Social fragmentation, deprivation and urbanicity: relation to first-admission rates for psychoses

<i>Declaration</i> <i>of</i> <i>interest</i>: None. <i>Background</i>: Social disorganisation, fragmentation and isolation have long been posited as influencing the rate of psychoses at area level. Measuring such societal constructsis difficult. A census-based index measuring social fragmentation has been proposed. <i>Aims</i>: To investigate the association between first-admission rates for psychosis and area-based measures of social fragmentation, deprivation and urban/rural index. <i>Method</i>: We used indirect standardisation methods and logistic regression models to examine associations of social fragmentation, deprivation and urban/rural categories with first admissions for psychoses in Scotland for the 5-year period 1989–1993. <i>Results</i>: Areas characterised by high social fragmentation had higher first-ever admission rates for psychosis independent of deprivation and urban/rural status. There was a dose–response relationship between social fragmentation category and first-ever admission rates for psychosis. There was no statistically significant interaction between social fragmentation, deprivation and urban/rural index. <i>Conclusions</i>: First-admission rates are strongly associated with measures of social fragmentation, independent of material deprivation and urban/rural category

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.<p></p> Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.<p></p> Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.<p></p> Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.<p></p> Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.<p></p&gt

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

Background: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors. Method: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance. Results: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset. Conclusions: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis

Impact of mental health problems on case fatality in male cancer patients

Background: Although mortality rates are elevated in psychiatric patients relative to their healthy counterparts, little is known about the impact of mental health on survival in people with cancer. / Methods and results: Among 16 498 Swedish men with cancer, survival was worse in those with a history of psychiatric hospital admissions: multiply-adjusted hazard ratio (95% confidence interval) comparing cancer mortality in men with and without psychiatric admissions: 1.59 (1.39, 1.83). / Conclusion: Survival in cancer patients is worse among those with a history of psychiatric disease. The mechanisms underlying this association should be further explored

Smoking Cessation Intervention for Severe Mental Ill Health Trial (SCIMITAR+) : study protocol for a randomised controlled trial

BACKGROUND: Smoking is highly prevalent among people who have experience of severe mental ill health, contributing to their poor physical health. Despite the 'culture' of smoking in mental health services, people with severe mental ill health often express a desire to quit smoking; however, the services currently available to aid quitting are those which are widely available to the general population and may not be suitable or effective for people with severe mental ill health. The aim of this study is to explore the effectiveness and cost-effectiveness of a bespoke smoking-cessation intervention specifically targeted at people with severe mental ill health. METHODS/DESIGN: SCIMITAR+ is a multicentre, pragmatic, two-arm, parallel-group, individually randomised controlled trial. We aim to recruit 400 participants aged 18 years and above with a documented diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder who smoke. Potentially eligible participants identified in primary or secondary care will be screened, and baseline data collected. Eligible, consenting participants will be randomly allocated to one of two groups. In the intervention arm, the participant will be assigned a mental health professional trained to deliver smoking-cessation interventions who will work with the participant and participant's GP or mental health specialist to provide an individually tailored smoking-cessation service. The comparator arm will be usual care - following current NICE guidelines for smoking cessation, in line with general guidance that is offered to all smokers, with no specific adaptation or enhancement in relation to severe mental ill health. The primary outcome will be self-reported smoking cessation at 12 months verified by expired carbon monoxide (CO) measurement. Secondary outcome measures include Body Mass Index at 12 months, the Fagerström Test for Nicotine Dependence, Motivation to Quit questionnaire, SF-12, PHQ-9, GAD-7, EQ-5D-5 L, and health service utilisation at 6 and 12 months. The economic evaluation at 12 months will be conducted in the form of an incremental cost-effectiveness analysis. DISCUSSION: SCIMITAR+ trial is the largest trial to our knowledge to investigate the effectiveness of a bespoke smoking-cessation service for people with severe mental ill health. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN72955454 . Registered on 16 January 2015

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: A naturalistic interventional study

Background People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. Methods Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3–6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. Results A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. Conclusions The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals.submittedVersio

STEPWISE - STructured lifestyle Education for People WIth SchizophrEnia : a study protocol for a randomised controlled trial

BACKGROUND: People with schizophrenia are two to three times more likely to be overweight than the general population. The UK National Institute of Health and Care Excellence (NICE) recommends an annual physical health review with signposting to, or provision of, a lifestyle programme to address weight concerns and obesity. The purpose of this randomised controlled trial is to assess whether a group-based structured education programme can help people with schizophrenia to lose weight. METHODS: Design: a randomised controlled trial of a group-based structured education programme. SETTING: 10 UK community mental health trusts. PARTICIPANTS: 396 adults with schizophrenia, schizoaffective, or first-episode psychosis who are prescribed antipsychotic medication will be recruited. Participants will be overweight, obese or be concerned about their weight. INTERVENTION: participants will be randomised to either the intervention or treatment as usual (TAU). The intervention arm will receive TAU plus four 2.5-h weekly sessions of theory-based lifestyle structured group education, with maintenance contact every 2 weeks and 'booster' sessions every 3 months. All participants will receive standardised written information about healthy eating, physical activity, alcohol and smoking. OUTCOMES: the primary outcome is weight (kg) change at 1 year post randomisation. Secondary outcomes, which will be assessed at 3 and 12 months, include: the proportion of participants who maintained or reduced their weight; waist circumference; body mass index; objectively measured physical activity (wrist accelerometer); self-reported diet; blood pressure; fasting plasma glucose, lipid profile and HbA1c (baseline and 1 year only); health-related quality of life (EQ-5D-5L and RAND SF-36); (adapted) brief illness perception questionnaire; the Brief Psychiatric Rating Scale; the Client Service Receipt Inventory; medication use; smoking status; adverse events; depression symptoms (Patient Health Questionnaire-9); use of weight-loss programmes; and session feedback (intervention only). Outcome assessors will be blind to trial group allocation. Qualitative interviews with a subsample of facilitators and invention-arm participants will provide data on intervention feasibility and acceptability. Assessment of intervention fidelity will also be performed. DISCUSSION: The STEPWISE trial will provide evidence for the clinical and cost-effectiveness of a tailored intervention, which, if successful, could be implemented rapidly in the NHS. TRIAL REGISTRATION: ISRCTN19447796 , registered on 20 March 2014

Mineral Composition is Altered by Osteoblast Expression of an Engineered Gs-Coupled Receptor

Activation of the Gs G protein–coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive Gs signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive Gs activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive Gs signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm3 (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous Gs activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass