Randomized Intervention Trial Research Articles

The Role of Alpha-Linolenic Acid and Other Polyunsaturated Fatty Acids in Mental Health: A Narrative Review.

The present review investigates the relationship between polyunsaturated fatty acids (PUFAs) and mental health disorders, such as dementia, psychosis, schizophrenia, Alzheimer's disease, anorexia nervosa, and impairment problems in animals and human models. Data were collected from a variety of studies: randomized intervention trials, observational and interventional studies, case reports, and epidemiological studies. The evidence suggests that PUFAs are beneficial for mental health, brain function, and behavior. ALA, EPA, and DHA have very significant neuroprotective properties, particularly in inducing changes to the synaptic membrane and modulating brain cell signaling. In the case of neurodegenerative disorders, PUFAs incorporated into cellular membranes have been shown to protect against cell atrophy and death. The formal analyses of the included studies pointed to a decrease in ALA, EPA, and DHA levels in various populations (e.g., children, adolescents, adults, and seniors) presenting with different types of mental disorders. These results indicate that PUFA supplementation may be considered as an innovative therapeutic strategy to reduce the risk of neuronal degeneration.

The HYdrocortisone for Bronchopulmonary Dysplasia Respiratory and Developmental (HYBRiD) outcomes study: protocol for a longitudinal cohort study

BackgroundBronchopulmonary dysplasia (BPD) affects up to half of extremely preterm infants, and is associated with adverse long-term respiratory, neurodevelopmental, and educational sequelae and costly health service and family economic outcomes. The NICHD Neonatal Research Network Hydrocortisone for Bronchopulmonary Dysplasia (BPD) Trial evaluated the efficacy and safety of hydrocortisone treatment to prevent BPD in high-risk infants. The trial enrolled 800 very preterm infants with respiratory failure and followed the participants until 2 years corrected age to assess safety of the trial intervention. Longer-term impacts of hydrocortisone exposure and severity of BPD on functional outcomes of high-risk infants remain unknown. The HYdrocortisone for BPD Respiratory and Developmental (HYBRiD) Outcomes Study extends follow-up of all surviving children enrolled in the Hydrocortisone for BPD Trial until early school age. It aims to characterize the childhood functional motor, cognitive, academic, and pulmonary outcomes of this large, well-phenotyped trial cohort.MethodsParents of surviving trial participants complete telephone questionnaires when their children are 3 and 4 years corrected age. A single in-person study visit takes place at early school age (5 years, 0 months to 7 years, 11 months corrected age). Children undergo a multidimensional assessment of functional outcomes and parents complete a battery of questionnaires. In 5 of 19 participating centers, respiratory mechanics are evaluated with impulse oscillometry.DiscussionThe HYBRiD Outcomes Study will be the largest and most comprehensive evaluation to date of the functional early school age outcomes of children with a history of severe neonatal lung disease and of children exposed to HC during infancy. This will substantially improve understanding of the longer-term implications of severe neonatal lung disease; provide data to facilitate the development of future randomized intervention trials in this population; and inform public policy by enhancing knowledge about school age resource requirements in children with a history of prematurity and lung disease.Trial registrationclinicaltrials.gov ID NCT01353313. Primary trial registration 5/11/11 modified to include followup through school age 12/13/17. This manuscript reflects version 3 of the trial manuscript, dated 10/12/2020.

Longer-term safety and efficacy of baricitinib for atopic dermatitis in pediatric patients 2 to

Background Baricitinib, an oral selective Janus kinase inhibitor, improved clinical signs and symptoms of moderate-to-severe atopic dermatitis (AD) at week 16 in the phase 3 pediatric study BREEZE-AD-PEDS. Objective To assess longer-term efficacy and safety of baricitinib in pediatric patients aged 2 to <18 years. Methods In BREEZE-AD-PEDS long-term extension, responders and partial responders (validated Investigator Global Assessment-Atopic Dermatitis [vIGA-AD®] 0/1/2) at Week 16 remained on double-blind treatment to which they were randomized (placebo, baricitinib [1-mg equivalent, 2-mg equivalent, or 4-mg equivalent); non-responders (vIGA-AD 3 or 4) at Week 16 transitioned to open-label baricitinib 4-mg equivalent. Safety was summarized for all randomized patients who received ≥1 dose of study treatment. Results In total 467 patients received baricitinib for 750.7 patient-years. Proportion of responders/partial responders (at Week 16) who achieved vIGA-AD 0/1 at Week 52 was greater for baricitinib 4-mg equivalent (56.8%) versus all other treatment groups (42.2%, 47.7%, and 39.7% for 2-mg equivalent, 1-mg equivalent, and placebo, respectively). Most treatment-emergent adverse events were mild/moderate in severity. No deaths, pulmonary emboli, deep vein thromboses or arterial thrombotic events, major adverse cardiovascular events, malignancies, tuberculosis events, or gastrointestinal perforations were reported. Conclusions Baricitinib demonstrated sustained long-term efficacy. No new safety signals were identified. Trial Registration ClinicalTrials.gov Identifier: NCT03952559

The goal-oriented collaborative approach with postural management strategies intervention via telehealth for children with non-ambulant cerebral palsy: Feasibility randomized clinical trial protocol

IntroductionChildren with non-ambulant Cerebral Palsy (CP), have limitations in terms of self-mobility and require the use of assistive technology with extensive adaptations. However, purchasing assistive technology equipment is expensive and difficult to access in low- and middle-income countries, like Brazil. Guidelines recommend a postural management program to children with CP and emphasize the need for high doses of practice to achieve functional goals. Furthermore, collaborative practices are recommended, with active parental participation in the intervention. AimsThis study describes a protocol for assessing the feasibility of a future randomized clinical trial using a goal-oriented collaborative approach with postural management strategies via telehealth for non-ambulant children with CP. MethodsEighteen children (1–5 years) with CP and their families will be randomized into two groups for 12 weeks: (A) goal-oriented collaborative approach with postural management strategies intervention via telehealth associated with conventional physical therapy or (B) conventional physical therapy. Feasibility measures will be verified, and outcomes will include parents' perceptions of performance and satisfaction, gross motor function, postural control, goal achievement and participation at home, preschool, and community. ImplicationsThe findings will inform the planning and preparation of a future randomized clinical trial of interventions for non-ambulant CP children via telehealth.

Antihypertensive therapy and unplanned maternal postpartum healthcare utilization in patients with mild chronic hypertension

ObjectiveTo test whether treatment of mild chronic hypertension (CHTN) in pregnancy is associated with lower rates of unplanned maternal healthcare utilization postpartum. MethodsThis was a secondary analysis of the CHTN and pregnancy study, a prospective, open-label, pragmatic, multicenter, randomized treatment trial of pregnant people with mild CHTN. All patients with a postpartum follow-up assessment were included. The primary outcome was unplanned healthcare utilization, defined as unplanned postpartum clinic visits, Emergency Department (ED) or triage visits, or unplanned hospital admissions within 6 weeks postpartum. Differences in outcomes were compared between study groups (Active Group: blood pressure goal of<140/90 mm Hg, and Control Group: blood pressure goal of <160/105 mm Hg), and factors associated with outcomes were examined using logistic regression. ResultsA total of 2293 patients were included with 1157 (50.5%) in the active group and 1136 (49.5%) in the control group. Rates of unplanned maternal postpartum healthcare utilization did not differ between treatment and control groups, (20.2% vs 23.3%, P=.07, aOR 0.84, 95% CI 0.69–1.03). However, ED or triage/maternity evaluation unit visits were significantly lower in the Active group (10.2% vs 13.2%, P=.03, aOR 0.76, 95% 0.58–0.99). Higher BMI at enrollment and cesarean delivery were associated with higher odds of unplanned postpartum healthcare utilization. ConclusionWhile treatment of mild CHTN during pregnancy and postpartum was not significantly associated with overall unplanned healthcare resource utilization, it was associated with lower rates of postpartum ED and triage visits.

Reducing Learning and Psychosocial Disparities in Latino Children with Cancer: A Randomized Intervention Trial.

We developed a high-intensity parenting intervention (HIP) to help parents support the academic success of childhood cancer survivors (CCSs), who often face post-treatment challenges affecting their school-related functioning. This randomized controlled trial (NCT03178617) evaluated HIP's efficacy compared to lower-intensity, single-session, treatment-as-usual services (LIP) in Latino families. Primary outcomes were parenting efficacy and CCSs' school functioning; secondary outcomes included parenting knowledge and measures of CCSs' academic performance, attention, and functioning outside of school. 106 Latino survivors of childhood leukemia and lymphoblastic lymphoma (aged 6-12 years) and their parents were randomly assigned to HIP (n = 54) or LIP (n = 52). Linear mixed-effects models evaluated group differences across baseline, 6-month (T2), and 12-month (T3) assessments. Parenting efficacy and knowledge improved significantly in the HIP arm, resulting in higher scores vs LIP at T2 and T3 (P ≤ .01). No significant between-group differences were found in child school functioning; however, HIP children showed significantly better social functioning and performance on one measure of attention (CPT-3 commissions) at T3 (P < .05). While HIP adherence challenges were observed, with only 33 (61%) completing the intervention, exploratory analyses suggest that benefits were most evident among those who fully engaged. Satisfaction and perceived benefit were greater for HIP vs LIP at both time points (P < .05). Our results suggest the potential value of parent-directed behavioral interventions like HIP for CCSs and their families. Further studies are needed to address participation barriers and enhance engagement to maximize and sustain benefits.

Intensified post-stroke care improves long-term dysphagia recovery after acute ischemic stroke: Results from the STROKE CARD trial.

Dysphagia is common after acute ischemic stroke and entails considerable morbidity and mortality. Here, we investigated the impact of intensified care on swallowing recovery after stroke. In this secondary analysis of STROKE-CARD, a randomized intervention trial of intensified post-stroke care, dysphagia was assessed by speech therapists at admission for acute ischemic stroke, at hospital discharge, and after 12-months. Patients randomized to STROKE-CARD care additionally received a detailed dysphagia follow-up at 3-months, including a standardized dysphagia examination, instructions on further exercises and compensation mechanisms and, if necessary, referral for further speech therapy. Dysphagia was present initially after stroke in 236 (16.6%; median age 82 (73-88), 44.1% female) of 1419 patients, with similar prevalence in both study groups at hospital admission (p = 0.239) and discharge (p = 0.870). At follow up, 14 (9.5%) of 147 in the intervention group and 18 (20.2%) of 89 in the control group suffered from persistent dysphagia (p = 0.020). There was better dysphagia recovery in the intervention group also under multivariable adjustment for age, sex, functional disability at 12-months, severe dysphagia at hospitalization, mode of feeding, cognitive impairment, thrombolysis, and stroke localization (odds ratio, 0.41, 95% confidence interval: 0.17 to 0.96). Intensified post-stroke care improved dysphagia recovery within 1 year after acute ischemic stroke, highlighting the potential of targeted interventions for enhancing stroke outcomes.

Differences in Mental Health Between Female Sexual Minority and Heterosexual Youth with a Substance Use Disorder Who Are Experiencing Homelessness.

Purpose: The purpose of this study was to examine differences in mental health outcomes of two groups within youth experiencing homelessness (YEH) and who have a substance use disorder (SUD): sexual minority (SM) and heterosexual females. Methods: This study used baseline data from four randomized clinical trials of substance use interventions for YEH with a SUD to examine differences in depression and suicidality between SM and heterosexual female youth. Participants were between 12 and 24 years of age. Meta-analytic methods were used to aggregate data across studies to estimate differences in mental health. Results: Results indicated that female SM-YEH had higher depression symptoms (Hedge's g [g]=0.20; 95% confidence interval [CI] 0.01-0.39), higher risk of a history of suicide behavior (risk ratio = 1.63; 95% CI: 1.17-2.27), and a greater number of suicide behaviors (g = 0.31; 95% CI: 0.09-0.54) compared to their heterosexual peers. These effect sizes were not moderated by age. Conclusion: Female SM-YEH had elevated levels of depression and suicidality compared to their heterosexual peers. The findings of this study align with research on mental health disparities between SM and heterosexual youth generally, which underscores the unique struggles and risks associated with identifying as a female SM-YEH with a SUD.

