Contemporary Clinical Trials Communications

1.This paper reports the statistical analysis plan for the AVERT-DOS trial: A Phase 3, Multi Arm, Multi Stage, Covariate Adjusted, Response Adaptive, Randomised Trial to Determine Optimal Early Mobility Training after Stroke. It contains a trial overview, regulatory information and details of the planned main analyses for the study protocol version Version 5; 15 June 2025.

Background: Black patients and individuals with low socioeconomic status (SES) face significant disparities in accessing curative therapies for hepatocellular carcinoma (HCC), including liver transplantation. This study aimed to develop provider-co-created intervention prototypes in response to patient-identified barriers and recommendations. Methods: A human-centered design session with hepatology and transplant providers at a large academic medical center was conducted. Prior to the session, participants were presented with barriers and preliminary solutions identified through an earlier human-centered design session with Black and low-SES patients. Using structured ideation methods, including brainwriting, challenge mapping, and concept voting, providers co-created intervention prototypes. Final concepts were synthesized from patient insights, provider input, and design methods using affinity diagramming and concept modeling. Results: Nine providers participated in the session. They focused on three key areas for intervention: inefficiencies in transplant pre-evaluation, inadequate social support, and information overload. Solutions included: (1) a structured triage pathway to standardize referrals and reduce delays; (2) a peer navigator model to guide patients through the transplant process; and (3) a multimodal transplant education roadmap to improve comprehension and engagement. These prototypes addressed both patient- and system-level barriers. Conclusions: Protypes developed through provider-led design, grounded in patient-identified barriers and co-created ideas, can yield actionable, scalable strategies to advance equity in HCC care. Future work will refine these prototypes through patient feedback and pilot them in clinical settings.

Objective: A questionnaire survey was conducted on the willingness and demand for acupuncture treatment in patients with malignant tumors, and the possible factors affecting patients' willingness and demand for acupuncture treatment were explored. Methods: A voluntary, anonymous survey was conducted between February and May 2025 among patients with malignant tumors aged 18 years and older who visited Beijing Cancer Hospital. The questionnaire included 16 questions addressing three dimensions:current medical purposes,Traditional Chinese Medicine(TCM) literacy, and acupuncture treatment needs.The questionnaire was posted online and completed by respondents using a smartphone interface. Results: A total of 511 valid questionnaires were retrieved in the survey, and 481 patients(94.1%) are willing to receive acupuncture treatment. Among the 481 patients willing to receive acupuncture treatment, the top five symptoms they hoped to improve with acupuncture were: disturbed sleep (245 participants, 50.9%); pain (229 participants, 47.6%); fatigue (177 participants, 36.8%); numbness (165 participants, 34.3%); and poor appetite (144 participants, 29.9%). Among patients who chose to "explicitly accept" acupuncture treatment and those who "accepted acupuncture treatment upon doctor's recommendation", 55% and 56% respectively had good knowledge of traditional Chinese medicine (TCM) culture. In contrast, this proportion was only 36.7% among patients who refused acupuncture treatment, and the difference was statistically significant (P<0.05). The survey results also show that Female patients reported significantly higher demands for pain relief and improved sleep than male patients, with statistically significant differences (P<0.05). Furthermore, those aged 18-45 and with better TCM literacy were more likely to desire acupuncture to improve sleep, with statistically significant differences (P<0.05). Conclusion: Differences in TCM literacy can influence patients' willingness to choose acupuncture treatment. Strengthening patient health education and improving TCM literacy will help increase cancer patients' willingness to choose TCM acupuncture treatment, thereby enabling them to benefit from acupuncture. For patients aged 18-45, those with good TCM literacy female with high acupuncture needs, acupuncture treatment may be recommended as a priority.

