Management of fatigue with physical activity and behavioural change support in vasculitis: a feasibility study.

OBJECTIVE: Patients with ANCA-associated vasculitis (AAV) experience high levels of fatigue, despite disease remission. This study assessed the feasibility and acceptability of a definitive randomized controlled trial of a behavioural-based physical activity intervention to support fatigue self-management in AAV patients. METHODS: AAV patients in disease remission with fatigue (Multidimensional Fatigue Inventory-20 general fatigue domain ≥14) were randomly allocated to intervention or standard care in this single-centre open-label randomized controlled feasibility study. The intervention lasted 12 weeks and comprised eight face-to-face physical activity sessions with a facilitator and 12 weekly telephone calls. Participants were encouraged to monitor their physical activity using a tracker device (Fitbit). Standard care involved sign-posting to fatigue websites. The primary outcome was feasibility of a phase III trial assessed against three stop/go traffic light criteria, (recruitment, intervention adherence and study withdrawal). A qualitative study assessed participant views about the intervention. RESULTS: A total of 248 patients were screened and 134 were eligible to participate (54%). Stop/go criteria were amber for recruitment; 43/134 (32%, 95% CI: 24, 40) eligible participants randomized, amber for adherence; 73% of participants attended all eight physical activity sessions, but only 11/22 (50%, 95% CI: 29, 71%) completed the intervention as per the intended schedule, and green for study withdrawal; 2/43 participants withdrew before 24 weeks (5%, 95% CI: 0, 11). Qualitative results suggested the intervention was acceptable. CONCLUSION: This study suggests a behavioural-based physical activity intervention targeting fatigue self-management was acceptable to patients with AAV, although recruitment and protocol adherence will need modification prior to a definitive trial. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11929227.

A randomised controlled trial of extended anticoagulation treatment versus standard treatment for the prevention of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (the ExACT study).

Venous thromboembolism (VTE) is prevalent and impactful, with a risk of death, morbidity and recurrence. Post-thrombotic syndrome (PTS) is a common consequence and associated with impaired quality of life (QoL). The ExACT study was a non-blinded, prospective, multicentred randomised controlled trial comparing extended versus limited duration anticoagulation following a first unprovoked VTE (proximal deep vein thrombosis or pulmonary embolism). Adults were eligible if they had completed ≥3 months anticoagulation (remaining anticoagulated). The primary outcome was time to first recurrent VTE from randomisation. The secondary outcomes included PTS severity, bleeding, QoL and D-dimers. Two-hundred and eighty-one patients were recruited, randomised and followed up for 24 months (mean age 63, male:female 2:1). There was a significant reduction in recurrent VTE for patients receiving extended anticoagulation [2·75 vs. 13·54 events/100 patient years, adjusted hazard ratio (aHR) 0·20 (95% confidence interval (CI): 0·09 to 0·46, P < 0·001)] with a non-significant increase in major bleeding [3·54 vs. 1·18 events/100 patient years, aHR 2·99 (95% CI: 0·81-11·05, P = 0·10)]. Outcomes of PTS and QoL were no different between groups. D-dimer results (on anticoagulation) did not predict VTE recurrence. In conclusion, extended anticoagulation reduced VTE recurrence but did not reduce PTS or improve QoL and was associated with a non-significant increase in bleeding. Results also suggest very limited clinical utility of D-dimer testing on anticoagulated patients.

Warfarin versus aspirin for prevention of cognitive decline in atrial fibrillation: randomized controlled trial (Birmingham Atrial Fibrillation Treatment of the Aged Study).

BACKGROUND AND PURPOSE: Atrial fibrillation is associated with decline of cognitive function. Observational evidence suggests that anticoagulation might protect against this decline. We report the first randomized controlled trial evidence on the effect of anticoagulation on cognitive function in elderly patients with atrial fibrillation. METHODS: A total of 973 patients aged≥75 years with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (n=488; target international normalized ratio, 2-3) or aspirin (n=485; 75 mg/d). Neither participants nor investigators were masked to group assignment. Follow-up was for a mean of 2.7 years (SD, 1.2). Cognitive outcome was assessed using the Mini-Mental State Examination at 9-, 21-, and 33-month follow-up. Participants who had a stroke were censored from the analysis, which was by intention to treat with imputation for missing data. RESULTS: There was no difference between mean Mini-Mental State Examination scores in people assigned to warfarin or aspirin at 9 or 21 months. At 33-month follow-up, there was a nonsignificant difference of 0.56 in favor of warfarin that decreased to 0.49 (95% confidence interval, -0.01 to 0.98) after imputation. CONCLUSIONS: We found no evidence that anticoagulation confers clinically important protection over aspirin against cognitive decline as measured by the Mini-Mental State Examination in atrial fibrillation in the first 33 months of treatment other than that provided by preventing clinical stroke. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN89345269.

A cross-sectional study of quality of life in an elderly population (75 years and over) with atrial fibrillation: secondary analysis of data from the Birmingham Atrial Fibrillation Treatment of the Aged study.

AIMS: To compare the quality of life (QoL) of those in atrial fibrillation (AF) aged 75 years and over with that of the general population, to explore what factors affect the QoL of those with AF, and to assess the sensitivity of the EuroQol (EQ-5D) and Short-Form 12 (SF-12) generic health questionnaires in detecting differences in health status in those with AF in this age group. METHODS AND RESULTS: The study population was 1762 men and women aged 75 years and over with confirmed AF who attended a randomization clinic for the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study, a primary care based trial of stroke prevention. Patients self-completed the EQ-5D and SF-12 questionnaires, and a simple measure of disability (Rankin). Cardiovascular co-morbidities were collected and number of drugs used as an additional proxy for co-morbidity. Quality-of-life outcomes were compared with general population samples of the same age. On multiple regression, female gender, greater medication use, and disability were independently associated with lower QoL scores in AF. Those in AF with a Rankin score ≥2 had lower QoL scores, while those with a Rankin score <2 had higher scores than the general population. Increasing co-morbidity was associated with reduced QoL scores, with the EQ-5D and SF-12 Physical Component Score showing similar sensitivity to these associations, and the SF-12 Mental Component Score showing less sensitivity. CONCLUSION: In the absence of co-morbidity, chronic AF has little impact on generic QoL in an elderly non-acutely ill population.

A 12-week commercial web-based weight-loss program for overweight and obese adults: randomized controlled trial comparing basic versus enhanced features.

BACKGROUND: The development and use of Web-based programs for weight loss is increasing rapidly, yet they have rarely been evaluated using randomized controlled trials (RCTs). Interestingly, most people who attempt weight loss use commercially available programs, yet it is very uncommon for commercial programs to be evaluated independently or rigorously. OBJECTIVE: To compare the efficacy of a standard commercial Web-based weight-loss program (basic) versus an enhanced version of this Web program that provided additional personalized e-feedback and contact from the provider (enhanced) versus a wait-list control group (control) on weight outcomes in overweight and obese adults. METHODS: This purely Web-based trial using a closed online user group was an assessor-blinded RCT with participants randomly allocated to the basic or enhanced 12-week Web-based program, based on social cognitive theory, or the control, with body mass index (BMI) as the primary outcome. RESULTS: We enrolled 309 adults (129/309, 41.8% male, BMI mean 32.3, SD 4 kg/m(2)) with 84.1% (260/309) retention at 12 weeks. Intention-to-treat analysis showed that both intervention groups reduced their BMI compared with the controls (basic: -0.72, SD 1.1 kg/m(2), enhanced: -1.0, SD 1.4, control: 0.15, SD 0.82; P < .001) and lost significant weight (basic: -2.1, SD 3.3 kg, enhanced: -3.0, SD 4.1, control: 0.4, SD 2.3; P < .001) with changes in waist circumference (basic: -2.0, SD 3.5 cm, enhanced: -3.2, SD 4.7, control: 0.5, SD 3.0; P < .001) and waist-to-height ratio (basic: -0.01, SD 0.02, enhanced: -0.02, SD 0.03, control: 0.0, SD 0.02; P < .001), but no differences were observed between the basic and enhanced groups. The addition of personalized e-feedback and contact provided limited additional benefits compared with the basic program. CONCLUSIONS: A commercial Web-based weight-loss program can be efficacious across a range of weight-related outcomes and lifestyle behaviors and achieve clinically important weight loss. Although the provision of additional personalized feedback did not facilitate greater weight loss after 12 weeks, the impact of superior participant retention on longer-term outcomes requires further study. Further research is required to determine the optimal mix of program features that lead to the biggest treatment impact over time. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): 12610000197033.

