Intervention Trial Research Articles

State of Geographic Access to Cancer Treatment Trials in the United States: Are Studies Located Where Patients Live?

In this study, we describe the geographic distribution of US cancer treatment trials to identify disparities and opportunities for targeted improvements in access to research for people with cancer. US-based phase I-III cancer treatment trials registered on ClinicalTrials.gov were tabulated for the years they were open to enrollment (2017-2022), overall and by county, and supplemented with data from the US Census Bureau, National Cancer Institute, Centers for Disease Control and Prevention, and US Department of Agriculture. We evaluated geographic differences in trial availability. We assessed 5-year trends in trials per capita and mapped 1-hour drive time areas around sites. A total of 6,710 trials were open to enrollment in 2022 across 1,836 sites. Trials increased by 4%, whereas sites decreased by 3% annually per capita from 2017. Seventy percent of US counties had no reported active trials in 2022 (2,211/3,143), representing 19% of people age ≥55 years. Eighty-six percent of nonmetropolitan counties had no trials versus 44% of metropolitan counties. Trial availability varied by county-level cancer mortality and social vulnerability (an index derived from demographic and socioeconomic data from the US Census). Eighteen percent of counties without trials had oncologist care sites (n = 618). Notably, 26% of people age ≥55 years lived beyond an hour drive of a site with ≥100 trials. Most US counties have limited to no trial offerings, a disparity magnified in counties that are nonmetropolitan, with high social vulnerability, and with high cancer mortality. Effort to facilitate diverse site participation is needed to promote equitable access to trials and to ensure patients participating in trials match the characteristics of patients who will receive interventions once approved. Counties with oncology care sites but no trials provide potential expansion areas.

Laryngeal Myasthenia Gravis in Voice Patients: Clinical, Serologic, and Neuromuscular Characterization of Seronegative Patients for Antibodies Against the Acetylcholine Receptor and Muscle-Specific Kinase

OBJECTIVELaryngeal myasthenia gravis (MG) is a focal manifestation of MG, and most patients are seronegative for antibodies against the acetylcholine receptor (AChR) and muscle specific kinase (MuSK). The purpose of this study was to determine the incidence of anti-AChR and anti-Musk antibodies in voice patients and to characterize the clinical and neuromuscular profiles of these patients in order to guide the diagnosis of laryngeal MG. STUDY DESIGNThis was a retrospective case-control study that included patients over the age of 18 who underwent laryngeal electromyography as part of their evaluation for neuromuscular junction dysfunction. METHODSCases and controls were evaluated serologically, for the anti-AChR, anti-MuSK, and anti-striational muscle antibodies, and neuromuscularly using the Tensilon test in some patients, repetitive nerve stimulation (RNS) test, and a treatment trial of pyridostigmine bromide. Cases were defined as either (1) positive anti-AChR or anti-MuSK, or (2) a positive Tensilon test or positive pyridostigmine bromide trial. RESULTSTwo hundred and eleven patients were screened; 61 (29%) patients were identified with laryngeal MG, and 77 (36%) patients were selected as controls. All case and control patients were seronegative for the anti-AChR and anti-MuSK antibodies with no significant difference between case and control status for seropositivity for anti-striational muscle antibodies. Of the case patients with an electrically positive Tensilon test (80.6%) who completed a treatment trial, 100% had symptom improvement. Of the case patients with a symptomatically positive Tensilon test (16.1%), only 60% of patients had improvement with a treatment trial. The RNS was more likely to be positive in case patients than control patients, and cases had a higher severity of paresis in all laryngeal muscles with LEMG evaluation. CONCLUSIONSLaryngeal MG is an underrecognized condition in the otolaryngology community owing in part to its seronegative presentation. Electrical improvement with a Tensilon test, or electrical or substantial symptomatic improvement with pyridostigmine bromide represent the most robust diagnostic criteria in these patients.

Core outcome set for studies evaluating interventions to prevent or treat delirium in long-term care older residents: international key stakeholder informed consensus study.

Trials of interventions to prevent or treat delirium in older adults resident in long-term care settings (LTC) report heterogenous outcomes, hampering the identification of effective management strategies for this important condition. Our objective was to develop international consensus among key stakeholders for a core outcome set (COS) for future trials of interventions to prevent and/or treat delirium in this population. We used a rigorous COS development process including qualitative interviews with family members and staff with experience of delirium in LTC; a modified two-round Delphi survey; and virtual consensus meetings using nominal group technique. The study was registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative (https://www.comet-initiative.org/studies/details/796). Item generation identified 22 delirium-specific outcomes and 32 other outcomes from 18 qualitative interviews. When combined with outcomes identified in our earlier systematic review, and following an item reduction step, this gave 43 outcomes that advanced to the formal consensus processes. These involved 169 participants from 12 countries, and included healthcare professionals (121, 72%), researchers (24, 14%), and family members/people with experience of delirium (24, 14%). Six outcomes were identified as essential to include in all trials of interventions for delirium in LTC, and were therefore included in the COS. These are: 'delirium occurrence'; 'delirium related distress'; 'delirium severity'; 'cognition including memory', 'admission to hospital' and 'mortality'. This COS, endorsed by the American Delirium Society and the European and Australasian Delirium Associations, is recommended for use in future clinical trials evaluating delirium prevention or treatment interventions for older adults residing in LTC.

Poor registration and publication practices in clinical trials of targeted therapeutics for endocrine and metabolic diseases: an observational study

ObjectiveTo assess the completeness and concordance of reporting in registries and corresponding publications of interventional trials on targeted therapeutics for endocrine and metabolic disorders. Study Design and SettingWe searched clinical trial registries in September 2022 for completed interventional trials of target therapeutics for endocrine and metabolic disorders registered from 2005 onwards. We used ClinicalTrials.gov and the World Health Organization International Clinical Trial Registration Platform (WHO ICTRP) registration requirements to extract data and assess the completeness of initial entry and final updates to trial registration and concordance with their published journal articles. ResultsAmong 149 clinical trials included, 121 (81%) had corresponding publications. Missing mandatory registration data items were identified in 88 (67%) trials at the initial registration, 17 (13%) at the last registration, and in 85 (77%) corresponding publications. All trials showed changes between initial registration and final registration update, and 98% showed changes from the initial registration to publication. Changes between initial registration and final update were most common in the categories ‘Completion date’ (92%), ‘Key secondary outcomes’ (82%), and ‘Date of first enrolment’ (70%). Changes between initial registration and publication were most common in categories ‘Sample size’ (91%), ‘Key inclusion and exclusion criteria’ (81%), ‘Key secondary outcomes’ (84%), and ‘Completion date’ (83%). ConclusionDespite the legal and journal registration requirements, the completeness and consistency of reporting mandatory data items in registries and corresponding publications regarding targeted therapeutics for endocrine and metabolic disorders are inadequate. Our findings raise questions about the integrity and reliability of clinical trials focusing on targeted therapeutics.

The Trial Enrollment Diversity Dashboard for Acute Leukemia Clinical Research: Intervention Development and Cohort Analysis.

