Pilot Study Research Articles

Effect of acupuncture on quality of life in atrial fibrillation: study protocol for a randomised controlled trial

IntroductionAtrial fibrillation (AF) is the prevalent cardiac arrhythmia and can significantly impair the quality of life (QoL). Although catheter ablation (CA) is an established treatment for AF,post-procedural complications or perceived...

Feasibility, safety and preliminary efficacy of telehealth-delivered group exercise for people with type 2 diabetes: A pilot trial.

Several barriers can preclude people with type 2 diabetes (T2D) from in-person exercise session participation. Telehealth may be an alternative mode of service delivery to increase uptake. We evaluated the feasibility, safety and preliminary efficacy of delivering group exercise via telehealth for people with T2D. Sixteen people with T2D (age 59.9 ± 12.7 years, 63% male, duration of T2D 11.5 ± 11.1 years) underwent an 8-week telehealth-delivered group exercise intervention. Weekly supervised sessions incorporated whole-body aerobic and resistance exercises, followed by education. Feasibility was evaluated by recruitment, enrolment, attendance and attrition rates, the practicality of telehealth delivery, and participant feedback. Adverse events were monitored throughout (safety). Preliminary efficacy was determined from changes in glycaemic control, body composition, blood pressure, exercise capacity, neuromuscular strength/fitness, quality of life and physical activity levels. The agreement/reliability of in-person clinician-measured versus telehealth-supervised participant-self-measured assessments was also evaluated. Feasibility was supported by high attendance (97.1%) and low attrition (81%). All (100%) participants reported they would participate in telehealth-delivered exercise interventions in the future and would recommend them to other people with T2D. No serious adverse events were reported. There were improvements in hip circumference (Cohen's d -0.50), diastolic blood pressure (-0.75), exercise capacity (1.72), upper body strength (1.14), grip strength (0.58), health-related quality of life (0.76-0.81) and self-reported physical activity (1.14). Participant-self-measured assessment of body weight, 2-min step test and 30-sec sit-to-stand test were deemed acceptable. Telehealth-delivered group exercise appears feasible, safe and efficacious for people with T2D. These findings warrant further exploration in a powered trial. Australian New Zealand Clinical Trials Registry (ACTRN12622000379718).

Nutritional intervention to enhance recovery after arthroscopic knee surgery in adults: a randomized controlled pilot trial.

Essential amino acid (EAA) and omega-3 fatty acid ingestion independently attenuate leg skeletal muscle disuse atrophy in uninjured persons. However, no data exist regarding the effectiveness of combined EAA and omega-3 fatty acid ingestion to mitigate skeletal muscle disuse atrophy in response to anterior cruciate ligament reconstruction (ACLR) surgery. This pilot trial will explore the feasibility of recruitment and retention of ACLR outpatients from a single center across 18 months to consume either a combination of omega-3 fatty acids and EAAs, or a placebo control, for 4 weeks before and 2 weeks after surgery. Thirty adult (≥ 18 years old) ACLR outpatients will be recruited for this single center, double-blind, two-arm randomized controlled feasibility pilot trial. Participants will consume either 5 g⋅day-1 of omega-3 fatty acids (fish oil) and 40 g⋅day-1 of EAAs or 5 g⋅day-1 of a control fatty acid mixture (safflower oil) and 40 g⋅day-1 of non-essential amino acids (NEAAs). Fatty acid supplements will be consumed 4 weeks before and for 2 weeks after ACLR surgery, whereas the EAAs and NEAAs will be consumed 1 week before and for 2 weeks after ACLR surgery. The primary outcomes are feasibility of recruitment and retention, with the goal to recruit 30 outpatients across 18 months and retain 22 participants upon completion of the study protocol following 12 weeks of data collection. These results will be reported using descriptive statistics, along with reasons and timepoints for study dropout. Secondary exploratory outcomes will be reported using inferential statistics for purposes of hypothesis generation and elucidation of mechanistic targets for future work; no inferences to clinical efficacy will be made. These outcomes include integrated rates of skeletal muscle protein synthesis, skeletal muscle protein content and expression of translation factors, skeletal muscle and erythrocyte phospholipid composition, and measures of skeletal muscle mass, strength, and power. This work will set the foundation for a future randomized controlled trialpowered to detect an effect of EAA + omega-3 fatty acid intake on skeletal muscle size or function in response to ACLR surgery. ClinicalTrials.gov, NCT06233825. Registered 31 January 2024. https://clinicaltrials.gov/study/NCT06233825?term=NCT06233825&rank=1.

