Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care

Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses

Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil

<p>Abstract</p> <p>Background</p> <p>Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil.</p> <p>Methods</p> <p>Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil.</p> <p>Results</p> <p>In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers.</p> <p>Conclusion</p> <p>This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.</p

Evaluating Depressive Symptoms in Schizophrenia: A Psychometric Comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale

Background: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. Sampling and Methods: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. Results: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS sub-scores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. Conclusions:The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients. Copyright (c) 2012 S. Karger AG, Base

The incidence of arthropathy adverse events in efalizumab-treated patients is low and similar to placebo and does not increase with long-term treatment: pooled analysis of data from Phase III clinical trials of efalizumab

A large-scale, pooled analysis of safety data from five Phase III clinical trials (including open-label extensions of two of these studies) and two Phase III open-label clinical trials of efalizumab was conducted to explore whether arthropathy adverse events (AEs) were associated with efalizumab treatment in patients with moderate-to-severe chronic plaque psoriasis. Data from patients who received subcutaneous injections of efalizumab or placebo were stratified for analysis into phases according to the nature and duration of treatment. These included: the ‘first treatment’ phase (0–12-week data from patients who received either efalizumab, 1 mg/kg once weekly, or placebo in the five placebo-controlled studies); the ‘extended treatment’ phase (13–24-week data from seven trials for all efalizumab-treated patients); and the ‘long-term treatment’ phase (data from efalizumab-treated patients who received treatment for up to 36 months in two long-term trials). Descriptive statistics were performed and the incidence of arthropathy AEs per patient-year was calculated using 95% confidence intervals (CIs). During the first treatment phase, a similar proportion of patients had an arthropathy AE in the efalizumab group (3.3%; 58/1740 patients) compared with the placebo group (3.5%; 34/979 patients); the incidence of arthropathy AEs per patient-year was 0.15 in the efalizumab group (95% CI 0.11–0.19) and 0.16 in the placebo group (95% CI 0.11–0.22). Analysis of first treatment phase data from one study (n = 793) showed that the incidence of psoriatic arthropathy per patient-year was lower in efalizumab-treated patients (0.10; 95% CI 0.05–0.18) than in those given placebo (0.17; 95% CI 0.08–0.30). During the extended treatment phase, the incidence of arthropathy remained low (0.17; 95% CI 0.14–0.22). Data from two long-term studies showed that there was no increase in the incidence of arthropathy AEs over time in patients treated with efalizumab for up to 36 months. Patients who had an arthropathy AE during treatment with efalizumab appeared to be more likely to have a history of arthropathy prior to treatment. Efalizumab does not appear to increase the risk of arthropathy AEs compared with placebo

Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea

Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates

Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER): a protocol for a program of research

Abstract Background The Enhancing Mental and Physical health of Women through Engagement and Retention or EMPOWER program represents a partnership with the US Department of Veterans Health Administration (VA) Health Service Research and Development investigators and the VA Office of Women’s Health, National Center for Disease Prevention and Health Promotion, Primary Care-Mental Health Integration Program Office, Women’s Mental Health Services, and the Office of Patient Centered Care and Cultural Transformation. EMPOWER includes three projects designed to improve women Veterans’ engagement and retention in evidence-based care for high-priority health conditions, i.e., prediabetes, cardiovascular, and mental health. Methods/Design The three proposed projects will be conducted in VA primary care clinics that serve women Veterans including general primary care and women’s health clinics. The first project is a 1-year quality improvement project targeting diabetes prevention. Two multi-site research implementation studies will focus on cardiovascular risk prevention and collaborative care to address women Veterans’ mental health treatment needs respectively. All projects will use the evidence-based Replicating Effective Programs (REP) implementation strategy, enhanced with multi-stakeholder engagement and complexity theory. Mixed methods implementation evaluations will focus on investigating primary implementation outcomes of adoption, acceptability, feasibility, and reach. Program-wide organizational-, provider-, and patient-level measures and tools will be utilized to enhance synergy, productivity, and impact. Both implementation research studies will use a non-randomized stepped wedge design. Discussion EMPOWER represents a coherent program of women’s health implementation research and quality improvement that utilizes cross-project implementation strategies and evaluation methodology. The EMPOWER Quality Enhancement Research Initiative (QUERI) will constitute a major milestone for realizing women Veterans’ engagement and empowerment in the VA system. EMPOWER QUERI will be conducted in close partnership with key VA operations partners, such as the VA Office of Women’s Health, to disseminate and spread the programs nationally. Trial registration The two implementation research studies described in this protocol have been registered as required: Facilitating Cardiovascular Risk Screening and Risk Reduction in Women Veterans: Trial registration NCT02991534 , registered 9 December 2016. Implementation of Tailored Collaborative Care for Women Veterans: Trial registration NCT02950961 , registered 21 October 2016

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (&#8805; 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

The impact of emotional well-being on long-term recovery and survival in physical illness: a meta-analysis

This meta-analysis synthesized studies on emotional well-being as predictor of the prognosis of physical illness, while in addition evaluating the impact of putative moderators, namely constructs of well-being, health-related outcome, year of publication, follow-up time and methodological quality of the included studies. The search in reference lists and electronic databases (Medline and PsycInfo) identified 17 eligible studies examining the impact of general well-being, positive affect and life satisfaction on recovery and survival in physically ill patients. Meta-analytically combining these studies revealed a Likelihood Ratio of 1.14, indicating a small but significant effect. Higher levels of emotional well-being are beneficial for recovery and survival in physically ill patients. The findings show that emotional well-being predicts long-term prognosis of physical illness. This suggests that enhancement of emotional well-being may improve the prognosis of physical illness, which should be investigated by future research

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors