropout rate was counterintuitively high, potentially due to technological issues and the absence of personal connections. The findings suggest that digital health-based exposure therapies may potentially resolve the issues of cost, distance, time, and human resources in the treatment of patients with PTSD. Future RCTs should employ larger sample sizes. Addressing technological challenges and the absence of personal connection may be important in resolving the high dropout rate.

Smartphone App-Delivered Mindfulness-Based Intervention for Mild Traumatic Brain Injury in Adolescents: Protocol for a Feasibility Randomized Controlled Trial.

Concussion in children and adolescents is a significant public health concern, with 30% to 35% of patients at risk for prolonged emotional, cognitive, sleep, or physical symptoms. These symptoms negatively impact a child's quality of life while interfering with their participation in important neurodevelopmental activities such as schoolwork, socializing, and sports. Early psychological intervention following a concussion may improve the ability to regulate emotions and adapt to postinjury symptoms, resulting in the greater acceptance of change; reduced stress; and recovery of somatic, emotional, and cognitive symptoms. The primary objective of this study is to assess the feasibility of conducting a parallel-group (1:1) randomized controlled trial (RCT) to evaluate a digital therapeutics (DTx) mindfulness-based intervention (MBI) in adolescents aged 12 to <18 years. The attention-matched comparator intervention (a math game also used in previous RCTs) will be delivered on the same DTx platform. Both groups will be provided with the standard of care guidelines. The secondary objective is to examine intervention trends for quality of life; resilience; self-efficacy; cognition such as attention, working memory, and executive functioning; symptom burden; and anxiety and depression scores at 4 weeks after concussion, which will inform a more definitive RCT. A subsample will be used to examine whether those randomized to the experimental intervention group have different brain-based imaging patterns compared with those randomized to the control group. This study is a double-blind Health Canada-regulated trial. A total of 70 participants will be enrolled within 7 days of concussion and randomly assigned to receive the 4-week DTx MBI (experimental group) or comparator intervention. Feasibility will be assessed based on the recruitment rate, treatment adherence to both interventions, and retention. All outcome measures will be evaluated before the intervention (within 7 days after injury) and at 1, 2, and 4 weeks after the injury. A subset of 60 participants will undergo magnetic resonance imaging within 72 hours and at 4 weeks after recruitment to identify the neurophysiological mechanisms underlying the potential benefits from MBI training in adolescents following a concussion. The recruitment began in October 2022, and the data collection is expected to be completed by September 2024. Data collection and management is still in progress; therefore, data analysis is yet to be conducted. This trial will confirm the feasibility and resolve uncertainties to inform a future definitive multicenter efficacy RCT. If proven effective, a smartphone-based MBI has the potential to be an accessible and low-risk preventive treatment for youth at risk of experiencing prolonged postconcussion symptoms and complications. ClinicalTrials.gov NCT05105802; https://classic.clinicaltrials.gov/ct2/show/NCT05105802. DERR1-10.2196/57226.

PREHAB FAI- Prehabilitation for patients undergoing arthroscopic hip surgery for Femoroacetabular Impingement Syndrome -Protocol for an assessor blinded randomised controlled feasibility study.