A Randomized Pilot Trial of Virtual Reality Surgical Planning for Head and Neck Oncologic Resection.

Application of virtual reality (VR) for surgical planning may improve clinical outcomes for head and neck cancer (HNC) resection. There is a lack of randomized trials and meaningful metrics to assess such technological applications. Our objective was to evaluate the feasibility of a VR protocol for oncologic surgical planning and assess the impact on surgical outcomes. A randomized controlled trial utilizing a VR Case Enhancement Protocol (VRCEP) versus standard of care (SOC) surgical planning was conducted. The primary endpoint was feasibility, defined as >80% successful VRCEPs. Metrics included surgeon task-load burden (TLB) using the NASA Task-Load Index and "margin events," defined as "the need for defect-driven margins, positive frozen margins, and/or positive final margins." Margin events were used to calculate a margin event score (MES) per case and margin event rate (MER) per cohort. Thirty-four patients were included in the final analysis (17 VRCEP, 17 SOC) with 94.4% of eligible VRCEP cases completed (17/18). Surgeon TLB was unchanged with VRCEP. Cases undergoing VRCEP were associated with a lower mean MES (0.27 vs. 0.94, p = 0.014) and MER (11.6% vs. 35.6%, p = 0.0041). VRCEP was associated with decreased defect-driven margins (10% vs. 53.3%, p = 0.032). Although not statistically significant, positive frozen and final margin rates were lower in VRCEP. Completion of the VRCEP was feasible with no significantincrease in surgeon TLB appreciated. VRCEP yielded fewer MEs. Further investigation into the benefit of VR in HNC resection is warranted. Margin events may represent useful metrics for assessing novel surgical technologies. 2 Laryngoscope, 2024.

SURG-32. OPTIMIZING TUMOR TREATING FIELDS THERAPY FOR FIRST RECURRENT GLIOBLASTOMA WITH SKULL REMODELING SURGERY. FINAL RESULTS FROM OPTIMALTTF-2, A MULTI-CENTER, RANDOMIZED, CLINICAL TRIAL

Abstract Studies indicate that increasing the electric field intensity of Tumor Treating Fields therapy (TTFields) may prolong survival for glioblastoma (GBM) patients. Skull remodeling surgery (SR-surgery) aims to increase electric field intensity by 30-100% by removing the poorly conductive skull, and OptimalTTF-1 (pilot trial) concluded that SR-surgery was safe with a median overall survival (mOS) of 15.5 months for first recurrence GBM (rGBM). OptimalTTF-2 is a 1:1 randomized, comparative, multi-center, investigator-initiated, interventional clinical phase 2 trial investigating the efficacy and safety of TTFields and standard of care with or without SR-surgery for 84 rGBM subjects, with a planned interim analysis after enrollment of the first 52. Randomization is solely for SR-surgery and involves five burr holes of 15mm each in diameter, located in the skull between the tumor and the transducer arrays. The trial was nationwide in Denmark and active from 2020-2024. Major eligibility criteria include age ≥18 years, histopathological confirmed first recurrence of supratentorial GBM, and KPS ≥70. The primary endpoint is OS after 12 months (OS12), while secondary endpoints include PFS, QoL, ORR, QoL, KPS, steroid dose, and toxicity. The trial recruited 58 subjects and 52 had follow-up of 12-months or longer. Randomization was balanced and both arms had a median age of 59 years and no statistical difference in prognostic markers. Intent-to-treat analysis revealed the following for the intervention and control respectively, OS12 55% [95%CI 37-74%] vs. 45% [95%CI 27-64%](p=0.4), mOS 12.2 [7.9-19.1,95%CI] vs. 11 [6.5-17.1, 95%CI] months, and PFS 4.5 [3.4-9.5,95%CI] vs. 3.5 [3-6.4,95%CI] months. All the secondary outcomes were statistically insignificant. The trial was terminated early after interim analysis indicated no survival benefit from SR-surgery and a conditional power calculation that showed a low expected survival benefit for the planned cohort of 84 subjects. Post hoc analysis examining potential negative outcome modifiers is needed.

A live online exercise program for older adults improves depression and life-space mobility: A mixed-methods pilot randomized controlled trial.

Aging is the primary risk factor for sarcopenia and mobility limitations. Exercise reduces these risks, but older adults have low levels of participation in physical activity and exercise. We investigated the preliminary effectiveness of a live, online exercise program on community-dwelling older adults' physical activity levels. A mixed-method pilot randomized controlled trial was conducted according to CONSORT 2010 statement: extension for pilot and feasibility trials. Sedentary older adults (65-80 years) were randomly assigned to the online exercise intervention (ACTIVE) or a waitlist control (CON) group. Outcomes were measured pre-randomization and following the 8-week intervention for ACTIVE and CON and two months following the end of the intervention for the ACTIVE group. Outcomes included habitual physical activity levels, depression, anxiety, loneliness, life-space mobility, nutrition risk, and feasibility. All participants were invited to participate post-intervention in individual semi-structured qualitative interviews. Reporting of the qualitative research followed the checklist for the Consolidated Criteria for Reporting research. Seventeen older adults (71% women) were allocated to ACTIVE group, while 15 were allocated to CON group (87% women). Following the intervention, participants in the ACTIVE group reported reduced symptoms of depression (ACTIVE: pre = 4.2 ± 2.5; post = 2.2 ± 1.9; CON: pre = 3.5 ± 2.1, post = 3.5 ± 2.1; p <0.001) and improved life-space mobility (ACTIVE: pre = 62.4 ± 14.7; post = 71.8 ± 16.0; CON: pre = 65.1 ± 19.0, post = 63.6 ± 22.0; p = 0.003) compared to waitlist control participants. The ACTIVE group had good adherence (97%) and acceptability (98%). Twenty-two participants participated in qualitative interviews. Five themes were identified, including (1) Feasibility of the online exercise program; (2) Perceived health benefits and improvements; (3) Registered Kinesiologists and Physiotherapists contributed to perceived safety; (4) Social connectivity associated with synchronous/live delivery; and (5) Growing old gracefully and preventing disability. Our online exercise program was acceptable to older adults, had good adherence, reduced depression, and increased life space. Participants reported improved functional and mental health benefits. Further research is warranted to expand on these findings. NCT04627493; 13/11/2020.

CTNI-78. PNOC008: A PILOT TRIAL TESTING THE CLINICAL BENEFIT OF USING MOLECULAR PROFILING TO DETERMINE AN INDIVIDUALIZED TREATMENT PLAN IN CHILDREN AND YOUNG ADULTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (EXCLUDING DIFFUSE INTRINSIC PONTINE GLIOMA)

Abstract BACKGROUND Despite multiple clinical trials in young patients with newly diagnosed high grade gliomas (HGG), survival remains poor. PNOC008 is a single-arm, multi-center pilot trial, investigating the feasibility, toxicity, and efficacy of a molecularly guided individualized treatment approach following radiotherapy. METHODS Patients aged ≤21 years with newly diagnosed, localized, hemispheric HGG (Stratum A) or non DIPG, diffuse midline glioma (DMG) (Stratum B) were eligible. Comprehensive molecular profiling (targeted gene panel, whole exome, and whole transcriptome sequencing) was performed on primary tumor tissue. The molecular data was reviewed by a dedicated tumor board that recommended an individualized treatment plan combining up to four FDA approved drugs. Patients were followed for toxicity and efficacy. Circulating tumor DNA (ctDNA), imaging, and quality of life (QOL) measures were collected at multiple timepoints. RESULTS Fifty-five HGG patients enrolled between 2018 and 2023 (median age 11 years [range 2-20], n=31 female, n=29 Stratum A), including H3K27-altered (n=17), H3/IDH-wildtype diffuse pediatric-type (n=16), and H3G34-mutant diffuse hemispheric glioma (n=12). In 44 patients that followed the recommended treatment, median overall survival (OS) from time of study enrollment was 26.5 months in Stratum A (lower 95% CI: 18.5) and 23.6 months in Stratum B (lower 95% CI: 16.8), and 30 months in H3G34-mutant patients (n=10, lower 95% CI:24.6) with median follow-up of 34.5 months for all patients (lower 95% CI: 32.2). The treatment recommendations most commonly included alkylator with targeted therapy combinations. The often novel drug combinations were generally well tolerated with grade 3 or 4 treatment-related adverse events being mostly hematologic. Central imaging, ctDNA, and QOL analyses are underway. CONCLUSIONS A personalized treatment approach using comprehensive transcriptomic and genomic analysis is feasible and well tolerated with encouraging survival data in children and young adults with HGG. Further analyses of molecular subgroups and correlatives are ongoing.

