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ObjectiveHeart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF.MethodsPopulation-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level.Results22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400–2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19–581).ConclusionsHigh baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes—such as a mandatory two-week HF diagnosis pathway—is urgently needed.

BACKGROUND: Newer flow diverters are enhanced with antithrombogenic surface modifications like the Pipeline Embolization Device with Shield Technology and the Derivo Embolization Device and are purported to facilitate deployment and reduce ischemic events. PURPOSE: Our aim was to review the safety and efficacy of surface-modified flow diverters in treating patients with cerebral aneurysms. DATA SOURCES: We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses–compliant systematic review and meta-analysis covering 3 major data bases and gray literature between 2014 and 2019. STUDY SELECTION: Two reviewers independently reviewed human studies of surface-modified flow diverters for eligibility based on predetermined criteria. DATA ANALYSIS: The random effects model and Freeman-Tukey arcsine transformation were used to pool efficacy outcomes (technical success, aneurysm occlusion at 6 and 12 months) and safety outcomes (mortality, morbidity, all ischemia, and serious ischemia). Subgroup analysis was performed to compare outcomes between 2 different flow diverters. DATA SYNTHESIS: Eight single-arm case series involving 911 patients and 1060 aneurysms were included. The median follow-up was 8.24 months. Pooled estimate for technical success was 99.6%, while the aneurysm occlusion at 6 and 12 months were 80.5%, and 85.6%, respectively. Pooled estimates for mortality, morbidity, total ischemia, and serious ischemia rates were 0.7%, 6.0%, 6.7%, and 1.8%, respectively. Most studies were of good quality, and no significant heterogeneity was observed. LIMITATIONS: Limitations include a retrospective, observational design in some studies; heterogeneous and underreported antiplatelet therapy; and potential performance and ecologic bias. CONCLUSIONS: Early-to-midterm safety and efficacy for surface-modified flow diverters appear comparable with older devices, especially for small, unruptured anterior circulation aneurysms. Long-term clinical data are required to further corroborate these results.

Summary Background Routine childhood immunisation with pneumococcal conjugate vaccine (PCV) has changed the epidemiology of pneumococcal disease across age groups, providing an opportunity to reconsider PCV dosing schedules. We aimed to evaluate the post-booster dose immunogenicity of ten-valent (PCV10) and 13-valent (PCV13) PCVs between infants randomly assigned to receive a single-dose compared with a two-dose primary series. Methods We did an open-label, non-inferiority, randomised study in HIV-unexposed infants at a single centre in Soweto, South Africa. Infants were randomly assigned to receive one priming dose of PCV10 or PCV13 at ages 6 weeks (6w + 1 PCV10 and 6w + 1 PCV13 groups) or 14 weeks (14w + 1 PCV10 and 14w + 1 PCV13 groups) or two priming doses of PCV10 or PCV13, one each at ages 6 weeks and 14 weeks (2 + 1 PCV10 and 2 + 1 PCV13 groups); all participants then received a booster dose of PCV10 or PCV13 at 40 weeks of age. The primary endpoint was geometric mean concentrations (GMCs) of serotype-specific IgG 1 month after the booster dose, which was assessed in all participants who received PCV10 or PCV13 as per the assigned randomisation group and for whom laboratory results were available at that timepoint. The 1 + 1 vaccine schedule was considered non-inferior to the 2 + 1 vaccine schedule if the lower bound of the 96% CI for the GMC ratio was greater than 0·5 for at least ten PCV13 serotypes and eight PCV10 serotypes. Safety was a secondary endpoint. This trial is registered with ClinicalTrials.gov ( NCT02943902 ) and is ongoing. Findings Of 1695 children assessed, 600 were enrolled and randomly assigned to one of the six groups between Jan 9 and Sept 20, 2017; 542 were included in the final analysis of the primary endpoint (86–93 per group). For both PCV13 and PCV10, a 1+1 dosing schedule (either beginning at 6 or 14 weeks) was non-inferior to a 2 + 1 schedule. For PCV13, the lower limit of the 96% CI for the ratio of GMCs between the 1 + 1 and 2 + 1 groups was higher than 0·5 for ten serotypes in the 6w+1 group (excluding 6B, 14, and 23F) and 11 serotypes in the 14w + 1 group (excluding 6B and 23F). For PCV10, the lower limit of the 96% CI for the ratio of GMCs was higher than 0·5 for all ten serotypes in the 6w+1 and 14w + 1 groups. 84 serious adverse events were reported in 72 (12%) of 600 participants. 15 occurred within 28 days of vaccination, but none were considered to be related to PCV injection. There were no cases of culture-confirmed invasive pneumococcal disease. Interpretation The non-inferiority in post-booster immune responses following a single-dose compared with a two-dose primary series of PCV13 or PCV10 indicates the potential for reducing PCV dosing schedules from a 2 + 1 to 1 + 1 series in low-income and middle-income settings with well established PCV immunisation programmes. Funding The Bill & Melinda Gates Foundation (OPP1 + 152352).

© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. Aims: To understand gender differences in the prognosis of women and men with heart failure, we compared mortality, cause of death and survival trends over time. Methods and results: We analysed UK primary care data for 26 725 women and 29 234 men over age 45 years with a new diagnosis of heart failure between 1 January 2000 and 31 December 2017 using the Clinical Practice Research Datalink, inpatient Hospital Episode Statistics and the Office for National Statistics death registry. Age-specific overall survival and cause-specific mortality rates were calculated by gender and year. During the study period 15 084 women and 15 822 men with heart failure died. Women were on average 5 years older at diagnosis (79.6 vs. 74.8 years). Median survival was lower in women compared to men (3.99 vs. 4.47 years), but women had a 14% age-adjusted lower risk of all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.84–0.88]. Heart failure was equally likely to be cause of death in women and men (HR 1.03, 95% CI 0.96–1.12). There were modest improvements in survival for both genders, but these were greater in men. The reduction in mortality risk in women was greatest for those diagnosed in the community (HR 0.83, 95% CI 0.80–0.85). Conclusions: Women are diagnosed with heart failure older than men but have a better age-adjusted prognosis. Survival gains were less in women over the last two decades. Addressing gender differences in heart failure diagnostic and treatment pathways should be a clinical and research priority.

AimTo report disability and visual outcomes following suspected abusive head trauma (AHT) in children under 2 years.MethodsWe present a retrospective case series (1995–2017) of children with suspected AHT aged ≤24 months. King’s Outcome Score of Childhood Head Injury (KOSCHI) was used to assess disability outcomes at hospital discharge and at follow-up. The study used a retinal haemorrhage score (RHS) to record findings at presentation and a visual outcome score at follow-up.ResultsWe included 44 children (median age 16 weeks). At presentation, 98% had a subdural haemorrhage and 93% had a retinal haemorrhage. At discharge, 61% had moderate-to-severe disability, and 34% a good recovery. A higher RHS was observed in those with more disability (r=−0.54, p=0.0002). At follow-up, 14% had a worse KOSCHI score (p=0.055). 35% children had visual impairment, including 9% with no functional vision. Those with poorer visual function had a higher RHS (r=0.53, p=0.003). 28% attended mainstream school without support; 50% were in foster care or had been adopted, 32% lived with birth mother and 18% with extended family.ConclusionIt is known that injuries from suspected AHT result in high levels of morbidity; our cohort showed significant rates of disability and visual impairment. Those with higher disability at discharge and poorer visual function showed more significant retinal changes. The extent of disability was not always apparent at hospital discharge, impacting on provision of prognostic information and targeted follow-up.

ObjectiveValvular heart disease (VHD) is present in half the population aged >65 years but is usually mild and of uncertain importance. We investigated the association between VHD and its phenotypes with all-cause and cause-specific mortality.MethodsThe OxVALVE (Oxford Valvular Heart Disease) population cohort study screened 4009 participants aged >65 years to establish the presence and severity of VHD. We linked data to a national mortality registry and undertook detailed outcome analysis.ResultsMortality data were available for 3511 participants, of whom 361 (10.3%) died (median 6.49 years follow-up). Most had some form of valve abnormality (n=2645, 70.2%). In adjusted analyses, neither mild VHD (prevalence 44.9%) nor clinically significant VHD (moderate or severe stenosis or regurgitation; 5.2%) was associated with increased all-cause mortality (HR 1.20, 95% CI 0.96 to 1.51 and HR 1.47, 95% CI 0.94 to 2.31, respectively). Conversely, advanced aortic sclerosis (prevalence 2.25%) and advanced mitral annular calcification (MAC, 1.31%) were associated with an increased risk of death (HR 2.05, 95% CI 1.28 to 3.30 and HR 2.51, 95% CI 1.41 to 4.49, respectively). Mortality was highest for people with both clinically significant VHD and advanced aortic sclerosis or MAC (HR 4.38, 95% CI 1.99 to 9.67).ConclusionsAdvanced aortic sclerosis or MAC is associated with a worse outcome, particularly for patients with significant VHD, but also in the absence of other VHD. Older patients with mild VHD can be reassured about their prognosis. The absence of an association between significant VHD and mortality may reflect its relatively low prevalence in our cohort.

Background The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. Methods and findings A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%–1.82%) and 0.41% (95% CI, 0.31%–0.53%) for 70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations., Nicole Lowres and colleagues report on stroke risk in people with atrial fibrillation detected by screening., Author summary Why was this study done? Atrial fibrillation is a common heart rhythm problem that often has no symptoms, so people are unaware they have this condition. People with atrial fibrillation can have a very high stroke risk if they are not appropriately treated with anticoagulant medications, and this risk increases with age. Screening for atrial fibrillation is recommended in many guidelines, although the precise age distribution and calculated stroke risk of atrial fibrillation detected by screening is not known. Accurate age-specific data are required for cost-effectiveness analysis, to inform the most appropriate age cutoff for screening based on the age distribution of the population to be screened. What did the researchers do and find? Investigators from 19 atrial fibrillation screening studies across the world agreed to collaborate and share patient-level data, providing a combined database of 141,220 people screened and 1,539 screen-detected cases of atrial fibrillation. Our study was able to quantify the yield and stroke risk for atrial fibrillation in 5-year age brackets, showing the exact relationship of how the yield of screening and stroke risk of screen-detected atrial fibrillation increases with age. The yield of screening was not influenced by the screening method used or the recruitment setting, indicating that screening programs can be established based on available resources. To our knowledge, this is the first study to demonstrate the precise relationship of the number that need to be screened to identify one new atrial fibrillation case, or one new atrial fibrillation case in whom anticoagulant treatment is guideline recommended, in 5-year age brackets. What do these findings mean? This study demonstrates the high calculated stroke risk of screen-detected AF and the high proportion with at least one additional stroke risk factor other than age or sex. These data allow for accurate simulations of cost-effectiveness of screening, including sensitivity analyses, based on the age distribution of the population to be screened. Ultimately, these data may be used to assist development of health policy around the development of atrial fibrillation screening programs, tailored to the specific health system and resources available.

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.

