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Aims: Current follow-up for head and neck cancer (HNC) is ineffective, expensive and fails to address patients' needs. The PETNECK2 trial will compare a new model of patient-initiated follow-up (PIFU) with routine scheduled follow-up. This article reports UK clinicians' views about HNC follow-up and PIFU, to inform the trial design. Materials and Methods: Online focus groups with surgeons (ear, nose and throat/maxillofacial), oncologists, clinical nurse specialists and allied health professionals. Clinicians were recruited from professional bodies, mailing lists and personal contacts. Focus groups explored views on current follow-up and acceptability of the proposed PIFU intervention and randomised controlled trial design (presented by the study co-chief investigator), preferences, margins of equipoise, potential organisational barriers and thoughts about the content and format of PIFU. Data were interpreted using inductive thematic analysis. Results: Eight focus groups with 34 clinicians were conducted. Clinicians highlighted already known limitations with HNC follow-up – lack of flexibility to address the wide-ranging needs of HNC patients, expense and lack of evidence – and agreed that follow-up needs to change. They were enthusiastic about the PETNECK2 trial to develop and evaluate PIFU but had concerns that PIFU may not suit disengaged patients and may aggravate patient anxiety/fear of recurrence and delay detection of recurrence. Anticipated issues with implementation included ensuring a reliable route back to clinic and workload burden on nurses and allied health professionals. Conclusions: Clinicians supported the evaluation of PIFU but voiced concerns about barriers to help-seeking. An emphasis on patient engagement, psychosocial issues, symptom reporting and reliable, quick routes back to clinic will be important. Certain patient groups may be less suited to PIFU, which will be evaluated in the trial. Early, meaningful, ongoing engagement with clinical teams and managers around the trial rationale and recruitment process will be important to discourage selective recruitment and address risk-averse behaviour and potential workload burden.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Objective Salivary glands are among the most sensitive target organs of medications with anticholinergic (AC) properties, interrupting the neural stimulation of saliva secretion and reducing saliva flow. Hyposalivation results in dry mouth, leading to dental caries, intraoral infection, orofacial pain, problems with speaking and swallowing, and diminished oral health--related quality of life. Current understanding of the pharmacokinetics of AC medications and their effect on muscarinic receptors in the salivary glands were reviewed to assist clinicians in predicting salivary damage in patients with AC medication–induced dry mouth. Study Design We summarized the literature related to the mechanisms and properties of AC medications, anticholinergic adverse effects, and their effect on salivary function and management strategies to prevent oral health damage. Results Although a large number of studies reported on the frequencies of medication-induced dry mouth, we found very limited data on predicting individual susceptibility to AC medication--caused hyposalivation and no prospective clinical studies addressing this issue. Conclusion Dry mouth is most frequently caused by medications with AC properties, which interrupt the neural stimulation of saliva secretion. Interdisciplinary care should guide pharmacotherapeutics and dental interventions should aim in preventing AC salivary adverse effects and reducing the oral health burden from AC medication–induced dry mouth.

The application of scientifically rigorous public engagement approaches is lacking. In this context, we present a “social vulnerability protocol” which has now been applied in several broad-scale p...

Psychosocial stress is a key contributing factor to the pathogenesis of hypertension and cardiovascular disease. We examined the association of urinary stress hormone levels with incident hypertension and cardiovascular events. This prospective cohort study included 412 adults (age 48–87 years) free of hypertension from the Multi-Ethnic Study of Atherosclerosis with measurements of urinary stress hormones (norepinephrine, epinephrine, dopamine, and cortisol). Multivariable Cox proportional hazard models were used to estimate the adjusted hazard ratio (aHR) of incident hypertension and cardiovascular events according to urinary stress hormone levels. The average age (SD) was 61.2 (9.1) years, and 50% were female. Over a median follow-up of 6.5 years, there was an increased risk of incident hypertension per doubling of norepinephrine (aHR, 1.31 [95% CI, 1.06–1.61]), epinephrine (aHR, 1.21 [95% CI, 1.03–1.41]), dopamine (aHR, 1.28 [95% CI, 1.00–1.64]), and cortisol (aHR, 1.23 [95% CI, 1.04–1.44]). The associations were generally stronger among participants P -for-interaction, 0.04) and cortisol ( P -for-interaction, 0.04). Over a median follow-up of 11.2 years, there was an increased risk of incident cardiovascular events per doubling of cortisol (aHR, 1.90 [95% CI, 1.16–3.09]), but not for catecholamines. In this multiethnic population study, higher urinary stress hormone levels were associated with an increased risk of incident hypertension. Urinary cortisol levels were also associated with an increased risk of incident cardiovascular events. Our findings highlight a potentially important role of stress hormones in the prevention and treatment of hypertension and cardiovascular diseases.

