The social genome of friends and schoolmates in the National Longitudinal Study of Adolescent to Adult Health

Our study reported significant findings of a “social genome” that can be quantified and studied to understand human health and behavior. In a national sample of more than 5,000 American adolescents, we found evidence of social forces that act to make friends and schoolmates more genetically similar to one another compared with random pairs of unrelated individuals. This subtle genetic similarity was observed across the entire genome and at sets of genomic locations linked with specific traits—educational attainment and body mass index—a phenomenon we term “social–genetic correlation.” We also find evidence of a “social–genetic effect” such that the genetics of a person’s friends and schoolmates influenced their own education, even after accounting for the person’s own genetics

Multidisciplinary Group Clinic Appointments: The Self-Management and Care of Heart Failure (SMAC-HF) Trial

Background—This trial tested the effects of multidisciplinary group clinic appointments on the primary outcome of time to first heart failure (HF) rehospitalization or death. Methods and Results—HF patients (n=198) were randomly assigned to standard care or standard care plus multidisciplinary group clinics. The group intervention consisted of 4 weekly clinic appointments and 1 booster clinic at month 6, where multidisciplinary professionals engaged patients in HF self-management skills. Data were collected prospectively for 12 months beginning after completion of the first 4 group clinic appointments (2 months post randomization). The intervention was associated with greater adherence to recommended vasodilators (P=0.04). The primary outcome (first HF-related hospitalization or death) was experienced by 22 (24%) in the intervention group and 30 (28%) in standard care. The total HF-related hospitalizations, including repeat hospitalizations after the first time, were 28 in the intervention group and 45 among those receiving standard care. The effects of treatment on rehospitalization varied significantly over time. From 2 to 7 months post randomization, there was a significantly longer hospitalization-free time in the intervention group (Cox proportional hazard ratio=0.45 (95% confidence interval, 0.21–0.98; P=0.04). No significant difference between groups was found from month 8 to 12 (hazard ratio=1.7; 95% confidence interval, 0.7–4.1). Conclusions—Multidisciplinary group clinic appointments were associated with greater adherence to selected HF medications and longer hospitalization-free survival during the time that the intervention was underway. Larger studies will be needed to confirm the benefits seen in this trial and identify methods to sustain these benefits

Genetic and seasonal determinants of vitamin D status in Confederated Salish and Kootenai Tribes (CSKT) participants

Background: Vitamin D is a hormone produced in the skin upon ultraviolet B (UVB) radiation. Vitamin D is a crucial regulator of calcium and phosphate levels for bone mineralization and other physiological roles. Vitamin D levels vary globally in human populations due to genetics, geography, and other demographic factors. It is estimated that 20-85 % of the variability in vitamin D levels is driven by genetic variation. To improve our understanding of contributors to vitamin D levels, we conducted a candidate-gene study in partnership with the Confederated Salish and Kootenai Tribes (CSKT). Methods: We recruited 472 CSKT study participants on the Flathead Reservation in Montana. Demographic factors included age, BMI, and gender (185 male and 287 female; ≥ 18 years old). Genomic DNA and plasma were isolated from whole blood. We sequenced 14 vitamin D regulatory candidate genes: CASR, CUBN, CYP2R1, CYP3A4,CYP24A1, CYP27B1, DHCR7, GC, RXRA, RXRB, RXRG, SULT2A1, UGT1A4, and VDR. We also measured plasma levels of vitamin D and vitamin D metabolites by liquid chromatography/mass-spectrometry (LC/MS), including the clinical marker of vitamin D status, 25-hydroxyvitamin D3 [25(OH)D3]. We tested demographic factors as well as common and rare genetic variants for statistical associations with vitamin D levels using bioinformatics software and R statistical programming language code. Results: We identified 7,370 total genetic variants with 8% (n = 585) of them being novel. We identified 60 genetic variants that may be of clinical significance (disease associated or predicted to influence medication response). Vitamin D levels were below sufficiency [25(OH)D3 + 25(OH)D2 levels \u3c 20 ng/mL] in 56 % of CSKT participants across the year. We observed seasonal vitamin D and metabolite level fluctuations in a seasonal, sinusoidal statistical model with peak concentrations in June – August and trough concentrations in December – February. In linear regression analysis, we found that age, BMI, season, and 5 variants in CUBN and CYP3A4 were significantly associated with 25(OH)D3 concentration (p-value\u3c 0.05). In logistic regression, we found that 4 variants in CUBN, CYP3A4, and UGT1A4 were associated with 25(OH)D sufficiency status [25(OH)D3 + 25(OH)D2 levels of 20 ng/mL] (p-value\u3c 0.05). Multivariate linear regression analysis revealed that genetic variation alone explained ~13% of the variability in 25(OH)D3 concentration in CSKT participants. Genetic variation and environmental factors together explained ~23 % of the variability in 25(OH)D3 concentration in CSKT participants. It is likely that genetic variation in additional genes and other environmental factors (e.g., dietary vitamin D intake) that were not included in this study explain the remaining variability in 25(OH)D3 concentration. Conclusion: This research addresses the need for increased inclusion of American Indian and Alaska Natives in precision medicine health research. We are the first to describe the contribution of season and genetics to vitamin D levels in an American Indian population. Our next steps will be to use these findings to perform mechanistic studies and develop interventional strategies for the CSKT people