The past decade has seen an exponential growth of minimally invasive surgical procedures. Procedures such as hip arthroscopy have rapidly grown and become the standard of care for patients with Femoroacetabular Impingement Syndrome (FAIS). Although, the results of such procedures are encouraging, a large proportion of patients do not achieve optimal outcomes due to chronicity and deconditioning as a result of delay in diagnosis and increased waiting times amongst other factors. In a recent systematic review and meta-analysis of randomised control trials, moderate certainty evidence supported prehabilitation over standard care in optimising several domains including muscle strength, pain and health related quality of life in patients undergoing orthopaedic surgical interventions. However, the role of prehabilitation in patients with FAI syndrome undergoing hip arthroscopy has received little attention. To evaluate the feasibility, suitability, acceptability and safety of a prehabilitation programme for FAI to inform a future definitive randomised control trial to assess effectiveness. A systematically developed prehabilitation intervention based on a literature review and international consensus will be utilised in this study. A mixed methodology encompassing a two-arm randomised parallel study alongside an embedded qualitative component will be used to answer the study objectives. Patients will be recruited from a tertiary referral NHS centre for young adult hip pathology in the UK. Patient reported outcomes such as iHOT-12, Brief Pain Inventory Scale (Short form), Hospital Anxiety and Depression Scale and Patient Global Impression of Change score will be obtained alongside objective measurements such as Muscle Strength and Star Excursion Balance Test at various time points. Outcome measures will be obtained at baseline (prior to prehabilitation intervention), after prehabilitation before surgery, and at 6 weeks+/- 4 weeks and 6 months +/- 4 weeks (planned primary endpoint for definitive RCT) postoperatively when participants attend the research site for clinical care and remotely at 12 months +/- 4 weeks postoperatively. Mean change and 95% CI, and effect size of outcome measures will be used to determine the sample size for a future RCT. For the qualitative component, in depth face-to-face semi-structured interviews with physiotherapists and focus groups with participants will be conducted to assess the feasibility, suitability, and acceptability of the prehabilitation intervention using a predetermined success criteria. All qualitative data will be recorded, transcribed verbatim and thematically analysed. This study will be first of its kind to evaluate a systematically developed prehabilitation intervention for patients with FAIS undergoing hip arthroscopy. This study will provide important preliminary data to inform feasibility of a definitive RCT in the future to evaluate effectiveness of a prehabilitation intervention. ISRCTN 15371248, 09/03/2023. Version 2.3, 26th June 2023.

Immediate versus early implant placement for single tooth replacement in the aesthetic area: A systematic review and meta-analysis.

To compare immediate implant placement (IIP) with early implant placement (EIP) for single tooth replacement in the aesthetic area in terms of aesthetic, clinical, and patient-reported outcomes. Two independent reviewers conducted an electronic literature search in PubMed, Web of Science, Embase, and Cochrane databases as well as a manual search to identify eligible clinical studies up to February 2023. Randomized Controlled Trials (RCTs) comparing IIP with EIP were included for a qualitative and quantitative analysis. The primary outcome was vertical midfacial soft tissue change. Secondary outcomes were horizontal midfacial soft tissue change, vertical papillary change, pink esthetic score (PES), implant survival, buccal bone thickness, marginal bone level change, patient discomfort, chair time, and patient satisfaction. Out of 1185 records, 6 RCTs were selected, reporting on 222 patients who received 222 single implants (IIP: 112 implants in 112 patients; EIP: 110 implants in 110 patients) in the anterior maxilla or mandible. Patients had a mean age ranging from 35.6 to 52.6 years and were followed between 8 and 24 months. Two RCTs showed some concerns, and four showed a high risk of bias. Four studies could be included in a meta-analysis on the primary outcome and three only considered cases with an intact buccal bone wall. Meta-analysis failed to demonstrate a significant difference in terms of vertical midfacial soft tissue change between IIP and EIP (mean difference: 0.31 mm, 95% CI [-0.23; 0.86], p = .260; I2 = 83%, p < .001). No significant differences were found for PES (standardized mean difference: 0.92, 95% CI [-0.23; 2.07], p = .120; I2 = 89%, p < .001), implant survival (RR: 0.98, 95% CI [0.93, 1.03], p = .480; I2 = 0%, p = .980), and marginal bone level change (mean difference: 0.03 mm, 95% CI [-0.12, 0.17], p = .700; I2 = 0%, p = .470). Insufficient data were available for meta-analyses of other secondary outcomes. In low-risk patients with an intact buccal bone wall, there seems to be no difference between IIP and EIP in terms of aesthetic and clinical outcomes. The strength of this conclusion is rated as low since studies showed an unclear or high risk of bias. In addition, state-of-the-art therapy was only delivered in a minority of studies. Future RCTs should also provide data on patient-reported outcomes since these have been underreported.