Participation in acute leukemia clinical trials is inequitable across multiple sociodemographic categories. Tools that provide researchers with performance feedback on the representativeness of the patients they enroll are limited. We aimed to develop an electronic health record (EHR)-based dashboard to provide such feedback and to describe any enrollment inequities uncovered. We created a visual dashboard linking leukemia clinical trial registration and EHR data at the Dana-Farber Cancer Institute. Accuracy of a patient inclusion and assignment algorithm was tested with a target area under the receiver-operator curve (AUROC) of >0.90 against manual review. Demographic metric identification, visualization construction, and dashboard refinement were performed through stakeholder cognitive testing. Analysis of a recent 5-year cohort generated by the final algorithm assessed bivariate associations between enrollment and demographic metrics. Multivariable logistic regression included significant bivariate results. The final algorithm assignment AUROC was 0.98. Metrics were identified and visualizations successfully constructed. Fourteen individuals participated in testing and identified areas for revision: category mergers, denominator filters, and data delivery preferences. In the initial cohort of 1,315 patients, 1,020 (77.6%) had enrolled in any study protocol: 553 (42.1%) in a treatment trial and 936 (71.2%) in a biobanking study. In a multivariable model, older age (odds ratio [OR], 0.83 [95% CI, 0.73 to 0.94]) and Non-Hispanic Black race-ethnicity (OR, 0.38 [95% CI, 0.18 to 0.82]) were associated with lower enrollment, and English primary language with higher enrollment (OR, 2.50 [95% CI, 1.30 to 4.79]). We developed a research participation equity performance feedback dashboard for clinical researchers, and we identified actionable inequities. Next steps include feasibility and efficacy testing as well as implementation.

Contextualizing the results of HELIOS-B in the broader landscape of clinical trials for the treatment of transthyretin cardiac amyloidosis.

This focused review will highlight the results of HELIOS-B, the first randomized outcomes trial evaluating a gene silencing treatment for transthyretin cardiac amyloidosis (ATTR-CM). In HELIOS-B, vutrisiran was tested against placebo and demonstrated a 28% reduction in the composite of all-cause mortality and recurrent cardiovascular events. Additionally, there were clinically significant benefits on the 6-min walk test, Kansas City Cardiomyopathy Questionnaire, and NYHA class. Discontinuation rates and adverse events were similar between treatment and control arms, suggesting that vutrisiran is well tolerated. In this review, these promising results are explored and compared with other treatment trials in ATTR-CM.

The effect of two speech and language approaches on speech problems in people with Parkinson's disease: the PD COMM RCT.

Speech impairments are common with Parkinson's disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson's disease to no speech and language therapy (control) and against each other. PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. United Kingdom outpatient and home settings. People with idiopathic Parkinson's disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson's Disease Questionnaire - Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD (n = 130), National Health Service speech and language therapy (n = 129) and control (n = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [-8.0 (99% confidence interval: -13.3, -2.6); p = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: -3.8, 7.1); p = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: -9.6 (-14.9, -4.4); p < 0.0001]. There were no reports of serious adverse events. Staff were confident with the trial interventions; a range of patient and therapist enablers of implementing Lee Silverman Voice Treatment LOUD were identified. The economic evaluation results suggested Lee Silverman Voice Treatment LOUD was more expensive and more effective than control or National Health Service speech and language therapy but was not cost-effective with incremental cost-effectiveness ratios of £197,772 per quality-adjusted life-year gained and £77,017 per quality-adjusted life-year gained, respectively. The number of participants recruited to the trial did not meet the pre-specified power. People that had access to Lee Silverman Voice Treatment LOUD described a significantly greater reduction in the impact of their Parkinson's disease-related speech problems 3 months after randomisation compared to people that had no speech and language therapy. There was no evidence of a difference between National Health Service speech and language therapy and those that received no speech and language therapy. Lee Silverman Voice Treatment LOUD resulted in a significantly lower impact of voice problems compared to National Health Service speech and language therapy 3 months after randomisation which was still present after 12 months; however, Lee Silverman Voice Treatment LOUD was not found to be cost-effective. Implementing Lee Silverman Voice Treatment LOUD in the National Health Service and identifying alternatives to Lee Silverman Voice Treatment LOUD for those who cannot tolerate it. Investigation of less costly alternative options for Lee Silverman Voice Treatment delivery require investigation, with economic evaluation using a preference-based outcome measure that captures improvement in communication. This study is registered as ISRCTN12421382. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 10/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 58. See the NIHR Funding and Awards website for further award information.

Evaluation of an electronic clinical decision support algorithm to improve primary care management of acute febrile illness in rural Cambodia: protocol for a cluster-randomised trial

IntroductionAcute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers...