BackgroundCare home residents have venous thromboembolism (VTE) risk profiles similar to medical inpatients; however, the epidemiology of VTE in care homes is unclear.AimTo determine the incidence of VTE in care homes.Design and settingObservational cohort study of 45 care homes in Birmingham and Oxford, UK.MethodA consecutive sample of care home residents was enrolled and followed up for 12 months. Data were collected via case note reviews of care home and GP records; mortality information was supplemented with Health and Social Care Information Centre (now called NHS Digital) cause of death data. All potential VTE events were adjudicated by an independent committee according to three measures of diagnostic certainty: definite VTE (radiological evidence), probable VTE (high clinical indication but no radiological evidence), or possible VTE (VTE cannot be ruled out). (Study registration number: ISTCTN80889792.)ResultsThere were 1011 participants enrolled, and the mean follow-up period was 312 days (standard deviation 98 days). The incidence rate was 0.71 per 100 person years of observation (95% confidence interval [CI] = 0.26 to 1.54) for definite VTE, 0.83 per 100 person years (95% CI = 0.33 to 1.70) for definite and probable VTE, and 2.48 per 100 person years (95% CI = 1.53 to 3.79) for definite, probable, and possible VTE.ConclusionThe incidence of VTE in care homes in this study (0.71–2.48 per 100 person years) is substantial compared with that in the community (0.117 per 100 person years) and in people aged ≥70 years (0.44 per 100 person years). Further research regarding risk stratification and VTE prophylaxis in this population is needed.

BackgroundSymptoms of breathlessness, fatigue, and ankle swelling are common in general practice but deciding which patients are likely to have heart failure is challenging.AimTo evaluate the performance of a clinical decision rule (CDR), with or without N-Terminal pro-B type natriuretic peptide (NT-proBNP) assay, for identifying heart failure.Design and settingProspective, observational, diagnostic validation study of patients aged >55 years, presenting with shortness of breath, lethargy, or ankle oedema, from 28 general practices in England.MethodThe outcome was test performance of the CDR and natriuretic peptide test in determining a diagnosis of heart failure. The reference standard was an expert consensus panel of three cardiologists.ResultsThree hundred and four participants were recruited, with 104 (34.2%; 95% confidence interval [CI] = 28.9 to 39.8) having a confirmed diagnosis of heart failure. The CDR+NT-proBNP had a sensitivity of 90.4% (95% CI = 83.0 to 95.3) and specificity 45.5% (95% CI = 38.5 to 52.7). NT-proBNP level alone with a cut-off ConclusionAt the low threshold of NT-proBNP

BACKGROUND Both the 13- and 10-valent pneumococcal conjugate vaccines (PCV-13; PCV-10) are immunogenic and effective against vaccine-type pneumococcal disease when given to young children. However, limited data are available regarding the interchangeability of these 2 vaccines. METHODS UK children (n = 178) who had previously been vaccinated with PCV-13 at 2 and 4 months were randomized to receive either a PCV-13 or a PCV-10 booster at 12 months of age. PCV-13 vaccine-type antipolysaccharide serum immunoglobulin G (IgG) concentrations and opsonophagocytic assay titers were measured before and at 1 and 12 months following vaccination. The primary objective was to assess noninferiority of PCV-10 compared with PCV-13. RESULTS For 8 of the PCV-10 serotypes at least 97% of participants in both groups had IgG concentrations ≥0.35 µg/mL at 1 month after vaccination; inferior responses were seen for serotypes 5 and 9V following the PCV-10 compared with the PCV-13 booster. Post booster geometric mean IgG concentrations and opsonophagocytic assay titers were significantly superior for most serotypes in PCV-13 compared with PCV-10 recipients, whereas similar or inferior responses were seen for serotypes 4, 18C, and 19F. Although some increase in antibody was seen in PCV-10 recipients against the serotypes 6A and 19A (serotypes that cross-react with 6B and 19F in PCV-10, respectively) at 1-month post booster, these responses were significantly lower than in the PCV-13 group. CONCLUSIONS In PCV-13 primed infants, a PCV-10 booster is generally less immunogenic than a PCV-13 booster. For the 3 serotypes in PCV-10 with higher antigen content and/or conjugation to diphtheria or tetanus toxoid carrier proteins, higher or similar booster responses were seen in PCV-10 recipients. Although these findings suggest that responses are generally better with a PCV-13 booster among PCV-13 primed children, the clinical significance of these differences in immunogenicity is unclear.

Objectives To report reliable estimates of short term and long term survival rates for people with a diagnosis of heart failure and to assess trends over time by year of diagnosis, hospital admission, and socioeconomic group. Design Population based cohort study. Setting Primary care, United Kingdom. Participants Primary care data for 55 959 patients aged 45 and over with a new diagnosis of heart failure and 278 679 age and sex matched controls in the Clinical Practice Research Datalink from 1 January 2000 to 31 December 2017 and linked to inpatient Hospital Episode Statistics and Office for National Statistics mortality data. Main outcome measures Survival rates at one, five, and 10 years and cause of death for people with and without heart failure; and temporal trends in survival by year of diagnosis, hospital admission, and socioeconomic group. Results Overall, one, five, and 10 year survival rates increased by 6.6% (from 74.2% in 2000 to 80.8% in 2016), 7.2% (from 41.0% in 2000 to 48.2% in 2012), and 6.4% (from 19.8% in 2000 to 26.2% in 2007), respectively. There were 30 906 deaths in the heart failure group over the study period. Heart failure was listed on the death certificate in 13 093 (42.4%) of these patients, and in 2237 (7.2%) it was the primary cause of death. Improvement in survival was greater for patients not requiring admission to hospital around the time of diagnosis (median difference 2.4 years; 5.3 v 2.9 years, Pv 4.1 years, P Conclusions Survival after a diagnosis of heart failure has shown only modest improvement in the 21st century and lags behind other serious conditions, such as cancer. New strategies to achieve timely diagnosis and treatment initiation in primary care for all socioeconomic groups should be a priority for future research and policy.

