How do child and adolescent mental health problems influence public sector costs? Interindividual variations in a nationally representative British sample.

Author's manuscript version. The final published version of the article is available from the publisher as an open access article via: DOI: 10.1111/jcpp.12327BACKGROUND: Policy and practice guidelines emphasize that responses to children and young people with poor mental health should be tailored to needs, but little is known about the impact on costs. We investigated variations in service-related public sector costs for a nationally representative sample of children in Britain, focusing on the impact of mental health problems. METHODS: Analysis of service uses data and associated costs for 2461 children aged 5-15 from the British Child and Adolescent Mental Health Surveys. Multivariate statistical analyses, including two-part models, examined factors potentially associated with interindividual differences in service use related to emotional or behavioural problems and cost. We categorized service use into primary care, specialist mental health services, frontline education, special education and social care. RESULTS: Marked interindividual variations in utilization and costs were observed. Impairment, reading attainment, child age, gender and ethnicity, maternal age, parental anxiety and depression, social class, family size and functioning were significantly associated with utilization and/or costs. CONCLUSIONS: Unexplained variation in costs could indicate poor targeting, inequality and inefficiency in the way that mental health, education and social care systems respond to emotional and behavioural problems.Department of Health (England)Wellcome Trus

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

The South West Area Mesothelioma and Pemetrexed trial - A multi-centre prospective observational study evaluating novel markers of chemotherapy response and prognostication

Background:Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.Methods:Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.Findings:Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NL

Report of the Lancet Commission on the Value of Death: bringing death back into life

The story of dying in the 21st century is a story of paradox. While many people are overtreated in hospitals with families and communities relegated to the margins, still more remain undertreated, dying of preventable conditions and without access to basic pain relief. The unbalanced and contradictory picture of death and dying is the basis for this Commission

The effect of chemotherapy on health-related quality of life in mesothelioma: Results from the SWAMP trial

© 2015 Cancer Research UK. All rights reserved. Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage

Immunization of young heifers with staphylococcal immune evasion proteins before natural exposure to Staphylococcus aureus induces a humoral immune response in serum and milk

Background: Staphylococcus aureus, a leading cause of mastitis in dairy cattle, causes severe mastitis and/or chronic persistent infections with detrimental effects on the cows' wellbeing, lifespan and milk production. Despite years of research there is no effective vaccine against S. aureus mastitis. Boosting of non-protective pre-existing immunity to S. aureus, induced by natural exposure to S. aureus, by vaccination may interfere with vaccine efficacy. The aim was to assess whether experimental immunization of S. aureus naïve animals results in an immune response that differs from immunity following natural exposure to S. aureus. Results: First, to define the period during which calves are immunologically naïve for S. aureus, Efb, LukM, and whole-cell S. aureus specific serum antibodies were measured in a cohort of newborn calves by ELISA. Rising S. aureus specific antibodies indicated that from week 12 onward calves mounted an immune response to S. aureus due to natural exposure. Next, an experimental immunization trial was set up using 8-week-old heifer calves (n = 16), half of which were immunized with the immune evasion molecules Efb and LukM. Immunization was repeated after one year and before parturition and humoral and cellular immunity specific for Efb and LukM was determined throughout the study. Post-partum, antibody levels against LukM and EfB were significantly higher in serum, colostrum and milk in the experimentally immunized animals compared to animals naturally exposed to S. aureus. LukM specific IL17a responses were also significantly higher in the immunized cows post-partum. Conclusions: Experimental immunization with staphylococcal immune evasion molecules starting before natural exposure resulted in significantly higher antibody levels against Efb and LukM around parturition in serum as well as the site of infection, i.e. in colostrum and milk, compared to natural exposure to S. aureus. This study showed that it is practically feasible to vaccinate S. aureus naïve cattle and that experimental immunization induced a humoral immune response that differed from that after natural exposure only.</p

Development of eConsult reflective learning tools for healthcare providers: a pragmatic mixed methods approach

BackgroundElectronic consultation (eConsult) programs are crucial components of modern healthcare that facilitate communication between primary care providers (PCPs) and specialists. eConsults between PCPs and specialists. They also provide a unique opportunity to use real-world patient scenarios for reflective learning as part of professional development. However, tools that guide and document learning from eConsults are limited. The purpose of this study was to develop and pilot two eConsult reflective learning tools (RLTs), one for PCPs and one for specialists, for those participating in eConsults.MethodsWe performed a four-phase pragmatic mixed methods study recruiting PCPs and specialists from two public health systems located in two countries: eConsult BASE in Canada and San Francisco Health Network eConsult in the United States. In phase 1, subject matter experts developed preliminary RLTs for PCPs and specialists. During phase 2, a Delphi survey among 20 PCPs and 16 specialists led to consensus on items for each RLT. In phase 3, we conducted cognitive interviews with three PCPs and five specialists as they applied the RLTs on previously completed consults. In phase 4, we piloted the RLTs with eConsult users.ResultsThe RLTs were perceived to elicit critical reflection among participants regarding their knowledge and practice habits and could be used for quality improvement and continuing professional development.ConclusionPCPs and specialists alike perceived that eConsult systems provided opportunities for self-directed learning wherein they were motivated to investigate topics further through the course of eConsult exchanges. We recommend the RLTs be subject to further evaluation through implementation studies at other sites