BI-REAL: A 12-session DBT skills group intervention adapted for bipolar disorder – A feasibility randomised pilot trial

International guidelines endorse psychological treatment for Bipolar Disorder (BD); however, the absence of a recognised gold-standard intervention requires further research. A Dialectical Behaviour Therapy (DBT) skills group intervention with 12 sessions was developed. This pilot randomised controlled trial (RCT) aims to evaluate the feasibility, acceptability, and outcomes variance of Bi-REAL – Respond Effectively, Assertively, and Live mindfully, tailored for individuals with BD, in preparation for a future RCT. Methods52 participants (female = 62.7 %; mean age = 43.2 ± 11.1) with BD were randomised by blocks to either the experimental group (EG; n = 26; Bi-REAL + Treatment as Usual, TAU) receiving 12 weekly 90-minute sessions, or the control group (CG; n = 26, TAU). Feasibility and acceptability were assessed with a multimethod approach (qualitative interviews, semi-structured clinical interviews and a battery of self-report questionnaires – candidate main outcomes Bipolar Recovery Questionnaire (BRQ) and brief Quality of Life for Bipolar Disorder (QoL.BD)). All participants were evaluated at baseline (T0), post-intervention (T1) and 3-month follow-up (T2). ResultsAcceptability was supported by participants' positive feedback and ratings of the sessions and programme overall, as well as the treatment attendance (86.25 % of sessions attended). The trial overall retention rate was 74.5 %, with CG having a higher dropout rate across the 3-timepoints (42.31 %). A significant Time × Group interaction effect was found for BRQ and QoL.BD with the intervention group presenting a larger decrease in symptoms (p < .05). LimitationsThe assessors were not blind at T1 (only at T2). Recruitment plan was impacted due to COVID-19 restrictions and replication is questionable. High attrition rates in the CG. ConclusionsThe acceptability of Bi-REAL was sustained, and subsequent feasibility testing will be necessary to establish whether the retention rates of the overall trial improve and if feasibility is confirmed, before progressing to a definitive trial.

The impact of egg consumption on cognitive function: a systematic literature review

Eggs provide several nutrients that have been linked to neurological function. Phospholipids, which comprise 30% of lipids in egg yolk, modulate neurotransmitter receptors and have been shown to lower reaction time in healthy adults(1). Eggs are also high in choline (340mg per egg), a building block for acetylcholine, a neurotransmitter involved in memory, learning and attention(2). Finally, eggs contain the omega-3 fatty acid docosahexaenoic acid (DHA) (25mg per egg), which has roles in neurological function including neurogenesis, synaptic plasticity and myelination(3). The impact of whole egg consumption on cognition has not been widely explored. This systematic review aimed to consolidate studies that investigated frequency of egg consumption or egg-supplemented diets on cognitive function. This review followed PRISMA guidelines and involved a search of five databases (Ovid Medline, Embase, CINAHL Plus, SCOPUS, and PsychInfo) from inception until April 2023. Included studies examined the link between whole chicken egg consumption and brain function, including cognitive decline, memory, risk-taking, reaction-time, decision-making, and executive function, in healthy adults (aged&gt;16 y). All studies underwent risk of bias assessment. Twelve studies were included in the review. Four were prospective cohort studies, 4 were retrospective, 3 cross-sectional and 1 was a randomised controlled trial (RCT). Participant numbers, with the exception of the RCT, ranged between 178-9028 and were aged between 42-97 years. Duration of prospective studies varied from 2-5 years. Egg intake was measured via food frequency questionnaires (n = 8), 24-hr diet recalls (n = 2), a 4-day food record (n = 1) and a 7-day food record (n = 1). The RCT provided 2 DHA-fortified eggs/day compared to 2 whole eggs/day for 8 weeks. The primary outcome across 9 studies was cognitive decline, followed by memory (n = 7), reaction-time (n = 2), attention (n = 2), and executive function (n = 1). For outcome measures, studies used 9 different validated task-oriented tools (including the Montreal Cognitive Assessment n = 3, and California Verbal Learning Test n = 2), or 4 self-completed questionnaires. Several studies found no significant associations between egg consumption and cognitive decline (n = 4) or memory (n = 2). Conversely, 5 studies reported significant inverse associations between egg consumption and rates of cognitive decline. The RCT found that reaction-times were faster on both whole eggs and DHA-eggs after 8 weeks (p&gt;0.05 between groups). Although conflicting results were found, more studies showed a greater frequency of habitual egg consumption to be associated with reduced cognitive decline. However, the variety of outcome measures across studies make direct comparisons challenging, preventing definitive conclusions about the impact of eggs on cognitive health. This review highlights the need for future RCTs.

