Enantio- and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation.

Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high enantioselectivity. Moreover, the final ketone reduction in the synthesis proceeds with high diastereoselectivity, leading to the expedient assembly of the stereotriad. In contrast to the original 16-step synthesis, this route avoids a lengthy bromination-oxidation sequence and introduces the sulfone functionality via nucleophilic aromatic substitution, obviating the need for transition metal catalysis.

Primary outcomes from Partner2Lose: A randomized controlled trial to evaluate partner involvement on long-term weight loss.

Background: Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in index participants. Purpose: To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on long-term weight loss. Methods: This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 74 years or younger, lived with a partner, and had no medical contraindications to weight loss; partners were aged 74 years or younger and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results: Among couples assigned to partner-assisted (n=115) or participant-only intervention (n=116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg]). There were no differences in 24-month average daily caloric intake (50 cal [95% CI: -233, 132 cal]) or steps (806 steps [95% CI: -1675, 64 steps]). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p=0.11). Conclusions: Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration: Clinicaltrials.gov NCT03801174.

Disparities in heart failure between White, Black, and Hispanic young adults: insights from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of heart failure (HF) is increasing among young adults in the United States with pervasive racial and ethnic differences in this population. OBJECTIVE: To evaluate contemporary associations between race and ethnicity, clinical comorbidities, and outcomes among young to middle-aged adults with HF. METHODS: A retrospective analysis was performed using the National Health and Nutrition Examination Survey. All participants with a self-report of HF aged 20-64 years from 2005 to 2018 were included and stratified by race and ethnicity [non-Hispanic (NH) Whites, NH Blacks, and Hispanics]. Data on baseline characteristics including age, sex, marital status, citizenship, education level, body mass index, insurance, waist circumference, cigarette smoking, marijuana use, and relevant clinical comorbidities were included. Weighted logistic regression was performed to estimate adjusted odds ratios (aOR) to determine the association of race and ethnicity with HF. Cox proportional-hazards models were used to assess the association of race and ethnicity with all-cause and cardiac mortality. RESULTS: A total of 1,940,447 young to middle-aged adults had self-reported HF between 2005 and 2018, of whom 61% were NH White, 40% were NH Black, and 22% were Hispanic. When compared with NH White adults, NH Black adults had higher odds of HF adjusted for age, sex, insurance status, marital status, education level, citizenship status, and clinical comorbidities (adjusted aOR 2.63, 95% CI: 1.71-4.05, p < 0.001). There was no significant difference in the odds of HF between Hispanic and NH White adults (aOR 1.18, 95% CI: 0.64-2.18, p = 0.585). NH Black adults had higher mean systolic and diastolic blood pressure, and a comparable or lower burden of cardiovascular and non-cardiovascular clinical comorbidities compared with NH White and Hispanic adults. No statistical significance was noted by race and ethnicity for all-cause and cardiac mortality during a follow-up of 5 years. CONCLUSION: NH Black young to middle-aged adults were more likely to have HF which may be related to higher blood pressure given the largely similar burden of clinically relevant comorbidities compared with other racial and ethnic groups.

A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

Racial and ethnic disparities in cardiovascular disease - analysis across major US national databases.

BACKGROUND: There are several studies that have analyzed disparities in cardiovascular disease (CVD) health using a variety of different administrative databases; however, a unified analysis of major databases does not exist. In this analysis of multiple publicly available datasets, we sought to examine racial and ethnic disparities in different aspects of CVD, CVD-related risk factors, CVD-related morbidity and mortality, and CVD trainee representation in the US. METHODS: We used National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, National Inpatient Sample, Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research, United Network for Organ Sharing, and American Commission for Graduate Medical Education data to evaluate CVD-related disparities among Non-Hispanic (NH) White, NH Black and Hispanic populations. RESULTS: The prevalence of most CVDs and associated risk factors was higher in NH Black adults compared to NH White adults, except for dyslipidemia and ischemic heart disease (IHD). Statins were underutilized in IHD in NH Black and Hispanic patients. Hospitalizations for HF and stroke were higher among Black patients compared to White patients. All-cause, CVD, heart failure, acute myocardial infarction, IHD, diabetes mellitus, hypertension and cerebrovascular disease related mortality was highest in NH Black or African American individuals. The number of NH Black and Hispanic trainees in adult general CVD fellowship programs was disproportionately lower than NH White trainees. CONCLUSION: Racial disparities are pervasive across the spectrum of CVDs with NH Black adults at a significant disadvantage compared to NH White adults for most CVDs.

