Tuberculosis incidence correlates with sunshine : an ecological 28-year time series study

Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods: We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results: There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion: A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence

Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT):a mixed methods, open-label, pragmatic randomised trial

Infliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness.In this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival-ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589.Between June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group vs 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI -22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group vs 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707-912] days in the infliximab group vs 744 [638-850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab vs ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients vs 25 in 17 patients); or deaths (three in the infliximab group vs none in the ciclosporin group).There was no significant difference between ciclosporin and infliximab in clinical effectiveness.NIHR Health Technology Assessment programme

Genetic differentiation among host-associated Alebra leafhoppers (Hemiptera: Cicadellidae)

The limited importance ascribed to sympatric speciation pro cesses via host race formation is partially due to the few cases of host races that have been reported among host populations. This work sheds light on the taxonomy of Alebra leafhoppers and examines the possible existence of host races among host-associated populations. The species of this genus show varying degrees of host association with deciduous trees and shrubs and, frequently, host popu lations of uncertain taxonomic status coexist and occasion ally become pests. Allozyme electrophoresis of 21 Greek populations including sympatric, local and geographically distant samples collected on 13 different plant species, show that they represent at least five species: A. albostriella Falle´n, A. viridis (Rey) (sensu Gillham), A. wahlbergi Bo Keywords: host races; leafhoppers; sympatric speciation; sibling species; allozymes; Alebra Introduction Sympatric speciation is a controversial subject in evol utionary biology (see Mayr, 1963; Futuyma and Mayer, 1980; Paterson, 1981; Via, 2001). One of the reasons for this controversy is that sympatric speciation seems to be an extremely rare phenomenon occurring only in very few groups of taxa, represented chiefly by phytophagous insects (Tauber and Tauber, 1977; Menken, 1981; Wood, 1993; Emelianov et al, 1995; Via, 1999; Finchak et al, 2000; Craig et al, 2001). The limited number of reported cases among organisms with sexual reproduction can be at least partially attributed to the fact that taxa undergoing sympatric speciation events must fulfill very restrictive biological and ecological requirements. Most sympatric speciation models demand that there is intraspecific genetic variation in traits that differentially affect the fitness of individuals that colonise new habitats or hosts (Dieckman and Doebeli, 1999; Hawthorne and Via, 2001 but see Higashi et al, 1999 and Takimoto et al, 2000). They assume that selection acting on these traits can prevent genetic exchange between populations (Bush, 1975; Tauber and Tauber, 1977; Diehl and Bush, 1989). In phytophagous insects, this means that host pref erences must be genetically determined and mating should occur on the host (Bush, 1975; Diehl and Bush, Correspondence: D Aguin-Pombo, Department of Biology, University of Madeira, Campus Universitario da Penteada, 9000 Funchal, Madeira, Portugal. E-mail: aguin uma.pt Received 12 December 2000; accepted 13 December 2001 heman and two new species. Of these, one is associated to Quercus frainetto and other is specific to Crataegus spp. Significant genetic differences among sympatric and local host populations were found only in A. albostriella, between populations on Turkey oak, beech and common alder. It is suggested that the last two of these host populations may represent different host races. The results show that both the host plant and geographical distance affect the patterns of differentiation in the genus. The formation of some spec ies seems to have been the result of allopatric speciation events while, for others, their origin can be equally explained either by sympatric or allopatric speciation.info:eu-repo/semantics/publishedVersio

From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke

<p>Abstract</p> <p>Background</p> <p>There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined.</p> <p>Methods/Design</p> <p>Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy.</p> <p>Discussion</p> <p>The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12608000042347.aspx">ACTRN12608000042347</a></p

Arachidonic Acid but not Eicosapentaenoic Acid (EPA) and Oleic Acid Activates NF-κB and Elevates ICAM-1 Expression in Caco-2 Cells