Multicentre Randomized Controlled Trial of a Nurse-Led Sexual Rehabilitation Intervention to Rebuild Sexuality and Intimacy After Treatment for Gynecological Cancer.

To evaluate the effectiveness of a sexual rehabilitation program, SEXHAB, in improving sexual functioning, reducing sexual distress, and enhancing marital satisfaction for women after gynecological cancer treatment. This is a randomized controlled trial that included 150 women newly diagnosed with gynecological cancer from three public hospitals in Hong Kong. Participants were randomly assigned to the intervention group (n=78) to receive the SEXHAB or to an attention control group (n=72) to receive attention. The SEXHAB comprises four individual- or couple-based sessions with three major components: information provision, cognitive-behavioral therapy and counseling using motivational interviewing skills. The outcomes were measured at baseline (T0), upon completion of the program (T1) and 12-month post-treatment (T2). Semi-structured interviews were also conducted with the SEXHAB group participants to explore their experiences with and opinions toward the program. At both follow-ups, there were no statistically significant differences between groups in improving sexual functioning, sexual distress and marital satisfaction. Nevertheless, participants in the SEXHAB group reported their partners having significantly greater sexual interest at T1 (76% vs. 52%, rate ratio: 1.46, 95% CI: 1.07 to 1.99, p=0.024) and T2 (74% vs. 48%, rate ratio: 1.55, 95% CI: 1.11 to 2.10, p=0.014). From the qualitative interviews, the interviewees who resumed sexual activity reported positive experiences in rebuilding sexuality and intimacy. Despite the quantitative results are negative, the qualitative findings suggest potential benefits of the SEXHAB for women resuming sexual activities after treatment for gynecological cancer. Further studies with longer intervention period and follow-ups are needed to confirm the intervention effects.

A pilot randomised controlled trial of a multidomain lifestyle intervention for outpatients with chronic or severe mental illness.

Lifestyle-related problems are common in people with mental illness, contributing to a decreased life expectancy and high societal and personal burden. This study aimed to investigate the feasibility, acceptability, and preliminary effectiveness on recovery of a multidomain lifestyle intervention in patients with severe or chronic mental illnesses. Twenty transdiagnostic outpatients were 1:1 randomised in intervention or control. The lifestyle intervention consisted of 11 three-hour group sessions about physical activity, nutrition, relaxation, sleep, substance use, and purpose and meaning. Self-report questionnaires, physical measurements, diary questions, and accelerometers were administered at baseline, halfway and post intervention. Outcomes included attrition, retention rates, protocol deviations, quantitative evaluations and effectiveness. Both the intervention and research protocol appeared feasible and acceptable, with relaxation, purpose and meaning and nutrition as highest appreciated themes. Intervention simplification and deepening was necessary to suit the heterogeneous participants. Preliminary effects were found in all recovery domains, with biggest effects in societal recovery and smallest effects in clinical recovery. To prevent dropout and match the outpatient population, small intervention adaptations are recommended. Effects can be expected in all domains of recovery and should be measured accordingly. Research with greater sample sizes is necessary.

Practical Resources for Effective Postpartum Parenting (PREPP): a randomized controlled trial of a novel parent-infant dyadic intervention to reduce symptoms of postpartum depression: RCT of the PREPP intervention for postpartum depression

BackgroundThere is little known about the effectiveness of psychological interventions to prevent postpartum depression that focus on the birthing parent and infant dyad. Risk factors for PPD include depression during pregnancy, low parenting self-efficacy, and disrupted parental nocturnal sleep. The brief Practical Resources for Effective Postpartum Parenting (PREPP) intervention is designed for pregnant individuals at-risk for postpartum depression, providing them with 1) caregiving strategies aimed at reducing infant fuss and cry behavior and increasing infant sleep, 2) self-reflection and mindfulness skills and 3) psychoeducation about the postpartum period and infant behavior. The aims are to set more realistic postpartum expectations, enhance parenting confidence and sleep via supporting infant regulatory behavior, improve parental affect regulation and ultimately reduce the risk of postpartum depression. ObjectivesAssess the effectiveness of PREPP compared to enhanced treatment as usual in reducing symptoms of depression and anxiety and episodes of infant fuss and cry behavior and improving parental and infant sleep in the early postpartum. Study designA randomized controlled trial was conducted of 175 pregnant individuals. Inclusion criteria were standard prenatal care for a singleton pregnancy, aged 18 to 45 and at increased risk of PPD as determined by a score of ≥19 on the Predictive Index of Postnatal Depression or ≥7 on the Edinburgh Postnatal Depression Scale. Participants assigned to the PREPP group (n=88) received three coaching sessions and two phone check-ins. Participants assigned to the enhanced treatment as usual group (n=87) received three sessions which included psychoeducation, mood assessments, and clinical referral and follow-up as indicated. Assessments were conducted at 28 to 32 weeks and 34 to 39 weeks gestation, and at six, 12 and 16 weeks postpartum and included measures of parental depression, anxiety and sleep (Edinburgh Postnatal Depression Scale, Patient Health Questionnaire (PHQ-9), Hamilton Rating Scales of Depression and Anxiety and Pittsburgh Sleep Quality Index) and infant sleep and fuss and cry behavior (Baby Day Diary). ResultsCompared to enhanced treatment as usual, PREPP significantly reduced depressive symptoms at six, 12 and 16 weeks postpartum with medium to large effect sizes (d=0.7-0.98). Compared to enhanced treatment as usual, participants receiving PREPP reported less of a decline in sleep quality at six weeks postpartum (p=0.035) and the effect size was large (d=0.83). Moreover, parents receiving the PREPP intervention reported less infant fussing and crying, with the largest effect for morning crying (p<0.001; d=-1.48). ConclusionsThe results provide evidence that PREPP, initiated during pregnancy, reduced symptoms of parental depression and infant fuss and cry behavior in the early postpartum, compared to enhanced treatment as usual, in a sample at-risk for postpartum depression.

Testing the effectiveness of a virtual sustained tobacco treatment: Initial reporting of findings from the EAQ171CD randomized clinical trial conducted by ECOG-ACRIN within the NCI Community Oncology Research Program (NCORP).

376 Background: Persistent smoking among patients diagnosed with cancer is associated with adverse clinical outcomes, yet clinical guidelines for tobacco use interventions have not been integrated into community oncology settings. We conducted a trial of a virtual sustained tobacco treatment intervention across community oncology settings nationally. Methods: This randomized clinical trial, conducted through ECOG-ACRIN, compared the effectiveness of sustained telehealth counseling plus medication (Virtual Sustained Treatment; VST) to referral to the NCI quitline (Enhanced Usual Care; EUC) in assisting recently diagnosed cancer patients to quit smoking. The VST group received up to 11 synchronous telehealth sessions (4 weekly, 4 biweekly, 3 monthly) of motivational counseling and up to 12-weeks of free NRT patch and/or lozenge. Eligibility criteria included adults within 4 months of a new cancer diagnosis, cigarette use in the past 30 days, English/Spanish speaking, and access to an internet-enabled device. The primary outcome is 6-month self-reported 7-day point prevalence abstinence. Results: From 08/2019 to 12/2022, 306 patients were randomized from 30 NCORP Community Sites and 7 Minority/Underserved NCORP sites. Participants were 70.9% female; 86.3% White; 8.8% Black; and 2.9% Hispanic; median age 57 years; 25.5% completed a college degree; 50.3% stages 0-2; 46.4% had non-smoking-related tumors. Median cigarettes per day was 12.0; 72.2% (n = 221/306) smoked within 30 minutes of waking; 49.0% (n = 150/306) were in precontemplation/contemplation stage of readiness to quit. 73.8% (222/301) and 72.2% (210/291) completed the 3 and 6-month outcome assessments. Classifying missing smoking status as smokers, 6-month abstinence rates were 28.4% (42/148) in the VST group vs. 14.7% (21/143) in the EUC group (p&lt;.005). For secondary outcomes, there were no significant differences when adjusted for multiple comparisons (α = 0.0025); abstinence at 3-months was 24.7% (38/154) in the VST group vs. 15.0% (22/147) in the EUC group (p=.035); continuous abstinence at 6 months was 18.9% (28/148) in the VST vs 9.1% (13/143) in the EUC (p=.016). 80.8% (126/156) of individuals randomized to VST participated in counseling; of those, 59.5% (75/126) completed at least 6 sessions, 46.0% (58/126) completed at least one monthly booster session, and 85.7% (108/126) were dispensed 4 weeks of NRT. Conclusions: Among recently diagnosed cancer patients, sustained remotely delivered telehealth counseling and free NRT produced a significantly higher 6-month quit rate than a quitline referral. Findings support adopting a policy of widespread sustained tobacco treatment and implementation of tobacco treatment into community oncology care settings nationwide. Clinical trial information: NCT03808818 .

Increasing physical activity among adults affected by COVID-19 social distancing restrictions: A feasibility trial of an online intervention.

In response to COVID-19 social distancing restrictions, digitally delivered health interventions present as a potential solution for maintaining or improving individuals' physical activity. This study explored the feasibility of a web-based intervention, informed by the multi-process action control (M-PAC) framework to promote PA among individuals affected by social distancing. Fifty adults self-reporting as insufficiently active were randomized to a 6-week web-intervention (n = 27) or wait-list control (n = 23). Primary feasibility outcomes included recruitment and retention rates and usability and satisfaction scores; secondary outcomes of MVPA and M-PAC constructs and tertiary outcomes of mental health and wellbeing were also assessed. Overall, feasibility of the intervention was high, with a 96% recruitment rate, 84% retention rate, high satisfaction and usability scores, and comparable website usage to similar eHealth interventions. Intervention participants trended towards improved MVPA and M-PAC constructs and outcomes of mental health and wellbeing. Findings suggest study extension to a full-scale RCT.

Cognitive Stimulation and Maternal Feeding Styles in Families with Low Incomes: Impacts from a Randomized Clinical Trial

ObjectiveTo examine associations between cognitive stimulation in the home at 6 months and maternal feeding styles at 24 months, direct intervention effects of Smart Beginnings (SB) on feeding styles, and potential indirect effects of SB on feeding styles via earlier intervention effects on cognitive stimulation. Study DesignSingle-blind, two-site randomized clinical trial (RCT) of the SB intervention. SB integrates PlayReadVIP, a universal, pediatric primary care-based program, and Family Check-Up (FCU), a targeted secondary home-based parenting intervention. Mother-infant dyads (N=327) were randomized at birth to standard pediatric care or the SB intervention. Linear regression analyses determined associations between cognitive stimulation at 6 months and maternal feeding styles at 24 months, a secondary data analysis. Direct intervention impacts on feeding styles, a secondary RCT outcome, were also assessed and mediation analyses explored intervention effects on feeding styles via earlier intervention impacts on cognitive stimulation. ResultsCognitive stimulation was significantly associated with higher responsive and lower indulgent feeding styles. SB mothers were less likely to exhibit pressuring styles compared with controls (Effect Size [ES]=-0.12, p=0.02). Although no direct intervention effects were found on responsive or indulgent feeding styles, indirect effects of SB were evident on these feeding styles through intervention-induced increases in cognitive stimulation in the SB group. ConclusionThis study found positive linkages between cognitive stimulation in the home and later feeding styles. Additionally, the SB intervention was associated with less pressured feeding and indirect pathways mediated by intervention effects on cognitive stimulation. Implications for early childhood parenting interventions are discussed.

Sleep Quality in High-Risk Pregnancies: Mixed Methods Results from a Randomized Controlled Trial of a Mindfulness Training Intervention.

