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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Gender trends in authorship of gastroenterology randomized controlled trial literature.

INTRODUCTION: We describe female authorship trends in gastroenterology (GI) randomized controlled trial (RCT) literature as a novel focus on gender bias in academic gastroenterology. METHODS: Using a systematic PubMed search, we extracted GI RCT reports published from 2011 through 2022. We describe time-trends in proportions of females among first and last authors overall, and within GI subspecialties and high-impact journals. RESULTS: The proportion of females increased from 25.4% to 36.8% and from 14.3% to 24.8% among first and last authors, respectively. Smaller increases in female authorship occurred in most subgroups, though there were proportionately fewer females among authors in high-impact journals and advanced therapeutic endoscopy publications.

Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Importance: Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. Objective: To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. Design, Setting, and Participants: This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Exposures: Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. Main Outcomes and Measures: The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Results: Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. Conclusions and Relevance: In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Understanding health behaviors that modify the risk for obesity in ADHD.

OBJECTIVE: Research provides support for the associated risk of inadequate sleep duration, limited physical activity, and excessive media use in attention-deficit/hyperactivity disorder (ADHD) and obesity. The present study aims to (1) examine the association between ADHD and overweight or obese status (OW/OB); (2) comprehensively examine sleep duration, physical activity, and media use as potential moderators of OW/OB; and (3) examine the moderating effects of these health behaviors cross-sectionally by comparing medicated youth with ADHD, unmedicated youth with ADHD, and youth without ADHD. METHODS: Data were acquired from the 2018 and 2019 National Survey of Children's Health, a nationally representative survey of caregivers conducted across the United States. The current study used data for youth 11-17 years old with a final sample size of 26,644. Hours of sleep, physical activity, and media use per day were dichotomized based on national recommendation guidelines for each health behavior (i.e., either meeting or not meeting guidelines). RESULTS: The OW/OB prevalence rate was 7% greater among unmedicated youth with ADHD than among medicated youth with ADHD. Medicated youth with ADHD and peers without ADHD had similar OW/OB rates. Among medicated youth with ADHD, physical activity, sleep duration, and media use did not contribute to OW/OB risk after controlling for family poverty level. However, among unmedicated youth with ADHD, meeting sleep duration guidelines was linked to a lower OW/OB risk. CONCLUSION: Overall, findings suggest that clinical providers and parents may wish to prioritize improved sleep duration in the management of OW/OB risk in youth with ADHD.

A Comparison of Chemodnervation to Incisional Surgery for Acute, Acquired, Comitant Esotropia: An International Study.

PURPOSE: To compare the efficacy of botulinum toxin injections to strabismus surgery in children with acute, acquired, comitant esotropia (ACE), and to investigate factors predicting success. DESIGN: International, multi-center nonrandomized comparative study METHODS: Setting: Cloud-based survey. STUDY POPULATION: Children aged 2 to 17 years who underwent a single surgical intervention for ACE. INTERVENTIONS: Botulinum toxin injection ("chemodenervation" group) or strabismus surgery ("surgery" group). MAIN OUTCOME MEASURES: Primary measure: success rate at 6 months in propensity-matched cohort, defined as total horizontal deviation of 10 prism diopters or less with evidence of binocular single vision. Secondary measure: Risk factors for poor outcomes in the full cohort. RESULTS: Surgeons from 19 centers contributed. There were 74 patients in the chemodenervation group and 97 patients in the surgery group. In the propensity-matched data (n = 98), success rate was not significantly different at 6 months (70.2% vs 79.6%; P = .2) and 12 months (62.9% vs 77.8%; P = .2), but was significantly lower in the chemodenervation group at 24 months (52% vs 86.4%; P = .015). Irrespective of treatment modality, treatment delay was associated with lower success rates at 6 months, with median time from onset to intervention 4.5 months (interquartile range (IQR): 2.1, 6.7) in the success group and 7.7 months (IQR: 5.6, 10.1) in the failure group (P < .001). CONCLUSIONS: In children with ACE, success rate after chemodenervation was similar to that of surgery for up to 12 months but lower at 24 months. Those with prompt intervention and no amblyopia had the most favorable outcomes, regardless of treatment modality.

Body-site effect on CPM efficiency in healthy subjects: Central vs. peripheral stimulation.