Health Impacts of a Remotely-Delivered Prolonged Nightly Fasting Intervention in Stressed Adults with Memory Decline and Obesity: A Nationwide Randomized Controlled Pilot Trial

Health Impacts of a Remotely-Delivered Prolonged Nightly Fasting Intervention in Stressed Adults with Memory Decline and Obesity: A Nationwide Randomized Controlled Pilot Trial

QOL-18. MANAGING CANCER AND LIVING MEANINGFULLY (CALM) IN PRIMARY AND SECONDARY MALIGNANT BRAIN TUMOR PATIENTS: INTERIM ANALYSIS OF A PHASE IIC RANDOMIZED CONTROL PILOT TRIAL

Abstract BACKGROUND Patients with both primary and secondary brain tumors demonstrate substantial psychological distress but have been historically excluded from psychological research. Managing Cancer and Living Meaningfully (CALM), a supportive- expressive- psychotherapy, has proven to reduce depression and death-anxiety in advanced cancer patients but trials in neuro-oncology have been limited. Interim analyses (50% accrual) of the first randomized control pilot trial (RCT) of CALM in neuro-oncology are presented here. METHODS In this ongoing NIH ORBIT model Phase IIc pilot RCT, 60 adults with primary or secondary malignant brain tumors and heightened distress (PHQ/DADDS) are randomized (2:1) to a six-session CALM intervention or usual care. Data collection includes established feasibility and acceptability metrics, intervention satisfaction surveys and interviews, and clinically meaningful changes in distress severity scores across three timepoints (pre-, post-CALM, follow-up). RESULTS Of 64 patients screened, 36 were eligible and 32 enrolled (n=20 CALM, n=12 Control; 65% female; 90% White; Mage=46yrs). A multimodal recruitment model was used. Currently, assessment completion rates are: post-CALM (80%) and follow-up (67%). Reasons for withdrawal include disinterest in intervention topics (n=1) and lost to follow-up (n=1). Intervention retention is currently at 90%, with 8 participants still in active treatment. No adverse events have been documented. Perceived benefit appears high (4.1/5) and all participants report they would recommend CALM to others. Pre- to post-CALM, depression severity reductions appear equal across arms (CALM PHQ-9=30%; Control=33%) but death anxiety severity reductions appear more prevalent in the treatment group (CALM DADDS=70%; Control=50%). CONCLUSIONS Interim data suggests promising feasibility and acceptability results in this pilot RCT. Enrollment, retention, and assessment completion rates appear adequate. Participants are reporting high benefit and recommendation of CALM. Improvement in death anxiety appears greater in those treated with CALM compared to controls. These interim RCT findings are promising and suggest completion of the current phase.

DDEL-08. MEGADOSE BOSWELLIA SERRATA CAUSES SIGNIFICANT DECREASE IN CEREBRAL EDEMA WITH MINIMAL TOXICITY IN BRAIN TUMOR PATIENTS

Abstract Boswellia serrata has been shown to reduce cerebral edema following radiation in brain tumors by Kirste et al in a prospective, randomized, placebo-controlled, double-blind pilot trial. In the study dose of Boswellia used was 4200mg/day, and was well tolerated. We report 2 patients who took doses 10x that which was recommended, after inadvertently buying much higher doses online. Both patients obtained significant reduction in cerebral edema and enhancing disease on MRI. The daily dose of 42000mg/day was tolerated well, with only mild dysphonia in one patient. The optimal dosing of Boswellia serrata to treat cerebral edema is not known, and should be studied further.