Introduction: A prominent symptom of post-acute sequelae of SARS-CoV-2 infection (i.e., Long COVID) is exercise intolerance with or without post-exertional malaise (PEM). PEM is characterized by the worsening of both symptoms and function following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. Individualized, supervised cardiopulmonary rehabilitation is considered a safe and effective intervention for many cardiac and pulmonary conditions, and has been effective in gradually improving function in previously hospitalized and nonhospitalized patients with severe COVID-19. While traditional cardiopulmonary rehabilitation approaches appear helpful in some situations, the exercise intolerance symptoms experienced by many individuals with Long COVID may require a different approach, especially when attempts to increase physical activity result in PEM. No clear consensus exists on the optimal treatment of PEM, and no major studies have evaluated the efficacy in individuals with Long COVID of either carefully supervised, individualized cardiopulmonary rehabilitation programs for exercise intolerance without significant PEM or activity pacing interventions designed to treat or prevent PEM. Methods and Analysis: The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative funded by the National Institutes of Health (NIH) included a prospective, multicenter, randomized controlled platform trial (RECOVER-ENERGIZE) designed to assess two interventions in patients with Long COVID and exercise intolerance: (1) cardiopulmonary rehabilitation for patients without significant PEM and (2) structured activity pacing to prevent or reduce PEM in participants who experience the symptom. The intervention duration will be 12 weeks. The primary endpoints for the trial include the Endurance Shuttle Walk Test as a measure of endurance capacity for the cardiopulmonary rehabilitation intervention and a modified version of the DePaul Symptom Questionnaire - Post-Exertional Malaise for the pacing intervention. Assessments will be completed at baseline, middle of intervention, end of intervention, and 12 weeks after completion of the intervention, and include physical performance measures and patient-reported surveys. Ethics and Dissemination: The RECOVER-ENERGIZE trial protocol has been approved by an institutional review board (Advarra), and written informed consent will be obtained from all participants prior to enrollment. The trial is registered on ClinicalTrials.gov (NCT06404047). Formally assessing PEM and developing a structured activity pacing intervention delivered by local pacing coaches are novel features of this trial. Results will be disseminated through peer-reviewed publications, presentations at scientific conferences, and communication with participants, patient advocacy organizations, and the broader Long COVID community. De-identified participant data will be made available through the NIH RECOVER data repository in accordance with NIH data-sharing policies. If successful, this protocol will provide accessible tools that clinicians can use to address exercise intolerance and PEM in patients with Long COVID.

BackgroundCognitive impairment has significant implications for function and quality of life and is common in individuals with post-acute sequelae of SARS CoV-2, also known as long COVID (LC). Emerging evidence suggests that sustained neuroinflammation, cerebrovascular dysfunction, and mitochondrial impairment are contributors to cognitive symptoms. Microtesla Magnetic Therapy (MMT) is a low-amplitude radiofrequency magnetic field intervention that has demonstrated anti-inflammatory and neuroprotective effects in preclinical models, suggesting it may be valuable in the management of cognitive impairment from LC and other neurological disorders. This study is the first randomized controlled trial to evaluate MMT for LC-related cognitive impairment. ObjectiveTo evaluate the feasibility, safety, and preliminary efficacy of an at-home MMT intervention in individuals with moderate-to-severe cognitive impairment from LC. MethodsIn this prospective feasibility study, 30 participants with LC-related cognitive impairment were randomized (2:1) to receive active or sham MMT. Participants self-administered 15-minute treatments at home with remote monitoring twice weekly for 4 weeks using a head-worn device that delivered a nonthermal radiofrequency magnetic field to the whole brain. Feasibility was defined as completion of at least 80% of prescribed treatments and all study visits. Secondary outcomes included safety, cognitive function, and self-reported mood and quality of life assessed at baseline, post-treatment (Week 4), and follow-up (Week 8). ResultsFeasibility was high, with 100% treatment adherence among participants who completed the study and strong usability ratings for at-home administration. There were no device-related adverse events. Compared with sham, participants receiving active MMT showed significantly greater improvements from baseline to Week 8 in WAIS-IV Digit Span Sequencing (p= 0.026), HVLT-R Recall (p= 0.044), and D-KEFS Color Naming (p= 0.049). Additional measures of attention, processing speed, and executive function demonstrated favorable trends in the active group. Emotional well-being, assessed by the SF-36, improved significantly in the active group at Week 8 compared with sham (p= 0.017), and mood symptoms showed clinically meaningful improvement. ConclusionsAdministration of the MMT intervention at home was feasible, safe, and well tolerated in individuals with cognitive impairment from LC. Preliminary findings suggest sustained clinically meaningful improvements in multiple cognitive domains and mood following treatment. Trial RegistrationClinicalTrials.gov NCT06739668, https://clinicaltrials.gov/study/NCT06739668, 2024-12-17