Clinical Value of Adding Dapagliflozin in Patients with Nephrotic Syndrome

Abstract Background The nephrotic syndrome has one of the best-known presentations of adult and pediatric kidney disease. The incidence of nephrotic syndrome is approximately 2 to 4 new cases per 100,000 population per year. While advances had been made in the treatment of various glomerulonephritides, some uncertainty still exists regarding the management of nephrotic syndrome owing to the lack of high-quality randomized trials of treatment or interventions and systematic reviews. Aim of the Work to assess whether dapagliflozin compared with placebo reduces edema and proteinuria in patients with nephrotic syndrome. Additional exploratory endpoints include changes in eGFR and bodyweight. Patients and Methods The present study was a randomized controlled trial conducted to assess the clinical value of adding dapagliflozin to the standard of care in patients with nephrotic syndrome. Results A notable and statistically significant mean difference in baseline proteinuria was observed between the two study groups (3645.17 ± 928.1 mg/g; p &amp;lt; 0.001). However, as the study progressed, this difference decreased and eventually became non-significant. Although the dapagliflozin arm started with markedly higher proteinuria and achieved remission similar to the control group, the specific impact of dapagliflozin could not be definitively determined due to both groups receiving immunosuppression therapy. The dapagliflozin group experienced an initial decline in renal function, with eGFR decreasing to 80.63 mL/min/1.73m². However, from Months 2 to 6, there was a progressive increase in eGFR, reaching 94.53 mL/min/1.73m² at 6 months. A post hoc analysis revealed a significant difference between the second month vs. months 4, 5, and 6, as well as the third month vs. months 4 and 6 (p &amp;lt; 0.001). In contrast, the control group's eGFR values remained relatively stable throughout the study period, ranging from 96.7 mL/min/1.73m² at baseline to 103.37 mL/min/1.73m² at 6 months (p = 0.463). These findings suggest that dapagliflozin may initially impact renal function with a temporary decrease in eGFR, but the effects are reversible as eGFR values gradually improved later on. Conclusion The evolving understanding of SGLT2 inhibitors' role in patients with nephrotic syndrome. The findings suggest their potential to influence proteinuria reduction, renal function improvement, weight management, glycemic control, and lipid profile enhancement. he manageable incidence of UTIs further supports the safety profile of dapagliflozin in this context. These findings contribute to the growing body of evidence on the clinical value of SGLT2 inhibitors in glomerular diseases, emphasizing their potential to complement standard treatments and enhance patient outcomes. Further research is warranted to fully elucidate the long-term benefits and safety of dapagliflozin in this patient population.

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. MethodsSingle-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. ConclusionsThis 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.

Theta Burst Stimulation Protocols for Schizophrenia

To date, several theta burst stimulation (TBS) protocols, such as intermittent TBS (iTBS), have been proposed; however, previous systematic reviews have revealed inconsistent efficacy findings in individual TBS studies for schizophrenia. To examine which TBS protocols are associated with the most favorable and acceptable outcomes in adults with schizophrenia. The Cochrane Library, PubMed, and Embase databases were searched for studies published before May 22, 2024. The inclusion criteria were as follows: (1) published and unpublished randomized clinical trials (RCTs) of any TBS treatment and (2) RCTs including individuals with schizophrenia spectrum disorders, other psychotic disorders, or both. This study followed the Cochrane standards for data extraction and data quality assessment and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for reporting. The risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis application was used to rate the certainty of evidence for meta-analysis results. At least 2 authors double-checked the literature search, data transfer accuracy, and calculations. The primary outcome of this study was improvement in scores related to negative symptoms. Our frequentist network meta-analysis used a random-effects model. The standardized mean difference (SMD) or odds ratio for continuous or dichotomous variables, respectively, was calculated with 95% CIs. A total of 30 RCTs of 9 TBS protocols, with 1424 participants, were included. Only iTBS over the left dorsolateral prefrontal cortex (L-DLPFC) was associated with reduced negative symptom scores (SMD, -0.89; 95% CI, -1.24 to -0.55), overall symptom scores (SMD, -0.81; 95% CI, -1.15 to -0.48), Positive and Negative Syndrome Scale general subscale scores (SMD, -0.57; 95% CI, -0.89 to -0.25), depressive symptom scores (SMD, -0.70; 95% CI, -1.04 to -0.37), and anxiety symptom scores (SMD, -0.58; 95% CI, -0.92 to -0.24) and improved overall cognitive impairment scores (SMD, -0.52; 95% CI, -0.89 to -0.15) compared with a sham. However, positive symptom score changes, all-cause discontinuation rate, discontinuation rate due to adverse events, headache incidence, and dizziness incidence did not significantly differ between any TBS protocols and sham. In this network meta-analysis, iTBS over the L-DLPFC was associated with improved scores for negative, depressive, anxiety, and cognitive symptoms in individuals with schizophrenia and was well tolerated by the participants. Other forms of TBS were not associated with benefit. Further research is needed to assess the potential role of TBS in the treatment of schizophrenia.