Structural changes in the peripheral nerve system in neuropathic states alter sensory capacity of the affected area, thus biasing results of conditioned pain modulation (CPM) responses. The aim of this study was to evaluate CPM efficiency of central (i.e. trunk) vs. peripheral (i.e. limb) application of 'test' and 'conditioning' stimuli. Methods: Healthy volunteers (ages 18-73 yrs) underwent two CPM protocols: 'CPM Limb' and 'CPM Trunk'. Each included two types of test stimuli (Ts) (pressure pain threshold: PPT; and contact heat) conditioned either to hand immersion in cold noxious water (CPM limb), or to noxious contact heat applied on lower back (CPM trunk). Results: Both protocols generated efficient pain inhibition for each of the applied Ts; the PPT-based protocol induced more efficient CPM when the conditioned stimulus was applied on the trunk (p = 0.016). Moreover, the PPT-based CPM responses were significantly correlated (ρ = 0.349; p = 0.007). Conclusions: An efficient CPM induced by both central and peripheral stimulation, along with significant correlation between PPT-based responses, advances using the central 'CPM Trunk' protocol in patients with peripheral neuropathy.

PROTACs Targeting BRM (SMARCA2) Afford Selective In Vivo Degradation over BRG1 (SMARCA4) and Are Active in BRG1 Mutant Xenograft Tumor Models.

The identification of VHL-binding proteolysis targeting chimeras (PROTACs) that potently degrade the BRM protein (also known as SMARCA2) in SW1573 cell-based experiments is described. These molecules exhibit between 10- and 100-fold degradation selectivity for BRM over the closely related paralog protein BRG1 (SMARCA4). They also selectively impair the proliferation of the H1944 "BRG1-mutant" NSCLC cell line, which lacks functional BRG1 protein and is thus highly dependent on BRM for growth, relative to the wild-type Calu6 line. In vivo experiments performed with a subset of compounds identified PROTACs that potently and selectively degraded BRM in the Calu6 and/or the HCC2302 BRG1 mutant NSCLC xenograft models and also afforded antitumor efficacy in the latter system. Subsequent PK/PD analysis established a need to achieve strong BRM degradation (>95%) in order to trigger meaningful antitumor activity in vivo. Intratumor quantitation of mRNA associated with two genes whose transcription was controlled by BRM (PLAU and KRT80) also supported this conclusion.

Considerations and Determinants of Discharge Decisions among Prenatal Substance Exposed Infants.

Limited research has examined a comprehensive set of predictors when evaluating discharge placement decisions for infants exposed to substances prenatally. Using a previously validated medical record data extraction tool, the current study examined prenatal substance exposure, infant intervention (i.e., pharmacologic, or non-pharmacologic), and demographic factors (e.g., race and ethnicity and rurality) as predictors of associations with discharge placement in a sample from a resource-poor state (N = 136; 69.9% Non-Hispanic White). Latent class analysis (LCA) was used to examine whether different classes emerged and how classes were differentially related to discharge placement decisions. Logistic regressions were used to determine whether each predictor was uniquely associated with placement decisions. Results of the LCA yielded a two-class solution comprised of (1) a Low Withdrawal Risk class, characterized by prenatal exposure to substances with low risk for neonatal abstinence syndrome (NAS) and non-pharmacologic intervention, and (2) a High Withdrawal Risk class, characterized by a high risk of NAS and pharmacologic intervention. Classes were not related to discharge placement decisions. Logistic regressions demonstrated that meth/amphetamine use during pregnancy was associated with greater odds of out of home placement above other substance types. Future research should replicate and continue examining the clinical utility of these classes.

Posterior Palatal Expansion via Subnasal Endoscopy (2PENN) for Maxillary Deficiency: A Pilot Study.