BackgroundPsilocybin has increasingly been studied as a therapeutic for psychiatric and neurologic conditions, yet comprehensive cardiovascular safety data are limited. Current trials often exclude individuals with blood pressure [&ge;]140/90 mmHg, criteria established conservatively without robust empirical support. ObjectiveCharacterize the blood pressure and heart rate response to typical therapeutic doses of psilocybin and provide an evidence base for cardiovascular eligibility criteria and monitoring protocols for future clinical trials and emerging therapeutic practice. MethodsWe pooled data from 536 psilocybin sessions (oral doses 20-47 mg) among 368 participants across 14 studies at Johns Hopkins University since 1999. Blood pressure and heart rate were measured at baseline and at least hourly up to 360 minutes post-administration. We quantified peak changes, threshold excursions, and excursion duration. ResultsPsilocybin produced modest, transient blood pressure elevations. Median peak systolic blood pressure (SBP) was 145 mmHg (IQR 134-156), representing a median increase of 22 mmHg from baseline. Blood pressure peaked at approximately 90 minutes and returned to near-baseline by 300 minutes. SBP exceeded 170 mmHg in 32 sessions (6.0%; median duration 8.5 minutes) and 180 mmHg in 17 sessions (3.2%; median duration 10 minutes). Antihypertensive medication was administered in only 1 session (0.2%). Higher baseline blood pressure was associated with smaller increases, suggesting a ceiling effect rather than exaggerated response. ConclusionsPsilocybin produces modest, transient blood pressure elevations comparable to moderate exercise. Current exclusion criteria of [&ge;]140/90 mmHg are not supported by these data. We recommend broadening eligibility to <160/100 mmHg while maintaining exclusions for established cardiovascular disease.

Background:Mild neurocognitive disorder (NCD) is a condition in which individuals experience mild cognitive decline but are independent in their activities of daily living. Due to the increasing number of people living with mild NCD and its negative impact on the quality of life, it poses a significant health burden worldwide. Thus, it warrants an urgent need for innovative approaches to address the lack of effective treatment options. Deep transcranial magnetic stimulation (dTMS), a non-invasive neuromodulation technique approved for the treatment of various neuropsychiatric disorders, could serve as a novel intervention for mild NCD. It can stimulate deeper and broader areas of the brain implicated in mild NCD, such as the prefrontal cortex, insula, and anterior cingulate cortex. Objectives:This study will examine the feasibility and tolerability of the Health Canada and Food and Drug Administration (FDA) approved dTMS coils (H1, H4 and H7 coils) in individuals with mild NCD. Secondarily, it will assess the impact of dTMS on cognition, mood, sleep, anxiety, brain activity (via electroencephalography), and blood biomarkers of neurodegeneration and inflammation. Methods: This open-label pilot study will recruit a total of N=30 participants between the ages of 60-90 with mild NCD. Participants will be assigned to one of the three dTMS coil conditions (H1, H4 & H7) and will complete a total of 20 dTMS sessions over 6 weeks. Data will be collected before, during, immediately after, and one-month following the intervention period. Discussion: This pilot study will generate necessary evidence regarding the feasibility and tolerability of dTMS in mild NCD. This will be used to determine whether a definitive trial is justified and inform the trial procedures. In the long term, dTMS may address a critical gap in therapeutic options for mild NCD. Clinical Trial registration:The protocol was registered on Clinicaltrials.gov (CT07038798) on June 2nd, 2025.

BackgroundHwa-byung (HB) is a Korean culture-bound syndrome characterised by prolonged suppression of anger and somatic complaints. No evidence-based digital therapeutic (DTx) has been developed for HB. We evaluated the feasibility, user experience (UX), and preliminary clinical effect of an acceptance and commitment therapy (ACT)-based DTx application, Hwa-free, for HB. MethodsAdults aged 19-80 years diagnosed with HB were enrolled in a four-week app-based intervention with assessment at baseline (Week 0), Week 2, Week 4, and Week 8 follow-up. The primary outcome was UX assessed via a 22-item survey at Week 4. Secondary outcomes included HB-related symptom and personality scales, depression, anxiety, anger expression, psychological flexibility, health-related quality of life, and heart rate variability. ResultsOf 45 screened, 30 were enrolled and 28 constituted the modified intention-to-treat population. Mean app use was 19.9 {+/-} 7.9 days (71.2% adherence over 28 days). Adverse events were infrequent and unrelated to the intervention. Positive response rates exceeded 80% for video content (items 2-4: 82.8-89.7%), HB self-assessment (86.2%), meditation therapy (86.2%), and in-app guidance (85.7%). Pre-post improvements from baseline to Week 4 were observed in 11 of 18 clinical scales, including HB Symptom Scale ({Delta} = -9.8, Cohens d = -0.92), Beck Depression Inventory-II ({Delta} = -13.3, d = -1.11), and state anger ({Delta} = -7.8, d = -0.96). The HB screening-positive rate declined from 100% at baseline to 55.6% at Week 8. ConclusionsHwa-free demonstrated adequate feasibility, acceptable UX, and preliminary evidence of clinically meaningful improvement in HB-related symptoms. Future randomised controlled trial is warranted. Trial registrationCRIS, KCT0011105