Precision computerised cognitive behavioural therapy (cCBT) for adolescents with depression: a pilot and feasibility randomised controlled trial protocol for SPARX-UK

BackgroundA serious game called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts), originally developed in New Zealand and incorporating cognitive behavioural therapy (CBT) principles, has been shown to help reduce symptoms of depression and anxiety in adolescents with mild to moderate depression in studies undertaken in Australasia. However, SPARX has never been trialled in the United Kingdom (UK), and there have been issues relating to low engagement when it has been used in a real-world context.AimsTo conduct the first pilot and feasibility randomised controlled trial (RCT) in England to explore the use of SPARX in different settings. The trial will explore whether SPARX supported by an e-coach (assistant psychologists) improves adherence and engagement compared with self-directed (i.e. self-help) use. The trial results will be used to inform the optimal mode of delivery (SPARX supported vs. SPARX self-directed), to calculate an appropriate sample size for a full RCT, and to decide which setting is most suitable.MethodsFollowing consultation with young people to ensure study suitability/appropriateness, a total of 120 adolescents (11–19 years) will be recruited for this three-arm study. Adolescents recruited for the study across England will be randomised to receive either SPARX with human support (from an e-coach), self-directed SPARX, or a waitlist control group. Assessments will be conducted online at baseline, week 4, and 8–10-week post-randomisation. The assessments will include measures which capture demographic, depression (Patient Health Questionnaire modified for adolescents [PHQ-A]) and anxiety (Revised Child Anxiety and Depression Scale [RCADS]) symptomatology, and health-related quality-of-life data (EQ-5D-Y and proxy version). Analyses will be primarily descriptive. Qualitative interviews will be undertaken with a proportion of the participants and clinical staff as part of a process evaluation, and the qualitative data gathered will be thematically analysed. Finally, feasibility data will be collected on recruitment details, overall study uptake and engagement with SPARX, participant retention, and youth-reported acceptability of the intervention.DiscussionThe findings will inform the design of a future definitive RCT of SPARX in the UK. If the subsequent definitive RCT demonstrates that SPARX is effective, then an online serious game utilising CBT principles ultimately has the potential to improve the provision of care within the UK’s health services if delivered en masse.Trial registrationISRCTN: ISRCTN15124804. Registered on 16 January 2023, https://www.isrctn.com/ISRCTN15124804.

Quality assurance in surgical trials of arteriovenous grafts for haemodialysis: A systematic review, a narrative exploration and expert recommendations.

Introducing new procedures and challenging established paradigms requires well-designed randomised controlled trials (RCT). However, RCT in surgery present unique challenges with much of treatment tailored to the individual patient circumstances, refined by experience and limited by organisational factors. There has been considerable debate over the outcomes of arteriovenous grafts (AVG) compared to AVF, but any differences may reflect differing practice and potential variability. It is essential, therefore, when considering an RCT of a novel surgical procedure or device that quality assurance (QA) is defined for both the new approach and the comparator. The aim of this systematic review was to evaluate the QA standards performed in RCT of AVG using a multi-national, multi-disciplinary approach and propose an approach for future RCT. The methods of this have been previously registered (PROSPERO: CRD420234284280) and published. In summary, a four-stage review was performed: identification of RCT of AVG, initial review, multidisciplinary appraisal of QA methods and reconciliation. QA measures were sought in four areas - generic, credentialing, standardisation and monitoring, with data abstracted by a multi-national, multi-speciality review body. QA in RCT involving AVG in all four domains is highly variable, often sub-optimally described and has not improved over the past three decades. Few RCT established or defined a pre-RCT level of experience, none documented a pre-trial education programme, or had minimal standards of peri-operative management, no study had a defined pre-trial monitoring programme, and none assessed technical performance. QA in RCT is a relatively new area that is expanding to ensure evidence is reliable and reproducible. This review demonstrates that QA has not previously been detailed, but can be measured in surgical RCT of vascular access, and that a four-domain approach can easily be implemented into future RCT.