OBJECTIVE: Surgically assisted rapid palatal expansion (SARPE) addresses transverse maxillary deficiency, a known contributor to nasal obstruction. The purpose of this study was to assess the feasibility, preliminary outcomes, and safety of posterior palatal expansion via subnasal endoscopy (2PENN), a modified SARPE procedure, aimed at achieving anterior and posterior maxillary expansion. METHODS: This prospective case series included consecutive adult patients with findings of transverse maxillary deficiency that underwent the 2PENN procedure from 4/2021 to 4/2022. Patients completed pre- and post-operative clinical evaluations, Nasal Obstruction and Septoplasty Effectiveness (NOSE) questionnaires, and computed tomography (CT), with measures including expansion at the level of the posterior nasal spine (PNS), first maxillary inter-molar distance (IMD), and anterior nasal spine (ANS). RESULTS: The cohort (N = 20) was middle-aged (39 ± 11 years), predominantly male (80%), and overweight (BMI 28 ± 4 kg/m2 ). The majority (85%) of patients had sleep breathing issues, of which 10 (59%) had polysomnography-confirmed obstructive sleep apnea (OSA). Full anterior-posterior separation of the mid-palatal suture line was evident on all post-operative CT scans, with mean expansion at the PNS of 3.6 ± 1.3 mm, IMD of 6.1 ± 1.6 mm and ANS of 7.0 ± 1.6 mm (p < 0.001). Following surgery, mean NOSE scores improved from 57 ± 23 to 14 ± 13 (p < 0.001). One patient required maxillary antrostomy for post-operative sinusitis. CONCLUSION: 2PENN is an effective and safe technique for achieving both anterior and posterior maxillary expansion in patients with transverse maxillary deficiency. Further study is warranted to better understand the effect of 2PENN in patients with OSA, particularly as it relates to improving pharyngeal patency. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1970-1977, 2024.

Empowering Lung Cancer Survivors in Post-Treatment Survivorship Care Using Participatory Action Research.

PURPOSE: To explore the experiences of lung cancer survivors (LCSs) and their informal and professional caregivers with post-treatment care and to empower them to implement action-based study findings. PARTICIPANTS & SETTING: Participants were recruited using purposeful and snowball sampling from patients at a National Cancer Institute-designated cancer center in the northeastern United States. METHODOLOGIC APPROACH: This study used a participatory action research (PAR) four-phase design. Phase 1 was a focused ethnography; phase 2 consisted of a core group of participants deciding on an action, which was implemented in phase 3; and phase 4 consisted of an evaluation of the action. FINDINGS: The study found 28 categories, eight patterns, and three themes. The themes were the need for resources and education, involvement in mentoring and advocacy, and the value of living versus surviving. The action was creating two flyers focused on resources and advocacy for post-treatment support for LCSs. All participants agreed with the themes and action. Tobacco management and smoking-related stigma for LCSs were the only topics of dissent. IMPLICATIONS FOR NURSING: Oncology nurses can use PAR to empower survivors in their post-treatment care. Future PAR cycles should focus on creating support groups and alleviating stigma for LCSs and their caregivers.

The integrated stress response in cancer progression: a force for plasticity and resistance.

During their quest for growth, adaptation, and survival, cancer cells create a favorable environment through the manipulation of normal cellular mechanisms. They increase anabolic processes, including protein synthesis, to facilitate uncontrolled proliferation and deplete the tumor microenvironment of resources. As a dynamic adaptation to the self-imposed oncogenic stress, cancer cells promptly hijack translational control to alter gene expression. Rewiring the cellular proteome shifts the phenotypic balance between growth and adaptation to promote therapeutic resistance and cancer cell survival. The integrated stress response (ISR) is a key translational program activated by oncogenic stress that is utilized to fine-tune protein synthesis and adjust to environmental barriers. Here, we focus on the role of ISR signaling for driving cancer progression. We highlight mechanisms of regulation for distinct mRNA translation downstream of the ISR, expand on oncogenic signaling utilizing the ISR in response to environmental stresses, and pinpoint the impact this has for cancer cell plasticity during resistance to therapy. There is an ongoing need for innovative drug targets in cancer treatment, and modulating ISR activity may provide a unique avenue for clinical benefit.

Assessing attitudes towards pediatric research participation across diverse populations: Psychometric properties of a novel tool.