In patients with inflammatory bowel disease (IBD), intestinal activation of the transcription factor NF-κB as well as intercellular adhesion molecule (ICAM)-1 expression, which is involved in recruiting leukocytes to the side of inflammation is increased. Moreover, colonic arachidonic acid (ARA) proportions are increased and oleic acid (OA) proportions are decreased. Fish oils are protective in IBD patients however, a side-by-side comparison between effects of fish oils, ARA and OA has not been made. We therefore, compared effects of eicosapentaenoic acid (EPA) versus ARA and OA on ICAM-1 expression in Caco-2 enterocytes. To validate our model we showed that dexamethasone, sulfasalazine and PPARα (GW7647) or PPARγ (troglitazone) agonists significantly lowered ICAM-1 expression. ICAM-1 expression of non-stimulated and cytokine stimulated Caco-2 cells cultured for 22 days with ARA was significant higher as compared to EPA and OA. Furthermore, ARA increased NF-κB activation in a reporter cell-line as compared to EPA. Antibody array analysis of multiple inflammatory proteins particularly showed an increased monocyte chemotactic protein (MCP)-1 and angiogenin production and a decreased interleukin (IL)-6 and IL-10 production by ARA as compared to EPA. Our results showed that ARA but not EPA and OA activates NF-κB and elevates ICAM-1 expression in Caco-2 enterocytes. It suggests that replacement of ARA by EPA or OA in the colon mucosa might have beneficial effects for IBD patients. Finally, we suggest that the pro-inflammatory effects of ARA versus EPA and OA are not related to PPARγ activation and/or eicosanoid formation

Poor glycated haemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes mellitus: Systematic review of observational studies

BACKGROUND: Glycaemic control in women with diabetes is critical to satisfactory pregnancy outcome. A systematic review of two randomised trials concluded that there was no clear evidence of benefit from very tight versus tight glycaemic control for pregnant women with diabetes. METHODS: A systematic review of observational studies addressing miscarriage, congenital malformations and perinatal mortality among pregnant women with type 1 and type 2 diabetes was carried out. Literature searches were performed in MEDLINE, EMBASE, CINAHL and Cochrane Library. Observational studies with data on glycated haemoglobin (HbA(1c)) levels categorised into poor and optimal control (as defined by the study investigators) were selected. Relative risks and odds ratios were calculated for HbA(1c )and pregnancy outcomes. Adjusted relative risk estimates per 1-percent decrease in HbA(1c )were calculated for studies which contained information on mean and standard deviations of HbA(1c). RESULTS: The review identified thirteen studies which compared poor versus optimal glycaemic control in relation to maternal, fetal and neonatal outcomes. Twelve of these studies reported the outcome of congenital malformations and showed an increased risk with poor glycaemic control, pooled odds ratio 3.44 (95%CI, 2.30 to 5.15). For four of the twelve studies, it was also possible to calculate a relative risk reduction of congenital malformation for each 1-percent decrease in HbA(1c), these varied from 0.39 to 0.59. The risk of miscarriage was reported in four studies and was associated with poor glycaemic control, pooled odds ratio 3.23 (95%CI, 1.64 to 6.36). Increased perinatal mortality was also associated with poor glycaemic control, pooled odds ratio 3.03 (95%CI, 1.87 to 4.92) from four studies. CONCLUSION: This analysis quantifies the increase in adverse pregnancy outcomes in women with diabetes who have poor glycaemic control. Relating percentage risk reduction in HbA(1c )to relative risk of adverse pregnancy events may be useful in motivating women to achieve optimal control prior to conception

The fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

Background: Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods

A population-based lifestyle intervention to promote healthy weight and physical activity in people with cardiac disease: The PANACHE (Physical Activity, Nutrition And Cardiac HEalth) study protocol

<p>Abstract</p> <p>Background</p> <p>Maintaining a healthy weight and undertaking regular physical activity are important for the secondary prevention of cardiovascular disease (CVD). However, many people with CVD are overweight and insufficiently active. In addition, in Australia only 20-30% of people requiring cardiac rehabilitation (CR) for CVD actually attend. To improve outcomes of and access to CR the efficacy, effectiveness and cost-effectiveness of alternative approaches to CR need to be established.</p> <p>This research will determine the efficacy of a telephone-delivered lifestyle intervention, promoting healthy weight and physical activity, in people with CVD in urban and rural settings. The control group will also act as a replication study of a previously proven physical activity intervention, to establish whether those findings can be repeated in different urban and rural locations. The cost-effectiveness and acceptability of the intervention to CR staff and participants will also be determined.</p> <p>Methods/Design</p> <p>This study is a randomised controlled trial. People referred for CR at two urban and two rural Australian hospitals will be invited to participate. The intervention (healthy weight) group will participate in four telephone delivered behavioural coaching and goal setting sessions over eight weeks. The coaching sessions will be on weight, nutrition and physical activity and will be supported by written materials, a pedometer and two follow-up booster telephone calls. The control (physical activity) group will participate in a six week intervention previously shown to increase physical activity, consisting of two telephone delivered behavioural coaching and goal setting sessions on physical activity, supported by written materials, a pedometer and two booster phone calls. Data will be collected at baseline, eight weeks and eight months for the intervention group (baseline, six weeks and six months for the control group). The primary outcome is weight change. Secondary outcomes include physical activity, sedentary time and nutrition habits. Costs will be compared with outcomes to determine the relative cost-effectiveness of the healthy weight and physical activity interventions.</p> <p>Discussion</p> <p>This study addresses a significant gap in public health practice by providing evidence for the efficacy and cost-effectiveness of a low cost, low contact, high reach intervention promoting healthy weight and physical activity among people with CVD in rural and urban areas in Australia. The replication arm of the study, undertaken by the control group, will demonstrate whether the findings of the previously proven physical activity intervention can be generalised to new settings. This population-based approach could potentially improve access to and outcomes of secondary prevention programs, particularly for rural or disadvantaged communities.</p> <p>Trial Registration</p> <p>ACTRN12610000102077</p