Health coaching intervention with or without the support of an exercise buddy to increase physical activity of people with chronic low back pain compared to usual care: a feasibility and pilot randomised controlled trial

BackgroundExercise buddies (people to exercise together with) might support people with low back pain (LBP) to become active. However, involving buddies in randomised controlled trials (RCT) might challenge recruitment, data collection and follow-up. ObjectivesTo explore the feasibility of the intervention, recruitment and data collection approaches and potential effects of a health coaching intervention (focused on physical activity) with or without exercise buddies’ support on physical activity of people with chronic LBP versus usual discharge care. DesignFeasibility and pilot RCT. MethodsAdults (n = 30) discharged from LBP treatment were randomised to the Buddy-Assisted (health coaching intervention with exercise buddy's support), Individual-Only (health coaching only), or usual care groups. Data were collected at baseline, three and six months. The feasibility of trial's procedures was assessed through recruitment rate (acceptable if >70%), data completion rate (acceptable if ≤ 20% missing data), and follow-up rate (successful if ≥ 85%). The intervention's acceptability was assessed via feedback questionnaires. Preliminary effects on physical activity and other outcomes were also explored. ResultsRecruitment and baseline data completion were acceptable. However, data collection and follow-up rates post-randomisation were not. 85% of the Buddy-Assisted Group believed the buddies helped them to increase physical activity and would recommend the intervention. 70% of the Individual-Only and Control groups believed exercise buddies would help them to become further active. ConclusionThe data collection and follow-up approaches were not successful and need amending before a large-scale RCT. Nonetheless, the buddy-assisted intervention was well-accepted. A future RCT will focus on differences in clinical outcomes. Trial registrationThe study was registered at the Australian New Zealand Clinical Trial Registry (ACTRN12620001118998).

The effects of intranasal oxytocin on the efficacy of psychotherapy for major depressive disorder: a pilot randomized controlled trial.

Although both pharmacotherapy and psychological treatments are considered to be efficacious in the treatment of major depressive disorder (MDD), one third of patients do not respond to treatment and many experience residual symptoms post-treatment. In this double-blind placebo-controlled randomized control trial (RCT), we assessed whether intranasal oxytocin (OT) augments the therapeutic efficacy of psychotherapy for MDD and improves the therapeutic alliance. Twenty-three volunteers (12 female) with MDD underwent 16 sessions of interpersonal therapy. Prior to each session, volunteers self-administered 24 International Units of intranasal OT (n = 12; Syntocinon) or placebo (n = 11). Depressive symptoms were assessed with the Inventory of Depressive Symptomatology at pre- and post-treatment, and at a six month follow-up. Multilevel modeling found a significant effect of OT on the negative slope of depressive symptoms over time (p < 0.05), with medium-large effect sizes at post-treatment (Cohen's d = 0.75) and follow-up (Cohen's d = 0.82). Drug intervention also predicted the intercept when examining the weekly ratings of the therapeutic alliance (p < 0.05), such that volunteers receiving OT, relative to placebo, reported improved therapeutic alliance at session 1. The agreement of goals between therapists and participants, a facet of the therapeutic alliance, mediated the relationship between drug intervention and clinical outcome. In this pilot study, the administration of intranasal OT, relative to placebo, improved the therapeutic alliance at the beginning of therapy and therapeutic efficacy of psychotherapy in persons with MDD. Future RCTs should attempt to replicate these findings in larger samples with different therapeutic modalities (ClinicalTrials.gov: NCT02405715).

Randomised trials conducted using cohorts: a scoping review

IntroductionCohort studies generate and collect longitudinal data for a variety of research purposes. Randomised controlled trials (RCTs) increasingly use cohort studies as data infrastructures to help identify and recruit trial...

