Negative Symptoms in Early-Onset Psychosis and Their Association With Antipsychotic Treatment Failure.

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordThe prevalence of negative symptoms (NS) at first episode of early-onset psychosis (EOP), and their effect on psychosis prognosis is unclear. In a sample of 638 children with EOP (aged 10-17 y, 51% male), we assessed (1) the prevalence of NS at first presentation to mental health services and (2) whether NS predicted eventual development of multiple treatment failure (MTF) prior to the age of 18 (defined by initiation of a third trial of novel antipsychotic due to prior insufficient response, intolerable adverse-effects or non-adherence). Data were extracted from the electronic health records held by child inpatient and community-based services in South London, United Kingdom. Natural Language Processing tools were used to measure the presence of Marder Factor NS and antipsychotic use. The association between presenting with ≥2 NS and the development of MTF over a 5-year period was modeled using Cox regression. Out of the 638 children, 37.5% showed ≥2 NS at first presentation, and 124 (19.3%) developed MTF prior to the age of 18. The presence of NS at first episode was significantly associated with MTF (adjusted hazard ratio 1.62, 95% CI 1.07-2.46; P = .02) after controlling for a number of potential confounders including psychosis diagnostic classification, positive symptoms, comorbid depression, and family history of psychosis. Other factors associated with MTF included comorbid autism spectrum disorder, older age at first presentation, Black ethnicity, and family history of psychosis. In EOP, NS at first episode are prevalent and may help identify a subset of children at higher risk of responding poorly to antipsychotics.J.D. received supported by a Medical Research Council (MRC) Clinical Research Training Fellowship (MR/L017105/1) and Psychiatry Research Trust Peggy Pollak Research Fellowship in Developmental Psychiatry. H.D. and S.L. have received salary support from the Foundation of Professional Services to Adolescents, UK. R.D.H. was funded by an MRC Fellowship (MR/J01219X/1). R.P. was funded by an MRC CRTF (MR/K002813/1). C.A., L.P-C., and C.M.D-C. have held grants from the Spanish Ministry of Economy, Industry and Competitiveness. Instituto de Salud Carlos III, co-financed by ERDF Funds from the European Commission, “A way of making Europe,” CIBERSAM, Madrid Regional Government (S2010/BMD-2422 AGES), European Union Structural Funds and European Union Seventh Framework Program under grant agreements FP7-HEALTH-2009-2.2.1-2-241909 (EU-GEI), FP7-HEALTH-2009-2.2.1-3-242114 (OPTiMISE), FP7-HEALTH-2013-2.2.1-2-603196 (PSYSCAN)and FP7- HEALTH-2013-2.2.1-2-602478 (METSY); European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No-115916; PRISM); Fundación Alicia Koplowitz and Fundación Mutua Madrileña. M.H., J.H.M. and H.S. receive salary support from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health

Designing a complex intervention for dementia case management in primary care

Background: Community-based support will become increasingly important for people with dementia, but currently services are fragmented and the quality of care is variable. Case management is a popular approach to care co-ordination, but evidence to date on its effectiveness in dementia has been equivocal. Case management interventions need to be designed to overcome obstacles to care co-ordination and maximise benefit. A successful case management methodology was adapted from the United States (US) version for use in English primary care, with a view to a definitive trial. Medical Research Council guidance on the development of complex interventions was implemented in the adaptation process, to capture the skill sets, person characteristics and learning needs of primary care based case managers. Methods: Co-design of the case manager role in a single NHS provider organisation, with external peer review by professionals and carers, in an iterative technology development process. Results: The generic skills and personal attributes were described for practice nurses taking up the case manager role in their workplaces, and for social workers seconded to general practice teams, together with a method of assessing their learning needs. A manual of information material for people with dementia and their family carers was also created using the US intervention as its source. Conclusions: Co-design produces rich products that have face validity and map onto the complexities of dementia and of health and care services. The feasibility of the case manager role, as described and defined by this process, needs evaluation in ‘real life’ settings

The Fischer 344 Rat Reflects Human Susceptibility to Francisella Pulmonary Challenge and Provides a New Platform for Virulence and Protection Studies

Background: The pathogenesis of Francisella tularensis, the causative agent of tularemia, has been primarily characterized in mice. However, the high degree of sensitivity of mice to bacterial challenge, especially with the human virulent strains of F. tularensis, limits this animal model for screening of defined attenuated vaccine candidates for protection studies. Methods and Findings: We analyzed the susceptibility of the Fischer 344 rat to pulmonary (intratracheal) challenge with three different subspecies (subsp) of F. tularensis that reflect different levels of virulence in humans, and characterized the bacterial replication profile in rat bone marrow-derived macrophages (BMDM). In contrast to the mouse, Fischer 344 rats exhibit a broader range of sensitivity to pulmonary challenge with the human virulent subsp. tularensis and holarctica. Unlike mice, Fischer rats exhibited a high degree of resistance to pulmonary challenge with LVS (an attenuated derivative o

Perceived barriers and enablers of physical activity in postpartum women: A qualitative approach