Tacrolimus-Induced Neurotoxicity After Transplant: A Literature Review.

Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used globally to prevent rejection after organ transplantation. Although it significantly improves outcomes for solid organ transplant patients, it is associated with various side effects such as nephrotoxicity and neurotoxicity. Tacrolimus-induced neurotoxicity is frequently encountered in clinical practice and can present with a variety of symptoms that may occur even at therapeutic levels. Although tacrolimus-induced neurotoxicity is well documented, there is limited literature available on pharmacologic management. Twenty-eight case reports of tacrolimus-induced neurotoxicity were identified and analyzed in addition to other literature including reviews, retrospective studies, and animal model studies. The severity of cases of tacrolimus-induced neurotoxicity reported ranged from mild symptoms that could be managed with symptomatic treatment to conditions such as posterior reversible encephalopathy syndrome and chronic inflammatory demyelinating polyradiculoneuropathy that may require more immediate intervention. This information was utilized in addition to clinical experience to compile potential management options for prevention and treatment of neurotoxic adverse events. This review is limited by the utilization of primarily retrospective studies and case reports. The available literature on the subject is largely narrative and there are no guidelines on treatment of tacrolimus-induced neurotoxicity at the time of this research. This comprehensive review may guide further studies to investigate the pathophysiology of tacrolimus-induced neurotoxicity and to define patient-specific strategies for mitigation or minimization of neurotoxicity. This is especially important given that management of tacrolimus-induced neurotoxicity can include changes to immunosuppression that can result in an increased risk of rejection.

Optimizing Care for Military Women: The Value of the Dual-Certified Family and Women's Health Nurse Practitioner.

The number of women in the military has more than tripled over the past 50 years, increasing from 5% in the 1970s to 17% in 2023, making them essential for global health engagement and military operations. Provider competence and confidence are barriers to the consistent availability of preventive, gynecologic, and reproductive services for women across service locations and duty platforms. The Defense Health Board recommends standardizing services and improving the availability and scope of services for women at every point of care. In direct conflict with these recommendations, however, is a congressional call for a drawdown of medical forces, which creates a need for operationally trained clinicians with a broad skill set including comprehensive care for women. Advanced practice registered nurses, such as family and women's health nurse practitioners, are key assets to fill this gap on military medical health-care teams. At the request of the U.S. Air Force, the Graduate School of Nursing at the Uniformed Services University began offering a Women's Health Nurse Practitioner (WHNP) program in 2014. The WHNP curriculum was layered onto the existing Family Nurse Practitioner program so that Family Nurse Practitioner students receive enhanced education in women's health and WHNP students are prepared to meet the holistic, primary care needs of patients across the lifespan in addition to caring for women with obstetric and urogenital health concerns. This article highlights the value of dual-certified Family Nurse Practitioners and WHNPs in the military health-care system. These Uniformed Services University alumni are uniquely prepared to provide comprehensive primary and specialty care for female warfighters across the lifecycle from stable, well-resourced duty stations to austere, operational settings or deployment platforms.

Women Veterans' Barriers to Care-Seeking for Cardiovascular Disease Prevention.

BACKGROUND: Women veterans have a high prevalence of traditional and nontraditional risks for cardiovascular disease (CVD) including obesity and posttraumatic stress disorder. Experts from the U.S. Department of Veterans Affairs have called for actions to improve the cardiovascular health of this population. One approach is to assess women veterans' barriers to care-seeking for CVD prevention, to inform future intervention research. OBJECTIVE: The objective of this study was to describe women veterans' barriers to care-seeking for CVD prevention, guided by the theory of care-seeking behavior and concept awareness. METHODS: Using a cross-sectional, descriptive design, a national sample of 245 women veterans participated in an online survey about barriers to care-seeking. Participants provided narrative responses to open-ended items, endorsements to closed-ended items, and rankings of their top five barriers. Researchers conducted poststratification weighting of numerical data to reflect the women veteran population. RESULTS: Narrative responses described unaffordable and inaccessible services, feeling harassed or not respected in healthcare settings, and lack of awareness of risks for CVD. Frequently endorsed barriers were unaffordable and inaccessible services. Frequently ranked barriers were feeling not respected in healthcare settings and clinicians not recommending CVD prevention. DISCUSSION: Findings support concepts in theory of care-seeking behavior and concept awareness. Understanding women veterans' barriers to care-seeking for CVD prevention can inform clinicians and researchers as they address these barriers.

"They Have Shown Me It Is Possible to Thrive within STEM": Incorporating Learning Assistants in General Chemistry Enhances Student Belonging and Confidence.

Students often experience social and psychological barriers to success in General Chemistry, which is a key gateway to many students' science pathways. Learning assistants (LAs) have the potential to reduce these barriers and to strengthen students' sense of belonging in General Chemistry and STEM more broadly. Here, we used a 17-item Likert scale to determine whether incorporating LAs into General Chemistry I and II enhances students' sense of belonging in these courses. The incorporation of LAs into General Chemistry I had a significant positive effect and a medium to large effect size for students in all student groups examined: women and men; students in both racially and ethnically underrepresented and well-represented groups; first- and continuing-generation students. In General Chemistry II, similar results were observed for women and men; students in well-represented racial and ethnic groups; continuing-generation students. Further, we asked students to reflect on the impact that working with LAs had on their sense of belonging in STEM and confidence in talking about science. Sixty percent of students indicated that working with LAs had a positive impact on their STEM belonging, with five themes describing LA impacts: reducing isolation, serving as inspirational role models, providing mentoring, increasing opportunities for engagement and confidence building, and serving as accessible and approachable sources of support. Sixty-one percent of students also indicated that working with LAs increased their confidence in talking about science, with three themes emerging: fostering an environment with a lower risk of negative judgment, providing increased opportunities for feedback, and supporting students as they practiced their growing skills. Together, these results indicate that LAs can be an important means to reduce social and psychological barriers for students in gateway science courses, increasing their sense that they belong to the class and STEM more broadly.

Effects of vehicle traffic on space use and road crossings of caribou in the Arctic.

Assessing the effects of industrial development on wildlife is a key objective of managers and conservation practitioners. However, wildlife responses are often only investigated with respect to the footprint of infrastructure, even though human activity can strongly mediate development impacts. In Arctic Alaska, there is substantial interest in expanding energy development, raising concerns about the potential effects on barren-ground caribou (Rangifer tarandus granti). While caribou generally avoid industrial infrastructure, little is known about the role of human activity in moderating their responses, and whether managing activity levels could minimize development effects. To address this uncertainty, we examined the influence of traffic volume on caribou summer space use and road crossings in the Central Arctic Herd within the Kuparuk and Milne Point oil fields on the North Slope of Alaska. We first modeled spatiotemporal variation in hourly traffic volumes across the road system from traffic counter data using gradient-boosted regression trees. We then used generalized additive models to estimate nonlinear step selection functions and road-crossing probabilities from collared female caribou during the post-calving and insect harassment seasons, when they primarily interact with roads. Step selection analyses revealed that caribou selected areas further from roads (~1-3 km) during the post-calving and mosquito seasons and selected areas with lower traffic volumes during all seasons, with selection probabilities peaking when traffic was <5 vehicles/h. Using road-crossing models, we found that caribou were less likely to cross roads during the insect seasons as traffic increased, but that response dissipated as insect harassment became more severe. Past studies suggested that caribou exhibit behavioral responses when traffic exceeds 15 vehicles/h, but our results demonstrate behavioral responses at much lower traffic levels. Our results illustrate that vehicle activity mediates caribou responses to road infrastructure, information that can be used in future land-use planning to minimize the behavioral responses of caribou to industrial development in sensitive Arctic landscapes.

Prevalence of Hospital-Onset Bacteremia Pre- and Post-Implementation of a Needleless Blood Sampling Device From Existing Peripheral Catheters.

Repeated access of peripheral intravenous (IV) devices theoretically increases the risk of bacterial exposure. PIVO™ (VelanoVascular) is a needleless, single-use device that enables blood sampling from an existing peripheral IV. The goal of this retrospective observational exploratory study was to evaluate the influence of PIVO use on rates of hospital-onset bacteremia and fungemia (HOB) by comparing HOB rates in the year before and after PIVO introduction in hospitals implementing PIVO and over similar time periods in "control" hospitals with no PIVO. Two hospitals implementing PIVO (Hospital 1, a large community hospital; Hospital 2, a tertiary oncology center), and 71 control hospitals were included. During the 1-year period before and after PIVO introduction, HOB rates decreased in hospitals 1 and 2 by 31.9% and 41.8%, respectively. Control hospitals that did not use PIVO had a 12.4% decrease in HOB rates. Multivariable logistic regression analyses found that PIVO was associated with a lower risk (Hospital 1 odds ratio [OR]: 0.63; 95% CI, 0.42-0.94) or no change (Hospital 2 OR: 1.05; 95% CI, 0.72-1.52) in HOB rates. Control hospitals also showed no change in HOB rates between the 2 time periods. These data do not support concerns about increased risk of bacteremia with PIVO.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease." METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Development of an integrated rheumatoid arthritis simulation that reinforces specialty pharmacy and managed care concepts.

BACKGROUND AND PURPOSE: As pharmacy services expand, it is critical for schools/colleges of pharmacy to prepare learners to provide patient care in a variety of settings and to subsequently assess skills that are necessary for clinical practice. The objectives of this study were to (1) develop and implement a simulation that required students to integrate knowledge from multiple courses and disciplines, (2) assess students' performance and perceptions of the activity, and (3) measure student confidence related to managed care, specialty pharmacy, and clinical and foundational concepts prior to and after the simulation. EDUCATIONAL ACTIVITY AND SETTING: Faculty developed an integrated simulation that required students to provide information for prior authorization of a new medication, counsel a patient on rheumatoid arthritis and the medication, and address patient questions about insurance formularies, cost, and prior authorization processes. Students completed pre- and post-surveys to determine changes in knowledge and perceptions of the simulation. Exam questions that corresponded to simulation concepts were also analyzed. FINDINGS: Analysis of pre-post surveys indicated that students' self-perceived knowledge and confidence significantly improved in all areas (P < .001 and P < .05, respectively). Student perceptions of the simulation were positive, with comments referencing the activity's realism. Correct answers on knowledge-based questions related to simulation concepts were selected by at least 90% of students on course examinations. SUMMARY: This integrated simulation was effective at increasing self-perceived student knowledge and confidence on concepts from all disciplines, and it can easily be replicated and adapted at other pharmacy institutions.

Monitoring for a new I3 resistance gene-breaking race of F. oxysporum f. sp. lycopersici (Fusarium wilt) in California processing tomatoes following recent widespread adoption of resistant (F3) cultivars: Challenges with race 3 and 4 differentiation methods.

Fusarium wilt, caused by Fusarium oxysporum f. sp. lycopersici (Fol), causes losses in tomato production worldwide, with major impacts on Californian tomato processing. Single-gene resistance is the primary management tool, but its efficacy has been compromised following the emergence of two successive resistance-breaking races, which, in California, emerged within 12 years of resistance deployment. Fol race 3-resistant (F3) processing tomato cultivars (containing the I3 resistance gene) were deployed in the state starting in approximately 2009. The emergence of a new resistance-breaking race (which would be called race 4) is imminent, and early detection will be critical to delay the spread while new resistance is sought. The detection of Fol race 4 is challenged by the lack of validated, rapid, and accurate diagnostic tools. In evaluating in planta phenotyping methods, this study found that rapid seedling phenotyping is not reliable and generates false positives for nonpathogens. Longer (10 weeks) mature plant assays are the most reliable, but may not be sufficiently timely. As an additional challenge, based on field and greenhouse studies, Fol race 3 can cause symptoms in resistant F3 cultivars at frequencies greater (30%) than expected for off-types (<2%). We developed a three-F3 cultivar in planta assay to overcome the challenges this posed to differentiating Fol race 3 and Fol race 4. Using the assay, we determined that all putative resistance-breaking cases were Fol race 3; Fol race 4 was not detected in these early survey efforts. These results highlight the need for developing rapid Fol race 4 detection tools and a better understanding of the factors underlying inconsistent I3 gene expression in Fol race 3.

Nickel-Catalyzed Sulfonylation of Aryl Bromides Enabled by Potassium Metabisulfite as a Uniquely Effective SO2 Surrogate.

The development and mechanistic investigation of a nickel-catalyzed sulfonylation of aryl bromides is disclosed. The reaction proceeds in good yields for a variety of substrates and utilizes an inexpensive, stench-free, inorganic sulfur salt (K2 S2 O5 ) as a uniquely effective SO2 surrogate. The active oxidative addition complex was synthesized, isolated, and fully characterized by a combination of NMR spectroscopy and X-ray crystallography analysis. The use of the isolated oxidative addition complex in both stoichiometric and catalytic reactions revealed that SO2 insertion occurs via dissolved SO2 , likely released upon thermal decomposition of K2 S2 O5 . Key to the success of the reaction is the role of K2 S2 O5 as a reservoir of SO2 that is slowly released, thus preventing catalyst poisoning.

High continuous positive airway pressures versus non-invasive positive pressure ventilation in preterm neonates: protocol for a multicentre pilot randomised controlled trial.

INTRODUCTION: Low pressure nasal continuous positive airway pressure (nCPAP) has long been the mainstay of non-invasive respiratory support for preterm neonates, at a constant distending pressure of 5-8 cmH2O. When traditional nCPAP pressures are insufficient, other modes including nasal intermittent positive pressure ventilation (NIPPV) are used. In recent years, high nCPAP pressures (≥9 cmH2O) have also emerged as an alternative. However, the comparative benefits and risks of these modalities remain unknown. METHODS AND ANALYSIS: In this multicentre pilot randomised controlled trial, infants <29 weeks' gestational age (GA) who either: (A) fail treatment with traditional nCPAP or (B) being extubated from invasive mechanical ventilation with mean airway pressure ≥10 cmH2O, will be randomised to receive either high nCPAP (positive end-expiratory pressure 9-15 cmH2O) or NIPPV (target mean Paw 9-15 cmH2O). Primary outcome is feasibility of the conduct of a larger, definitive trial as assessed by rates of recruitment and protocol violations. The main secondary outcome is failure of assigned treatment within 7 days postrandomisation. Multiple other clinical outcomes including bronchopulmonary dysplasia will be ascertained. All randomised participants will be analysed using intention to treat. Baseline and demographic variables as well as outcomes will be summarised and compared using univariate analyses, and a p<0.05 will be considered significant. ETHICS AND DISSEMINATION: The trial has been approved by the respective research ethics boards at each institution (McMaster Children's Hospital: Hamilton integrated REB approval #2113; Royal Alexandra Hospital: Health Research Ethics Board approval ID Pro00090244; Westmead Hospital: Human Research Ethics Committee approval ID 2022/ETH01343). Written, informed consent will be obtained from all parents/guardians prior to study enrolment. The findings of this pilot study will be disseminated via presentations at national and international conferences and via publication in a peer-reviewed journal. Social media platforms including Twitter will also be used to generate awareness. TRIAL REGISTRATION NUMBER: NCT03512158.

Effect of a Telephone Health Coaching Intervention on Hypertension Control in Young Adults: The MyHEART Randomized Clinical Trial.

Importance: Uncontrolled hypertension (ie, a 24-hour ambulatory systolic blood pressure of ≥130 mm Hg and diastolic blood pressure of ≥80 mm Hg or clinic systolic blood pressure of ≥140 mm Hg and diastolic blood pressure of ≥90 mm Hg) in young adults is a US public health burden. Objective: To evaluate the effect of a telephone coaching and blood pressure self-monitoring intervention compared with usual care on changes in systolic and diastolic blood pressures and behaviors at 6 and 12 months. Design, Setting, and Participants: This randomized clinical trial included male and female participants aged 18 to 39 years with uncontrolled hypertension confirmed by 24-hour ambulatory blood pressure testing. This was a geographically diverse, multicentered study within 2 large, Midwestern health care systems. Data were collected from October 2017 to February 2022 and analyzed from February to June 2022. Interventions: The My Hypertension Education and Reaching Target (MyHEART) intervention consisted of telephone coaching every 2 weeks for 6 months, with home blood pressure monitoring. Control participants received routine hypertension care. Main Outcomes and Measures: The co-primary clinical outcomes were changes in 24-hour ambulatory and clinic systolic and diastolic blood pressure at 6 and 12 months. The secondary outcomes were hypertension control (defined as ambulatory systolic blood pressure <130 mm Hg and diastolic blood pressure <80 mm Hg or clinic systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and changes in hypertension self-management behavior. Results: A total of 316 participants were randomized (159 to the control group and 157 to the intervention group) from October 2017 to December 2020. The median (IQR) age was 35 (31-37) years, 145 of 311 participants (46.6%) were female, and 166 (53.4%) were male; 72 (22.8%) were Black, and 222 (70.3%) were White. There were no differences in baseline characteristics between groups. There was no significant difference between control and intervention groups for mean 24-hour ambulatory systolic or diastolic blood pressure or clinic systolic or diastolic blood pressure at 6 or 12 months. However, there was appreciable clinical reduction in blood pressures in both study groups (eg, mean [SD] change in systolic blood pressure in intervention group at 6 months, -4.19 [9.77] mm Hg; P < .001). Hypertension control did not differ between study groups. Participants in the intervention group demonstrated a significant increase in home blood pressure monitoring at 6 and 12 months (eg, 13 of 152 participants [8.6%] checked blood pressure at home at least once a week at baseline vs 30 of 86 [34.9%] at 12 months; P < .001). There was a significant increase in physical activity, defined as active by the Godin-Shephard Leisure-Time Physical Activity Questionnaire, in the intervention group at 6 months (69 of 100 [69.0%] vs 51 of 104 [49.0%]; P = .004) but not at 12 months (49 of 86 [57.0%] vs 49 of 90 [54.4%]; P = .76). There was a significant reduction in mean (SD) sodium intake among intervention participants at 6 months (3968.20 [1725.17] mg vs 3354.72 [1365.75] mg; P = .003) but not 12 months. There were no significant differences in other dietary measures. Conclusions and Relevance: The MyHEART intervention did not demonstrate a significant change in systolic or diastolic blood pressures at 6 or 12 months between study groups; however, both study groups had an appreciable reduction in blood pressure. Intervention participants had a significant reduction in dietary sodium intake, increased physical activity, and increased home blood pressure monitoring compared with control participants. These findings suggest that the MyHEART intervention could support behavioral changes in young adults with uncontrolled hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT03158051.