Background: Medical and doctoral students in health sciences represent a strategic public health lever as future professionals who will have a lasting influence on healthcare practices and the overall quality of health systems. Impaired quality of life and mental health issues among these students, coupled with scarce prevention programmes, led us to develop PROMESS-Group, an innovative multimodal programme designed to promote healthier lifestyle habits among university students. Methods: We will conduct a 2-arm randomised, controlled, superiority monocentric trial to assess the effect of this programme on medical and doctoral students compared to a control group. The intervention will consist of six sessions covering stress, sleep and physical activity domains. Each session will include group and individual meetings led by trained peer experts, focusing on needs assessment, self-care education, and personalised goals setting. Students' quality of life, academic self-efficacy, and broader health outcomes will be assessed using validated questionnaires and objective tools at baseline, during, and post-intervention. Data will be analysed according to the intention-to-treat principle and presented in accordance with CONSORT guidelines. Ethical approval was obtained from the institutional review board (IRB2025021802). All procedures will be performed in adherence to the Helsinki Declaration. Discussion: This study will enable the generation of high-quality evidence to evaluate the programme's effects on students' quality of life and related psychosocial outcomes, and may inform evidence-based health promotion strategies in university settings. Trial registration: ClinicalTrials.gov: NCT07030751 (https://clinicaltrials.gov/study/NCT07030751?locStr=Lyon,%20France&country=FR&state=Auvergne-Rh%C3%B4ne-Alpes&city=Lyon&cond=promess%20group&rank=1), 06.12.2025 - retrospectively registered. This protocol study follows the SPIRIT guidelines (Appendix 1). Keywords: Doctoral student, health behaviour, medical student, quality of life, physical activity, sleep, stress

The transition to higher education is characterized by increased academic demands and psychosocial stress, which may negatively affect cognitive functioning and student well-being. Executive functions (working memory, inhibitory control, and cognitive flexibility) are critical for academic adaptation and can be enhanced through structured interventions. Physical exercise, mind-body practices, and cognitive training have demonstrated potential benefits for executive functioning and stress reduction; however, few randomized controlled trials have directly compared interventions with different physical and cognitive demands in university students, particularly in Latin America. In addition, most studies have relied on self-report measures and physiological stress biomarkers such as salivary cortisol. This protocol describes a three-arm, parallel-group randomized controlled trial designed to evaluate the effects of a 12-week intervention on executive functions and stress in first-year university students. The study will recruit 120 first-year health-science students aged 18-25 years. Participants will be randomly assigned (1:1:1), using block randomization stratified by sex, to one of three interventions delivered twice weekly (24 sessions of 60 minutes): (1) moderate-to-vigorous motor-cognitive dual-task exercise (DT); (2) low-to-moderate intensity Tai Chi (TC); or (3) supervised digital cognitive stimulation (CS) using structured graphomotor tasks. Primary outcomes include executive functions assessed through standardized neuropsychological measures. Secondary outcomes include stress will be evaluated using the Academic Stress Inventory, Depression Anxiety Stress Scales and salivary cortisol collected in the morning using passive drool and analyzed by competitive ELISA.Other outcomes include physical activity levels, anthropometric and body composition measures, and handgrip strength. Data will be analyzed following an intention-to-treat approach using repeated-measures models, with multiple imputation for missing data. The study has received institutional ethics and biosafety approval. Trial registration: ClinicalTrials.gov Identifier: NCT07443904.