Background Canada has one of the highest rates of multiple sclerosis (MS) in the world. Treatments and supports for people with MS (PwMS) have become increasingly complex, requiring individualized and adaptive care. Specialized NPs provide advanced skills to those with complex medical conditions, with potential to enhance the health, functioning, and quality of life for PwMS. This study aims to determine the effect of a Nurse Practitioner (NP) on depression and anxiety levels in PwMS. Methods We will perform a parallel randomized controlled trial. PwMS who are followed by general private-practice neurologists will be randomly assigned to the intervention group (NP-led care) or the ‘usual care’ control group (general neurologist or family physician and registered nurse support). In the intervention group, the NP will assess and provide care to the MS patient and their caregiver at a baseline visit, with 3-month and 6-month follow-up visits. PwMS in the control group will receive usual care provided by their community neurologists or family physicians with the standard assistance provided by registered nurses experienced in MS care. The primary outcome will be the difference in change in the patient’s anxiety and depression scores as measured by the validated Hospital Anxiety and Depression Scale (HADS) questionnaire at 3 months. Secondary outcomes will include difference in change in HADS at 6 months; Modified Fatigue Impact Scale scores (MSIF) at 3 and 6 months; EQ-5D scores at 3 and 6 months; caregiver health-related quality of life in MS measures (CAREQOL-MS) at 3 and 6 months; number of visits and phone calls to healthcare professionals recorded by patient, and satisfaction with NP-led care vs usual care measured by the validated Consultant Satisfaction Questionnaire. Discussion Findings from this study will contribute to exploring benefits of advanced nursing practitioner interventions for PwMS followed by general neurologists and family physicians in a community setting. It will provide evidence of the benefits of NP-led care for PwMS and offer an alternative healthcare resource for management of MS. Trial registration ClinicalTrials.govPro00069595. Retrospectively registered on June 26, 2020. Protocol version: January 2017, version 1.

The coronavirus disease 2019 (COVID-19) pandemic was caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has challenged civilization and modern science in ways that few infectious diseases and natural disasters have previously, causing globally significant human morbidity and mortality and triggering economic downturns across financial markets that will be dealt with for generations. Despite this, the pandemic has also brought an opportunity for humanity to come together and participate in a shared scientific investigation. Clinically, SARS-CoV-2 is associated with lower mortality rates than other recently emerged coronaviruses, such as SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). However, SARS-CoV-2 exhibits efficient human-to-human spread, with transmission often occurring before symptom recognition; this feature averts containment strategies that had worked previ- ously for SARS-CoV and MERS-CoV. Severe COVID-19 disease is characterized by dysregulated inflammatory responses associated with pulmonary congestion and intravascular coagulopathy leading to pneumonia, vascular insults, and multiorgan disease. Approaches to treatment have combined supportive care with antivirals, such as remdesivir, with immunomodulatory medications, including corticosteroids and cytokine-blocking antibody therapies; these treatments have advanced rapidly through clinical trials. Innovative approaches to vaccine development have facilitated rapid advances in design, testing, and distribution. Much remains to be learned about SARS-CoV-2 and COVID-19, and further biomedical research is necessary, including comparative medicine studies in animal models. This overview of COVID-19 in humans will highlight important aspects of disease, relevant pathophysiology, underlying immunology, and therapeutics that have been developed to date.

Both left atrial and left ventricular functional parameters influence the prognosis of patients with cardiovascular diseases. This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) in a population without history of cardiovascular diseases at baseline. Participants of the Multi-Ethnic Study of Atherosclerosis who underwent a baseline cardiovascular magnetic resonance study were analyzed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular end-diastolic volume. Cox proportional hazard models were used to evaluate the association between LACI and atrial fibrillation, heart failure, coronary heart disease death, and hard cardiovascular disease defined by myocardial infarction, resuscitated cardiac arrest, fatal and nonfatal stroke, or coronary heart disease death. Among the 4124 participants (61.5±10.1 years, 47.4% men), 1074 cardiovascular events were observed (mean follow-up, 13.0±3.2 years). Greater LACI was independently associated with atrial fibrillation (hazard ratio, 1.86 [95% CI, 1.69–2.04]), heart failure (hazard ratio, 1.50 [95% CI, 1.38–1.62]), hard cardiovascular disease (1.23 [95% CI, 1.13–1.34]), and coronary heart disease death (hazard ratio, 1.29 [95% CI, 1.15–1.45]; all P

Group assessment is an important collaborative learning structure for development of graduate teamwork competencies. However, group assessments are often associated with poorer learning outcomes due to highly negative student experiences involving tension and conflict. In this study, an online tool incorporating four strategic ‘GATES’ (Team structure, Communication, Leadership, and Situation monitoring/Mutual support) was designed to support the social processes required for team cohesion. The ‘GATES’ tool was evaluated using mixed methods in an observational, correlational (cross-sectional) study of 693 undergraduate and post-graduate university students and five academics in five Allied Health university courses with a group assessment task. Participants completed two anonymous questionnaires (previous experiences and current experiences) that generated both quantitative and qualitative data. In the first, 95.19% (178/187) of respondents reported a previous group assessment experience, and the experience was negative for 19.1% (34/178) of these students, with 85.3% (29/34) attributing this to group member behaviour. All academics reported issues with previous group assessments they had delivered. Of the students who used the tool (n = 52), there was no statistically significant association between gender, CALD status, or age with group assessment experience. However, 56.9% (29/52) of students and all five academics found the tool useful for getting the group started early, and for managing team issues. The tool appeared most helpful with organisation and planning than in managing team issues, potentially due to the tool negating issues before they arose. Overall, our study’s findings indicate that ‘GATES’ keeps students on track and provides timely support during the team management process.