The impact of telehealth support for patients with diabetes or chronic obstructive pulmonary disease on unscheduled secondary care utilisation: a service evaluation.

BACKGROUND: Telehealth has been promoted as an adjunct to managing patients with long-term conditions. It has been used in various settings and for different disease groups. However, robust evidence for the efficacy of telehealth is currently lacking. OBJECTIVES: To evaluate the impact of a telehealth service on emergency admissions and emergency department (ED) attendances. METHODS: We evaluated a telehealth service providing supported self-management to patients that was implemented in Nottingham City. Two groups of patients ('graduates' of the Nottingham telehealth service and service 'decliners') were compared for two periods; 2009 (pre-service implementation) and 2011. Eighty-nine pairs of graduates and decliners were identified who were matched for age and sex. The number and cost of emergency admissions and ED attendances for these patients were then collated and analysed. RESULTS: Graduates had significantly fewer emergency admissions and ED attendances compared with decliners in 2011. However, differences of a similar magnitude in emergency admissions and ED attendances were found in 2009. Telehealth service users were likely to be qualitatively different from decliners, reflecting a degree of self-selection. This suggests that decliners were more likely to have a confounding reason for not engaging with telehealth, such as greater disease severity. CONCLUSIONS: This service review found no evidence that the Nottingham telehealth service has had a significant impact on secondary care utilisation in the short term. Longer term follow up is needed to establish conclusively whether telehealth initiatives like the Nottingham telehealth service does lead to tangible patient benefits and provide value for money.

Cost effectiveness of warfarin versus aspirin in patients older than 75 years with atrial fibrillation.

BACKGROUND AND PURPOSE: Oral anticoagulants are effective at reducing stroke compared with aspirin in atrial fibrillation patients older than 75 years. Although the benefits of reduced stroke risk outweigh the risks of bleeding, the cost effectiveness of warfarin in this patient population has not yet been established. METHODS: An economic evaluation was conducted alongside a randomized, controlled trial; 973 patients ≥75 years of age with atrial fibrillation were recruited from primary care and randomly assigned to either take warfarin or aspirin. Follow-up was for a mean of 2.7 years. Costs of thrombotic and hemorrhagic events, anticoagulation clinic visits, and primary care utilization were determined. Clinical benefits were expressed in terms of a primary event avoided: fatal/nonfatal disabling stroke, intracranial hemorrhage, or systemic embolism. A cost-utility analysis was performed using quality-adjusted life years as the benefit measure. RESULTS: Total costs over 4 years were lower in the warfarin group (difference, -£165; 95% CI, -£452-£89), primarily driven by the difference in primary event costs. The primary event rate over 4 years was lower in the warfarin group (0.049 versus 0.099), and the quality-adjusted life years score was higher (difference, 0.02; 95% CI, -0.07-0.11). With lower costs and a higher quality-adjusted life years score, warfarin is the dominant treatment, but the differences in both costs and effects are small. CONCLUSIONS: Warfarin is cost-effective compared with aspirin in atrial fibrillation patients age ≥75 years. These data support the anticoagulant therapy option in this high-risk patient population. However, the small differences in costs and effects indicate the importance of exploring patient preferences.

Protocol for Past BP: a randomised controlled trial of different blood pressure targets for people with a history of stroke of transient ischaemic attack (TIA) in primary care.

BACKGROUND: Blood pressure (BP) lowering in people who have had a stroke or transient ischaemic attack (TIA) leads to reduced risk of further stroke. However, it is not clear what the target BP should be, since intensification of therapy may lead to additional adverse effects. PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting, and whether more intensive therapy is associated with adverse effects on quality of life. METHODS/DESIGN: This is a randomised controlled trial (RCT) in patients with a past history of stroke or TIA. Patients will be randomised to two groups and will either have their blood pressure (BP) lowered intensively to a target of 130 mmHg systolic, (or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg) compared to a standard group where the BP will be reduced to a target of 140 mmHg systolic. Patients will be managed by their practice at 1-3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months.610 patients will be recruited from approximately 50 general practices. The following exclusion criteria will be applied: systolic BP <125 mmHg at baseline, 3 or more anti-hypertensive agents, orthostatic hypotension, diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness.The primary outcome will be change in systolic BP over twelve months. Secondary outcomes include quality of life, adverse events and cardiovascular events.In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals understanding and views of BP management. DISCUSSION: The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care, and help determine whether or not further research is required before recommending such targets for this population. TRIAL REGISTRATION: ISRCTN29062286.