Background: Individuals with mild cognitive impairment (MCI) experience cognitive and functional declines that can negatively impact mood and reduce feelings of self-efficacy. These changes can also lead to elevated distress in care partners (CPs). Therefore, interventions that address quality of life and psychosocial factors in people with MCI and their CPs are needed. Objective: The present study evaluated the impact of a multidomain lifestyle program, the Cognitive Empowerment Program (CEP), on changes in psychosocial functioning, particularly empowerment, in people with MCI and their CPs. Methods: Participants were 94 people with MCI (Mean= 75.1 years old, 45.7% female, 81.9% white) and their CPs (Mean= 69.1 years old, 71.3% female, 87.3% white) that completed the 12-month CEP program comprised of physical, cognitive, and psychosocial interventions. Questionnaires were administered pre- and post-program to assess empowerment, self-efficacy, meaning and purpose, depression, and stress in participants with MCI alongside empowerment, depression, stress, and caregiving burden in CPs. Results: After completing the CEP program, participants with MCI endorsed higher empowerment and self-efficacy as well as fewer symptoms of depression and perceived stress. CPs endorsed feeling more empowered despite elevated caregiver burden. Conclusions: These results suggest multidomain lifestyle programs can positively impact wellbeing in MCI. Future research should focus on refining delivery models, exploring integration with pharmacological treatments, prioritizing inclusion of diverse populations, and measuring long-term outcomes to strengthen the reach and impact of programs like CEP.

(1) Background: Brain cancer is the ninth leading cause of cancer death in the US, with approximately 76,000 newly diagnosed cases annually. Studies show that at time of diagnosis, up to six-months post-treatment, 50%-80% of brain cancer survivors (BCS) report cognitive dysfunction. Mild cognitive impairment (MCI) has gained increasing attention as a persistent disability experienced by up to 75% of all BCS, which affects memory, concentration, executive function, etc. Studies show cognitive training with computerized gaming as improving cognitive function for patients with stroke, dementia, and Parkinsons. It is of significant clinical interest to develop innovative interventions that reduce MCI. Aim: To improve cognitive performance of BCS suffering with MCI by evaluating the feasibility, acceptability and effect of a Virtual Reality Cognitive Rehabilitation Training (VR-CRT) platform during four weeks of cognitive training. (2) Methods: We employed a quasi-experimental pretest/posttest non-randomized/non-blinded single-arm design for 4 weeks, with an experimental group (n=6, after attrition) using VR-CRT. Participants were selected based on convenience sampling using the electronic medical record to identify qualified patients, guided by inclusion/exclusion criteria. Feasibility was defined by retention as >80%, with usability testing using the System Usability Scale (SUS) and NASA-TLX surveys. The Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) test, and Trail Making A-B (TM-A/B) test were used to measure cognitive performance, comparing baseline to post week-four. (3) Results: The feasibility criteria of >80% was met. All SUS and NASA scores were in the higher index, suggesting a high degree of usability, with low workload demand. For effect, the COWA findings showed a significant improvement (41.38%), with a paired sample T-Test confirming that the participants COWA scores improved significantly from pre- to post-intervention (p = 0.03), indicating enhanced verbal fluency and executive functioning after intervention. HVLT (combined) showed improvements of 18.75% for Form A and 11.32% for Form B, which also showed a significant improvement (p = .04) in the retention discrimination index from pre- to post-test. The TM-A/B test showed an improvement (25.97%), suggesting that the participants spent less time completing both parts A and B, but was not statistically significant. (4) Conclusion: This study fulfilled our aim to demonstrate modest to significant cognitive improvement using VR-CRT with brain cancer patients with MCI. Despite the small sample size, we believe the use of virtual reality will lead to important advances for patients with MCI, particularly the frontal lobe brain region, expressed in executive function.

Abstract Background: Resilience is acknowledged to be an important component for successful aging in older adults, but there is scant evidence with which to inform public health interventions for this age group. The aim of this study is to determine whether the public health intervention, mindfulness for later life is both feasible and acceptable to older adults. Methods: Participants were recruited from September 2021 to June 2022 through older adult organisations and charities, such as the University of the Third Age, Age UK, and Age Concern, and by adverts distributed through village newsletters and support organisations. Participants were offered six weekly sessions of mindfulness therapy, the program was based on the mindfulness-based stress reduction program, each session was two hours long with 10-15 participants per program. The following two pre-defined indicators of success needed to be met for the program to be deemed feasible: successful uptake (recruitment of 30 participants over nine months) and initial engagement. Results: Thirty-three potential participants were screened for eligibility over nine months, 31 of whom were recruited to the study (103% of the target sample). Of these, 28 participants (90%) completed four or more online sessions. Thus, predefined indicators of feasibility were met. Conclusions: This study supports the feasibility of delivering the mindfulness for later life program as a public health intervention, including recruitment and treatment completion. A full-scale trial to assess the clinical- and cost-effectiveness of the intervention including its long-term effects is warranted.