OBJECTIVE We examined diabetes as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors. RESEARCH DESIGN AND METHODS We pooled four U.S. cohorts (Atherosclerosis Risk in Communities [ARIC], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], and Framingham Heart Study Offspring Cohort [FHS-Offspring]) and classified subjects into groups by baseline diabetes/CVD status (positive or negative). CVD risks of the diabetes mellitus (DM)+/CVD− group versus DM−/CVD+ group were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD− versus DM−/CVD+. RESULTS The pooled cohort included 27,730 subjects (mean age 58.5 years, 44.6% male). CVD rates per 1,000 person-years were 16.5, 33.4, 43.2, and 71.4 among those DM−/CVD−, DM+/CVD−, DM−/CVD+, and DM+/CVD+, respectively. Compared with those DM−/CVD+, CVD risks were similar or higher for those with HbA1c ≥ 7%, diabetes duration ≥10 years, or diabetes medication use, while those with less severe diabetes had lower risks. Hazard ratios (95% CI) for DM+/CVD− vs. DM−/CVD+ were 0.96 (95% CI 0.86–1.07), 0.97 (0.88–1.07), 0.96 (0.82–1.13), 1.18 (0.98–1.41), 0.93 (0.85–1.02), and 1.00 (0.89–1.13) among women and those of White race, age CONCLUSIONS Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, and those of younger age or with higher triglycerides or hs-CRP or reduced kidney function.

Incorporating stakeholder engagement into environmental management may help in the pursuit of novel approaches for addressing complex water resource problems. However, evidence about how and under ...

Background: The uptake of clinical practice guidelines into practice is limited for many chronic conditions, including hypertension. The aim of this study was to ascertain the importance of the educational competencies for the development of the Hypertension Canada Professional Certification Program (HC-PCP) among frontline, primary care professionals (e.g., pharmacists, physicians, nurses). Methods: A group of hypertension experts developed 15 competencies believed to be important for primary care professionals to master when providing hypertension management. These competencies were surveyed for consensus by frontline clinicians through the Hypertension Canada e-newsletter in 2018. Clinicians were asked to rank the importance of each competency for a primary care provider to acquire when undertaking a certification in hypertension management, using a Likert scale from 1 (not important) to 5 (very important). Results: A total of 121 clinicians responded to the survey. Of these, 38% were pharmacists, 31.4% were registered nurses, 10.7% were physicians and 7% were nurse practitioners. There was at least 1 respondent from each Canadian province and territory, except for the Northwest Territories. All 15 competencies received a mean rank of at least 4. The competency with the highest ranking was Competency 6: Ability to screen and identify hypertension (mean 4.83 [0.04]). The competencies with the lowest average ranks were Competency 1: Demonstrates a sound knowledge of the epidemiology of hypertension (mean 4.07 [0.85]) and Competency 5: Demonstrates an understanding of the validation process for blood pressure devices (mean 4.15 [0.08]). Conclusions: Clinicians generally ranked all 15 competencies to be of high importance for a provider who is certified in hypertension management to possess. These competencies and the current Hypertension Canada guidelines were used as the foundation for the development of an education program called the Hypertension Canada Professional Certification Program. Can Pharm J (Ott) 2021;154:xx-xx.

BACKGROUND: Fish is a primary source of protein and n-3 PUFA but also contains methylmercury (MeHg), a naturally occurring neurotoxicant to which, at sufficient exposure levels, the developing fetal brain is particularly sensitive. OBJECTIVES: To examine the association between prenatal MeHg and maternal status of n-3 and n-6 PUFA with neurodevelopment, and to determine whether PUFA might modify prenatal MeHg associations with neurodevelopment. METHODS: We examined the Seychelles Child Development Study Nutrition Cohort 2 (NC2) at age 7 y. We used a sophisticated and extensive neurodevelopmental test battery that addressed 17 specific outcomes in multiple neurodevelopmental domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Analyses were undertaken on 1237 mother-child pairs with complete covariate data (after exclusions) and a measure of at least 1 outcome. We examined the main and interactive associations of prenatal MeHg exposure (measured as maternal hair mercury) and prenatal PUFA status (measured in maternal serum at 28 weeks' gestation) on child neurodevelopmental outcomes using linear regression models. We applied the Bonferroni correction to account for multiple comparisons and considered P values

Multiple factors, including tight patient scheduling, complex electronic medical records, and increasing numbers of implanted devices, increase chances of MR imaging safety event occurrence. Several MR imaging safety incidents are described in this article, including the safety conditions and other factors that contributed to the events. MR imaging safety policy and procedural improvements that address these are also described. Specific new revision points in the American College of Radiology Manual on MR Safety are viewed in the context of these events, with emphasis on how their implementation could reduce probability of similar event recurrence.

New implanted medical devices continue to be made available for treatment of medical conditions. Many recipients can benefit from the diagnostic power of MR imaging. Provisions must be made to determine if these patients can be safely scanned. Metal-containing devices can be considered either MR unsafe or conditional. It is essential that all components of an implanted system are completely and accurately identified, with the most restrictive MR safety condition dictating the scanning approach. MR safety considerations for major classes of implanted devices are discussed, recognizing that there have been reports of serious device-related MR safety incidents.

OBJECTIVE To evaluate adverse events and feasibility of performing 1.5-T MRI in patients with cochlear implants (CI) and auditory brainstem implants (ABI). SETTING Single tertiary academic referral center. PATIENTS CI and ABI recipients undergoing 1.5-T MRI without internal magnet removal. INTERVENTION(S) MRI after tight headwrap application. MAIN OUTCOME MEASURES Adverse events, patient tolerance. RESULTS A total of 131 MR studies in 79 patients were performed, with a total of 157 study ears. Sixty-one patients (77%) had unilateral devices. Four patients (5%) underwent MRI with ABI magnets in place. Sixteen patients (20%) had MRI-compatible devices that did not require a head wrap. There were no instances of device stimulation, device malfunction, or excessive heating of the receiver-stimulator package. Magnet tilt requiring manual repositioning occurred during seven studies (4.5%) and magnet displacement requiring operative intervention occurred during seven studies (4.5%). Significant pain where imaging had to be discontinued occurred during three episodes (2%). No adverse events were noted among patients who underwent MRI with an MRI-compatible magnet. CONCLUSIONS MRI with CI or ABI magnets in place is associated with a low prevalence of adverse events when performed in a controlled setting. Many partial magnet displacements can be corrected with firm manual pressure. Devices with magnets that align with the field within their housing were not associated with any adverse events and do not require immobilization of the magnet during the scan. These may be valuable in patients with known or anticipated need for MRI.