Emerging models and trends in mental health crisis care in England: a national investigation of crisis care systems

Background: Inpatient psychiatric care is unpopular and expensive, and development and evaluation of alternatives is a long-standing policy and research priority around the world. In England, the three main models documented over the past fifty years (teams offering crisis assessment and treatment at home; acute day units; and residential crisis services in the community) have recently been augmented by several new service models. These are intended to enhance choice and flexibility within catchment area acute care systems, but remain largely undocumented in the research literature. We therefore aimed to describe the types and distribution of crisis care models across England through a national survey. Methods: We carried out comprehensive mapping of crisis resolution teams (CRTs) using previous surveys, websites and multiple official data sources. Managers of CRTs were invited to participate as key informants who were familiar with the provision and organisation of crisis care services within their catchment area. The survey could be completed online or via telephone interview with a researcher, and elicited details about types of crisis care delivered in the local catchment area. // Results: We mapped a total of 200 adult CRTs and completed the survey with 184 (92%). Of the 200 mapped adult CRTs, there was a local (i.e., within the adult CRT catchment area) children and young persons CRT for 84 (42%), and an older adults CRT for 73 (37%). While all but one health region in England provided CRTs for working age adults, there was high variability regarding provision of all other community crisis service models and system configurations. Crisis cafes, street triage teams and separate crisis assessment services have all proliferated since a similar survey in 2016, while provision of acute day units has reduced. // Conclusions: The composition of catchment area crisis systems varies greatly across England and popularity of models seems unrelated to strength of evidence. A group of emerging crisis care models with varying functions within service systems are increasingly prevalent: they have potential to offer greater choice and flexibility in managing crises, but an evidence base regarding impact on service user experiences and outcomes is yet to be established

Job satisfaction dimensions in public accounting practice

This paper investigates gender differences in reported job satisfaction and career choices revealed by a postal survey of accountants from the Queensland Division of the Institute of Chartered Accountants in Australia. Of particular interest are levels of satisfaction with remuneration and promotion. Two moderating factors of career age and firm size are also considered. Consistent with prior research, female accountants reported dissatisfaction with their opportunities for promotion. However, unlike prior research there was no evidence of a gender effect in remuneration levels, and in reported satisfaction with remuneration. Nor were there differences in satisfaction across age bands, and public accounting firms of different size. The link between satisfaction levels of female accountants and their career choices of leaving their current employer, moving to parttime employment, or leaving the accounting profession was also investigated. Consistent with a large body of organisational and accounting research, low levels of job satisfaction were associated with higher turnover intentions for female accountants

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society