The conceptual and practical ethical dilemmas of using health discussion board posts as research data.

Increasing numbers of people living with a long-term health condition are putting personal health information online, including on discussion boards. Many discussion boards contain material of potential use to researchers; however, it is unclear how this information can and should be used by researchers. To date there has been no evaluation of the views of those individuals sharing health information online regarding the use of their shared information for research purposes

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group

Assessing health centre systems for guiding improvement in diabetes care

BACKGROUND: Aboriginal people in Australia experience the highest prevalence of diabetes in the country, an excess of preventable complications and early death. There is increasing evidence demonstrating the importance of healthcare systems for improvement of chronic illness care. The aims of this study were to assess the status of systems for chronic illness care in Aboriginal community health centres, and to explore whether more developed systems were associated with better quality of diabetes care. METHODS: This cross-sectional study was conducted in 12 Aboriginal community health centres in the Northern Territory of Australia. Assessment of Chronic Illness Care scale was adapted to measure system development in health centres, and administered by interview with health centre staff and managers. Based on a random sample of 295 clinical records from attending clients with diagnosed type 2 diabetes, processes of diabetes care were measured by rating of health service delivery against best-practice guidelines. Intermediate outcomes included the control of HbA1c, blood pressure, and total cholesterol. RESULTS: Health centre systems were in the low to mid-range of development and had distinct areas of strength and weakness. Four of the six system components were independently associated with quality of diabetes care: an increase of 1 unit of score for organisational influence, community linkages, and clinical information systems, respectively, was associated with 4.3%, 3.8%, and 4.5% improvement in adherence to process standards; likewise, organisational influence, delivery system design and clinical information systems were related to control of HbA1c, blood pressure, and total cholesterol. CONCLUSION: The state of development of health centre systems is reflected in quality of care outcome measures for patients. The health centre systems assessment tool should be useful in assessing and guiding development of systems for improvement of diabetes care in similar settings in Australia and internationally

Patient Care Teams in treatment of diabetes and chronic heart failure in primary care: an observational networks study

Contains fulltext : 97203.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Patient care teams have an important role in providing medical care to patients with chronic disease, but insight into how to improve their performance is limited. Two potentially relevant determinants are the presence of a central care provider with a coordinating role and an active role of the patient in the network of care providers. In this study, we aimed to develop and test measures of these factors related to the network of care providers of an individual patient. METHODS: We performed an observational study in patients with type 2 diabetes or chronic heart failure, who were recruited from three primary care practices in The Netherlands. The study focused on medical treatment, advice on physical activity, and disease monitoring. We used patient questionnaires and chart review to measure connections between the patient and care providers, and a written survey among care providers to measure their connections. Data on clinical performance were extracted from the medical records. We used network analysis to compute degree centrality coefficients for the patient and to identify the most central health professional in each network. A range of other network characteristics were computed including network centralization, density, size, diversity of disciplines, and overlap among activity-specific networks. Differences across the two chronic conditions and associations with disease monitoring were explored. RESULTS: Approximately 50% of the invited patients participated. Participation rates of health professionals were close to 100%. We identified 63 networks of 25 patients: 22 for medical treatment, 16 for physical exercise advice, and 25 for disease monitoring. General practitioners (GPs) were the most central care providers for the three clinical activities in both chronic conditions. The GP's degree centrality coefficient varied substantially, and higher scores seemed to be associated with receiving more comprehensive disease monitoring. The degree centrality coefficient of patients also varied substantially but did not seem to be associated with disease monitoring. CONCLUSIONS: Our method can be used to measure connections between care providers of an individual patient, and to examine the association between specific network parameters and healthcare received. Further research is needed to refine the measurement method and to test the association of specific network parameters with quality and outcomes of healthcare

Analysis of symmetries in models of multi-strain infections

In mathematical studies of the dynamics of multi-strain diseases caused by antigenically diverse pathogens, there is a substantial interest in analytical insights. Using the example of a generic model of multi-strain diseases with cross-immunity between strains, we show that a significant understanding of the stability of steady states and possible dynamical behaviours can be achieved when the symmetry of interactions between strains is taken into account. Techniques of equivariant bifurcation theory allow one to identify the type of possible symmetry-breaking Hopf bifurcation, as well as to classify different periodic solutions in terms of their spatial and temporal symmetries. The approach is also illustrated on other models of multi-strain diseases, where the same methodology provides a systematic understanding of bifurcation scenarios and periodic behaviours. The results of the analysis are quite generic, and have wider implications for understanding the dynamics of a large class of models of multi-strain diseases

Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis

Introduction: Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytokines regulate DKK1 synthesis in synovial fibroblasts during inflammatory arthritis.Methods: We examined expression and regulation of DKK1 in primary cultures of human synovial fibroblasts isolated from patients with inflammatory arthritis. The effect of TNFα, IL-1β and glucocorticoids on DKK1 mRNA and protein expression was examined by real-time PCR and ELISA. The ability of inflammatory cytokine-induced expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to sensitise fibroblasts to endogenous glucocorticoids was explored. Global expression of Wnt signalling and target genes in response to TNFα and glucocorticoids was assessed using a custom array.Results: DKK1 expression in human synovial fibroblasts was directly regulated by glucocorticoids but not proinflammatory cytokines. Glucocorticoids, but not TNFα, regulated expression of multiple Wnt agonists and antagonists in favour of inhibition of Wnt signalling. However, TNFα and IL-1β indirectly stimulated DKK1 production through increased expression of 11β-HSD1.Conclusions: These results demonstrate that in rheumatoid arthritis synovial fibroblasts, DKK1 expression is directly regulated by glucocorticoids rather than TNFα. Consequently, the links between synovial inflammation, altered Wnt signalling and bone remodelling are not direct but are dependent on local activation of endogenous glucocorticoids

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Untargeted LC-HRMS-based metabolomics to identify novel biomarkers of metastatic colorectal cancer

Colorectal cancer is one of the main causes of cancer death worldwide, and novel biomarkers are urgently needed for its early diagnosis and treatment. The utilization of metabolomics to identify and quantify metabolites in body fluids may allow the detection of changes in their concentrations that could serve as diagnostic markers for colorectal cancer and may also represent new therapeutic targets. Metabolomics generates a pathophysiological ‘fingerprint’ that is unique to each individual. The purpose of our study was to identify a differential metabolomic signature for metastatic colorectal cancer. Serum samples from 60 healthy controls and 65 patients with metastatic colorectal cancer were studied by liquid chromatography coupled to high-resolution mass spectrometry in an untargeted metabolomic approach. Multivariate analysis revealed a separation between patients with metastatic colorectal cancer and healthy controls, who significantly differed in serum concentrations of one endocannabinoid, two glycerophospholipids, and two sphingolipids. These findings demonstrate that metabolomics using liquid-chromatography coupled to high-resolution mass spectrometry offers a potent diagnostic tool for metastatic colorectal cancer.This study was supported by a grant (n° 15CC056/DTS17/00081- ISCIII-FEDER) from the Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO) and Roche Pharma S.L. Authors from the Fundación MEDINA acknowledge the receipt of financial support from this public-private partnership of Merck Sharp & Dohme de España S.A. with the University of Granada and Andalusian Regional Government (PIN-0474-2016)