Large Treatment Effects Research Articles

Uphill Treadmill Running and Joint Mobilization Improve Dynamic Stability and Ankle Dorsiflexion Range of Motion in Young Adults With Chronic Ankle Instability: A Four-Arm Randomized Controlled Trial

ObjectiveTo observe the effect of uphill running and the combined effect of uphill running plus joint mobilizations on dynamic stability and ankle dorsiflexion in young adults with chronic ankle instability (CAI). DesignFour-arm randomized controlled trial. SettingA college rehabilitation center. ParticipantsIndividuals with CAI (N=73). InterventionsParticipants were randomly assigned to 4 groups: combined uphill running and joint mobilization (URJM), uphill running alone (UR), joint mobilization alone (JM), and control group. The URJM and UR groups received 20-minute running sessions, and the URJM and JM groups received ankle joint mobilizations, all 3 times a week for 4 weeks. Main Outcome MeasuresCumberland Ankle Instability Tool (CAIT) and Y-balance test (YBT) in anterior, posteromedial (PM), and posterolateral (PL) directions for dynamic stability; weight-bearing lunge test and non-weight-bearing ankle dorsiflexion degree using a goniometer (NWBG) for dorsiflexion. ResultsThe UR group showed significant improvements in CAIT, YBT-PL, YBT-PM, and NWBG compared to the control group. The URJM group demonstrated large treatment effects in NWBG compared to both UR and JM groups. Responder analysis indicated that the UR, JM, and URJM groups had a higher likelihood of achieving clinically significant changes (exceeding minimal detectable change or minimal clinically important difference) in CAIT, YBT-PM, YBT-PL, and NWBG compared with the control group. Additionally, the combination of UR and JM was superior to either intervention alone for NWBG, with success rates 1.55 times greater than UR alone and 2.08 times greater than JM alone. ConclusionsA 4-week UR program improves the subjective feeling of instability, dynamic postural control, and ankle dorsiflexion in young adults with CAI. Compared to UR or JM alone, their combined application can better improve the non-weight-bearing ankle dorsiflexion range of motion.

Reception to and Efficacy of a Serious Video Game for Correctional Intervention: Project Choices

Project Choices ( PC), a newly developed videogame for correctional intervention, consists of realistic decision-making scenarios and cognitive behavioral skills feedback. A pilot study investigated PC engagement and immersion by employing a cross-over design with a sample of 24 men on probation remanded to residential treatment. The study also examined effects of gameplay on criminogenic thinking, self-perceived criminogenic risk, and social problem-solving. As hypothesized, relative to a leisure video game ( Tetris), participants generally appeared comparably engaged by and immersed in PC. Most hypothesized effects of PC on treatment-relevant outcomes were not statistically significant; however, PC contributed to moderate to large treatment effects across most outcomes of interest. Although results are promising, PC requires further validation to determine whether it could serve as a useful adjunctive tool for practitioners hoping to further reach and engage corrections clients in criminogenic risk-reduction services. Future research directions for technology like PC are numerous and encouraged.

Nurse-delivered sleep restriction therapy to improve insomnia disorder in primary care: the HABIT RCT.

Insomnia is a prevalent and distressing sleep disorder. Multicomponent cognitive-behavioural therapy is the recommended first-line treatment, but access remains extremely limited, particularly in primary care where insomnia is managed. One principal component of cognitive-behavioural therapy is a behavioural treatment called sleep restriction therapy, which could potentially be delivered as a brief single-component intervention by generalists in primary care. The primary objective of the Health-professional Administered Brief Insomnia Therapy trial was to establish whether nurse-delivered sleep restriction therapy in primary care improves insomnia relative to sleep hygiene. Secondary objectives were to establish whether nurse-delivered sleep restriction therapy was cost-effective, and to undertake a process evaluation to understand intervention delivery, fidelity and acceptability. Pragmatic, multicentre, individually randomised, parallel-group, superiority trial with embedded process evaluation. National Health Service general practice in three regions of England. Adults aged ≥ 18 years with insomnia disorder were randomised using a validated web-based randomisation programme. Participants in the intervention group were offered a brief four-session nurse-delivered behavioural treatment involving two in-person sessions and two by phone. Participants were supported to follow a prescribed sleep schedule with the aim of restricting and standardising time in bed. Participants were also provided with a sleep hygiene leaflet. The control group received the same sleep hygiene leaflet by e-mail or post. There was no restriction on usual care. Outcomes were assessed at 3, 6 and 12 months. Participants were included in the primary analysis if they contributed at least one post-randomisation outcome. The primary end point was self-reported insomnia severity with the Insomnia Severity Index at 6 months. Secondary outcomes were health-related and sleep-related quality of life, depressive symptoms, work productivity and activity impairment, self-reported and actigraphy-defined sleep, and hypnotic medication use. Cost-effectiveness was evaluated using the incremental cost per quality-adjusted life-year. For the process evaluation, semistructured interviews were carried out with participants, nurses and practice managers or general practitioners. Due to the nature of the intervention, both participants and nurses were aware of group allocation. We recruited 642 participants (n = 321 for sleep restriction therapy; n = 321 for sleep hygiene) between 29 August 2018 and 23 March 2020. Five hundred and eighty participants (90.3%) provided data at a minimum of one follow-up time point; 257 (80.1%) participants in the sleep restriction therapy arm and 291 (90.7%) participants in the sleep hygiene arm provided primary outcome data at 6 months. The estimated adjusted mean difference on the Insomnia Severity Index was -3.05 (95% confidence interval -3.83 to -2.28; p < 0.001, Cohen's d = -0.74), indicating that participants in the sleep restriction therapy arm [mean (standard deviation) Insomnia Severity Index = 10.9 (5.5)] reported lower insomnia severity compared to sleep hygiene [mean (standard deviation) Insomnia Severity Index = 13.9 (5.2)]. Large treatment effects were also found at 3 (d = -0.95) and 12 months (d = -0.72). Superiority of sleep restriction therapy over sleep hygiene was evident at 3, 6 and 12 months for self-reported sleep, mental health-related quality of life, depressive symptoms, work productivity impairment and sleep-related quality of life. Eight participants in each group experienced serious adverse events but none were judged to be related to the intervention. The incremental cost per quality-adjusted life-year gained was £2075.71, giving a 95.3% probability that the intervention is cost-effective at a cost-effectiveness threshold of £20,000. The process evaluation found that sleep restriction therapy was acceptable to both nurses and patients, and delivered with high fidelity. While we recruited a clinical sample, 97% were of white ethnic background and 50% had a university degree, which may limit generalisability to the insomnia population in England. Brief nurse-delivered sleep restriction therapy in primary care is clinically effective for insomnia disorder, safe, and likely to be cost-effective. Future work should examine the place of sleep restriction therapy in the insomnia treatment pathway, assess generalisability across diverse primary care patients with insomnia, and consider additional methods to enhance patient engagement with treatment. This trial is registered as ISRCTN42499563. The award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/84/01) and is published in full in Health Technology Assessment; Vol. 28, No. 36. See the NIHR Funding and Awards website for further award information.

Dynamic Deconstructive Psychotherapy for Suicidal Adolescents: Effectiveness of Routine Care in an Outpatient Clinic.

Suicidal behavior and demand for services have been increasing in adolescents. Many of the current treatments are focused on symptom mitigation, crisis management, and safety planning; however, few are aimed at remediating underlying vulnerabilities that may be contributing to suicide risk. Dynamic Deconstructive Psychotherapy (DDP) has been found to be effective for suicidal adults but has never been studied for adolescents. The present study examined real-world outcomes of 65 suicidal adolescents, aged 13-17 years, receiving weekly DDP in an outpatient clinic. The primary outcome was change in suicide ideation from baseline to 6 months of treatment as assessed by the Suicide Ideation Subscale of the Columbia Suicide Severity Rating Scale. In intent-to-treat analyses, suicide ideation significantly decreased over the 6 months with a large treatment effect (d = 1.19). Secondary measures, such as suicide attempts, self-harm, depression, anxiety, disability, self-compassion, and inpatient utilization, also improved significantly. Among the 42 adolescents (65%) who completed at least 6 months of treatment, suicide attempts decreased by 84%. DDP may be effective in reducing suicide ideation and other risk factors in suicidal adolescents and may be cost-effective given reduced inpatient utilization. These initial promising findings warrant further research and development.

Exploratory subgroup identification in the heterogeneous Cox model: A relatively simple procedure.

For survival analysis applications we propose a novel procedure for identifying subgroups with large treatment effects, with focus on subgroups where treatment is potentially detrimental. The approach, termed forest search, is relatively simple and flexible. All-possible subgroups are screened and selected based on hazard ratio thresholds indicative of harm with assessment according to the standard Cox model. By reversing the role of treatment one can seek to identify substantial benefit. We apply a splitting consistency criteria to identify a subgroup considered "maximally consistent with harm." The type-1 error and power for subgroup identification can be quickly approximated by numerical integration. To aid inference we describe a bootstrap bias-corrected Cox model estimator with variance estimated by a Jacknife approximation. We provide a detailed evaluation of operating characteristics in simulations and compare to virtual twins and generalized random forests where we find the proposal to have favorable performance. In particular, in our simulation setting, we find the proposed approach favorably controls the type-1 error for falsely identifying heterogeneity with higher power and classification accuracy for substantial heterogeneous effects. Two real data applications are provided for publicly available datasets from a clinical trial in oncology, and HIV.

Investigating the efficacy of digital cognitive behavioural therapy in comparison to a sleep-monitoring application via integrated diary and actigraphy: A randomised-controlled trial.

Dissemination of digital cognitive behavioural therapy is a promising approach for treating insomnia in the broad population. Current evidence supports the effectiveness of the digital format, but clinical findings are often limited by the choice of control group and lack of in-depth therapeutic measures. This study was designed to investigate the specific effects of digital cognitive behavioural therapy in comparison to a self-monitoring application. Participants meeting criteria for insomnia were randomly allocated (1:1) to 8 weeks of digital cognitive behavioural therapy or 8 weeks of digital sleep monitoring (control application). The primary outcome, insomnia severity, was assessed at baseline, 8- and 16-weeks post-randomisation. Secondary outcomes included the assessment of sleep via application-integrated sleep diaries and actigraphy. Linear-mixed models were fitted to assess between-group differences. Fifty-six participants (48 females, mean age: M = 45.55 ± 13.70 years) were randomised to either digital cognitive behavioural therapy (n = 29) or digital sleep monitoring (n = 27). At 8- and 16-weeks post-randomisation, large treatment effects (d = 0.87-1.08) indicated robust reductions (-3.70 and -2.97, respectively; p ≤ 0.003) in insomnia severity in the digital cognitive behavioural therapy arm, relative to digital sleep monitoring. Treatment effects in favour of digital cognitive behavioural therapy were also found for self-reported and actigraphy-derived sleep continuity variables, indicating that sleep improved throughout the 8-week intervention period. Our study reinforces the role of digital cognitive behavioural therapy in achieving clinical improvements for patients with insomnia, affirming previous findings and supporting the specific effects of cognitive behavioural therapy.

Stratified Patient Profiling for Vedolizumab Effectiveness in Crohn's Disease: Identifying Optimal Subgroups for Enhanced Treatment Response in the EVOLVE Study.

This analysis evaluated the relative performance of vedolizumab and anti-tumor necrosis factor alpha (anti-TNFα) agents in subpopulations of biologic therapy-naive patients with Crohn's disease (CD) and assessed whether patients in whom vedolizumab would have a larger treatment effect vs anti-TNFα agents could be identified. Data were from EVOLVE, a real-world, multicountry, retrospective cohort study of patients with inflammatory bowel disease who initiated first-line biologic treatment with vedolizumab (n = 195) or anti-TNFα agents (n = 245). Prediction models for time to clinical remission were developed in vedolizumab- and anti-TNFα-treated patients and used to estimate effect scores, a metric of predicted comparative efficacy, for each patient. Patients were ranked by effect scores and potential subpopulations were investigated. Simplified rules to identify these subpopulations were also developed using classification tree analysis. Among all patients, median time to clinical remission was 7.8months (vedolizumab) and 11.1months (anti-TNFα) (P < 0.05). Among patients in the top 40% of the effect score distribution, the median time to clinical remission was 4.8months (vedolizumab) vs 18.1months (anti-TNFα) (adjusted hazard ratio 2.0, 95% confidence interval 1.3-2.9). A simplified rule for identifying a subpopulation more likely to benefit from vedolizumab was based on having an ongoing CD exacerbation, no prior emergency visits, and non-stricturing disease. Subpopulations of biologic-naive patients with CD in whom vedolizumab appeared to have a larger effect relative to anti-TNFα agents for the outcome of clinical remission were identified. Validation of the identified subpopulations and simplified rules are warranted to confirm these findings. NCT03710486. Graphical Abstract available for this article.

Internet-delivered therapy for alcohol misuse: engagement, satisfaction, and outcomes when patients select their preference for therapist- or self-guided treatment

BackgroundAlcohol misuse is common and causes substantial harm. Internet-delivered cognitive behaviour therapy (ICBT) is effective in reducing alcohol misuse; however, the literature investigating how treatment outcomes are impacted by patients’ preferences for therapist- versus self-guided ICBT for alcohol misuse is sparse.MethodsIn this preference trial, 74 eligible patients (who reported ≥ 14 drinks in the previous week and obtained scores suggesting hazardous or harmful drinking) chose between enrolling in either therapist- or self-guided ICBT for alcohol misuse. We investigated whether those who chose therapist- versus self-guided ICBT differed in their (a) drinking outcomes—as measured by Timeline Follow-Back (TLFB) and heavy drinking days (HDD) at post-treatment and 3-month follow-up—and (b) post-treatment ICBT engagement and satisfaction.ResultsThe majority (81.1%) of eligible patients chose therapist-guided ICBT. These patients reported higher psychotropic medication use, drinking difficulties, and anxiety symptoms. For both the therapist- and self-guided patients, a modified intention-to-treat analysis revealed large within-group treatment effects for TLFB (β = − 2.64, SE 0.66; p < 0.001) and HDD (β = − 0.34, SE 0.07; p < 0.001), with large pre-to-post-treatment Cohen’s effect sizes of d = 0.97 (95% CI [0.49, 1.45]) for TLFB and d = 1.19 (95% CI [0.69, 1.68]) for HDD. The interaction comparing the effects of therapist- to self-guided ICBT over time was not significant for TLFB (p = 0.34) or HDD (p = 0.06). With treatment, for both therapist- and self-guided patients, there was a significant improvement in drinking difficulties, cravings, and confidence with controlling cravings, as well as in anxiety, depression, and functional impairment. Further, the majority (75.7%) of patients completed five or more lessons, as well as reported overall satisfaction with the treatment (88.9%) and increased confidence in managing their symptoms (86.7%); these outcomes also did not differ between therapist- and self-guided patients.ConclusionsThe current study shows that ICBT for alcohol misuse is associated with reduced drinking and comorbid mental health difficulties over time, irrespective of whether patients chose to complete the course on their own or with therapist guidance.Trial registration number: NCT04611854 (https://clinicaltrials.gov/ct2/show/NCT04611854).

Responsibility for impairment shapes the perceived deservingness of welfare claimants with disabilities

AbstractWhen do people support government assistance for people with disabilities? Disability welfare programs account for large shares of national welfare budgets, but little is known about public attitudes toward disabled welfare claimants. Drawing on psychological research in stereotype content, we argue that attitudes toward welfare for people with disabilities are likely to be more conditional than previously acknowledged. In two nationally representative, preregistered survey experiments in Wales (N = 3393) and Scotland (1707), we ask respondents to evaluate the deservingness of a fictitious disabled claimant to government assistance. We manipulate the claimant's outgroup status and the manner in which they acquired their impairment. We find that disabled claimants perceived as even somewhat responsible for their impairments are considered substantially less deserving of government assistance than those perceived not responsible, even when their needs for assistance are identical. Contrary to expectations, we find relatively modest and inconsistent outgroup penalties in perceived deservingness. Finally, we find large heterogeneous treatment effects among respondents holding to more authoritarian social values. These results challenge conventional wisdom regarding the universality of support for disability welfare and help explain why voters may not be inclined to punish politicians who propose cuts to programs for even stereotypically high‐deserving groups.

The effectiveness of cervical rehabilitation interventions for pain in adults with myogenic temporomandibular disorders: A systematic review and meta-analysis.