Evaluation of a commercial web-based weight loss and weight loss maintenance program in overweight and obese adults: a randomized controlled trial.

BACKGROUND: Obesity rates in adults continue to rise and effective treatment programs with a broad reach are urgently required. This paper describes the study protocol for a web-based randomized controlled trial (RCT) of a commercially available program for overweight and obese adult males and females. The aim of this RCT was to determine and compare the efficacy of two web-based interventions for weight loss and maintenance of lost weight. METHODS/DESIGN: Overweight and obese adult males and females were stratified by gender and BMI and randomly assigned to one of three groups for 12-weeks: waitlist control, or basic or enhanced online weight-loss. Control participants were re-randomized to the two weight loss groups at the end of the 12-week period. The basic and enhanced group participants had an option to continue or repeat the 12-week program. If the weight loss goal was achieved at the end of 12, otherwise on completion of 24 weeks of weight loss, participants were re-randomized to one of two online maintenance programs (maintenance basic or maintenance enhanced), until 18 months from commencing the weight loss program. Assessments took place at baseline, three, six, and 18 months after commencing the initial weight loss intervention with control participants repeating the initial assessment after three month of waiting. The primary outcome is body mass index (BMI). Other outcomes include weight, waist circumference, blood pressure, plasma markers of cardiovascular disease risk, dietary intake, eating behaviours, physical activity and quality of life.Both the weight loss and maintenance of lost weight programs were based on social cognitive theory with participants advised to set goals, self-monitor weight, dietary intake and physical activity levels. The enhanced weight loss and maintenance programs provided additional personalized, system-generated feedback on progress and use of the program. Details of the methodological aspects of recruitment, inclusion criteria, randomization, intervention programs, assessments and statistical analyses are described. DISCUSSION: Importantly, this paper describes how an RCT of a currently available commercial online program in Australia addresses some of the short falls in the current literature pertaining to the efficacy of web-based weight loss programs.Australian New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12610000197033.

Prevention of excessive hypothermia in infants with hypoxic ischemic encephalopathy prior to admission to a quaternary care center: a neonatal outreach educational project.

OBJECTIVE: Excessive hypothermia is common in infants that receive passive cooling for hypoxic ischemic encephalopathy (HIE). Our goal was to reduce the number of infants with admission temperature <33 °C from 33% to less than 10% by December 2017. METHODS: Outcome measures included the number of infants with admission temperature <33 °C and number of infants with temperature within therapeutic range. Interventions included implementation of passive cooling guidelines and outreach education to birth hospitals and transport team. We used statistical process control chart to compare outcomes over a 3 year period. RESULTS: The number of infants with admission temperature <33 °C decreased from 33.3% to 5.5% (p = 0.013). The number of infants with admission temperature within target range for hypothermia therapy increased from 61.1% to 77.7% (p = 0.014). Balancing measures and complications remained unchanged. CONCLUSION: Implementation of passive cooling guidelines and outreach education led to significant decrease in excessive hypothermia in infants with HIE.

Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial.

BACKGROUND: Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation, but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown. We assessed whether warfarin reduced risk of major stroke, arterial embolism, or other intracranial haemorrhage compared with aspirin in elderly patients. METHODS: 973 patients aged 75 years or over (mean age 81.5 years, SD 4.2) with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (target international normalised ratio 2-3) or aspirin (75 mg per day). Follow-up was for a mean of 2.7 years (SD 1.2). The primary endpoint was fatal or disabling stroke (ischaemic or haemorrhagic), intracranial haemorrhage, or clinically significant arterial embolism. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN89345269. FINDINGS: There were 24 primary events (21 strokes, two other intracranial haemorrhages, and one systemic embolus) in people assigned to warfarin and 48 primary events (44 strokes, one other intracranial haemorrhage, and three systemic emboli) in people assigned to aspirin (yearly risk 1.8%vs 3.8%, relative risk 0.48, 95% CI 0.28-0.80, p=0.003; absolute yearly risk reduction 2%, 95% CI 0.7-3.2). Yearly risk of extracranial haemorrhage was 1.4% (warfarin) versus 1.6% (aspirin) (relative risk 0.87, 0.43-1.73; absolute risk reduction 0.2%, -0.7 to 1.2). INTERPRETATION: These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation, unless there are contraindications or the patient decides that the benefits are not worth the inconvenience.

Treatment of fatigue with physical activity and behavioural change support in vasculitis: study protocol for an open-label randomised controlled feasibility study.

INTRODUCTION: Fatigue is a major cause of morbidity, limiting quality of life, in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The aetiology of fatigue is multifactorial; biological and psychosocial mediators, such as sleep deprivation, pain and anxiety and depression, are important and may be improved by increasing physical activity. Current self-management advice is based on expert opinion and is poorly adhered to. This study aims to investigate the feasibility of increasing physical activity using a programme of direct contact and telephone support, to provide patient education, encourage behaviour self-monitoring and the development of an individual change plan with defined goals and feedback to treat fatigue compared with standard of care to inform the design of a large randomised controlled trial to test the efficacy and cost effectiveness of this programme. METHODS AND ANALYSIS: Patients with AAV and significant levels of fatigue (patient self-report using multidimensional fatigue index score questionnaire ≥14) will be randomised in a 1:1 ratio to the physical activity programme supported by behavioural change techniques or standard of care. The intervention programme will consist of 8 visits of supervised activity sessions and 12 telephone support calls over 12 weeks with the aim of increasing physical activity to the level advised by government guidelines. Assessment visits will be performed at baseline, 12, 24 and 52 weeks. The study will assess the feasibility of recruitment, retention, the acceptability, adherence and safety of the intervention, and collect data on various assessment tools to inform the design of a large definitive trial. A nested qualitative study will explore patient experience of the trial through focus groups or interviews. ETHICS AND DISSEMINATION: All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, patient networks and academic publications. TRIAL REGISTRATION NUMBER: ISRCTN11929227.

Exploring demand reduction through design, durability and 'usership' of fashion clothes.

Global planetary boundaries confer limits to production and consumption of material goods. They also confer an obligation to experiment, as individuals and collectively as society, with less-materially-intensive, but no less exuberant, ways of living. This paper takes up this mantle and explores materials demand reduction through a focus on design, fashion garments and the universal, everyday activity of wearing clothes. It takes as its starting point the design of longer-lasting products, a widely favoured strategy for increasing materials efficiency and reducing materials demand in many sectors, including fashion. Drawing on scholarship in the field of design for sustainability and ethnographic research conducted in 16 locations in nine countries about already-existing practices of intensive use and maintenance of clothing, this paper critiques the effectiveness of durability strategies to reduce the amount of materials used. It argues for an update in the familiar preference within sustainability debates for the 'techno-fix' to explore instead resourceful use of materials as emerging from human actions and relationships with material goods. It suggests that, while facilitated by design, technology and engineering, opportunities to reduce materials demand begin in individual and collective practices, which, in turn, have dynamic implications for use of materials.This article is part of the themed issue 'Material demand reduction'.

Cost-effectiveness analysis of use of a polypill versus usual care or best practice for primary prevention in people at high risk of cardiovascular disease.