Ghost-ileostomy versus conventional loop ileostomy in patients undergoing low anterior resection for rectal cancer: results of a randomised controlled multicentre pilot trial (DRKS00013997).

The objective of the current pilot trial was to evaluate whether ghost ileostomy is a safe alternative to the current standard of care in terms of a conventional loop ileostomy in patients undergoing low anterior resection with total mesorectal excision (LAR/TME) for rectal cancer. This randomized controlled pilot trial included patients undergoing LAR/TME, randomly assigning them to ghost ileostomy or conventional loop ileostomy intraoperatively. Follow-up spanned 6months, evaluating the following endpoints: comprehensive complication index (CCI), postoperative morbidity, transformation of ghost ileostomy, presence of ostomy at 6months, Wexner score, and quality of life (EORTC QLQ-C30 & CR29). Exploratory statistical analysis based on the intention-to-treat principle was conducted. Recruiting 30 patients from May 2018 to September 2022, the trial was prematurely stopped due to slow recruitment. The mean CCI was comparable between groups at any point of time (at 6months: 30.7 vs. 29.7, p = 0.889). There was no mortality and no need for creation of a terminal ostomy. Anastomotic leakage rates were similar in ghost ileostomy and loop ileostomy groups (p > 0.99). The ghost ileostomy was converted into a conventional loop ileostomy in 6 of 15 (40.0%) patients. Neither postoperative function, nor the overall quality of life showed significant differences. Ghost ileostomy appears as a viable and safe option for selectively deciding ileostomy creation in LAR/TME for rectal cancer. However, challenges in patient selection, excluding those at high risk for anastomotic leakage, limit widespread application and call for optimization in future research. German Clinical Trials Register ( https://drks.de/ ): DRKS00013997; date of registration: April 9th 2018.

Energy metabolism dysregulation, cerebrovascular aging, and time-restricted eating: Current evidence and proof-of-concept findings

Abstract Dysregulated energy metabolism is a hallmark of aging, including brain aging; thus, strategies to restore normal metabolic regulation are at the forefront of aging research. Intermittent fasting, particularly time-restricted eating (TRE), is one of these strategies. Despite its well-established effectiveness in improving metabolic outcomes in older adults, the effect of TRE on preserving or improving cerebrovascular health during aging remains underexplored. We explored how aging itself affects energy metabolism and contextualized these age-related changes to cerebrovascular health. We also conducted a literature search on PubMed and Scopus to identify and summarize current studies on TRE in older adults. Finally, we provided preliminary data from our proof-of-concept pilot trial on the effect of 6-month TRE on cerebrovascular health in older adults. Current evidence shows the potential of TRE to improve energy metabolism and physiological outcomes in older adults. TRE may improve cerebrovascular function indirectly due to its effect on glucose homeostasis. However, to date, direct evidence of the effect of TRE on cerebrovascular parameters is lacking. TRE is a well-tolerated and promising dietary intervention for promoting and maintaining cerebrovascular health in older adults. Further studies on TRE in older adults must be better controlled for energy balance to elucidate its independent effects from those of caloric restriction.

A sleep promotion program for insufficient sleep among adolescents: a pilot feasibility randomized controlled trial.