Background Cyclones can significantly impact on communities and their healthcare services. Community members with chronic diseases, including opioid dependence, who rely on these healthcare services are placed at an increased risk of treatment disruption during a disaster event. Disruptions to the continuity of the opioid replacement therapy (ORT) service can potentially lead to relapse, withdrawal, and risky behaviours in clients with potential repercussions for the community. Objective To explore the effects of Queensland (QLD) cyclones on opioid treatment programs within Queensland community and hospital pharmacies from three perspectives. Method Qualitative research methods were used. Participants comprised five community pharmacists, four Queensland opioid treatment program (QOTP) employees, and five public hospital pharmacists. Participants were identified as they had worked in Townsville, Rockhampton, Mackay, or Yeppoon in a community impacted by a cyclone and involved with ORT supply. Interviews were recorded and data were analysed by two methods - manual coding and the text analytics software Leximancer®. Results The two themes that emerged from the manual coding process were ‘disaster preparedness’ and ‘continuity of service’. The key themes from the Leximancer® analysis aligned with the two manual coding themes with no new themes identified. Primary dosing site closures in disaster-affected areas led to increased pressures on hospitals and other community pharmacy dosing sites to supply ORT doses to clients. However, a lack of dosing information available to pharmacists and strict legislative requirements made continuity of ORT supply during these cyclones difficult. Conclusion Continuation of ORT services during and in the aftermath of a cyclone event is complex. This research highlighted a need for a coordination of efforts and shared dosing information between QOTP employees, community pharmacists, and hospital pharmacists. To improve continuity of ORT services, it is essential that these stakeholders engage with each other in preparing for and responding to future events.

Objective To provide an initial report that patients with magnetic resonance imaging (MRI) non-conditional cardiac implanted electronic device (CIED) can undergo state-of-the-art magnetic resonance imaging–guided focused (MRgFUS) ablation procedures with careful planning and integration of the procedure into an established CIED MRI practice. Patient and Methods We describe an MRgFUS ablation treatment of lumbar facet joints in a patient with an MRI non-conditional CIED (pacemaker), completed in accordance with our institutional CIED/MRI practice guidelines. Results A risk-benefit analysis by a coordinated multidisciplinary team before this treatment was performed to account for the risks associated with the MRI non-conditional pacemaker in the context of the MRgFUS procedure. Conclusion The patient had no adverse cardiac event during or following this procedure.

Purpose Long-chain polyunsaturated fatty acids (LCPUFA) can be synthesised endogenously from linoleic acid (LA) and α-linolenic acid (ALA) in a pathway involving the fatty acid desaturase (FADS) genes. Endogenous synthesis is inefficient; therefore, dietary intake of preformed LCPUFA from their richest source of fish is preferred. This study investigated the effect of fish consumption on PUFA concentrations in women of childbearing age while stratifying by FADS genotype. The influence of fish consumption on lipid profile, and markers of inflammation and oxidative stress was also examined. Methods Healthy women (n = 49) provided a buccal swab which was analysed for FADS2 genotype (rs3834458; T/deletion). Participants were stratified according to genotype and randomised to an intervention group to receive either no fish (n = 18), 1 portion (n = 14) or 2 portions (n = 17) (140 g per portion) of fish per week for a period of 8 weeks. Serum PUFA was analysed at baseline and post-intervention. Lipid profile, and markers of inflammation and oxidative stress were also analysed. Results Participants consuming 2 portions of fish per week had significantly higher concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 PUFA, and a lower n-6:n-3 ratio compared to those in the no fish or 1 portion per week group (all p Conclusion Consumption of 2 portions of fish per week has beneficial effects on biological n-3 PUFA concentrations in women of childbearing age; however, no effects on oxidative stress, inflammation or lipid profile were observed. This trial was registered at www.clinicaltrials.gov (NCT03765580), registered December 2018.

BACKGROUND: Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. OBJECTIVE: Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. METHODS: From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. RESULTS: In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, β = 0.205, P = 0.03; TC compared with CC, β = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, β = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, β = 0.109, P = 0.04). CONCLUSIONS: In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations. (Less)

Aldosterone is a steroid hormone regulating fluid and electrolyte homeostasis and is known to increase the risk of atherosclerosis. In this study, we examined the associations of serum aldosterone concentrations with subclinical atherosclerosis and all-cause mortality. This study included 948 adults aged 46 to 88 years from the MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity and not taking antihypertensive medications. Coronary calcification was longitudinally assessed using Agatston coronary artery calcium score from computed tomography scans. All-cause mortality was ascertained from the medical record. The average age (SD) was 62.3 (9.4) years and 53% were male. Among 700 subjects who had follow-up coronary artery calcium score (median follow-up of 6.4 years), higher aldosterone levels (per 100 pg/mL) were associated with higher coronary artery calcium (relative ratio, 1.17 [95% CI, 1.04–1.32]), with the association being stronger in individuals with suppressed plasma renin activity (≤0.5 μg/L/hr). Systolic or diastolic blood pressure mediated around 45% of the total effect of aldosterone on coronary artery calcium. Over a median follow-up of 12.5 years (120 deaths identified among 948 subjects), aldosterone was associated with the increased risk of all-cause mortality when plasma renin activity was suppressed; hazard ratio per 100 pg/mL, 1.70 (95% CI, 1.10–2.63). In this study, we found that higher aldosterone levels were associated with the increased risk of subclinical coronary atherosclerosis and all-cause mortality particularly when renin was suppressed. Our findings indicate the importance of aldosterone levels (even within the reference range) with respect to the cardiovascular system and overall health.