IntroductionThere is a growing body of research showing that the menstrual cycle can affect mood, although research in those with an existing depressive disorder is still scarce. Studies estimate that 60% of women with depression experience premenstrual exacerbation (PME) of their depressive symptoms. AimsWith the TIDE study, we aim to 1) examine the feasibility of daily symptom tracking for two consecutive menstrual cycles to track PME, 2) estimate the prevalence of PME in depression in a clinical cohort and 3) examine whether PME is associated with other hormone-related mood symptoms (i.e., hormonal contraceptive side effects, peripartum depression). MethodsWe aim to recruit 60 female participants aged 18 to 45, who are in treatment for a depressive episode and who have a regular natural menstrual cycle. Participants will participate in questionnaires at baseline, inquiring about demographic characteristics and previous experiences with hormonal contraceptives and pregnancy. Participants will complete retrospective menstruation questionnaires on days 1 and 10 of each menstrual cycle, as well as daily diaries for two consecutive menstrual cycles, inquiring about menstruation and mood symptoms. After completion of the diaries, participants will receive a symptom report, as well as a study evaluation questionnaire. Results and conclusionWe expect that providing the menstrual cycle overview of symptom severity will lead to increased symptom course insights in participants with PME, and that participants with PME will find it clinically relevant and significant to gain insight into symptom trajectories across the menstrual cycle. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/26352210v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1d6545eorg.highwire.dtl.DTLVardef@3ceb57org.highwire.dtl.DTLVardef@17ea0faorg.highwire.dtl.DTLVardef@7aa9f6_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background and AimsSteatotic liver disease (SLD) is characterized by excessive lipid accumulation in hepatocytes, and alcohol consumption may modify the disease course, but the evidence is inclusive. This systematic review and meta-analysis aimed to holistically evaluate the impact of mild, moderate, and high levels of alcohol consumption on hepatic and extrahepatic outcomes in SLD. MethodsWe systematically searched EMBASE, MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials for relevant studies. The study outcomes included liver related events, malignancy, mortality and cardiovascular disease among adults with SLD who consumed alcohol. ResultsOf 2228 records identified, twenty-six studies comprising 466611 adults with SLD were included. High alcohol consumption was associated with an increased risk of liver-related events compared with abstinence (2.97, 95% CI 1.61-5.50; p<0.001), and a similar association was observed among alcohol drinkers overall (HR 1.93, 95% CI 1.60-2.33; p<0.001). Moderate alcohol consumption was associated with a higher incidence of malignancy (HR 1.41, 95% CI 1.13-1.78; p=0.677). In contrast, mild alcohol consumption was associated with lower all-cause mortality compared with abstinence (HR 0.88, 95% CI 0.78-0.98; p=0.001). No association was observed between alcohol consumption and cardiovascular disease incidence or hepatocellular carcinoma ConclusionsAlcohol intake may increase the risk of liver-related complications and cancer risk in individuals with SLD. Mild alcohol consumption was associated with lower all-cause mortality, and alcohol intake showed no association with cardiovascular disease incidence. Further studies are needed to clarify the dose-dependent effects of alcohol on hepatic and extrahepatic outcomes in SLD.