Objectives: Sleep difficulties in pregnancy are common and increase the risk for obstetric complications. Past research shows that mindfulness training (MT) is helpful for improving sleep in non-pregnant adults and may improve sleep during pregnancy. However, it is unknown if MT improves sleep among pregnant people at risk for obstetric complications. We examined the effects of MT on sleep quality in individuals at risk of developing hypertensive disorders of pregnancy. Methods: Twenty-nine participants (mean age, 32 ± 4 years; mean gestational age, 16 ± 3weeks) at risk for hypertensive disorders in pregnancy (HDP) were randomized to an 8-week phone-delivered MT intervention (n = 15) or treatment as usual (TAU; n = 14), designed to test MT feasibility and acceptability. As part of the study, participants completed the Pittsburgh Sleep Quality Index and participated in a semi-structured individual qualitative interview which queried for sleep changes over pregnancy. Results: Participants randomized to MT reported less daytime sleep dysfunction compared to TAU (F = 5.79, p = 0.03, ηp2 = 0.28). Qualitative data illustrated the common experiences of sleep disturbance across both study groups; however, MT participants reported an improved ability to initiate sleep and return to sleep using mindfulness skills. About half of the participants in the MT condition reported an improvement in overall sleep quality due to less interference related to anxiety and restlessness, while other MT participants reported no change in sleep quality. Conclusions: Results from this study confirm that pregnant individuals frequently encounter sleep challenges. Findings also suggest that MT may be a helpful tool in improving sleep quality among pregnant people at risk for obstetric complications.

The Impact of Antidepressant Discontinuation Prior to Treatment with Psilocybin for Treatment-Resistant Depression

It has been suggested that the recent use and discontinuation of antidepressant drugs compromises the action of psilocybin. As evidence is only available from small or uncontrolled samples, this post hoc analysis investigated this using data from the largest, phase II, randomized controlled trial of psilocybin treatment to date. Data from 233 participants with treatment-resistant depression (TRD) who received 25mg, 10mg, or 1mg of investigational drug COMP360 psilocybin (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.), administered with psychological support, were compared for groups of participants who either discontinued one or more antidepressant drugs during screening or entered the trial antidepressant drug free. Measures of depression symptom severity change during the antidepressant drug discontinuation period, baseline suicidality, acute subjective psychedelic effects, and the study’s primary endpoint (change in depression symptom severity between Baseline and Week 3) are described for both groups. Antidepressant drug discontinuation was not related to worsening of depression severity before Baseline. Suicidality was comparable between groups at Baseline. Psilocybin treatment efficacy and the subjective psychedelic experience did not appear to be compromised by antidepressant drug discontinuation. Thus, it does not limit the feasibility of psilocybin treatment for the future. These findings also support the overall homogeneity of our findings with psilocybin treatment as a monotherapy for TRD. The prior contradictory reports may come to appear misleading.

Summary of Research: Effects of Adalimumab-adbm Versus Adalimumab Reference Product on Patient-Reported Outcomes in Rheumatoid Arthritis: Results from VOLTAIRE-RA.

This Summary of Research overviews the results of a study that looked at patient-reported outcomes in the VOLTAIRE-RA trial (NCT02137226), originally published in Rheumatology and Therapy. A biosimilar is a biologic medicine made to be very similar to the original biologic medicine (also known as the reference product). The VOLTAIRE-RA trial compared the efficacy and safety of an adalimumab biosimilar (Cyltezo®, adalimumab-admb) with the adalimumab reference product, Humira®, in people with rheumatoid arthritis. As part of the VOLTAIRE-RA study, participants took either adalimumab-adbm or adalimumab reference product for 24weeks. Patient-reported outcomes were captured after 12weeks and after 24weeks of treatment to assess the effects of treatment on each participant's health-related quality of life. People with rheumatoid arthritis who were given adalimumab-adbm or adalimumab reference product experienced similar clinically meaningful improvements in their health-related quality of life after 12weeks of treatment. A high proportion of people in this trial who were given adalimumab-adbm or adalimumab reference product reported greater improvement versus a reference US population matched by age and sex. This is notable, as it represents a treatment goal that was difficult to achieve in earlier rheumatoid arthritis trials of non-biologic treatments.