BACKGROUND: Clinical trials suggest that use of fixed-dose combination therapy ('polypills') can improve adherence to medication and control of risk factors of people at high risk of cardiovascular disease (CVD) compared to usual care, but cost-effectiveness is unknown. OBJECTIVE: To determine whether a polypill is cost-effective compared to usual care and optimal guideline-recommended treatment for primary prevention in people already on statins and/or blood pressure lowering therapy. METHODS: A Markov model was developed to perform a cost-utility analysis with a one year time cycle and a 10 year time horizon to compare the polypill with usual care and optimal implementation of NICE Guidelines, using patient level data from a retrospective cross-sectional study. The model was run for ten age (40 years+) and gender-specific sub-groups on treatment for raised CVD risk with no history of CVD. Published sources were used to estimate impact of different treatment strategies on risk of CVD events. RESULTS: A polypill strategy was potentially cost-effective compared to other strategies for most sub-groups ranging from dominance to up to £18,811 per QALY depending on patient sub-group. Optimal implementation of guidelines was most cost-effective for women aged 40-49 and men aged 75+. Results were sensitive to polypill cost, and if the annual cost was less than £150, this approach was cost-effective compared to the other strategies. CONCLUSIONS: For most people already on treatment to modify CVD risk, a polypill strategy may be cost-effective compared with optimising treatment as per guidelines or their current care, as long as the polypill cost is sufficiently low.

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke--Blood Pressure) randomised controlled trial.

OBJECTIVE: To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. DESIGN: Open label randomised controlled trial. SETTING: 99 general practices in England, with participants recruited in 2009-11. PARTICIPANTS: People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. INTERVENTIONS: Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. MAIN OUTCOME MEASURE: Change in systolic blood pressure between baseline and 12 months. RESULTS: 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). CONCLUSIONS: Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure.Trial registration Current Controlled Trials ISRCTN29062286.

Cost-effectiveness analysis of different systolic blood pressure targets for people with a history of stroke or transient ischaemic attack: Economic analysis of the PAST-BP study.

BACKGROUND: The PAST-BP trial found that using a lower systolic blood pressure target (<130 mmHg or lower versus <140 mmHg) in a primary care population with prevalent cerebrovascular disease was associated with a small additional reduction in blood pressure (2.9 mmHg). OBJECTIVES: To determine the cost effectiveness of an intensive systolic blood pressure target (<130 mmHg or lower) compared with a standard target (<140 mmHg) in people with a history of stroke or transient ischaemic attack on general practice stroke/transient ischaemic attack registers in England. METHODS: A Markov model with a one-year time cycle and a 30-year time horizon was used to estimate the cost per quality-adjusted life year of an intensive target versus a standard target. Individual patient level data were used from the PAST-BP trial with regard to change in blood pressure and numbers of primary care consultations over a 12-month period. Published sources were used to estimate life expectancy and risks of cardiovascular events and their associated costs and utilities. RESULTS: In the base-case results, aiming for an intensive blood pressure target was dominant, with the incremental lifetime costs being £169 lower per patient than for the standard blood pressure target with a 0.08 quality-adjusted life year gain. This was robust to sensitivity analyses, unless intensive blood pressure lowering reduced quality of life by 2% or more. CONCLUSION: Aiming for a systolic blood pressure target of <130 mmHg or lower is cost effective in people who have had a stroke/transient ischaemic attack in the community, but it is difficult to separate out the impact of the lower target from the impact of more active management of blood pressure.

Visceral leishmaniasis and immunocompromise as a risk factor for the development of visceral leishmaniasis: a changing pattern at the hospital for tropical diseases, london.

METHODS AND PRINCIPAL FINDINGS: A retrospective study of imported VL to the HTD, London including patients diagnosed and/or managed at the HTD between January 1995 and July 2013. We analyse patient demographics, risk factors for developing VL, diagnosis, investigation, management and outcome. Twenty-eight patients were treated for VL at the HTD over an 18 year period. The median age at VL diagnosis was 44 years (range 4-87 years) with a male to female ratio of 2:1. Most patients were British and acquired their infection in the Mediterranean basin. The median time from first symptom to diagnosis was six months with a range of 1-12 months and diagnosis included microscopic visualisation of leishmania amastigotes, positive serological tests (DAT and k39 antibody) or identification of leishmania DNA. Nineteen patients had some form of immunocompromise and this has increased proportionally compared to previously described data. Within the immunocompromised group, the ratio of those with autoimmune disease has increased. Immunocompromised patients had lower cure and higher relapse rates. CONCLUSIONS: The rise of VL in patients with immunocompromise secondary to autoimmune disease on immunomodulatory drugs presents new diagnostic and therapeutic challenges. VL should be a differential diagnosis in immunocompromised patients with pyrexia of unknown origin returning from travel in leishmania endemic areas.