Platelet-Rich Plasma Versus Alternative Injections for Osteoarthritis of the Knee: A Systematic Review and Statistical Fragility Index-Based Meta-analysis of Randomized Controlled Trials.

Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. To evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. Systematic review and meta-analysis; Level of evidence, 2. All RCTs comparing PRP with alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse FI were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from ≥1 trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. In total, this analysis included outcomes from 1993 patients with a mean ± SD age of 58.0 ± 3.8 years. The mean number of events required to reverse significance of individual RCTs (FI) was 4.57 ± 5.85. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid (P = .002; odds ratio [OR], 2.19; 95% CI, 1.33-3.62), as well as higher rates of patient-reported symptom relief (P = .019; OR, 1.55; 95% CI, 1.07-2.24), not requiring a reintervention after the initial injection treatment (P = .002; OR, 2.17; 95% CI, 1.33-3.53), and achieving the minimal clinically important difference (MCID) for pain improvement (P = .007; OR, 6.19; 95% CI, 1.63-23.42) when compared with all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. Conclusions drawn from individual RCTs evaluating PRP for knee OA demonstrated slight robustness. On meta-analysis, PRP demonstrated a significant advantage over hyaluronic acid as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared with alternative nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and health care. Future RCTs and meta-analyses should consider reporting FIs and fragility quotients to facilitate interpretation of results in their proper context.

Effect of home-based lifestyle interventions on cognition in older adults with mild cognitive impairment: a systematic review

BackgroundMild Cognitive Impairment (MCI) is frequently a precursor to dementia, affecting aspects of cognition such as language, thinking, or memory. Lifestyle interventions are increasingly studied as potential means to slow the progression from MCI to dementia.ObjectiveA systematic review was conducted to investigate the effectiveness of home-based lifestyle interventions in reducing cognitive decline in older adults with MCI.MethodsA systematic review of randomized controlled trials (RCTs) was conducted to identify home-based lifestyle interventions for individuals with MCI from 1980 to 2023. These interventions were either single-component or multi-component and included diet, physical activity, stress-reduction, or cognitive stimulation treatments to assess their impact on cognition. We performed a comprehensive search in the PubMed, Web of Science, Google Scholar, Embase, and MEDLINE databases.ResultsFrom 320 abstracts, 20 (6.25%) studies met the criteria for inclusion, with five multi-component and fifteen single-component studies. Eighteen home-based lifestyle interventions for MCI patients were focused on physical activity, diet, and/or cognitive training, while two studies were identified that incorporated stress reduction training as a method to improve cognitive function. Nineteen studies reported significant improvements in cognitive performance between the experimental and control groups post-intervention for at least one aspect of cognition. Four studies reported nonsignificant improvements in cognitive function between the two groups for at least one area of cognition.ConclusionsHome-based lifestyle interventions have the potential to improve cognition in elderly patients with MCI. However, future RCTs with larger sample sizes and longer intervention durations are needed to confirm these findings.

Role of Preoperative Radiation Therapy for Resectable Gastric Cancer.

While surgery is the primary curative treatment for resectable gastric and gastroesophagealjunction (GEJ) cancer, rates of locoregional and distant recurrence remain high with surgery alone,especially in more advanced disease. Multimodal approaches with perioperative therapy includingchemotherapy and/or radiation therapy (RT) have thus evolved as ways to reduce the rates of diseaserecurrence and improve survival outcomes. This review article provides a comprehensive literaturereview on the role of preoperative RT for resectable gastric and GEJ cancer. A literature review on the role of preoperative RT for resectable gastric and GEJ cancer wasconducted. Preoperative RT has the potential to facilitate tumor downstaging and improved R0 resection,allowing for better locoregional control and thereby survival. For resectable locally advanced GEJ cancer,preoperative chemoradiotherapy (CRT) is currently a standard of care option along with perioperativechemotherapy, based on evidence from randomized trials. In resectable gastric cancer, however, therole of preoperative CRT is less defined with no randomized data to date, although phase II single-armstudies have shown promising results. Current standard of care for gastric cancer remains perioperativechemotherapy, with consideration for preoperative CRT in select cases. Results from ongoing and future randomized controlled trials are expected to help definethe role of preoperative CRT compared to perioperative chemotherapy alone as well as postoperativeCRT for gastric and GEJ cancer.

