Mental health: A cause or consequence of injury? A population-based matched cohort study

BACKGROUND: While a number of studies report high prevalence of mental health problems among injured people, the temporal relationship between injury and mental health service use has not been established. This study aimed to quantify this relationship using 10 years of follow-up on a population-based cohort of hospitalised injured adults. METHODS: The Manitoba Injury Outcome Study is a retrospective population-based matched cohort study that utilised linked administrative data from Manitoba, Canada, to identify an inception cohort (1988–1991) of hospitalised injured cases (ICD-9-CM 800–995) aged 18–64 years (n = 21,032), which was matched to a non-injured population-based comparison group (n = 21,032). Pre-injury comorbidity and post-injury mental health data were obtained from hospital and physician claims records. Negative Binomial regression was used to estimate adjusted rate ratios (RRs) to measure associations between injury and mental health service use. RESULTS: Statistically significant differences in the rates of mental health service use were observed between the injured and non-injured, for the pre-injury year and every year of the follow-up period. The injured cohort had 6.56 times the rate of post-injury mental health hospitalisations (95% CI 5.87, 7.34) and 2.65 times the rate of post-injury mental health physician claims (95% CI 2.53, 2.77). Adjusting for comorbidities and pre-existing mental health service use reduced the hospitalisations RR to 3.24 (95% CI 2.92, 3.60) and the physician claims RR to 1.53 (95% CI 1.47, 1.59). CONCLUSION: These findings indicate the presence of pre-existing mental health conditions is a potential confounder when investigating injury as a risk factor for subsequent mental health problems. Collaboration with mental health professionals is important for injury prevention and care, with ongoing mental health support being a clearly indicated service need by injured people and their families. Public health policy relating to injury prevention and control needs to consider mental health strategies at the primary, secondary and tertiary level

KamLAND Sensitivity to Neutrinos from Pre-Supernova Stars

In the late stages of nuclear burning for massive stars (M>8~M_{\sun}), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of 25~M_{\sun} at a distance less than 690~pc with 3$\sigma$ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community.Comment: 19 pages, 6 figures, 1 tabl

Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial

BACKGROUND: The ICON8 study reported no significant improvement in progression-free survival (a primary endpoint) with weekly chemotherapy compared with standard 3-weekly treatment among patients with epithelial ovarian cancer. All ICON8 patients were eligible to take part in the accompanying health-related quality-of-life study, which measured the effect of treatment on self-reported wellbeing, reported here. METHODS: In this open-label, randomised, controlled, phase 3, three-arm, Gynecologic Cancer Intergroup (GCIG) trial done at 117 hospital sites in the UK, Australia, New Zealand, Mexico, South Korea, and Republic of Ireland, women (aged at least 18 years) with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage IC-IV ovarian cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1:1) centrally using minimisation to group 1 (intravenous carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 intravenous paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 weekly and 80 mg/m2 paclitaxel weekly). Randomisation was stratified by GCIG group, disease stage, and outcome and timing of surgery. Patients and clinicians were not masked to treatment assignment. Patients underwent immediate or delayed primary surgery according to clinicians' choice. Patients were asked to complete European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OV28 questionnaires at enrolment, before each chemotherapy cycle, then 6-weekly up to 9 months, 3-monthly up to 2 years, and 6-monthly up to 5 years. Quality of life was a prespecified secondary outcome of the ICON8 study. Within the quality-of-life study, the co-primary endpoints were QLQ-C30 global health score at 9 months (cross-sectional analysis) and mean QLQ-C30 global health score from randomisation to 9 months (longitudinal analysis). Data analyses were done on an intention-to-treat basis. The trial is registered on ClinicalTrials.gov, NCT01654146 and ISRCTN Registry, ISRCTN10356387, and is currently in long-term follow up. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 patients were recruited into ICON8 (522 were included in group 1, 523 in group 2, and 521 in group 3). Baseline quality-of-life questionnaires were completed by 1438 (92%) of 1566 patients and 9-month questionnaires by 882 (69%) of 1280 patients. We observed no significant difference in global health score at 9 months (cross-sectional analysis) between study groups (group 2 vs group 1, difference in mean score 2·3, 95% CI -0·4 to 4·9, p=0·095; group 3 vs group 1, -0·8, -3·8 to 2·2, p=0·61). Using longitudinal analysis, we found lower global health scores for those receiving weekly paclitaxel than for those receiving 3-weekly chemotherapy (group 2 vs group 1, mean difference -1·8, 95% CI -3·6 to -0·1, p=0·043; group 3 vs group 1, -2·9, -4·7 to -1·1, p=0·0018). INTERPRETATION: We found no evidence of a difference in global quality of life between treatment groups at 9 months; however, patients receiving weekly treatment reported lower mean quality of life across the 9-month period after randomisation. Taken together with the lack of progression-free survival benefit, these findings do not support routine use of weekly paclitaxel-containing regimens in the management of newly diagnosed ovarian cancer. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board Ireland, Irish Cancer Society, and Cancer Australia

Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial

Background: The ICON8 study reported no significant improvement in progression-free survival (a primary endpoint) with weekly chemotherapy compared with standard 3-weekly treatment among patients with epithelial ovarian cancer. All ICON8 patients were eligible to take part in the accompanying health-related quality-of-life study, which measured the effect of treatment on self-reported wellbeing, reported here. Methods: In this open-label, randomised, controlled, phase 3, three-arm, Gynecologic Cancer Intergroup (GCIG) trial done at 117 hospital sites in the UK, Australia, New Zealand, Mexico, South Korea, and Republic of Ireland, women (aged at least 18 years) with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage IC–IV ovarian cancer and an Eastern Cooperative Oncology Group performance status of 0–2 were randomly assigned (1:1:1) centrally using minimisation to group 1 (intravenous carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 intravenous paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 weekly and 80 mg/m2 paclitaxel weekly). Randomisation was stratified by GCIG group, disease stage, and outcome and timing of surgery. Patients and clinicians were not masked to treatment assignment. Patients underwent immediate or delayed primary surgery according to clinicians' choice. Patients were asked to complete European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OV28 questionnaires at enrolment, before each chemotherapy cycle, then 6-weekly up to 9 months, 3-monthly up to 2 years, and 6-monthly up to 5 years. Quality of life was a prespecified secondary outcome of the ICON8 study. Within the quality-of-life study, the co-primary endpoints were QLQ-C30 global health score at 9 months (cross-sectional analysis) and mean QLQ-C30 global health score from randomisation to 9 months (longitudinal analysis). Data analyses were done on an intention-to-treat basis. The trial is registered on ClinicalTrials.gov, NCT01654146 and ISRCTN Registry, ISRCTN10356387, and is currently in long-term follow up. Findings: Between June 6, 2011, and Nov 28, 2014, 1566 patients were recruited into ICON8 (522 were included in group 1, 523 in group 2, and 521 in group 3). Baseline quality-of-life questionnaires were completed by 1438 (92%) of 1566 patients and 9-month questionnaires by 882 (69%) of 1280 patients. We observed no significant difference in global health score at 9 months (cross-sectional analysis) between study groups (group 2 vs group 1, difference in mean score 2·3, 95% CI −0·4 to 4·9, p=0·095; group 3 vs group 1, −0·8, −3·8 to 2·2, p=0·61). Using longitudinal analysis, we found lower global health scores for those receiving weekly paclitaxel than for those receiving 3-weekly chemotherapy (group 2 vs group 1, mean difference −1·8, 95% CI −3·6 to −0·1, p=0·043; group 3 vs group 1, −2·9, −4·7 to −1·1, p=0·0018). Interpretation: We found no evidence of a difference in global quality of life between treatment groups at 9 months; however, patients receiving weekly treatment reported lower mean quality of life across the 9-month period after randomisation. Taken together with the lack of progression-free survival benefit, these findings do not support routine use of weekly paclitaxel-containing regimens in the management of newly diagnosed ovarian cancer. Funding: Cancer Research UK, Medical Research Council, Health Research Board Ireland, Irish Cancer Society, and Cancer Australia

Narrowing the gap between eye care needs and service provision: the service-training nexus

<p>Abstract</p> <p>Background</p> <p>The provision of eye care in the developing world has been constrained by the limited number of trained personnel and by professional cultures. The use of personnel with specific but limited training as members of multidisciplinary teams has become increasingly important as health systems seek to extract better value from their investments in personnel. Greater positive action is required to secure more efficient allocation of roles and resources. The supply of professional health workers is a factor of the training system, so it stands to reason that more cost-effective, flexible and available education methods are needed. This paper presents a highly flexible competencies-based multiple entry and exit training system that matches and adapts training to the prevailing population and service needs and demands, while lifting overall standards over time and highlighting the areas of potential benefit.</p> <p>Methods</p> <p>Literature surveys and interviews in five continents were carried out. Based on this and the author's own experience, a encies-based multiple entry and exit scheme for eye care in a developing country was derived, modeled and critically reviewed by interested parties in one country.</p> <p>Results</p> <p>The scheme was shown to be highly cost-effective and readily adaptable to the anticipated eye care needs of the population. Eye care players in one selected country have commented favourably on the scheme.</p> <p>Conclusion</p> <p>The underlying principles used to derive this model can be applied to many eye care systems in many developing countries. The model can be used in other disciplines with similar constructs to eye care.</p

Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease

RATIONALE: We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES: Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS: In a FEV(1 )% matched population of 100 men and women with COPD we measured: age, MMRC, FEV(1), FVC, TLC, IC/TLC, PaO(2), PaCO(2), D(LCO), P(imax), P(0.1), Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations. RESULTS: MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV(1 )% (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO(2 )(men:-0.59, p < 0.001), PaCO(2 )(men:0.27, p = 0.05), D(LCO )(men:-0.54, p < 0.001), P(0.1)/P(imax )(men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P(0.1)/P(imax )in women (r(2 )= 0.30) and BMI, DL(CO), PaO(2 )and P(0.1)/P(imax )in men (r(2 )= 0.81) were the strongest predictors of MMRC scores. CONCLUSION: In mild to severe COPD patients attending a pulmonary clinic, P(0.1)/P(imax )was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD

Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes

BACKGROUND:Cardiovascular disease (CVD) and its most common manifestations - including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes.METHODS:In 1345 Framingham Heart Study participants from the largest 310 pedigrees (54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs (Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD (n = 142; myocardial infarction, stroke, CHD death), major CHD (n = 118; myocardial infarction, CHD death), AF (n = 151), and HF (n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency [greater than or equal to]0.10, genotype call rate [greater than or equal to]0.80, and Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001.RESULTS:Six associations yielded p <10-5. The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10-6; major CHD, rs2549513, p = 9.7 x 10-6; AF, rs958546, p = 4.8 x 10-6; HF: rs740363, p = 8.8 x 10-6. Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD (p 1.7 - 1.9 x 10-5) and major CHD (p 2.5 - 3.5 x 10-4) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF (p = 9.4 x 10-6) and HF (p = 1.2 x 10-4). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies

An Administrative Claims Model for Profiling Hospital 30-Day Mortality Rates for Pneumonia Patients

Outcome measures for patients hospitalized with pneumonia may complement process measures in characterizing quality of care. We sought to develop and validate a hierarchical regression model using Medicare claims data that produces hospital-level, risk-standardized 30-day mortality rates useful for public reporting for patients hospitalized with pneumonia.Retrospective study of fee-for-service Medicare beneficiaries age 66 years and older with a principal discharge diagnosis of pneumonia. Candidate risk-adjustment variables included patient demographics, administrative diagnosis codes from the index hospitalization, and all inpatient and outpatient encounters from the year before admission. The model derivation cohort included 224,608 pneumonia cases admitted to 4,664 hospitals in 2000, and validation cohorts included cases from each of years 1998-2003. We compared model-derived state-level standardized mortality estimates with medical record-derived state-level standardized mortality estimates using data from the Medicare National Pneumonia Project on 50,858 patients hospitalized from 1998-2001. The final model included 31 variables and had an area under the Receiver Operating Characteristic curve of 0.72. In each administrative claims validation cohort, model fit was similar to the derivation cohort. The distribution of standardized mortality rates among hospitals ranged from 13.0% to 23.7%, with 25(th), 50(th), and 75(th) percentiles of 16.5%, 17.4%, and 18.3%, respectively. Comparing model-derived risk-standardized state mortality rates with medical record-derived estimates, the correlation coefficient was 0.86 (Standard Error = 0.032).An administrative claims-based model for profiling hospitals for pneumonia mortality performs consistently over several years and produces hospital estimates close to those using a medical record model

Population Analysis of the Fusarium graminearum Species Complex from Wheat in China Show a Shift to More Aggressive Isolates

A large number of Fusarium isolates was collected from blighted wheat spikes originating from 175 sampling sites, covering 15 provinces in China. Species and trichothecene chemotype determination by multilocus genotyping (MLGT) indicated that F. graminearum s. str. with the 15-acetyl deoxynivalenol (15ADON) chemotype and F. asiaticum with either the nivalenol (NIV) or the 3-acetyl deoxynivalenol (3ADON) chemotype were the dominant causal agents. Bayesian model-based clustering with allele data obtained with 12 variable number of tandem repeats (VNTR) markers, detected three genetic clusters that also show distinct chemotypes. High levels of population genetic differentiation and low levels of effective number of migrants were observed between these three clusters. Additional genotypic analyses revealed that F. graminearum s. str. and F. asiaticum are sympatric. In addition, composition analysis of these clusters indicated a biased gene flow from 3ADON to NIV producers in F. asiaticum. In phenotypic analyses, F. asiaticum that produce 3ADON revealed significant advantages over F. asiaticum that produce NIV in pathogenicity, growth rate, fecundity, conidial length, trichothecene accumulation and resistance to benzimidazole. These results suggest that natural selection drives the spread of a more vigorous, more toxigenic pathogen population which also shows higher levels of fungicide resistance