BACKGROUND: Detection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital. DESIGN: A decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care. METHODS: Data from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective. RESULTS: The current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4400 per quality adjusted life year (QALY) gained compared to a "do nothing" strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥400pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses. CONCLUSIONS: This represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.

BACKGROUND: Care home residents with stroke-related disabilities have significant activity limitations. Phase II trial results suggested a potential benefit of occupational therapy (OT) in maintaining residents' capacity to engage in functional activity. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of a targeted course of OT in maintaining functional activity and reducing further health risks from inactivity for UK care home residents living with stroke-related disabilities. DESIGN: Pragmatic, parallel-group, cluster randomised controlled trial with economic evaluation. Cluster randomisation occurred at the care-home level. Homes were stratified according to trial administrative centre and type of care provided (nursing or residential), and they were randomised 1 : 1 to either the intervention or the control arm. SETTING: The setting was 228 care homes which were local to 11 trial administrative centres across England and Wales. PARTICIPANTS: Care home residents with a history of stroke or transient ischaemic attack, including residents with communication and cognitive impairments, not receiving end-of-life care. INTERVENTION: Personalised 3-month course of OT delivered by qualified therapists. Care workers participated in training workshops to support personal activities of daily living. The control condition consisted of usual care for residents. MAIN OUTCOME MEASURES: Outcome data were collected by a blinded assessor. The primary outcome at the participant level was the Barthel Index of Activities of Daily Living (BI) score at 3 months. The secondary outcomes included BI scores at 6 and 12 months post randomisation, and the Rivermead Mobility Index, Geriatric Depression Scale-15 and European Quality of Life-5 Dimensions, three levels, questionnaire scores at all time points. Economic evaluation examined the incremental cost per quality-adjusted life-year (QALY) gain. Costs were estimated from the perspective of the NHS and Personal Social Services. RESULTS: Overall, 568 residents from 114 care homes were allocated to the intervention arm and 474 residents from another 114 care homes were allocated to the control arm, giving a total of 1042 participants. Randomisation occurred between May 2010 and March 2012. The mean age of participants was 82.9 years, and 665 (64%) were female. No adverse events attributable to the intervention were recorded. Of the 1042 participants, 870 (83%) were included in the analysis of the primary outcome (intervention, n = 479; control, n = 391). The primary outcome showed no significant differences between groups. The adjusted mean difference in the BI score between groups was 0.19 points higher in the intervention arm [95% confidence interval (CI) -0.33 to 0.70, p = 0.48; adjusted intracluster correlation coefficient 0.09]. Secondary outcome measures showed no significant differences at all time points. Mean incremental cost of the Occupational Therapy intervention for residents with stroke living in UK Care Homes intervention was £438.78 (95% CI -£3360.89 to £1238.46) and the incremental QALY gain was 0.009 (95% CI -0.030 to 0.048). LIMITATIONS: A large proportion of participants with very severe activity-based limitations and cognitive impairment may have limited capacity to engage in therapy. CONCLUSION: A 3-month individualised course of OT showed no benefit in maintaining functional activity in an older care home population with stroke-related disabilities. FUTURE WORK: There is an urgent need to reduce health-related complications caused by inactivity and to provide an enabling built environment within care homes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00757750. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 15. See the Health Technology Assessment programme website for further project information.

Aim: To develop age-, sex-, and ethnic-Appropriate normative reference ranges for standard echocardiographic measurements of the left heart by combining echocardiographic measurements obtained from adult volunteers without clinical cardiovascular disease or significant cardiovascular risk factors, from multiple studies around the world.Methods and results: The Echocardiographic Normal Ranges Meta-Analysis of the Left heart (EchoNoRMAL) collaboration was established and population-based data sets of echocardiographic measurements combined to perform an individual person data meta-Analysis. Data from 43 studies were received, representing 51 222 subjects, of which 22 404 adults aged 18-80 years were without clinical cardiovascular or renal disease, hypertension or diabetes. Quantile regression or an appropriate parametric regression method will be used to derive reference values at the 5th and 95th centile of each measurement against age. Conclusion: This unique data set represents a large, multi-ethnic cohort of subjects resident in a wide range of countries. The resultant reference ranges will have wide applicability for normative data based on age, sex, and ethnicity. © The Author 2013.

The role of CD19 + CD5 + and CD19 + CD5 − B cell subpopulations in the antibody response to pneumococcal capsular polysaccharides (caps-PSs) is controversial. In the present study, we evaluated the role of human CD19 + CD5 + and CD19 + CD5 − cell populations in the serotype-specific antibody response to caps-PS. After vaccination of 5 healthy human adults with Pneumovax (23-valent pneumococcal polysaccharide vaccine [PPV23]), IgG anti-caps-PS serotype 4 antibody-producing cells resided mainly in the CD19 + CD5 − B cell subset, as assessed by enzyme-linked immunosorbent spot (ELISpot) analysis. Moreover, in a humanized SCID mouse model, CD19 + CD5 − B cells were more effective than CD19 + CD5 + cells in producing IgG anti-cap-PS antibodies. Finally, an association was found between the level of IgG anti-caps-PS antibodies and the number of CD19 + CD5 − B cells in 33 humans vaccinated with PPV23. Taken together, our data suggest that CD5 defines a functionally distinct population of B cells in humans in the anti-caps-PS immune response.

Background: Infants in the UK were first offered a pneumococcal conjugate vaccine (PCV7) in 2006, given at 2 and 4 months of age and a booster dose at 13 months (2 + 1 schedule). A 13-valent vaccine (PCV13) replaced PCV7 in 2010. We aimed to compare the post-booster antibody response in UK infants given a reduced priming schedule of PCV13 (ie, a 1 + 1 schedule) versus the current 2 + 1 schedule and to assess the potential effect on population protection. Methods: In this multicentre, parallel group, randomised controlled trial, we recuited infants due to receive their primary immunisations aged up to 13 weeks on first vaccinations by information booklets mailed out via the NHS Child Health Information Service and the UK National Health Application and Infrastructure Services. Eligible infants were randomly assigned (1:1) to receive PCV13 at 2, 4, and 12 months (2 + 1 schedule) or 3 and 12 months of age (1 + 1 schedule) delivered with other routine vaccinations. Randomisation was done by computer-generated permuted block randomisation, with a block size of six. Participants and clinical trial staff were not masked to treatment allocation. The primary endpoint was serotype-specific immunoglobulin G concentrations values (geometric mean concentrations [GMC] in μg/mL) measured in blood samples collected at 13 months of age. Analysis was by modified intention to treat with all individuals included by randomised group if they had a laboratory result. This trial is registered on the EudraCT clinical trial database, number 2015-000817-32, and ClinicalTrials.gov, number NCT02482636. Findings: Between September, 2015, and June, 2016, 376 infants were assessed for eligibility. 81 infants were excluded for not meeting the inclusion criteria (n=50) or for other reasons (n=31). 213 eligible infants were enrolled and randomly allocated to group 1 (n=106; 2 + 1 schedule) or to group 2 (n=107; 1 + 1 schedule). In group 1, 91 serum samples were available for analysis 1 month after booster immunisation versus 86 in group 2. At month 13, post-booster, GMCs were equivalent between schedules for serotypes 3 (0·61 μg/mL in group 1 vs 0·62 μg/mL in group 2), 5 (1·74 μg/mL vs 2·11 μg/mL), 7F (3·98 μg/mL vs 3·36 μg/mL), 9V (2·34 μg/mL vs 2·50 μg/mL), and 19A (8·38 μg/mL vs 8·83 μg/mL). Infants given the 1 + 1 schedule had significantly greater immunogenicity post-booster than those given the 2 + 1 schedule for serotypes 1 (8·92 μg/mL vs 3·07 μg/mL), 4 (3·43 μg/mL vs 2·55 μg/mL), 14 (16·9 μg/mL vs 10·49 μg/mL), and 19F (14·76 μg/mL vs 11·12 μg/mL; adjusted p value range Interpretation: Our findings show that for nine of the 13 serotypes in PCV13, post-booster responses in infants primed with a single dose are equivalent or superior to those seen following the standard UK 2 + 1 schedule. Introducing a 1 + 1 schedule in countries with a mature PCV programme and established herd immunity is likely to maintain population control of vaccine-type pneumococcal disease.

© 2017 Jowett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 subgroups ranging from dominance to up to £18,811 per QALY depending on patient subgroup. 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.

Background Although both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) are widely used, it is unclear how interchangeable they are in terms of immunogenicity. Methods Two phase 3, open-label, multicenter studies were conducted to assess the immunogenicity and safety of a booster dose of PCV13 in children primed with PHiD-CV or PCV13. In the Czech Republic, 12–15-month-old children received a PCV13 booster after 3-dose priming with either PHiD-CV or PCV13. In Slovakia, 11–12-month-old children received PCV13 following 2-dose priming with either PHiD-CV or PCV13. Serum IgG concentrations were assessed by enzyme-linked immunosorbent assay and functional antibodies were assessed by opsonophagocytic assay (OPA) before the booster and at 1 and 12 months afterward. The primary objective of these studies was to assess non-inferiority of OPA titers for serotype 19A in PHiD-CV-primed subjects compared to those in PCV13-primed children 1 month post-booster. Results A total of 98 subjects in the Czech Republic and 89 subjects in Slovakia were included. One month after the PCV13 booster dose, the IgG and OPA immune responses to serotype 19A in subjects primed with 2 or 3 doses of PHiD-CV were non-inferior to those in subjects primed with PCV13. Non-inferior and persistent immune responses to most other vaccine serotypes were also observed after the PCV13 booster in PHiD-CV-primed subjects. No safety issues were raised in either study. Conclusions Overall, robust IgG and OPA immunological responses were observed after booster vaccination with PCV13 in children primed with 2 or 3 doses of PHiD-CV or PCV13, including for serotypes not included in PHiD-CV. These results suggest that these vaccines are interchangeable in terms of safety and immunogenicity and that PCV13 can be used as a booster in the context of mixed schedules. (EudraCT numbers: 2012-005366-35 and 2012-005367-27).

Background It is not known whether infants exposed to intermittent maternal fasting at conception are born smaller or have a higher risk of premature birth than those who are not. Doctors are therefore unsure about what advice to give women about the safety of Ramadan fasting. This cohort study aimed to investigate these questions in Muslim mother–infant pairs to inform prenatal care. Methods Routinely collected data accessed from maternity records were the source for information. Mothers were considered exposed if they were Muslim and Ramadan overlapped with their infant conception date, estimated to be 14 days after the last menstrual period. Infants were included as exposed if their estimated conception date was in the first 21 days of Ramadan or 7 days prior to Ramadan. Results After adjusting for gestational age, maternal age, infant gender, maternal body mass index at booking, smoking status, gestational diabetes, parity and year of birth, there was no significant difference in birth weight between infants born to Muslim mothers who were conceived during Ramadan (n=479) and those who were not (n=4677) (adjusted mean difference =24.3 g, 95% CI −16.4 to 64.9). There was no difference in rates of premature births in exposed and unexposed women (5.2% vs 4.9%; OR=1.08, 95% CI 0.71 to 1.65). Conclusions Healthy Muslim women considering becoming pregnant prior to, or during Ramadan, can be advised that fasting does not seem to have a detrimental effect on the size (weight) of their baby and it appears not to increase the likelihood of giving birth prematurely.