BACKGROUND: Clinical trials play a crucial role in advancing medical knowledge and improving health outcomes. However, there is a recognized need for greater representation of marginalized groups to ensure that research findings can be generalized and effectively applied to all individuals. While the Pediatric Research Participation Questionnaire (PRPQ) was developed to assist pediatric clinical trials research by identifying benefits and barriers to research participation among children with chronic medical conditions, there is still limited insight into the structure of the PRPQ when administered in diverse samples, including the general pediatric population. Therefore, the current study examined the factor structure of the PRPQ in a general pediatric population to investigate whether rural-urban differences exist in the PRPQ factor structure. METHODS: Caregivers (N = 600) of children under age 18 completed the PRPQ in a population-based survey in Mississippi. Sampling was stratified to ensure equal representation in rural (n = 300) and urban areas (n = 300). Exploratory and confirmatory factor analyses were conducted to determine the factor structure of the PRPQ. RESULTS: A five-factor structure was identified, compromising: social pressure, direct benefit, reasons for participation, mistrust in research/researchers, reasons against participation. While results were similar among urban participants, a three-factor structure emerged for rural participants. CONCLUSIONS: This study contributes to the broader understanding of research participation among underrepresented groups. The findings suggest that clinical researchers should consider tailoring recruitment strategies to increase clinical trial participation among children in rural areas. Understanding factors that influence pediatric research participation, particularly among marginalized communities, is crucial for developing effective recruitment and retention strategies.

Caspase-2 is essential for proliferation and self-renewal of nucleophosmin-mutated acute myeloid leukemia.

Mutation in nucleophosmin (NPM1) causes relocalization of this normally nucleolar protein to the cytoplasm ( NPM1c+ ). Despite NPM1 mutation being the most common driver mutation in cytogenetically normal adult acute myeloid leukemia (AML), the mechanisms of NPM1c+-induced leukemogenesis remain unclear. Caspase-2 is a pro-apoptotic protein activated by NPM1 in the nucleolus. Here, we show that caspase-2 is also activated by NPM1c+ in the cytoplasm, and DNA damage-induced apoptosis is caspase-2-dependent in NPM1c+ AML but not in NPM1wt cells. Strikingly, in NPM1c+ cells, loss of caspase-2 results in profound cell cycle arrest, differentiation, and down-regulation of stem cell pathways that regulate pluripotency including impairment in the AKT/mTORC1 and Wnt signaling pathways. In contrast, there were minimal differences in proliferation, differentiation, or the transcriptional profile of NPM1wt cells with and without caspase-2. Together, these results show that caspase-2 is essential for proliferation and self-renewal of AML cells that have mutated NPM1. This study demonstrates that caspase-2 is a major effector of NPM1c+ function and may even be a druggable target to treat NPM1c+ AML and prevent relapse.

A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m2, however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m2. Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.

Understanding the Challenges Faced by Esophageal and Gastroesophageal Junction Cancer Survivors.

The primary aim of this study is to characterize long-term quality of life (QOL) in patients with esophageal and gastroesophageal junction (EGEJ) cancers who underwent curative intent treatment. EGEJ survivors were recruited to participate in a one-time cross-sectional survey study using validated questionnaires assessing QOL. Chart review was conducted for patient demographics and clinical characteristics. Spearman correlation coefficients, Wilcoxon signed-rank test, and Fisher's exact test were used to assess relationships between patient characteristics and long-term outcomes. QOL was relatively high in this sample, as evidenced by high median scores on the functional scales and low median scores in the symptom domains of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, with an overall median global health score of 75.0 (range 66.7-83.3). Patients using opiates at the time of survey reported lower role functioning (P = .004), social functioning (P = .052), and overall global health (P = .041). Younger patients had significantly higher rates of reflux (P = .019), odynophagia (P = .045), choking (P = .005), and cough (P = .007). Patients using opiates or of younger age had lower QOL and higher symptoms in this cohort of long-term EGEJ survivors.

The longitudinal influence of ADHD status and stimulant medication on body mass index and blood pressure among youth with obesity.

BACKGROUND: Youth with attention-deficit hyperactivity disorder (ADHD) are more vulnerable to developing obesity. Stimulant medication use, an evidence-based treatment for ADHD, is associated with lower body mass index (BMI) and higher blood pressure among non-overweight youth. OBJECTIVES: The purpose of this study was to examine the longitudinal influence of ADHD and stimulant medication use on BMI and blood pressure among a sample of 456 youth with overweight and obesity treated in a paediatric weight management clinic. METHODS: Mixed linear modelling examined the main and interactive effects of time by ADHD status and stimulant medication use on BMI and blood pressure. RESULTS: Youth without ADHD experienced a significantly faster decrease in BMI compared to youth with ADHD (p < 0.001). Youth with ADHD who were taking stimulant medication had a significantly faster decrease in BMI compared to youth with ADHD who were not taking stimulant medication (p = 0.009). There was no significant effect of ADHD status or stimulant medication use on diastolic or systolic blood pressure trajectories over time (ps >0.05). CONCLUSIONS: Results from this study suggest that youth with ADHD who are not taking stimulant medication may not benefit from clinical weight management to the same extent as either youth without ADHD or youth with ADHD who are taking a stimulant medication.