To examine the feasibility, acceptability, and impact of a Sleep Promotion Program (SPP). This pilot trial randomized adolescents (13-15y) with insufficient sleep duration and irregular sleep timing to SPP-continuation (n=24; SPP in month 1, continuation treatment in month 2) or monitoring-SPP (n=20; monitoring in month 1, SPP in month 2). SPP included one clinician session and at-home delivery of web-based reports of each youth's sleep diary data with accompanying intervention questions that prompt youth to engage in sleep behavior change. Attrition rate primarily measured feasibility. Program satisfaction measured acceptability. Total sleep time (TST), sleep timing, and sleep timing regularity were measured via sleep diary at baseline, follow-up 1, and follow-up 2 (each ∼1 month apart). Linear mixed effects models compared treatment arms on changes in sleep from baseline to follow-up 1 (month 1). We also compared changes in sleep during month 1 to changes in sleep during month 2 among SPP-continuation participants. Attrition rate was 8.5%. 96.5% participants rated the quality of care received as good or excellent. In month 1, SPP-continuation youth showed a significantly greater increase in mean TST than monitoring-SPP youth (0.57 vs. -0.38 hours; contrast=0.95; CI=0.14, 1.76, p=0.024). SPP-continuation participants showed an increase in TST during month 1 (0.51h) but a decrease during month 2 (-0.74 h; contrast=-1.24, CI=-2.06, -0.42, p=0.005). No other significant effects were observed. SPP is highly feasible, acceptable, and associated with a significant increase in TST early in treatment. Registry: ClinicalTrials.gov; Name: Targeted Intervention for Insufficient Sleep among Typically-Developing Adolescents; Identifier: NCT04163003; URL: https://clinicaltrials.gov/ct2/show/NCT04163003.

Pilot Trial of a Speech-Language Pathology Telehealth Service to Enhance Postdischarge Dysphagia Care in Singapore.

Patients and caregivers in Singapore experience issues managing dysphagia care at home following hospital discharge, and they prioritized improving access to postdischarge dysphagia care and support. Hence, a postdischarge dysphagia telehealth service was developed. This study aimed to evaluate the feasibility of this service by examining patient and service outcomes, preliminary costs, and consumer satisfaction. Patients with dysphagia and their caregivers attended one or more telehealth sessions over the initial month post-hospital discharge. Reviews of dietary adherence and preparation, swallowing function, and therapy progress were conducted. If needed, clinical support and intervention were provided. Data related to patient and service outcomes, preliminary costs, and consumer satisfaction were collected and analyzed using descriptive statistics and content analysis. Twenty patients attended 42 telehealth sessions. No support was provided during 10 sessions, minor support was provided during 13 sessions, and major support and intervention were provided to address patient and swallowing safety during 19 sessions. Out of 20 patients, 19 required support and intervention during the first week postdischarge, but they experienced fewer issues with each subsequent session. They were highly satisfied with the service. The average session duration was 29.6 min. No sessions were cancelled. This service can be delivered with minimal additional health service resources and at a low cost to consumers. This service is feasible, cost-effective, and well accepted by consumers. It facilitates early identification and management of swallowing and patient safety during the initial month post-hospital discharge. Wider implementation of this service model should be considered. https://doi.org/10.23641/asha.27327345.

Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial.

Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).

STRIVE pilot trial: a protocol for a multicentre pragmatic internal pilot randomised controlled trial of Structured TRaining to Improve fitness in a Virtual Environment (STRIVE) before surgery

IntroductionHome-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an...

Yoga-based lifestyle intervention for antenatal depression (YOGA-D): study protocol for a pilot randomized controlled trial

Background Depression during pregnancy is associated with pre-term labor, low birthweight, post-partum depression and adverse child outcomes. There are concerns about the safety of anti-depressant medications during pregnancy. Many pregnant women with antenatal depression are neither aware about their depression nor do they have access to non-pharmacological interventions for depression. Evidence suggests that pre-natal yoga can improve antenatal depression. Yoga is native to the Indian culture and women can practice yoga as a ‘self-care’ intervention with minimal training. There is no study till date on the efficacy of yoga on antenatal depression in pregnant women in a low resource (rural) setting in India. This pilot randomized controlled trial aims to study the feasibility, acceptability, and preliminary efficacy of a YOGA -based lifestyle intervention for Antenatal D epression (YOGA-D) in Maharashtra, India. Methods We will undertake a single-blind individual randomized parallel group-controlled pilot trial with 1:1 allocation ratio. Adult women with 12–26 weeks of pregnancy, without any obstetric or medical complications will be randomly allocated to either the active intervention group (Yoga-Sanskar (YS)) or the Enhanced Usual Care (EUC) group. Trained yoga instructors will teach a pre-defined yoga sequence to the participants in the YS arm. In the EUC arm, participants will receive a single session of health education. We will assess trial feasibility using the recruitment, retention, and study completion rates. The primary outcome of depression will be measured using the translated Marathi version of the Patient Health Questionnaire-9. Assessments will be at the baseline, three-months post-randomization, and post-delivery. Discussion This study will help us to understand the barriers in implementation of a yoga-based intervention for antenatal depression in a low-resource/rural setting in Maharashtra, India. Based on the learnings of this pilot trial, we plan to undertake an explanatory randomized controlled trial in the next few months. Registration CTRI (CTRI/2024/05/067176; 10/05/2024).