Objective: To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design: Pragmatic, parallel group, cluster randomised controlled trial. Setting: 228 care homes (> 10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants: 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n = 568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n = 474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention: Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures: Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results: 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P = 0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions: This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies. Trial registration Current Controlled Trials ISRCTN00757750

Background Detection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital. Design A decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care. Methods Data from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective. Results The current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4,400 per Quality Adjusted Life Year (QALY) gained compared to a “do nothing” strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥ 400pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses. Conclusions This represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.

© 2017 Asia Oceania Association for the Study of Obesity Background Finding effective referral policies for weight management services would have important public health implications. Aim Here we compare percentage weight change by referral methods, BMI categories and participants who have had attended weight loss programmes multiple times. Design and settings A prospective cohort study of 15,621 participants referred to 12-week behavioural weight loss programmes funded by the public health service in Birmingham, UK. Methods Comparisons were made between GP versus self-referrals, BMI ≥40 kg/m2–

We would like to thank Zito et al for their letter in response to our article.1 We agree that comprehensive geriatric assessment of the study population would have aided interpretation of the study, but note that the randomized nature of the study means that differences between groups in this domain are unlikely to have contributed to the null finding. We agree that there are limitations with the Mini-Mental State Examination and that detailed …

The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist, and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and common colonizers of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analyzed a diverse data set of ∼1,000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analyzed the genetic diversity among serogroup 6 pneumococci, and investigated whether pneumococcal conjugate vaccine-induced serotype 6A and 6B antibodies mediate the killing of serotype 6E pneumococci. We found that 43% of all genomes were of serotype 6E, and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term because of the emergence of serotypes that can evade vaccine-induced immunity.

Objective: To determine the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in screening for and predicting prognosis in heart failure by examining diagnosis and survival of patients with a raised NT-proBNP at screening. Design: Survival analysis. Setting: Prospective substudy of the Echocardiographic Heart of England Screening study (ECHOES) to investigate 10-year survival in participants with an NT-proBNP level at baseline. Participants: 594 participants took part in the substudy. Records of all participants in the ECHOES cohort were flagged during the screening phase which ended on 25 February 1999. All deaths until 25 February 2009 were coded. Outcome measures: Logistic regression was used to examine whether NT-proBNP is useful in predicting heart failure at screening after adjustment for age, sex and cohort. Kaplan-Meier curves and log rank tests were used to compare survival times of participants according to NT-proBNP level. Cox regression was carried out to assess the prognostic effect of NT-proBNP after allowing for significant covariates and receiver operator curves were used to determine test reliability. Results: The risk of heart failure increased almost 18-fold when NT-proBNP was 150 pg/mL or above (adjusted OR=17.7, 95% CI 4.9 to 63.5). 10-year survival in the general population cohort was 61% (95% CI 48% to 71%) for those with NT-proBNP ≥150 pg/mL and 89% (95% CI 84% to 92%) for those below the cut-off at the time of the initial study. After adjustment for age, sex and risk factors for heart failure, NT-proBNP level ≥150 pg/mL was associated with a 58% increase in the risk of death within 10 years (adjusted HR=1.58, 95% CI 1.09 to 2.30). Conclusions: Raised NT-proBNP levels, when screening the general population, are predictive of a diagnosis of heart failure (at a lower threshold than guidelines for diagnosing symptomatic patients) and also predicted reduced survival at 10 years.

Context: Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment. Objective: The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. Design, Setting, and Participants: A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom. Exclusions: Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. Outcome Measure: Tests of thyroid function (TSH concentration and free T 4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. Explanatory Variables: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004) Analysis: Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction Results: A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained. Conclusions: Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population. Copyright © 2006 by The Endocrine Society.

Objectives: Rescreen a large community cohort to examine the progression to heart failure over time and the role of natriuretic peptide testing in screening. Design: Observational longitudinal cohort study. Setting: 16 socioeconomically diverse practices in central England. Participants: Participants from the original Echocardiographic Heart of England Screening (ECHOES) study were invited to attend for rescreening. Outcome measures: Prevalence of heart failure at rescreening overall and for each original ECHOES subgroup. Test performance of N Terminal pro-B-type Natriuretic Peptide (NT-proBNP) levels at different thresholds for screening. Results: 1618 of 3408 participants underwent screening which represented 47% of survivors and 26% of the original ECHOES cohort. A total of 176 (11%, 95% CI 9.4% to 12.5%) participants were classified as having heart failure at rescreening; 103 had heart failure with reduced ejection fraction (HFREF) and 73 had heart failure with preserved ejection fraction (HFPEF). Sixty-eight out of 1232 (5.5%, 95% CI 4.3% to 6.9%) participants who were recruited from the general population over the age of 45 and did not have heart failure in the original study, had heart failure on rescreening. An NT-proBNP cut-off of 400 pg/mL had sensitivity for a diagnosis of heart failure of 79.5% (95% CI 72.4% to 85.5%) and specificity of 87% (95% CI 85.1% to 88.8%). Conclusions: Rescreening identified new cases of HFREF and HFPEF. Progression to heart failure poses a significant threat over time. The natriuretic peptide cut-off level for ruling out heart failure must be low enough to ensure cases are not missed at screening.