Background: Psychological distress is common in chronic kidney disease (CKD) and is associated with reduced quality of life, treatment non-adherence, and worse clinical outcomes. Distress in CKD is also linked to difficulties adjusting to the demands of illness management. Despite this, psychological support remains inconsistently integrated within kidney care pathways, and existing interventions often lack clear theoretical specification and explicit targeting of mechanisms underpinning adjustment to CKD. Objectives: To describe the systematic development of iADJUST, a theory-informed patient co-designed digital psychological intervention targeting key cognitive and behavioural mechanisms involved in adjustment to CKD. Methods: Intervention development was guided by the Medical Research Council framework for complex interventions. A structured, iterative process integrated empirical evidence, psychological theory, and patient and public involvement and engagement. The Common-Sense Model of Self-Regulation and cognitive behavioural theories informed the identification of modifiable maintaining mechanisms associated with adjustment to CKD. Intervention components were mapped onto these mechanisms and refined through co-design with people living with CKD. Results: iADJUST is a six-session self-guided digital psychological intervention delivered over 12 weeks and supplemented by therapist contact. The intervention targets illness-related uncertainty, fatigue-related activity dysregulation, catastrophic what-if thinking, self-critical evaluation, and behavioural withdrawal. It integrates psychoeducation, cognitive and behavioural strategies, maintenance planning, and elements from acceptance and commitment therapy and compassion-focused approaches. Content is delivered through video, audio, and guided tasks and activities. Conclusion: iADJUST provides a theory-informed, evidence-based psychological intervention for CKD explicitly mapping intervention components to maintaining cognitive and behavioural mechanisms implicated in adjustment. Feasibility evaluation is underway.

Improving diversity in U.S. Alzheimers disease (AD) research is a pressing need. By 2050, Hispanic and Latino Americans will comprise 30% of the population. Hispanics are 1.5 times more likely and Blacks are twice as likely to develop AD compared to Whites, yet both remain vastly underrepresented in clinical trials research. Aging and AD research mentorship of underrepresented STEM undergraduates is designed to promote entry into related professions by students committed to decreasing disparities in AD research participation and clinical care. The NIA-funded MADURA program recruited 93 students from backgrounds historically underrepresented in STEM majors and/or from NIH-defined disadvantaged backgrounds. Trainees were placed in aging/AD research labs and received weekly training and mentorship from faculty research PIs and other types of supervisors (postdoctoral researchers, graduate students, research assistant staff...) Our study examined student ratings of the program and mentor behaviors, using a program-specific survey and the Mentoring Competency Assessment-21 (MCA-21). Trainees were highly satisfied with both mentoring relationships and the overall program. Student rated MCA-21 competency areas were quite high for both P.I.s and other types of research mentors. However, there were striking differences in associations between competencies and relationship and program satisfaction, by mentor type. For PI mentors, no MCA-21 competencies were associated with relationship satisfaction, but five of six competencies were associated with relationship satisfaction for other mentor types. Similarly, no PI mentor competencies were significantly correlated with overall placement satisfaction, but all six competencies were correlated with overall placement satisfaction for other mentor types. The authors discuss the likelihood of differing student expectations of faculty PI versus other types of research mentors, recommendations for assessing role-specific student expectations (including functions primarily possible only for senior faculty PIs), and utilizing nearer-peer plus PI faculty mentors to comprehensively address the gamut of mentee needs.

Background and AimsAcute pancreatitis (AP) can lead to systemic inflammatory response (SIRS), paralytic intestinal obstruction, and in severe cases, intra-abdominal hypertension (IAH), organ failure (OF), and even death. Early magnesium sulphate (MS) catharsis treatment can relieve paralytic intestinal obstruction and IAH, thus reducing the incidence of severe acute pancreatitis (SAP) as well as mortality. Methods850 patients with AP at high risk of systemic complications (potential SAP (p-SAP)) were recruited. These p-SAP patients were categorized into two groups based on the treatment they received: the routine group (RT group, standard treatment for AP) and the MS group (early MS catharsis added to standard treatment). The final cohort had an allocation ratio of 2.5:1 (RT : MS). The primary composite endpoints were clinically finally diagnosed SAP (d-SAP) and mortality. The intensive care unit (ICU) admission, OF, inflammatory factors, length of hospital stay, and hospitalization costs, etc. were also compared and analyzed. ResultsIt demonstrated that early MS catharsis treatment was highly effective in preventing patients with p-SAP of various aetiologies from deteriorating to d-SAP and reducing their mortality significantly. In addition, it significantly reduced the incidence of OFs, pancreatic necrosis, ICU admissions, CRRT utilisation, and the cost and length of stay of hospitalisation for these patients. ConclusionsIt showed that early MS catharsis had a significant therapeutic effect on p-SAP patients, which would profoundly contribute to the clinical management of AP.