Little evidence exists for the most effective conservative treatment approach for adults with myogenic temporomandibular disorders (MTMD). We aim to assess the effectiveness of cervical rehabilitation interventions on pain intensity and sensitivity in adults with MTMD compared to comparison intervention such as placebo, sham treatment, education or no intervention. For this systematic review and meta-analysis, we searched PubMed, EMBASE, Medline, PEDro databases, forward and backward citations and grey literature studies through PROSPERO, clinical trials and data registries without language or date restrictions between inception and 1 December 2021. We selected randomised controlled trials (RCTs) based on adult populations with MTMD who had a cervical rehabilitation intervention which was defined as any conservative intervention targeting the anatomical structures of the cervical spine. The primary outcome measures for pain were self-reported pain intensity and pain sensitivity through the pressure pain threshold (PPT) of the masseter and temporalis muscles. Secondary outcome measures of maximal mouth opening (on MMO) were included. Included studies were assessed for bias with the Cochrane risk of bias tool for randomised trials. Evidence from RCTs was synthesised to determine treatment effect size as differences between standardised mean difference (SMD) for changes in pain intensity, PPT and MMO comparing adults with MTMD who were treated with cervical rehabilitation interventions compared to a control group. This study is registered on Prospero, number CRD 42021289299. Our general search yielded 2647 studies where seven RCTs met eligibility criteria with low to some concerns in their risk of bias. Pain intensity (five studies, n = 223, SMD -0.98, 95% CI -1.67 to -0.28, I2 = 79%), PPT of the masseter muscle (six studies, n = 395, SMD 0.64, 95% CI 0.43 to 0.86, I2 = 90%) and the temporalis muscles (five studies, n = 295, SMD 0.76, 95% CI 0.07 to 1.45, I2 = 84%) showed large treatment effect estimates favouring cervical rehabilitation interventions compared to no treatment, sham cervical treatment, patient education or non-cervical neuromuscular techniques. Compared to control interventions, one type of cervical rehabilitation intervention, cervical manual therapy alone or in combination with a neck exercise program was associated with statistically significant, large treatment effect estimates on pain intensity (four studies, n = 203, SMD -1.52, 95% CI -2.50 to -0.55). This review found that in the short-term, cervical rehabilitation interventions especially upper cervical MT alone or in combination with a neck exercise program are effective in improving multiple pain outcomes in adults with MTMD. However, further research is needed to measure the long-term effects of this type of intervention.

Comparison of Vaginal Pessaries to Standard Care or Pelvic Floor Muscle Training for Treating Postpartum Urinary Incontinence: a Pragmatic Randomized Controlled Trial.

To compare three conservative treatment options, standard care, pelvic floor muscle training (PFMT), and vaginal pessaries, for postpartum urinary incontinence (UI) that are accessible to most patients and practitioners in a generalizable cohort. A multicenter, open-label, parallel group, pragmatic randomized controlled clinical trial comparing standard care, PFMT, and vaginal cube pessary for postpartum urinary incontinence was conducted in six outpatient clinics. Sample size was based on large treatment effects (Cramers' V>0.35) with a power of 80% and an alpha of 0.05 for a 3×3 contingency table, 44 patients needed to be included in the trial. Outcomes were analyzed according to the intention-to-treat principle. Group comparisons were made using analysis of variance (ANOVA), Kruskal-Wallis, and chi-square test as appropriate. P<0.05 was considered statistically significant. Of the 516 women screened, 111 presented with postpartum UI. Of these, 52 were randomized to one of three treatment groups: standard care (n=17), pelvic floor muscle training (n=17), or vaginal cube pessary (n=18). After 12 weeks of treatment, treatment success, as measured by patient satisfaction, was significantly higher in the vaginal pessary group (77.8%, n=14/18), compared to the standard care group (41.2%, n=7/17), and the PFMT (23.5%, n=4/17; χ 2 2,n=52 =14.55; p=0.006, Cramer-V=0.374). No adverse events were reported. SUI and MUI accounted for 88.4% of postpartum UI. Vaginal pessaries were superior to standard care or PFMT to satisfyingly reduce postpartum UI symptoms. No complications were found.

A psychoeducational intervention to improve sexual functioning in male rectal and anal cancer patients: A pilot randomized controlled trial study.

Male rectal and anal cancer patients demonstrate high rates of sexual dysfunction. This pilot randomized controlled trial tested a psychoeducational intervention designed to improve psychosexual adjustment. Rectal or anal cancer patients were randomized to a Sexual Health Intervention for Men (intervention) or to a referral and information control (control). The intervention included control activities plus 4 sexual health intervention sessions every 4-6 weeks and 3 brief telephone calls timed between these sessions. Assessments were completed pre-intervention (baseline) and 3 months (follow-up 1) and 8 months (follow-up 2) post-intervention. Differences were assessed with statistical significance and Cohen's d effect sizes (d = 0.2, small effect; d = 0.5, moderate effect; d = 0.8, large effect). Ninety subjects enrolled. Forty-three participants completed at least 1 follow-up assessment (intervention, n = 14; control n = 29). At follow-up 1, men in intervention, compared to control, improved on all domains of the International Index of Erectile Function (IIEF) (p < 0.001 to p < 0.05) and demonstrated large effects (d = 0.8 to d = 1.5). Similarly, at follow-up 2, changes in all domains of the IIEF except the orgasm domain were either statistically significant or marginally statistically significant (p = 0.01 to p = 0.08) and demonstrated moderate to large treatment effects for intervention versus control (d = 0.5 to d = 0.8). Men in the intervention, compared to control, demonstrated decreased sexual bother at follow-up 1 (p = 0.009, d = 1.1), while Self-Esteem and Relationship (SEAR) total scores and the SEAR sexual relationship subscale demonstrated moderate increases for intervention versus control (d = 0.4 to d = 0.6). This study provides initial evidence for combining a psychoeducational intervention with medical interventions to address sexual dysfunction following rectal and anal cancer. Trials register number: NCT00712751 (date of registration: 7/10/2008).

Acupuncture for Combat-Related Posttraumatic Stress Disorder

Current interventions for posttraumatic stress disorder (PTSD) are efficacious, yet effectiveness may be limited by adverse effects and high withdrawal rates. Acupuncture is an emerging intervention with positive preliminary data for PTSD. To compare verum acupuncture with sham acupuncture (minimal needling) on clinical and physiological outcomes. This was a 2-arm, parallel-group, prospective blinded randomized clinical trial hypothesizing superiority of verum to sham acupuncture. The study was conducted at a single outpatient-based site, the Tibor Rubin VA Medical Center in Long Beach, California, with recruitment from April 2018 to May 2022, followed by a 15-week treatment period. Following exclusion for characteristics that are known PTSD treatment confounds, might affect biological assessment, indicate past nonadherence or treatment resistance, or indicate risk of harm, 93 treatment-seeking combat veterans with PTSD aged 18 to 55 years were allocated to group by adaptive randomization and 71 participants completed the intervention protocols. Verum and sham were provided as 1-hour sessions, twice weekly, and participants were given 15 weeks to complete up to 24 sessions. The primary outcome was pretreatment to posttreatment change in PTSD symptom severity on the Clinician-Administered PTSD Scale-5 (CAPS-5). The secondary outcome was pretreatment to posttreatment change in fear-conditioned extinction, assessed by fear-potentiated startle response. Outcomes were assessed at pretreatment, midtreatment, and posttreatment. General linear models comparing within- and between-group were analyzed in both intention-to-treat (ITT) and treatment-completed models. A total of 85 male and 8 female veterans (mean [SD] age, 39.2 [8.5] years) were randomized. There was a large treatment effect of verum (Cohen d, 1.17), a moderate effect of sham (d, 0.67), and a moderate between-group effect favoring verum (mean [SD] Δ, 7.1 [11.8]; t90 = 2.87, d, 0.63; P = .005) in the intention-to-treat analysis. The effect pattern was similar in the treatment-completed analysis: verum d, 1.53; sham d, 0.86; between-group mean (SD) Δ, 7.4 (11.7); t69 = 2.64; d, 0.63; P = .01). There was a significant pretreatment to posttreatment reduction of fear-potentiated startle during extinction (ie, better fear extinction) in the verum but not the sham group and a significant correlation (r = 0.31) between symptom reduction and fear extinction. Withdrawal rates were low. The acupuncture intervention used in this study was clinically efficacious and favorably affected the psychobiology of PTSD in combat veterans. These data build on extant literature and suggest that clinical implementation of acupuncture for PTSD, along with further research about comparative efficacy, durability, and mechanisms of effects, is warranted. ClinicalTrials.gov Identifier: NCT02869646.

Addressing Participation in Adults With Postconcussive Symptoms Using Cognitive Strategy Training: A Feasibility Trial.

Some people experience persistent symptoms after a concussion that greatly affect occupational performance. To evaluate the feasibility and preliminary effect of metacognitive strategy training in a sample of adults with postconcussive symptoms. Single-group, prospective design. University research laboratory. Adults with persistent concussive symptoms affecting function (N = 14). Ten 45-min sessions of a metacognitive strategy training intervention, Cognitive Orientation to daily Occupational Performance (CO-OP). Assessed feasibility outcomes included recruitment, retention, and adherence rates, and intervention acceptability was evaluated with the Client Satisfaction Questionnaire-8. The preliminary effect was measured on occupational performance (Canadian Occupational Performance Measure), concussive symptoms (Neurobehavioral Symptom Inventory), sleep (Pittsburgh Sleep Quality Inventory), vision (College of Optometrists in Vision Development-Quality of Life Outcomes Assessment), and cognition outcomes (Dysexecutive Questionnaire, Weekly Calendar Planning Activity, and National Institutes of Health Toolbox Cognition Battery). Acceptable recruitment (32%), retention (93%), and adherence rates (100%) were observed, along with a high level of acceptability to participants. Large intervention effects were present for occupational performance, general concussive symptoms, and cognitive functioning. Findings suggest that the CO-OP is feasible to administer for adults with postconcussive symptoms and perceived as suitable for the needs of this population. Feasibility findings, coupled with improvements in occupational performance outcomes, provide the foundation for a future larger scale trial. Plain-Language Summary: The Cognitive Orientation to daily Occupational Performance intervention is practical to use to address the functional impact of persistent concussive symptoms in adults. Further research is needed to evaluate the efficacy of the CO-OP intervention with this population.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

Early developmental intervention programmes provided post hospital discharge to prevent motor and cognitive impairment in preterm infants.

SIFT IT: A feasibility and preliminary efficacy randomized controlled trial of a social cognition group treatment programme for people with acquired brain injury

ABSTRACT Making sense of social situations requires social cognitive skills, which can be impaired after acquired brain injury (ABI), yet few evidence-based treatment options are available. This study aimed to evaluate the feasibility of a multi-faceted social cognition group treatment programme, SIFT IT, for people after ABI using an RCT design. Twenty-eight participants were recruited, and 23 were randomized into either Treatment or Waitlist. SIFT IT consisted of 14 weekly 90-minute small group sessions facilitated by a Clinical Psychologist. Topics included: emotion self-awareness, emotion perception, perspective taking, and choosing adaptive social responses. Preliminary efficacy outcomes were assessed at baseline, post-treatment, and three-month follow-up. Demand for treatment was evident with 61% recruitment and 91% post-treatment retention rates, with 63% attending at least 13/14 sessions. Large between-group treatment effects (with non-zero 95% confidence intervals) were observed for emotion perception, detecting hints, and informant ratings of social cognitive deficits. Implementation challenges recruiting to groups and maintaining group allocation fidelity, with a small sample size does, however, raise questions about the appropriateness of an RCT design in a future efficacy trial. Overall, this study showed there is demand for social cognitive interventions after ABI and the SIFT IT programme was practicable and acceptable to participants. Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12617000405314.

Abstract 40: Relationship of Collateral Status With Clinical Outcomes in Endovascular Thrombectomy for Large Core Stroke: A SELECT2 Subanalysis

Background: Previous studies demonstrating association of collateral status with clinical outcomes after endovascular thrombectomy (EVT) excluded patients with large core infarcts. We analyzed the association of collateral status with clinical outcomes and EVT treatment effect in SELECT2. Methods: In SELECT2, a central core lab adjudicated CT-angiographic collateral status using collateral scores (CS) by Tan et al. Patients were stratified based on CS into poor (CS 0-1) vs good (CS 2-3) collaterals. The primary outcome was the distribution of modified Rankin Scale score at 90-day follow-up. Models were adjusted for core volume, ASPECTS in addition to age, stroke severity and time to randomization. Results: Of 352 patients, 180 received EVT. Median collateral status was 2(IQR 1-2). Patients presenting &lt;6h after last known well (LKW) (n=100) had poorer collaterals than those presenting at 6-24 hours (n=252), median 1 (1-2) vs 2 (1-2), p&lt;0.001. Collateral status inversely correlated with CTP core volume (Rho=-0.32, p&lt;0.0001), but not with CT ASPECTS (Rho=0.07, p=0.16). Overall, point estimates favored EVT in patients with poor (CS 0-1) [aGenOR: 1.32, 95% CI: 0.98-1.79, p=0.068] and good (CS 2-3) collaterals [aGenOR: 1.97, 95% CI: 1.43-2.72, p&lt;0.001] without significant heterogeneity [p-interaction=0.094]. However, in the earlier 0-6h time window, there was evidence of treatment effect hetermogeneity with a larger treatment effect when good collaterals were present [aGenOR: 4.10, 95% CI: 1.81-9.29] and an absent treatment effect when only poor collaterals were observed [aGenOR: 1.26, 95% CI: 0.79-1.99], p-interaction=0.023. In the late time window, (6-12h), the EVT treatment effect did not differ significantly between poor collaterals (aGenOR: 1.35, 95% CI: 0.91-2.01) and good collaterals (aGenOR: 1.78, 95% CI: 1.24-2.56, p-interaction=0.50). Conclusion: Collateral status was worse in large core patients presenting in early (&lt;6 hours) window; and correlated with ischemic core volume but not ASPECTS. Collaterals status modified EVT treatment effect in the early but not the late time window, in which both good and poor collaterals still benefited from EVT. Clinicaltrials.gov registration: NCT03876457