Objectives: To assess the accuracy in diagnosing heart failure of clinical features and potential primary care investigations, and to perform a decision analysis to test the impact of plausible diagnostic strategies on costs and diagnostic yield in the UK health-care setting. Data sources: MEDLINE and CINAHL were searched from inception to 7 July 2006. 'Grey literature' databases and conference proceedings were searched and authors of relevant studies contacted for data that could not be extracted from the published papers. Review methods: A systematic review of the clinical evidence was carried out according to standard methods. Individual patient data (IPD) analysis was performed on nine studies, and a logistic regression model to predict heart failure was developed on one of the data sets and validated on the other data sets. Cost-effectiveness modelling was based on a decision tree that compared different plausible investigation strategies. Results: Dyspnoea was the only symptom or sign with high sensitivity (89%), but it had poor specificity (51 %). Clinical features with relatively high specificity included history of myocardial infarction (89%), orthopnoea (89%), oedema (72%), elevated jugular venous pressure (70%), cardiomegaly (85%), added heart sounds (99%), lung crepitations (81%) and hepatomegaly (97%). However, the sensitivity of these features was low, ranging from 11% (added heart sounds) to 53% (oedema). Electrocardiography (ECG), B-type natriuretic peptides (BNP) and N-terminal proB-type natriuretic peptides (NT-proBNP) all had high sensitivities (89%, 93% and 93% respectively). Chest X-ray was moderately specific (76-83%) but insensitive (67-68%). BNP was more accurate than ECG, with a relative diagnostic odds ratio of ECG/BNP of 0.32 (95% CI 0.12-0.87). There was no difference between the diagnostic accuracy of BNP and NT-proBNP. A model based upon simple clinical features and BNP derived from one data set was found to have good validity when applied to other data sets. A model substituting ECG for BNP was less predictive. From this a simple clinical rule was developed: in a patient presenting with symptoms such as breathlessness in whom heart failure is suspected, refer directly to echocardiography if the patient has a history of myocardial infarction or basal crepitations or is a male with ankle oedema; otherwise, carry out a BNP test and refer for echocardiography depending on the results of the test. On the basis of the cost-effectiveness analysis carried out, such a decision rule is likely to be considered cost-effective to the NHS in terms of cost per additional case detected. The cost-effectiveness analysis further suggested that, if likely benefit to the patient in terms of improved life expectancy is taken into account, the optimum strategy would be to refer all patients with symptoms suggestive of heart failure directly for echocardiography. Conclusions: The analysis suggests the need for important changes to the NICE recommendations. First, BNP (or NT-proBNP) should be recommended over ECG and, second, some patients should be referred straight for echocardiography without undergoing any preliminary investigation. Future work should include evaluation of the clinical rule described above in clinical practice. © 2009 Queen's Printer and Controller of HMSO. All rights reserved.

BACKGROUND: The PAST-BP trial found that using a lower systolic blood pressure target (

Aims Diagnosis of heart failure in primary care is often inaccurate, and access to and use of echocardiography is suboptimal. This study aimed to develop and provisionally validate a clinical prediction rule to optimize referral for echocardiography of people identified in primary care with suspected heart failure. Methods and resultsA systematic review identified studies of diagnosis of heart failure set in primary care. The individual patient data for five of these studies were obtained. Logistic regression models to predict heart failure were developed on one of the data sets and validated on the others using area under the receiver operating characteristic curve (AUROC), and goodness-of-fit calibration plots. A model based upon four simple clinical features (Male, history of myocardial Infarction, Crepitations, Edema: MICE) and natriuretic peptide had good validity when applied to other data sets, with AUROCs between 0.84 and 0.93, and reasonable calibration. The rule performed well across the data sets, with sensitivity between 81 and 96 and specificity between 57 and 74. ConclusionsA simple clinical rule based upon gender, history of myocardial infarction, presence of ankle oedema, and presence of basal lung crepitations can discriminate between people with suspected heart failure who should be referred straight for echocardiography and people for whom referral should depend upon the result of a natriuretic peptide test. Prospective validation and an implementation evaluation of the rule is now warranted. © 2012 The Author.

BACKGROUND: Colorectal cancer (CRC) is a major cause of death in the United Kingdom. Regular screening could significantly reduce CRC-related morbidity and mortality. However, screening programmes in the United Kingdom have to date seen uptake rates of less than 60%. Attitudes towards screening are the primary factors determining patient uptake. METHODS: A questionnaire was sent to people aged 50-69 years who were registered with general practices in the West Midlands. A total of 11 355 people (53%) completed the questionnaire. Multivariable logistic regression analyses were performed to identify those factors (gender, age, ethnicity, deprivation, number of symptoms, and their duration) that most strongly contributed to negative/positive attitudes in the primary care population. RESULTS: Fourteen percent of respondents had a negative attitude towards screening. Men, older people, and those with Indian ethnic backgrounds were more likely to have negative attitudes toward screening, whereas people with Black-Caribbean ethnic background, people with multiple symptoms and those reporting abdominal pain, bleeding, and tiredness were more likely to have a positive attitude. CONCLUSION: Culturally relevant screening strategies should aim to increase knowledge of the symptoms and signs related to bowel cancer among South Asian ethnic groups in the United Kingdom. It is also important to find ways to increase the acceptability of screening among asymptomatic patients.

