Personality Disorder and Physical Health Comorbidities: A Link With Bone Health?

We examined whether personality disorders (PDs) (any, cluster A/B/C) were associated with bone mineral density (BMD) in a population-based sample of Australian women (n = 696). Personality and mood disorders were assessed using semi-structured diagnostic interviews. BMD was measured at the spine, hip, and total body using dual-energy x-ray absorptiometry (GE-Lunar Prodigy). Anthropometrics, medication use, physical conditions, and lifestyle factors were documented. The association between PDs (any, cluster A/B/C) and BMD (spine/hip/total body) was examined with multiple linear regression models. The best models were identified by backward elimination including age, weight, physical activity, smoking status, alcohol consumption, dietary calcium intake, mood disorders, physical multimorbidity, socioeconomic status, and medications affecting bone. The variables were retained in the model if p < 0.05. All potential interactions in final models were tested. Those with cluster A PD, compared to those without, had 6.7% lower hip BMD [age, weight adjusted mean 0.853 (95% CI 0.803–0.903) vs. 0.910 (95% CI 0.901–0.919) g/cm2, p = 0.027] and 3.4% lower total body BMD [age, weight, smoking, alcohol, calcium adjusted mean 1.102 (95% CI 1.064–1.140) vs. 1.139 (95% CI 1.128–1.150) g/cm2, p = 0.056]. No associations were observed between cluster B/C PDs and hip/total body BMD or between any of the PD clusters and spine BMD. To our knowledge, this study is the first to investigate the bone health of women with PD in a population-based sample. Given the paucity of literature, replication and longitudinal research including the examination of underlying mechanisms and sex differences are warranted

Associations between personality and musculoskeletal disorders in the general population: A systematic review protocol

There is growing evidence of the comorbidity between personality disorder (PD) and musculoskeletal disorders (MSDs). However, there are no systematic reviews including critical appraisal and meta-analyses that identify, evaluate, and synthesize the available evidence on these associations. Therefore, we present here a protocol of the methodology to undertake a systematic review, with the objective to evaluate associations between PD and MSDs in epidemiological population-based studies. A systematic review of observational studies will be conducted. A complete search strategy will be developed in consultation with a health librarian. To identify peer-reviewed literature, the search will be translated for, and implemented in Medline Complete, CINAHL Complete, and PsycINFO via the EBSCOhost platform from 1990 to the present. Gray literature will be identified. Studies will be eligible if they examine general population participants aged 15 years and over. Associations of interest are the presence of threshold or positive screen according to the DSM-V/5 (groupings: any, Clusters A, B, C, specific PD) or ICD-10 for PD in relation to arthritis, back/neck conditions, fibromyalgia, osteopenia/osteoporosis, and/or “any” of these MSDs. Data extraction and critical appraisal will be conducted in line with the Joanna Briggs Institute (JBI) guidance for systematic reviews of etiology and risk. The results from all studies will be presented in tables, text, and figures. A descriptive synthesis will present the characteristics of included studies, critical appraisal results, and descriptions of the main findings. Where appropriate, meta-analyses will be performed. If heterogeneity (e.g., I2 = 50%) is detected, subgroup/sensitivity analysis may be used to explore the possible sources. The systematic review does not require ethics approval. The proposed systematic review will strengthen the evidence base on what is known regarding associations between PD and MSDs by identifying, evaluating, and synthesizing the findings of existing observational studies including meta-analyses, where appropriate

A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity

A multidisciplinary approach identifies novel biochemical activities involved in the synthesisof C. elegans bile acid-like steroids, which act as hormones that regulate sterol metabolism and longevity

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after 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 radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, 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 distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

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

Exploring the barriers and facilitators to accessing and utilising mental health services in regional, rural, and remote Australia: A scoping review protocol.

IntroductionAustralians from regional, rural, and remote areas face diverse and complex challenges in accessing and utilising mental health services. Previous research has pointed to a range of individual, community, structural, and systemic barriers at play, however, limited literature has synthesised the knowledge on this topic. Parallel to this, information on the facilitators to accessing and utilising mental health services for this group is not well documented. This protocol describes the methodology to undertake a scoping review, which aims to explore the barriers and facilitators associated with accessing and utilising mental health services in regional, rural, and remote Australia. In addition, the scoping review aims to geographically map the identified barriers and facilitators.MethodsThis protocol is guided by Arksey and O'Malley's methodological framework. A search strategy will be developed and implemented to identify relevant peer-reviewed and grey literature. Studies will be included if they report on the barriers and/or facilitators associated with accessing and/or utilising mental health services in regional, rural, and remote Australia. Two reviewers will independently screen the data at the title/abstract and full-text stage. One reviewer will extract the relevant data using a predetermined charting form and a second reviewer will validate the included data. A Geographical Information System program will be used to map the location of the studies; locations will be stratified according to the Modified Monash Model and relationships between barriers and facilitators will be analysed. Key findings will be presented in a narrative account and in text, tables, and maps.DiscussionThis scoping review will provide a contemporary account on the barriers and facilitators to accessing and utilising mental health services for regional, rural, and remote Australians. It is anticipated that the results of this scoping review will have national policy relevance and may be useful to healthcare providers

Exploring the barriers and facilitators to accessing and utilising mental health services in regional, rural, and remote Australia: A scoping review protocol

Introduction Australians from regional, rural, and remote areas face diverse and complex challenges in accessing and utilising mental health services. Previous research has pointed to a range of individual, community, structural, and systemic barriers at play, however, limited literature has synthesised the knowledge on this topic. Parallel to this, information on the facilitators to accessing and utilising mental health services for this group is not well documented. This protocol describes the methodology to undertake a scoping review, which aims to explore the barriers and facilitators associated with accessing and utilising mental health services in regional, rural, and remote Australia. In addition, the scoping review aims to geographically map the identified barriers and facilitators. Methods This protocol is guided by Arksey and O’Malley’s methodological framework. A search strategy will be developed and implemented to identify relevant peer-reviewed and grey literature. Studies will be included if they report on the barriers and/or facilitators associated with accessing and/or utilising mental health services in regional, rural, and remote Australia. Two reviewers will independently screen the data at the title/abstract and full-text stage. One reviewer will extract the relevant data using a predetermined charting form and a second reviewer will validate the included data. A Geographical Information System program will be used to map the location of the studies; locations will be stratified according to the Modified Monash Model and relationships between barriers and facilitators will be analysed. Key findings will be presented in a narrative account and in text, tables, and maps. Discussion This scoping review will provide a contemporary account on the barriers and facilitators to accessing and utilising mental health services for regional, rural, and remote Australians. It is anticipated that the results of this scoping review will have national policy relevance and may be useful to healthcare providers

PCC (population/concept/context).

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