Development and implementation of a physiotherapy exercise intervention with tailored support for exercise adherence for people with vertebral fragility fractures (OPTIN trial)

ObjectivesThe OsteoPorosis Tailored exercise adherence INtervention (OPTIN) trial is a two-arm, multi-centre randomised controlled trial. It compares the effectiveness of physiotherapy exercise rehabilitation with integrated support for exercise adherence, to physiotherapy exercise rehabilitation alone, for people with vertebral fragility fracture (VFF) and back pain. This paper describes the development of the physiotherapist-led adherence enhanced intervention. MethodsWe used an intervention mapping approach and followed Medical Research Council guidelines for developing complex interventions. We co-created the intervention involving expert clinicians, service managers, researchers, and adults with long-term musculoskeletal conditions, including osteoporosis. We identified a theoretical framework, reviewed the evidence, used a feasibility study, and considered clinical practice and deliverability within UK National Health Service (NHS) outpatient physiotherapy secondary care. Through a collaborative workshop, we refined the intervention, involved patients again and re-tested the intervention. Finally, we manualised the intervention, produced patient and physiotherapist materials and trained physiotherapists for delivery. ResultsThe OPTIN intervention uses a motivational interviewing approach and captures information about patient goals, barriers, and facilitators to exercise. Physiotherapists assess exercise capability, opportunities and motivation and utilise at least three behaviour change approaches, selecting from an intervention toolkit of nine approaches to support exercise behaviour. Ninety minutes of additional physiotherapy are provided to deliver the intervention, integrated within the assessment and six follow-up visits. ConclusionsA theory-informed intervention to support exercise adherence was developed and delivered by physiotherapists trained in the intervention to older adults with VFF and back pain in the intervention arm (n = 63) of the OPTIN trial. Trial Registration numberISRCTN 14465704. Contribution of Paper•Describes the development of an intervention to support adherence to physiotherapy exercise for people with vertebral fragility fracture.•Reports in detail the intervention for replication.

A randomized trial of aerobic exercise in colorectal cancer: Rationale, design, recruitment, and exercise adherence results

BackgroundPhysical activity is associated with improved disease-free survival in colorectal cancer survivors. This report describes the purpose, design, recruitment, and exercise adherence results of the National Cancer Institute (NCI)-sponsored Exercise and Colorectal Cancer Treatment (EXACT) trial. MethodsThe primary objective of the EXACT trial is to determine if randomization to 150 min per week of moderate-intensity aerobic exercise reduces systemic inflammation among stage I-III colorectal cancer survivors compared with a waitlist control group over 12 weeks. Participants were provided with an in-home treadmill and heart rate monitor. Characteristics associated with randomization were identified using χ2 or Fisher's exact test for categorical variables and t-tests or analysis of covariance (ANCOVA). Exercise adherence was calculated as the total minutes exercised by total minutes prescribed. ResultsBetween August 2019 and February 2023, 3082 colorectal cancer survivors were invited to participate, 89 were screened, and 60 were randomized to the study protocol. Younger age (P = 0.02), female sex (P = 0.002), white race (P = 0.01), proximal time since tumor resection (P = 0.02), and regional tumor stage (P < 0.001) were associated with study participation. Average exercise adherence was 92.2 % (95 % CI: 85.5, 98.8) and all study participants achieved ≥80 % exercise adherence. Endpoint data collection was completed for all participants in May 2023. ConclusionThe results from the EXACT trial will characterize the changes that occur from exercise to advance our understanding of the biological mechanisms by which exercise may prevent tumor recurrence and death in colorectal cancer survivors.

ID: 342895 Assessment of Psychosocial Factors and Success of Neuromodulation Trials for Treatment of Persistent Pain

ID: 342895 Assessment of Psychosocial Factors and Success of Neuromodulation Trials for Treatment of Persistent Pain