A pragmatic cluster randomised controlled trial of a Diabetes REcall And Management system: the DREAM trial

BACKGROUND: Following the introduction of a computerised diabetes register in part of the northeast of England, care initially improved but then plateaued. We therefore enhanced the existing diabetes register to address these problems. The aim of the trial was to evaluate the effectiveness and efficiency of an area wide 'extended,' computerised diabetes register incorporating a full structured recall and management system, including individualised patient management prompts to primary care clinicians based on locally-adapted, evidence-based guidelines. METHODS: The study design was a pragmatic, cluster randomised controlled trial, with the general practice as the unit of randomisation. Set in 58 general practices in three Primary Care Trusts in the northeast of England, the study outcomes were the clinical process and outcome variables held on the diabetes register, patient-reported outcomes, and service and patient costs. The effect of the intervention was estimated using generalised linear models with an appropriate error structure. To allow for the clustering of patients within practices, population averaged models were estimated using generalized estimating equations. RESULTS: Patients in intervention practices were more likely to have at least one diabetes appointment recorded (OR 2.00, 95% CI 1.02, 3.91), to have a recording of a foot check (OR 1.87, 95% CI 1.09, 3.21), have a recording of receiving dietary advice (OR 2.77, 95% CI 1.22, 6.29), and have a recording of blood pressure (BP) (OR 2.14, 95% CI 1.06, 4.36). There was no difference in mean HbA1c or BP levels, but the mean cholesterol level in patients from intervention practices was significantly lower (-0.15 mmol/l, 95% CI -0.25, -0.06). There were no differences in patient-reported outcomes or in patient-reported use of drugs, or uptake of health services. The average cost per patient was not significantly different between the intervention and control groups. Costs incurred in administering the system at the register and in general practice were in addition to these. CONCLUSION: This study has shown benefits from an area-wide, computerised diabetes register incorporating a full structured recall and individualised patient management system. However, these benefits were achieved at a cost. In future, these costs may fall as electronic data exchange becomes a reliable reality. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) Register, ISRCTN32042030

Health-related quality of life and strain in caregivers of Australians with Parkinson’s disease : An observational study

Background: The relationship between health-related quality of life (HRQoL) in people with Parkinson&rsquo;s disease and their caregivers is little understood and any effects on caregiver strain remain unclear. This paper examines these relationships in an Australian sample. Methods: Using the generic EuroQol (EQ-5D) and disease-specific Parkinson&rsquo;s Disease Questionnaire-39 Item (PDQ- 39), HRQoL was evaluated in a sample of 97 people with PD and their caregivers. Caregiver strain was assessed using the Modified Caregiver Strain Index. Associations were evaluated between: (i) caregiver and care-recipient HRQoL; (ii) caregiver HRQoL and caregiver strain, and; (iii) between caregiver strain and care-recipient HRQoL. Results: No statistically significant relationships were found between caregiver and care-recipient HRQoL, or between caregiver HRQoL and caregiver strain. Although this Australian sample of caregivers experienced relatively good HRQoL and moderately low strain, a significant correlation was found between HRQoL of people with PD and caregiver strain (rho 0.43, p&lt;.001). Conclusion: Poor HRQoL in people with PD is associated with higher strain in caregivers. Therapy interventions may target problems reported as most troublesome by people with PD, with potential to reduce strain on the caregive