Targeting Anhedonia in Adolescents: A Single Case Series of a Positive Imagery-Based Early Intervention

AbstractInterventions targeting anhedonia in depression demonstrate encouraging results in adults but are lacking for adolescents. Here, we have adapted a brief imagery-based intervention (IMAGINE), which has shown promising results in reducing symptoms of depression in young people, to focus specifically on reducing symptoms of anhedonia (IMAGINE-Positive). We augment positive mental imagery generation with techniques to upregulate positive affect. Eight participants completed the four-session intervention. Data on feasibility and acceptability were collected. Questionnaires of symptomology and cognitive mechanisms (e.g. depression, anhedonia and future imagery vividness) were administered at pre-intervention, post-intervention and 3-month follow-up. The intervention was feasible to deliver and acceptable to participants. There was a large reduction in depression symptom scores from pre- to post-intervention (d = 1.12) and 63% of participants showed reliable improvement (RI), which was maintained at follow-up (d = 2.51, RI = 86%). Although there were only small reductions in anhedonia from pre to post (d = 0.38, RI = 0), there was a large reduction from pre to follow-up (d = 1.28, RI = 29%). There were also large increases in positive future imagery vividness (post, d =  − 1.08, RI = 50%; follow-up, d =  − 2.02, RI = 29%). Initial evidence suggests that IMAGINE-Positive is feasible and acceptable and may have clinical utility, but future randomised controlled trials are needed to further evaluate efficacy.

Drop-out, adherence, and compliance in randomized controlled trials of exercise training in multiple sclerosis: Short report

We documented reporting and rates of drop-out, adherence, and compliance from 40 randomized controlled trials (RCTs) included in our meta-analysis on safety of exercise training (ET) in MS. We adopted definitions and metrics of adherence and compliance provided by the MoXFo adherence group. Drop-out was reported in 100% of the RCTs and approximated 10% for intervention and control conditions. Adherence and compliance were reported in approximately 50% and 10% of the RCTs, respectively, and approximated 80% and 70%, respectively. Standardized metrics for reporting adherence and compliance are important in future RCTs for understanding the impact on outcomes and translation of research evidence into practice.

The intensity paradox: A systematic review and meta-analysis of its impact on the cardiorespiratory fitness of older adults.

The present systematic review and meta-analysis aimed to compare the effect of moderate- versus high-intensity aerobic exercise on cardiorespiratory fitness (CRF) in older adults, taking into account the volume of exercise completed. The databases MEDLINE (Ovid), EMBASE (Ovid), and CENTRAL (Cochrane Library) were searched to identify randomized controlled trials (RCTs). Two reviewers extracted data and assessed bias. Comprehensive Meta-Analysis software calculated overall effect size, intensity differences, and performed meta-regression analyses using pre-to-post intervention or change scores of peak oxygen uptake (V̇O2 peak). The review included 23 RCTs with 1332 older adults (intervention group: n = 932; control group: n = 400), divided into moderate-intensity (435 older adults) and high-intensity (476 older adults) groups. Meta-regression analysis showed a moderate, but not significant, relationship between exercise intensity and improvements in V̇O2 peak after accounting for the completed exercise volume (β = 0.31, 95% CI = [-0.04; 0.67]). Additionally, studies comparing moderate- versus high-intensity revealed a small, but not significant, effect in favor of high-intensity (Hedges' g = 0.20, 95% CI = [-0.02; 0.41]). Finally, no significant differences in V̇O2 peak improvements were found across exercise groups employing various methods, modalities, and intensity monitoring strategies. Findings challenge the notion that high-intensity exercise is inherently superior and indicate that regular aerobic exercise, irrespective of the specific approach and intensity, provides the primary benefits to CRF in older adults. Future RCTs should prioritize valid and reliable methodologies for monitoring and reporting exercise volume and adherence among older adults.