© 2016 Saligheh et al.Background: Postpartum women's recovery from birth can be assisted through increased physical activity (PA). However, women face substantial barriers to participating in exercise and require support to enable them to benefit from increased PA. Methods: This study sought to explore women's beliefs about and experiences of PA and exercise during the 6 weeks to 12 months postpartum period. A cohort of 14 postpartum women from a survey study of the barriers and enablers to exercise participation agreed to take part in interview sessions to provide an in-depth understanding of the women's perceptions of the postpartum period and their physical activity during this time. Results: Findings are presented with reference to the social ecological framework and indicate postpartum women face substantial personal and environmental barriers to PA and exercise participation: fatigue, a lack of motivation and confidence, substantial time constraints, lack of access to affordable and appropriate activities and poor access to public transport. In contrast, enablers such as possessing greater social support, in particular partner support, improved PA and exercise participation. Conclusions: The findings encourage facilitation of exercise through mothers' groups, mothers' exercise clubs or postnatal classes suggesting behavioral and social change is needed. Interaction between individuals, community, organizations and policy makers is required. In addition, the provision of specifically tailored and appropriate exercise programs could potentially enable increased PA in postpartum women, thereby improving their health

The timing of ostomy closure in infants with necrotizing enterocolitis: a systematic review

Item does not contain fulltextPURPOSE: The optimal timing of ostomy closure is a matter of debate. We performed a systematic review of outcomes of early ostomy closure (EC, within 8 weeks) and late ostomy closure (LC, after 8 weeks) in infants with necrotizing enterocolitis. METHODS: PubMed, EMbase, Web-of-Science, and Cinahl were searched for studies that detailed time to ostomy closure, and time to full enteral nutrition (FEN) or complications after ostomy closure. Patients with Hirschsprung's disease or anorectal malformations were excluded. Analysis was performed using SPSS 17 and RevMan 5. RESULTS: Of 778 retrieved articles, 5 met the inclusion criteria. The median score for study quality was 9 [range 8-14 on a scale of 0 to 32 points (Downs and Black, J Epidemiol Community Health 52:377-384, 1998)]. One study described mean time to FEN: 19.1 days after EC (n = 13) versus 7.2 days after LC (n = 24; P = 0.027). Four studies reported complication rates after ostomy closure, complications occurred in 27% of the EC group versus 23% of the LC group. The combined odds ratio (LC vs. EC) was 1.1 [95% CI 0.5, 2.5]. CONCLUSION: Evidence that supports early or late closure is scarce and the published articles are of poor quality. There is no significant difference between EC versus LC in the complication rate. This systematic review supports neither early nor late ostomy closure

What explains electoral responses to the 'Great Recession in Europe?

The ?Great Recession? in Europe started in early 2008 and was the greatest economic crisis facing the continent since the Great Depression of the 1930s. It produced a largescale loss of support for many incumbent parties. The purpose of this paper is to explain responses to the crisis among European electorates with the assistance of three rival models of electoral choice. The first is the cleavages model associated with Rokkan and Lipset which highlights the importance of social groups as the sources of electoral support. The second is the spatial model of party competition which focuses on the ideological distance between voters and parties in relation to divisive issues in society. The third is the valence model which argues that voters will support parties that deliver policies over which there is widespread agreement about what should be done. The paper models electoral support for incumbent parties using data from the European Social Surveys of 2006, conducted prior to the recession, and again in 2012 some four years into the crisis. The results show that all three models are relevant for understanding mass political responses to the crisis. It is also apparent that an ideological shift to the right occurred in electoral support between the two periods and this happened among both the voters and also the incumbent parties in Europe

Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review

Background: Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. Methods: We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. Results: The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Conclusion: Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation

Physical activity in pregnancy: a qualitative study of the beliefs of overweight and obese pregnant women

<p>Abstract</p> <p>Background</p> <p>Whilst there has been increasing research interest in interventions which promote physical activity during pregnancy few studies have yielded detailed insights into the views and experiences of overweight and obese pregnant women themselves. The qualitative study described in this paper aimed to: (i) explore the views and experiences of overweight and obese pregnant women; and (ii) inform interventions which could promote the adoption of physical activity during pregnancy.</p> <p>Methods</p> <p>The study was framed by a combined Subtle Realism and Theory of Planned Behaviour (TPB) approach. This enabled us to examine the hypothetical pathway between beliefs and physical activity intentions within the context of day to day life. The study sample for the qualitative study was chosen by stratified, purposive sampling from a previous study of physical activity measurements in pregnancy. Research participants for the current study were recruited on the basis of Body Mass Index (BMI) at booking and parity. Semi-structured, in-depth interviews were conducted with 14 overweight and obese pregnant women. Data analysis was undertaken using a Framework Approach and was informed by TPB.</p> <p>Results</p> <p>Healthy eating was often viewed as being of greater importance for the health of mother and baby than participation in physical activity. A commonly cited motivator for maintaining physical activity during pregnancy is an aid to reducing pregnancy-related weight gain. However, participants often described how they would wait until the postnatal period to try and lose weight. A wide range of barriers to physical activity during pregnancy were highlighted including both internal (physical and psychological) and external (work, family, time and environmental). The study participants also lacked access to consistent information, advice and support on the benefits of physical activity during pregnancy.</p> <p>Conclusions</p> <p>Interventions to encourage recommended levels of physical activity in pregnancy should be accompanied by accessible and consistent information about the positive effects for mother and baby. More research is required to examine how to overcome barriers to physical activity and to understand which interventions could be most effective for overweight/obese pregnant women. Midwives should be encouraged to do more to promote activity in pregnancy.</p

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

&lt;p&gt;Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.&lt;/p&gt; &lt;p&gt;Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (&#60;2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).&lt;/p&gt; &lt;p&gt;Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).&lt;/p&gt

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org