Post-diagnostic health behaviour scores and risk of prostate cancer progression and mortality.

BACKGROUND: Individual behaviours are associated with prostate cancer (PC) progression. Behavioural scores, comprised of multiple risk factors, allow assessment of the combined impact of multiple behaviours. METHODS: We examined the association between six a priori scores and risk of PC progression and mortality among 2156 men with PC in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) cohort: two scores developed based on the PC survivorship literature ('2021 Score [+ Diet]'); a score developed based on pre-diagnostic PC literature ('2015 Score'); and three scores based on US recommendations for cancer prevention ('WCRF/AICR Score') and survival ('ACS Score [+ Alcohol]'). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for progression and PC mortality via parametric survival models (interval censoring) and Cox models, respectively. RESULTS: Over a median (IQR) of 6.4 (1.3, 13.7) years, we observed 192 progression and 73 PC mortality events. Higher (i.e., healthier) 2021 Score + Diet and WCRF/AICR Scores were inversely associated with risk of PC progression (2021 + Diet: HRcontinuous = 0.76, 95% CI: 0.63-0.90. WCRF/AICR: HRcontinuous = 0.83, 95% CI: 0.67-1.02) and mortality (2021 + Diet: HRcontinuous = 0.65, 95% CI: 0.45-0.93. WCRF/AICR: HRcontinuous = 0.71; 95% CI: 0.57-0.89). The ACS Score + Alcohol was only associated with progression (HRcontinuous = 0.89, 95% CI: 0.81-0.98) while the 2021 Score was only associated with PC mortality (HRcontinuous = 0.62, 95% CI: 0.45-0.85). The 2015 was not associated with PC progression or mortality. CONCLUSION: Findings strengthen the evidence that behavioural modifications following a prostate cancer diagnosis may improve clinical outcomes.

Mandibular advancement device versus CPAP in lowering 24-hour blood pressure in patients with obstructive sleep apnoea and hypertension: the CRESCENT trial protocol.

INTRODUCTION: Although treatment of obstructive sleep apnoea (OSA) using continuous positive airway pressure (CPAP) reduces blood pressure (BP), adherence to CPAP is often suboptimal. A mandibular advancement device (MAD) is a guideline-endorsed alternative therapy for OSA. Still, there is limited evidence on the relative efficacy between MAD and CPAP on BP reduction. We evaluate whether treatment of moderate-to-severe OSA using MAD can improve BP and other health-related outcomes compared with CPAP. METHODS AND ANALYSIS: This is a randomised, controlled, non-inferiority trial conducted. We will recruit 220 Asians with a history of hypertension and high cardiovascular risk for an overnight polysomnography screening. Those with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events/hour) will be randomised to treatment with either MAD or CPAP in a 1:1 ratio. Stratified by age (60 vs <60 years old), body mass index (25 vs <25 kg/m2) and apnoea-hypopnoea index (30 vs <30 events/hour), an adaptive randomisation scheme with permuted blocks constructed in real-time is implemented to restrict imbalance. The overall study duration is 12 months. The primary endpoint is the 24-hour mean arterial BP difference between baseline and 6-month follow-up. The secondary endpoints include other measures of ambulatory BP monitoring, arrhythmia based on a 4-day electrocardiographic monitoring, biomarker and proteomic analysis, cardiovascular magnetic resonance-derived myocardial fibrosis and remodelling and quality-of-life questionnaires. Recruitment began in October 2019 and ended in December 2022. Comparison between MAD and CPAP will be performed using covariance (ANCOVA) analysis of the changes in 24-hour mean arterial BP while adjusting for the baseline 24-hour mean arterial BP. We will compare the 95% CIs around the treatment difference point estimate with the prespecified non-inferiority margin (1.5 mm Hg). If the upper limit of the 95% CI is <1.5 mm Hg and crosses 0, non-inferiority of the MAD relative to CPAP will be established. ETHICS AND DISSEMINATION: The Domain Specific Review Board-C, National Healthcare Group under approved the study protocol (NHG DSRB Ref: 2019/00359, approved on 28 August 2019). Study findings will be disseminated to various local, national, and international audiences through abstract presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04119999.