Nicotinamide riboside (NR), an endogenous precursor to the essential coenzyme nicotinamide adenine dinucleotide (NAD+), is characterized as safe and effective at longitudinally elevating NAD+ in blood and tissues, when administered orally. Preclinical research on NR as an augmenter of NAD+ has demonstrated great promise in support of healthy aging, metabolic health, and several diseases, though clinical translation of thesefindings has been limited. Interest in alternative routes of administration of NR has increased in recent years and led to the development of pharmaceutical-grade NR for intravenous and injectable administration. Two separate Phase 1 pilot clinical trials were conducted evaluating NR via bolus injections. While the designs of the two studies are different, the similarities warrant combined presentation to note the similarities, particularly with regards to safety-related outcomes. Trial 1 involved 45 participants that were randomized to a 3x3 design, accounting for three interventions, placebo, NR, and NAD+ and three routes of administration, intramuscular (IM), intravenous (IV), and subcutaneous (SC), resulting in a 9-arm study (placebo IM, n=5; placebo IV, n=5; placebo SC, n=5; NR IM, n=6; NR IV, n=5; NR SC, n=4; NAD+ IM, n=4; NAD+ IV, n=5; and NAD+ SC, n=6). Participants were administered NR once daily for three days, followed by a 7-day washout period. In Trial 2 (n=39), the 2x2 study design incorporated 4-arms for phase 1, where the participants were randomized to 50 or 100 mg of NR, administered either IM or SC in-clinic for 3 consecutive days, followed by a 7-day washout (50 mg IM, n=7; IM, 100 mg IM, n=11; 50 mg SC, n=11; and 100 mg SC, n=10). Phase 2 of Trial 2 involved participants self-administering either 50 or 100 mg of NR subcutaneously. Safety assessments for both trials included vitals, blood biomarkers, participant reported outcomes regarding the experience, and adverse event monitoring. Participant retention for both studies was 100%, and the injections did not result in any attributable unexpected adverse events or experiences. The experiences described by the participants regarding the actual injection varied. In Trial 2, pain more than two minutes after the injection and muscle soreness and tightness were reported by 45.9 and 43.2% of the participants, respectively, regardless of the route of administration or dose. Vitals remained generally consistent throughout both trials, and reductions in systolic blood pressure observed in both trials should be evaluated in larger, properly powered studies. Blood chemistry biomarkers for both trials did not elicit treatment-related patterns. Both trials presented within-group reductions in hsCRP in the NR SC arms, however, given baseline imbalance and small samples size, this finding should be considered hypothesis-generating, only. Overall, in both trials, the interventions, regardless of route of administration were associated with some discomfort but were well tolerated and did not produce any concerning safety signals. It is recommended that comprehensive metabolic and inflammatory panels should continue to be employed in future studies and clinical settings to assess whether consistent patterns emerge in larger populations.

Background Insomnia symptoms are common in older adults. While observational studies suggest physical activity (PA) timing affects health outcomes, its effect on sleep remains unclear. We compared morning versus evening PA effects on insomnia severity and sleep quality in older adults with insomnia symptoms. Methods Eligible participants were aged 60 to 80 years with (sub)clinical insomnia (Insomnia Severity Index [ISI] score [&ge;]10). In a randomized cross-over trial, participants engaged in coached PA in the morning (10:00 - 11:00) or evening (19:30 - 20:30) for 14 days each. ISI scores were assessed post-intervention. Objective sleep parameters; duration, latency, efficiency, and timing, were assessed with a Withings Sleep Analyzer under the mattress. Subjective sleep quality was reported daily via smartphone app. Salivary dim light melatonin onset (DLMO) was measured on the final day of each intervention. Results Of 37 participants (mean ISI 14.3 {+/-} 3.3), 27 completed the study (mean age 69.8 {+/-} 5; 63% women). ISI scores improved after both morning ({Delta} - 2.5; 95% CI: - 1.14, - 3.83) and evening ({Delta} - 2.0; 95% CI: - 0.63, - 3.38) activity relative to baseline, but were not different between interventions. Compared to evening activity, sleep midpoint occurred earlier with morning activity (03:40 vs 04:00; {Delta} - 20 min; 95% CI: - 31, - 8). No differences in subjective sleep quality or DLMO were found. Exploratory analyses suggested insomnia scores improved specifically in late chronotypes following morning activity. Conclusions While morning vs. evening PA timing did not impact most sleep quality measures, it influenced sleep timing. Larger studies are needed to define optimal and personalized PA timing for improving sleep.