Background High quality maternity care is increasingly understood to represent a continuum of care. As well as ensuring a positive experience for mothers and families, integrated maternity care is responsive to mental health needs of mothers. The aim of this paper is to summarize differences in women’s experiences of maternity care between women with and without a self-reported mental health condition. Methods Secondary analyses of a randomized, stratified sample patient experience survey of 4787 women who gave birth in a New South Wales public hospital in 2017. We focused on 64 measures of experiences of antenatal care, hospital care during and following birth and follow up at home. Experiences covered eight dimensions: overall impressions, emotional support, respect for preferences, information, involvement, physical comfort and continuity. Multivariable logistic regression was used to compare experiences of women with and without a self-reported longstanding mental health condition. Results Compared to women without a condition, women with a longstanding mental health condition (n = 353) reported significantly less positive experiences by eight percentage points on average, with significant differences on 41 out of 64 measures after adjusting for age, education, language, parity, type of birth and region. Disparities were pronounced for key measures of emotional support (discussion of worries and fears, trust in providers), physical comfort (assistance, pain management) and overall impressions of care. Most women with mental health conditions (75% or more) reported positive experiences for measures related to guidelines for maternity care for women with mental illness (discussion of emotional health, healthy behaviours, weight gain). Their experiences were not significantly different from those of women with no reported conditions. Conclusions Women with a mental health condition had significantly less positive experiences of maternity care across all stages of care compared to women with no condition. However, for some measures, including those related to guidelines for maternity care for women with mental illness, there were highly positive ratings and no significant differences between groups. This suggests disparities in experiences of care for women with mental health conditions are not inevitable. More can be done to improve experiences of maternity care for women with mental health conditions.

Integrating nonclinical in vitro, in silico, and in vivo datasets holistically can improve hazard characterization and risk assessment. In pharmaceutical development, cardiovascular liabilities are a leading cause of compound attrition. Prior to clinical studies, functional cardiovascular data are generated in single-dose safety pharmacology telemetry studies, with structural pathology data obtained from repeat-dose toxicology studies with limited concurrent functional endpoints, eg, electrocardiogram via jacketed telemetry. Relationships between datasets remain largely undetermined. To address this gap, a cross-pharma collaboration collated functional and structural data from 135 compounds. Retrospective functional data were collected from good laboratory practice conscious dog safety pharmacology studies: effects defined as hemodynamic blood pressure or heart rate changes. Morphologic pathology findings (mainly degeneration, vacuolation, inflammation) from related toxicology studies in the dog (3–91 days repeat-dosing) were reviewed, harmonized, and location categorized: cardiac muscle (myocardium, epicardium, endocardium, unspecified), atrioventricular/aortic valves, blood vessels. The prevalence of cardiovascular histopathology changes was 11.1% of compounds, with 53% recording a functional blood pressure or heart rate change. Correlations were assessed using the Mantel-Haenszel Chi-square trend test, identifying statistically significant associations between cardiac muscle pathology and (1) decreased blood pressure, (2) increased heart rate, and between cardiovascular vessel pathology and increased heart rate. Negative predictive values were high, suggesting few compounds cause repeat-dose cardiovascular structural change in the absence of functional effects in single-dose safety pharmacology studies. Therefore, observed functional changes could prompt moving (sub)chronic toxicology studies forward, to identify cardiovascular liabilities earlier in development, and reduce late-stage attrition.

Background Cigarette smoking remains one of the leading public health threats worldwide. Electronic cigarettes (e-cigs) provide an alternative to conventional cigarette smoking; however, the evidence base of risks and benefits of e-cig use is new and growing. In this cross-sectional pilot study, the effect of e-cig use on biological profiles in saliva and gingival crevicular fluid (GCF) was assessed and compared with the profiles of cigarette smokers (CS), dual users, and non-users. The systemic inflammatory mediators between e-cig users (EC) and these other groups were also assessed. Methods This pilot cross-sectional study recruited volunteer participants consisting of four groups, non-smokers (NS), CS, EC, and dual EC and cigarette smokers (DS). Saliva and GCF samples were collected and analyzed for biomarkers of inflammation, oxidative stress, anti-inflammatory lipid mediators, tissue injury and repair, and growth factors with immunoassay (enzyme-linked immunosorbent assay and Luminex). Results Smoking status was confirmed via salivary cotinine. Prostaglandin E2 level was significantly increased in CS compared with EC and DS, but not significantly different in EC and DS groups compared with non-smokers (NS). Statistically significant differences were observed between groups of EC and NS (myeloperoxidase [MPO], matrix metalloproteinase-9) as well as between DS and EC for biomarkers of inflammatory mediators (receptor for advanced glycation end products [RAGE], MPO, uteroglobin/CC-10); between groups of DS and NS for extracellular newly identified RAGE binding protein and between CS and NS for MPO. No statistically significant differences in biomarkers of immunity (S100A8, S100A9, galectin-3), tissue injury and repair (Serpine1/PAI-1) and growth factors (brain-derived neurotrophic factor, fibroblast growth factors, platelet-derived growth factor-AA, vascular endothelial growth factor, and others) were found between any of groups. Conclusion Statistically significant differences in measurable health outcomes were found between different smoking status groups, suggesting that smoking/vaping produces differential effects on oral health.

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research.

Context Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying. Objective To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D. Methods We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D). Results The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat, and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r = 0.65, P = 0.002). Conclusion In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients.

Rationale: Lung function peaks in early adulthood and declines thereafter. We hypothesized that increasing age would be associated with smaller airway tree caliber across the adult lifespan. Methods: A sample of non-smoking adults age 20 to 97 years old free of clinical lung disease was created by harmonization of four studies: MESA Lung, CanCOLD, SPIROMICS, and the Iowa Computed Tomography (CT) Study which performed computed tomography to quantify airway lumen diameters and total lung volume. Airway tree caliber was quantified as the mean of 19 airway lumen diameters at standard locations (trachea-to-subsegments) in standardized units. Sex-specific airway tree caliber regression models were fit with restricted cubic spline terms for age, body height and total lung volume. Age and airway tree caliber relationship was assessed while keeping body height and total lung volume fixed. Sensitivity analyses stratified by sex, study, scanner, and race-ethnicity. Results: Among 1,056 participants (median [range] age: 67 [20-97] years, 57% female), increasing age from 20 to 50 years was associated with larger airway caliber followed by a plateau (Figure). Compared with aged 51-60 years, participants aged 20-30, 31-40, and 41-50 years exhibited mean standardized differences in caliber of -0.53, -0.33 and -0.13 SD respectively with p Conclusion: Increasing age from early to mid-adulthood was associated with larger airway tree caliber

ObjectiveThe aim of this study was to describe the association of individual-level characteristics (sex, race/ethnicity, birth weight, maternal education) with child BMI within each US Census region and variation in child BMI by region.MethodsThis study used pooled data from 25 prospective cohort studies. Region of residence (Northeast, Midwest, South, West) was based on residential zip codes. Age- and sex-specific BMI z scores were the outcome.ResultsThe final sample included 14,313 children with 85,428 BMI measurements, 49% female and 51% non-Hispanic White. Males had a lower average BMI z score compared with females in the Midwest (β=-0.12, 95% CI: -0.19 to -0.05) and West (β=-0.12, 95% CI: -0.20 to -0.04). Compared with non-Hispanic White children, BMI z score was generally higher among children who were Hispanic and Black but not across all regions. Compared with the Northeast, average BMI z score was significantly higher in the Midwest (β=0.09, 95% CI: 0.05 to 0.14) and lower in the South (β=-0.12, 95% CI: -0.16 to -0.08) and West (β=-0.14, 95% CI: -0.19 to -0.09) after adjustment for age, sex, race/ethnicity, and birth weight.ConclusionsRegion of residence was associated with child BMI z scores, even after adjustment for sociodemographic characteristics. Understanding regional influences can inform targeted efforts to mitigate BMI-related disparities among children.

The under-representation of women in cardiology is widely recognized. In 2017, women represented 42% of internal medicine residents and only 23% of cardiology fellows ([1][1]). These disproportionate numbers have been attributed to workplace barriers faced by women, including gender and parenting

This article describes the author’s efforts to build a combined job-preference/job-preview measure as an alternative to conventional interest inventories for use in U.S. Navy recruiting, as most applicants have no previous exposure to Navy-specific jobs. Criteria for building a successful instrument (i.e., JOIN) that can identify the best match between the Sailor and his/her assigned job are presented. The resulting taxonomy (i.e., JOIN’s classification of Navy jobs based on Community (e.g., aviation), Work Styles/Environments (e.g., outdoor), and specific Work Activity process-content pairs (e.g., maintain mechanical equipment)), is described. Psychometric properties of JOIN are presented based on data from 6,988 U.S. Navy Sailors, as well as gender differences and factor structure. Preliminary evidence of JOIN’s predictive validity with five service-related outcome measures is presented, with modest yet significant findings. Although the development of JOIN may be considered non-traditional, JOIN promises to have a direct impact on training, promotion, and retention.

Background and aims: Whey protein and guar gum have both been reported to reduce postprandial glycemia in health and type 2 diabetes, associated with stimulation of glucagon-like peptide-1 (GLP-1) and/or slowing of gastric emptying. Our aim was to evaluate, in type 2 diabetes, the acute effects of low dose “preloads” of whey and guar, given alone or in combination before a meal, on postprandial glycemia, insulin, GLP-1, and gastric emptying. Methods: 21 patients with type 2 diabetes, managed by diet or metformin alone, were each studied on 4 days. They received a preload “shake” 15min before a mashed potato meal (368.5 kcal) labeled with 13C-octanoic-acid. The preloads comprised either (i) 17 g whey (W), (ii) 5 g guar (G), (iii) 17 g whey + 5 g guar (WG) each sweetened with 60 mg sucralose, and (iv) 60 mg sucralose alone (control; C), all dissolved in 150 mL water. Venous blood was sampled frequently for measurements of glucose, insulin, and GLP-1 concentrations. Gastric half-emptying time (T50) was calculated from breath 13CO2 excretion over 240 min. Results: Postprandial blood glucose concentrations were lower with W and WG compared to C (each P < 0.0001, treatment × time interaction), and lower after G than C only at 30min. Insulin, GLP-1, and glucagon concentrations were higher after W than WG, G, or C (P < 0.05, treatment × time interaction), without differences between the latter three. Gastric emptying was slower with W (T50: 179.6 ± 6.1 min, P < 0.05) and WG (T50: 197.6 ± 9.7 min, P < 0.0001) when compared to C (T50: 162.9 ± 6.2 min), but did not differ between G (T50: 171.3 ± 7.0) and C (P > 0.99). Conclusion: Both whey and whey/guar preloads reduced postprandial glycemia, associated with slowing of gastric emptying. Low dose guar was less effective as a preload for glucose-lowering and did not slow gastric emptying usc Refereed/Peer-reviewed