The Effect of Vitamin D Supplementation with or without Calcium on Vitamin D Epimer and Metabolites.

A possible role of vitamin D epimers and metabolites in the measurement and response to treatment of vitamin D has been reported recently. Furthermore, the influence of underlying vitamin D receptor (VDR) genetic polymorphisms which have been linked to diseases such as obesity remains unclear. We therefore aimed to examine the influence of vitamin D3 and calcium supplements on vitamin D epimer and metabolite concentrations in subjects with and those without vitamin D receptor (VDR) gene polymorphisms. A total of 277 participants who were part of a randomized intervention trial of vitamin D3 and calcium or a placebo for 6 months had clinical and anthropometric assessments. Blood samples were taken for measurements of vitamin D, epimers and metabolites of vitamin D, four vitamin D receptor gene polymorphism SNPs, namely, BsmI, FokI, TaqI, and ApaI, metabolic and inflammatory markers, and related biochemical variables. Repeated-measures analysis of variance was used to assess the between-group difference in cumulative changes in vitamin D epimers and metabolites at 6 months after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. Overall, 277 participants, with a mean (±SD) age of 41 ± 12 and 204 (74%) of whom were female, were included in the study. We found no statistically significant differences in vitamin D metabolites or (epimers) between male and females or younger subjects compared to those over 40 years of age except in 7C4 BL (p < 0.05). There was a statistically significant difference in 1,25(OH)2D3 concentrations between subjects with and those without genotypes AG and the allele G SNP2_Taql VDR gene polymorphism. Vitamin D3 concentrations were also significantly lower in subjects with the CC SNP3_Apal gene polymorphism compared to those without the CC SNP3 gene. No statistically significant effects were seen on vitamin D epimers and metabolites concentration in response to supplements before or after adjusting for the presence of the 4 VDR genotypes and allele gene polymorphisms. The CC SNP3 gene had statistically significant influence on vitamin D3 levels. Vitamin D and/or calcium supplements, however, had no effects on vitamin D epimer and metabolite concentration before or after adjusting for the presence of the 4 VDR genotypes and alleles.

Systematic review and meta analysis of psychological interventions to prevent or treat pediatric chronic disease in rural communities.

The purpose of this systematic review and meta-analysis was to examine the effectiveness of psychological interventions at improving physical or mental health outcomes for youth living in rural communities who have, or are at-risk for, any chronic medical condition in comparison to control interventions conducted in rural communities. Following prospective registration (OSF.IO/7TDQJ), 7 databases were searched through July 1, 2023. Studies were included if they were a randomized control trial of a psychological intervention conducted with youth living in a rural area who had, or were at-risk for, a chronic medical condition. Risk of bias was assessed with the Cochrane risk of bias version 2 tool. A qualitative synthesis and meta-analysis were conducted. 15 studies met inclusion criteria. Obesity studies (n = 13) primarily focused on body mass index metrics, with limited significant findings across studies. Asthma treatment interventions (n = 2) showed no impact on hospitalizations. 3 studies evaluated mental health outcomes with no significant group differences observed. We meta-analytically analyzed 9 studies that evaluated body mass index z-scores and identified an overall null effect (Hedge's g = 0.01, 95% CI [-0.07, 0.09], p = .85). Most included studies focused on pediatric obesity, and there was a limited range of health outcomes reported. Compared to controls, minimal significant improvements in health outcomes were identified for psychological interventions for youth living in rural communities. Future efforts may benefit from situating this work more systematically within a health disparities framework with a focus on understanding mechanisms of disparities and translating this work into interventions and policy changes.