Safety and efficacy of Angong Niuhuang Pills in patients with moderate-to-severe acute ischemic stroke (ANGONG TRIAL): A randomized double-blind placebo-controlled pilot clinical trial.

Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. There were 57 and 60 patients in the ANP and placebo groups finally included respectively for modified intention-to-treat analysis. The median age was 66 years, and the median NIHSS score at baseline was 12. The changes in cerebral infarct volume at day 14 were 0.3mL and 0.4mL in the ANP and placebo groups, respectively (median difference: -7.1mL; interquartile range [IQR]: -18.3 to 2.3 mL, P=0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4mL and 4.0mL, respectively (median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P=0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups (P=0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P=0.03). ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. Clinicaltrials.gov, No. NCT04475328.

Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma.

Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the targeted AMPA receptor antagonist perampanel on peritumoral hyperexcitability. An open-label trial was performed comparing perampanel with standard of care (SOC) in patients undergoing resection of newly diagnosed radiologic high-grade glioma. Perampanel was administered as a preoperative loading dose followed by maintenance therapy until progressive disease or up to 12 months. SOC treatment involved levetiracetam for 7 days or as clinically indicated. The primary outcome of hyperexcitability was defined by intraoperative electrocorticography high-frequency oscillation (HFO) rates. Seizure freedom and overall survival were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and correlative biomarkers were measured by mass spectrometry. HFO rates were similar between patients treated with perampanel and levetiracetam. The trial was terminated early after a planned interim analysis, and outcomes assessed in 11 patients (seven perampanel treated; four treated with SOC). Over a median 281 days of postenrollment follow-up, 27% of patients had seizures, including 14% maintained on perampanel and 50% treated with SOC. Overall survival in perampanel-treated patients was similar to that in a glioblastoma reference cohort. Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Glioma peritumoral glutamate concentrations correlated with high-gamma oscillation rates. Targeting glutamatergic activity with perampanel achieved similar electrocorticographic hyperexcitability levels as in levetiracetam-treated patients.

Proximal and distal minority stressors and mental health among young gay and bisexual men and other men who have sex with men (GBMSM) in Kisumu, Kenya.

Young gay and bisexual men and other men who have sex with men (GBMSM) in Kenya experience pervasive intersectional stigma and discrimination, contributing to elevated levels of negative mental health symptoms. Grounded in the Minority Stress Model, this paper explores associations of proximal and distal minority stressors with three types of negative mental health outcomes among young HIV-negative GBMSM (n = 63) between the ages of 19-34 who participated in a pilot trial of a sexual health intervention. Using the PHQ-9, GAD-7, and PC-PTSD-5 screening measures, levels of clinically significant symptoms were reported as follows: 15.8% depressive symptoms, 12.7% anxiety symptoms, 31.7% posttraumatic stress symptoms. Results from stepwise linear regression analyses suggest that GBMSM-related stigma (distal stressor) was the strongest correlate for all three mental health outcomes, and concealment motivation (proximal stressor) was an additional significant correlate only in the depressive symptoms model. These findings should be viewed with caution and seen as initial observations given the small sample which limits our interpretations of the findings. Structural-level interventions are needed to decrease GBMSM's exposure to intersectional stigma and discrimination, such as decriminalization of same-sex sexual activity, as well as individual and group-level interventions that assist GBMSM with improving their adaptive coping strategies.