Neonatal brain development can be disrupted by infection that results in microglial cell activation and neuroinflammation. Studies indicate that polyunsaturated fatty acids (PUFAs) and their metabolites can resolve inflammation. It is not known if dietary PUFA increases lipid metabolites in brain or reduces neuroinflammation in neonates. We hypothesized that dietary PUFAs might suppress neuroinflammation by inhibiting pro-inflammatory cytokine over-production and promoting inflammatory resolution in the periphery and brain. Piglets were obtained on postnatal day (PD) 2 and randomly assigned to herring roe oil (HRO) or control (CON) diet. HRO was included at 2 g/kg powdered diet. HRO increased DHA levels in occipital lobe and the DHA to arachidonic acid (ARA) ratio in hippocampal tissue. HRO decreased ARA metabolites in occipital lobe. HRO failed to attenuate microglial pro-inflammatory cytokine production ex vivo. HRO did not affect fever or circulating resolvin D1 levels. HRO decreased circulating neutrophils and liver inflammatory gene expression, but increased resolution marker gene expression in liver post LPS. HRO upregulated CXCL16, TGFBR1, and C1QA in microglial cells. HRO supplementation exerted beneficial effects on inflammation in the periphery, but further studies are needed to evaluate the specific effects of omega-3 supplementation on microglial cell physiology in the neonate.

Objective To rigorously compare automated atlas‐based and manual tracing hippocampal segmentation for accuracy, repeatability, and clinical acceptability given a relevant range of imaging abnormalities in clinical epilepsy. Methods Forty‐nine patients with hippocampal asymmetry were identified from our institutional radiology database, including two patients with significant anatomic deformations. Manual hippocampal tracing was performed by experienced technologists on 3T MPRAGE images, measuring hippocampal volume up to the tectal plate, excluding the hippocampal tail. The same images were processed using NeuroQuant and FreeSurfer software. Ten subjects underwent repeated manual hippocampal tracings by two additional technologists blinded to previous results to evaluate consistency. Ten patients with two clinical MRI studies had volume measurements repeated using NeuroQuant and FreeSurfer. Results FreeSurfer raw volumes were significantly lower than NeuroQuant (P 0.75) for both automated methods. Asymmetry index reproducibility was excellent (>0.75) for manual tracing and FreeSurfer segmentation and fair (0.4–0.59) for NeuroQuant segmentation. Both automatic segmentation methods failed on the two cases with anatomic deformations. Segmentation errors were visually identified in 25 NeuroQuant and 27 FreeSurfer segmentations, and nine (18%) NeuroQuant and six (12%) FreeSurfer errors were judged clinically significant. Interpretation Automated hippocampal volumes are more reproducible than hand‐traced hippocampal volumes. However, these methods fail in some cases, and significant segmentation errors can occur.

Context Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking. Objective To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor. Design Multicenter, prospective study. Setting Twelve centers within the T1D Exchange Clinic Network. Patients or Participants Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index. Intervention Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days. Main Outcome Measures CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. Results A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels Conclusion By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies.

Background Extreme heat (EH) events are increasing in frequency and duration and cause more deaths in Australia than any other extreme weather event. Consequently, EH events lead to an increase in the number of patient presentations to hospitals. Methods Climatic observations for Hobart’s region and Royal Hobart Hospital (RHH) emergency department admissions data were collected retrospectively for the study period of 2003–2010. A distributed lag non-linear model (DLNM) was fitted using a generalized linear model with quasi-Poisson family to obtain adjusted estimates for the relationship between temperature and the relative risk of being admitted to the RHH. Results The model demonstrated that relative to the annual mean temperature of 14°C, the relative risk of being admitted to the RHH for the years 2003–2010 was significantly higher for all temperatures above 27°C (P < 0.05 in all cases). The peak effect upon admission was noted on the same day as the EH event, however, the model suggests that a lag effect exists, increasing the likelihood of admission to the RHH for a further 14 days. Conclusions To relieve the added burden on emergency departments during these events, adaptation strategies adopted by public health organizations could include preventative health initiatives.

Cardiovascular disease is the number one cause of death for women in the United States. Of the 1.3 million active duty service members, 16.3% are currently women, and the number of women veterans is expected to increase. Women veterans have higher rates of cardiovascular disease than civilian women and present a unique population. We focus on 5 key areas regarding cardiovascular disease care for women veterans: (1) the rapidly changing demographic; (2) prevalence of traditional risk factors; (3) prevalence of less traditional risk factors (eg, homelessness, military sexual trauma, and mental health disorders); (4) treatment and outcomes of cardiovascular disease; and (5) the current state and future directions of research in this area. This review is a call to action for continued improvements in the cardiovascular care and research for this rapidly growing, at-risk, and under-represented population. Visual Overview: A visual overview is available for this article.

Background COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44–45 weeks) between the first and second dose, and response to a third dose as a booster given 28–38 weeks after the second dose. Methods In this substudy, volunteers aged 18–55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44–45 weeks after first dose) or a third dose of the vaccine (28–38 weeks after second dose). Data from volunteers aged 18–55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. Findings Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44–45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83–91·08] vs 1·75 EUs [1·60–1·93]). 32 participants received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525–1764] with an 8–12 week interval; 1860 EUs [917–4934] with a 15–25 week interval; and 3738 EUs [1824–6625] with a 44–45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047–6420]) than 28 days after a second dose (median 1792 EUs [IQR 899–4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127–389] immediately before the third dose to 399 SFUs per milion PBMCs [314–662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. Interpretation An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. Funding UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome.

BackgroundDifferent 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown.ObjectivesThe aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation.MethodsA total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n=499) or placebo (n=167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations from baseline to 16 wk.ResultsAmong 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: -5; 95% CI: -8, -2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30ng/mL as the reference, 25(OH)D

ImportanceIn the last two decades, hypertension control in the U.S. population has not improved, and there are widening disparities. Less is known, however, about progress in reducing hospitalizations related to hypertensive emergencies.ObjectivesTo describe trends in national hospitalization rates for hypertensive emergencies, overall and by demographic and geographical subgroups.Design, Setting and, ParticipantsSerial cross-sectional analysis of Medicare fee-for-service beneficiaries aged 65 years or older between 1999 and 2019 using Medicare denominator and inpatient files.Main Outcome and MeasuresTrends in hospitalization for hypertensive emergencies, overall and by specific subgroups.ResultsThe sample consisted of 397,238 individual Medicare fee-for-service beneficiaries. From 1999 through 2019, the annual hospitalization rates for hypertensive emergencies increased significantly from 51.5 to 125.9 per 100,000 beneficiary-years; this increase was most pronounced among the following subgroups: adults ≥85 years (66.8 to 274.1), females (64.9 to 160.1), Blacks (144.4 to 369.5), and Medicare-Medicaid insured (dual eligible, 93.1 to 270.0). Across all subgroups, Black adults had the highest hospitalization rate in 2019, and there was a significant increase in the differences in hospitalizations between Blacks and Whites from 1999 to 2019. Marked geographic variation was also present, with the highest hospitalization rates in the South (so-called “Stroke Belt”). Among 3,143 counties and county-equivalents included in the study, less than 1% of counties either had no change (n=7) or decreased (n=20) hospitalization rates since 1999. Among patients hospitalized for a hypertensive emergency, the observed 30-day all-cause mortality rate decreased from 2.6% to 1.7% and 30-day all-cause readmission rate decreased from 15.7% to 11.8%.Conclusions and RelevanceAmong Medicare fee-for-service beneficiaries aged 65 years or older, hospitalization rates for hypertensive emergencies increased substantially and significantly from 1999 to 2019. Black adults had the largest increase in hospitalization rates across age, sex, race, and dual-eligible strata. There was significant national variation, with the highest rates generally in the South.KEY POINTSQuestionHow have hospitalization rate for hypertensive emergencies among US adults aged 65 years and older changed between 1999 and 2019 and are there any differences across demographic and geographical subgroups?FindingsIn this serial cross-sectional study that included 397,238 individual Medicare fee-for-service beneficiaries, there was a marked increase in hospitalization rates for hypertensive emergencies from 1999 to 2019, and this increase was most pronounced among Black adults across age, sex, race, and dual-eligible strata. Significant national variation was observed, with the highest hospitalization rates generally in the South.MeaningBetween 1999 and 2019, hospitalization rates for hypertensive emergencies increased substantially and differences across demographic and geographic subgroups persisted.

Author(s): An, Eunjoo; Irwin, Michael R; Doering, Lynn V; Brecht, Mary-Lynn; Watson, Karol E; Corwin, Elizabeth; Macey, Paul M | Abstract: Background and aimsHTN affects nearly 50% of U.S. adults and is the leading modifiable cardiovascular risk factor. A healthy diet and exercise can improve BP control, but adherence to these interventions is low. We tested whether a multimodal mind-body program, Mindful Awareness Practices (MAP) could improve BP and lifestyle behaviors associated with HTN when compared to a Health Promotion Program (HPP).MethodsAdults with BP g120/80 were randomized to MAP or HPP. Outcome measurements of BP, self-reported diet, and exercise were analyzed with intent-to-treat group comparisons using repeated measures linear mixed models.ResultsThere was an MAP-HPP between-group difference in interactions of time-by-systolic BP (Pn= 0.005) and time-by-diastolic BP (Pn= .003). The mean drops in SBP from baseline to week 13 for the MAP group was 19 mm Hg (138 ± 15 mm Hg-119 ± 6 mm Hg) compared to 7 mm Hg (134 ± 18 mm Hg-127 ± 22 mm Hg) in the HPP group. Similarly, a greater reduction in DBP was observed in the MAP group compared to the HPP group, 12 mm Hg (89 mm Hg ± 11-77 ± 7 mm Hg) and 1 mm Hg (81 ± 16 mm Hg-80 ± 18 mm Hg), respectively. Mediational analysis of the MAP group showed the total effect of mindfulness practice minutes on SBP with indirect effect (ab) of -.057 was significant, resulting in a 40% lower SBP for total effect (c) compared to direct (c') effect alone. The mediational model suggests MAP has a modest positive influence on participants initiating lifestyle behavior change, which partially explains the greater reduction in BP by the MAP group.ConclusionOur findings suggest a multimodal mind-body program involving mindfulness practice may improve BP control in adults with HTN.