Dietary Fiber Intake and Clinical Outcomes in Chronic Kidney Disease: A Report From the Chronic Renal Insufficiency Cohort Study

ObjectiveDietary interventions are the mainstay of chronic diseases prevention in general population, but the evidence to support such therapeutic approaches in patients with chronic kidney disease (CKD) is less robust. The objective of this study is to examine the association between dietary fiber intake and adverse cardiovascular and kidney outcomes and all-cause mortality in participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Design and MethodsA total of 3791 CRIC participants with self-reported dietary fiber intake were included in the analyses stratified by tertiles of dietary fiber at study baseline. Hazard Ratios for occurrence of all-cause mortality, composite cardiovascular events and composite kidney events were calculated using Cox Proportional Hazards models adjusted for demographic, clinical, and laboratory characteristics, including levels of inflammatory markers, C-reactive protein (CRP) and Interleukin-6 (IL-6). ResultsMean daily dietary fiber intake was 15.2 g/d. During a median (SD) follow up of 14.6 (4.4) years, 1074 deaths from any cause occurred. In multivariable adjusted models, participants in the middle and low dietary fiber tertiles had a 19% (HR [95%CI]), 1.19 [1.02, 1.39]) and 11% (1.11 [0.95, 1.31]) greater risk of death respectively, compared to those in the highest fiber intake tertile. No statistical significant associations were observed between dietary fiber intake and adverse cardiovascular and kidney outcomes. Higher dietary fiber intake was not significantly associated with lower levels of CRP and IL-6. ConclusionA lower intake of dietary fiber was not associated with all-cause mortality in participants with CKD after adjustments for kidney function and inflammatory biomarkers. There was no significant association between dietary fiber intake and adverse kidney and cardiovascular outcomes. Future randomized intervention trials are needed to identify whether a high dietary fiber intake translates into improved clinical outcomes in CKD.

SNF-CLIMEDIN: A prospective randomized trial of digital intervention in patients with advanced NSCLC—A HeCOG study.

1520 Background: The purpose of this trial is to investigate the effectiveness of online digital intervention to NSCLC patients in terms of quality of life (QoL), cost and the interrelation with clinical and molecular characteristics. Methods: This prospective randomized trial recruited 200 advanced NSCLC patients (3/22-10/23). All had NGS tissue analysis for 161 genes and received standard treatment (predominantly immuno-chemotherapy). Through the CareAcross online platform they received information about their disease and treatment, and periodically reported any of 22 preplanned adverse events (AEs). Patients were randomized 1:1 in the intervention (A) and control (B) arm; patients in arm A received digitally, additionally, evidence-based guidance for the reported AEs. The study was designed to assess QoL improvement (measured per patient as reduction of the number of AEs reported at last contact, compared to those previously reported). EQ5D-5L scores were collected. Patient-case level hospitalizations data were collected and costs were estimated based on reimbursed costs as defined by the Ministry of Health. Results were correlated with patients’ clinical and molecular characteristics. Results: Clinical and molecular characteristics will be presented during ASCO Congress. For all patients, responses were: CR: 2%, PR: 35.5%, SD: 35%, PD: 10.5%. Median PFS was 7.0 months (95%CI: 5-8), 1-year 18% (38%-55%). Median OS: 12 months (11-14), 1-year 47% (38%-55%). No difference was found between the two arms in any of the above, nor in OS in relation to clinical and molecular characteristics. The most common AEs that patients reported were fatigue, cough, anorexia, nausea. More patients submitted AE reports online than their clinicians (89% vs 68% of patients, p&lt;0.01); more AEs were reported per submission, compared to their clinicians. Patients in arm Α reported marginally higher improvement compared to B (77.2% vs 75.7%); 15 of 22 AEs were associated with higher (14) or same (1) improvement in arm A vs B (not statistically significant); of the most common: fatigue (61.3% vs 48.6%), anorexia (86.5% vs 70.2%; p&lt;0.05) and nausea (93.0% vs 87.2%). Baseline EQ5D was similar in both arms; comparing post-treatment (6th cycle) results shows higher improvement in all 5 dimensions in arm A vs B, especially in Anxiety/Depression (final values: 1.9 vs 2.2). The mean AE-related costs in Euros in arm A vs B were: hospitalization: 455.4 (95%CI: 91.9-941.5) vs 779.5 (346.6-1328.5) (p&lt;0.001); diagnostics: 20.3 (0.5-50.8) vs 73.3 (1.3-186.1) (p&lt;0.001). Follow up is ongoing. Conclusions: Digital oncology is feasible, cost-effective by reducing hospitalizations, improves certain AEs and tends to improve QoL of NSCLC patients regardless of clinical and molecular status. Patients report digitally more informative AEs for clinical and research analysis. Online platforms can complement the Oncology team. Clinical trial information: NCT05372081 .

Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction

The gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.

Characterising methamphetamine/amphetamine use among opioid agonist therapy-seeking adults with prescription-type opioid use disorder in Canada.

There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription-type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada. Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not). The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non-fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use. In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population. Available at: ClinicalTrials.gov NCT03033732.

A protocol for the conduct of a multicentre, prospective, randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures.

Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England - Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024.

Poor reporting limited consideration of EDI in the Australian guidelines for the clinical care of people with COVID-19

ObjectivesActively addressing issues of equity, diversity, and inclusion (EDI) in healthcare guidelines provides an important avenue ensure that individuals and communities receive high-quality healthcare that meets their needs. In 2020, the National Clinical Evidence Taskforce was charged with developing Australian living guidelines for COVID-19 (the Guidelines). It was intended that the Guidelines would consider the biological and social determinants of health (BSDH) underpinning evidence-based recommendations for of the treatment of COVID-19. The objective of this paper is to describe the evidence available on BSDH that is reported in published trials of disease-modifying therapies for COVID-19. Study Design and SettingPublished papers of randomized controlled trials that informed clinical recommendations (for and against drug therapies for COVID-19) in the Guidelines were reviewed retrospectively using a case series design. We extracted reported characteristics relating to BSDH. These included age, sex, gender, geographical location, ethnicity (including indigenous), disability, migrant status, income, education, employment, and social support. A descriptive analysis was conducted to illustrate the characteristics available for use in guideline development. ResultsA total of 115 peer-reviewed papers describing randomized control trials of drug interventions for the treatment of COVID-19 were included. BSDH characteristics were poorly reported. Geographical location of the study was the only category reported in all papers. While age and sex were reported in most papers (n = 109 and 108, respectively), ethnicity was reported in only one-third of papers (n = 40), social support was reported in only three papers, and employment in one paper. No paper reported on gender, disability, migrant status, income, or education. ConclusionConsideration of EDI issues is a crucial component of guideline development. Although these issues were widely recognized to impact on health outcomes from COVID-19, reporting of these characteristics was poor in COVID trials. Urgent action is needed to improve reporting of EDI characteristics if they are to be meaningfully considered in guideline processes, and health inequity is overcome.

Study Protocol of Implementation and Evaluation of Aging Home Modification Intervention Program (AhMIP) for Iranian Community-Dwelling Older Adults

Introduction With the rapid increase in the older population in Iran, the housing needs of this age group are also changing. The residential environment plays an important role in the ability of older adults to perform daily activities. This study will be conducted to implement and evaluate a home modification intervention program to support older adults. Method This paper describes the protocol for a triangulation mixed methods design study with three substudies. The first substudy is a cross-sectional study to be conducted on 422 community-dwelling older adults to assess their current status at home, functional abilities, fear of falling, and quality of life. In the second substudy, a randomized clinical intervention trial will be conducted on 116 older adults (58 intervention group and 58 control group) with the intervention of home modifications based on the results of the Home Falls and Accidents Screening Tool. The third substudy is a qualitative study with an in-depth, semi-structured interview approach to find out about older adults’ experienecs regarding AhMIP. Conclusion The quantitative and qualitative findings of this study can be useful in designing intervention programs to improve the living environment of older Iranian adults and promote their quality of life.