A Two-Stage Covariate-Adjusted Response-Adaptive Enrichment Design

In the precision medicine paradigm, it is of interest to identify subgroups that benefit most from the treatment. However, the subgroup often cannot be identified until after a large-scale clinical trial. Clinical trials are often designed under the assumption of no treatment-by-covariate interaction effect and enroll all comers. This makes many patients go through unnecessary treatment and may decrease the efficiency of the trial. We propose a two-stage enrichment design that uses covariate-adjusted response-adaptive (CARA) allocation and a novel interaction pseudo-randomization test to evaluate the interaction effect in the interim analysis for binary and continuous outcomes. A pre-defined alpha level is used as the threshold to decide whether a subgroup will be identified and recruited in the second stage. If a below-threshold interaction effect is found, a regression model will be fit and the stratum with the largest treatment effect will be chosen as the best stratum. The trial will continue to the second stage with patients from the best stratum only. If the p-value from the interim analysis is above the threshold, the trial continues with all patients. The primary aim is to test the treatment effect between treatment groups. Different CARA procedures are compared in terms of type I error rates, power, and ethical considerations. The CARA procedure that balances better between efficiency and ethics is used in the proposed two-stage enrichment design.

Effects of a remotely supervised resistance training program on muscle strength and body composition in adults with cystic fibrosis: Randomized controlled trial

AbstractIntroductionAmong the limited studies on physical exercise interventions in adults with cystic fibrosis (CF), few have specifically addressed the improvement of peripheral muscle strength and body fat‐free mass. The aim of this study was to examine the impacts of a remotely supervised, individualized 8‐week resistance training program of moderate to high intensity on strength and body composition in these subjects.MethodsThis was a randomized controlled trial performed in adults with CF. The exercise group (EX) performed three 1‐h resistance training sessions per week over 8 weeks. The control group (CON) followed the physical activity recommendations of their physician. The main outcomes were muscle strength and body composition, with secondary measures including pulmonary function and quality of life. Two‐way repeated measures analysis was used.ResultsIn 23 participants (age 32.13 ± 7.72 years), the intervention showed a significant beneficial effect on leg press strength, with a large effect size, both in absolute (p = 0.011; = 0.281) and relative (p = 0.007; = 0.310) terms. Large intervention effects were observed on total fat mass (p &lt; 0.001; = 0.415), body adiposity index (p &lt; 0.001; = 0.436), and fat mass index (p &lt; 0.001; = 0.445), all showing reduction in the EX group. In addition, significant large size effects were detected on total fat‐free mass (p = 0.046; = 0.177), trunk fat‐free mass (p = 0.039; = 0.188), and fat‐free mass index (p = 0.048; = 0.174), all favoring exercise. No significant effects were observed on pulmonary function and quality of life.ConclusionsAn 8‐week remotely supervised resistance training program, with moderate to high intensity, effectively improved lower limb muscle strength and body composition.

Comparison of cardiac magnetic resonance imaging, functional and haemodynamic variables in pulmonary arterial hypertension: insights from REPAIR.

Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 European Society of Cardiology/European Respiratory Society guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (cMRI) comparable with functional and haemodynamic variables? REPAIR (ClinicalTrials.gov: NCT02310672) was a prospective, multicentre, single-arm, open-label, 52-week phase 4 study evaluating the effect of macitentan 10 mg, with or without a phosphodiesterase 5 inhibitor (PDE5i), on right ventricular (RV) remodelling, cardiac function and cardiopulmonary haemodynamics. Both cMRI and functional assessments were performed at screening and at weeks 26 and 52; haemodynamic measurements were conducted at screening and week 26. In this post hoc analysis, STES were estimated using the parametric Cohen's d and non-parametric Cliff's delta tests. At week 26, large STES (Cohen's d) were observed for 10 of the 20 cMRI variables assessed, including the prognostic measures of RV and left ventricular stroke volume and RV ejection fraction and the haemodynamic trial end-point, pulmonary vascular resistance; medium STES were observed for 6-min walk distance (6MWD). The STES were consistent in treatment-naïve patients and those escalating therapy and maintained at week 52. Similar results were obtained using the non-parametric Cliff's delta method. The treatment effect of macitentan, alone or in combination with a PDE5i, was comparable for several cMRI and haemodynamic variables with prognostic value in PAH, and greater than that of 6MWD in patients with PAH, highlighting the emerging relevance of cMRI in PAH.