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 (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

BackgroundCare home residents with stroke-related disabilities have significant activity limitations. Phase II trial results suggested a potential benefit of occupational therapy (OT) in maintaining residents’ capacity to engage in functional activity.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of a targeted course of OT in maintaining functional activity and reducing further health risks from inactivity for UK care home residents living with stroke-related disabilities.DesignPragmatic, parallel-group, cluster randomised controlled trial with economic evaluation. Cluster randomisation occurred at the care-home level. Homes were stratified according to trial administrative centre and type of care provided (nursing or residential), and they were randomised 1 : 1 to either the intervention or the control arm.SettingThe setting was 228 care homes which were local to 11 trial administrative centres across England and Wales.ParticipantsCare home residents with a history of stroke or transient ischaemic attack, including residents with communication and cognitive impairments, not receiving end-of-life care.InterventionPersonalised 3-month course of OT delivered by qualified therapists. Care workers participated in training workshops to support personal activities of daily living. The control condition consisted of usual care for residents.Main outcome measuresOutcome data were collected by a blinded assessor. The primary outcome at the participant level was the Barthel Index of Activities of Daily Living (BI) score at 3 months. The secondary outcomes included BI scores at 6 and 12 months post randomisation, and the Rivermead Mobility Index, Geriatric Depression Scale-15 and European Quality of Life-5 Dimensions, three levels, questionnaire scores at all time points. Economic evaluation examined the incremental cost per quality-adjusted life-year (QALY) gain. Costs were estimated from the perspective of the NHS and Personal Social Services.ResultsOverall, 568 residents from 114 care homes were allocated to the intervention arm and 474 residents from another 114 care homes were allocated to the control arm, giving a total of 1042 participants. Randomisation occurred between May 2010 and March 2012. The mean age of participants was 82.9 years, and 665 (64%) were female. No adverse events attributable to the intervention were recorded. Of the 1042 participants, 870 (83%) were included in the analysis of the primary outcome (intervention,n = 479; control,n = 391). The primary outcome showed no significant differences between groups. The adjusted mean difference in the BI score between groups was 0.19 points higher in the intervention arm [95% confidence interval (CI) –0.33 to 0.70,p = 0.48; adjusted intracluster correlation coefficient 0.09]. Secondary outcome measures showed no significant differences at all time points. Mean incremental cost of the Occupational Therapy intervention for residents with stroke living in UK Care Homes intervention was £438.78 (95% CI –£3360.89 to £1238.46) and the incremental QALY gain was 0.009 (95% CI –0.030 to 0.048).LimitationsA large proportion of participants with very severe activity-based limitations and cognitive impairment may have limited capacity to engage in therapy.ConclusionA 3-month individualised course of OT showed no benefit in maintaining functional activity in an older care home population with stroke-related disabilities.Future workThere is an urgent need to reduce health-related complications caused by inactivity and to provide an enabling built environment within care homes.Trial registrationCurrent Controlled Trials ISRCTN00757750.FundingThis project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 15. See the Health Technology Assessment programme website for further project information.

Summary 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.

Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients ( n = 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [ r ] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group ( r = −0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes ( r = 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients.

The pneumococcus is a leading pathogen infecting children and adults. Safe, effective vaccines exist and they work by inducing antibodies to the polysaccharide capsule (unique for each serotype) that surrounds the cell; however, current vaccines are limited by the fact that only a few of the nearly 100 antigenically-distinct serotypes are included in the formulations. Within the serotypes, serogroup 6 pneumococci are a frequent cause of serious disease and a common coloniser of the nasopharynx in children. Serotype 6E was first reported in 2004 but was thought to be rare; however, we and others have detected serotype 6E among recent pneumococcal collections. Therefore, we analysed a diverse dataset of ∼1000 serogroup 6 genomes, assessed the prevalence and distribution of serotype 6E, analysed the genetic diversity among serogroup 6 pneumococci and investigated whether pneumococcal conjugate vaccine (PCV)-induced serotype 6A and 6B antibodies mediated the killing of serotype 6E pneumococci. We found that 43% of all genomes were serotype 6E and they were recovered worldwide from healthy children and patients of all ages with pneumococcal disease. Four genetic lineages, three of which were multidrug-resistant, described ∼90% of the serotype 6E pneumococci. Serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to elicit killing of serotype 6E pneumococci. We also revealed three major genetic clusters of serotype 6A capsular sequences, discovered a new hybrid 6C/6E serotype, and identified 44 examples of serotype switching. Therefore, while vaccines appear to offer protection against serotype 6E, genetic variants may reduce vaccine efficacy in the longer term due to the emergence of serotypes that can evade vaccine-induced immunity. IMPORTANCE: A key virulence factor for the pneumococcus is the polysaccharide capsule, which is also the target for vaccine-mediated protection. Within serogroup 6 there are eight different types, the most common of which were thought to be serotypes 6A, 6B and 6C. Our study characterised ~1000 serogroup 6 pneumococcal genomes and the data showed that serotype 6E, previously thought to be rare, was the predominant serotype. Earlier detection of serotype 6E pneumococci was obscured because they cross-react to the serotype 6B antisera used in the traditional serotyping assay, and it was only by inspection of the capsular locus sequences that the high prevalence and global distribution of serotype 6E was realised. Fortunately, vaccine-induced antibodies elicited killing of serotype 6E pneumococci; however, we also revealed considerable nucleotide sequence variation among serogroup 6 and thus ongoing genome sequence-based surveillance is essential.

Background Smoking increases the risk of developing type 2 diabetes. However, several population studies also show a higher risk in people 3–5 years after smoking cessation than in continuing smokers. After 10–12 years the risk equates to that of never-smokers. Small cohort studies suggest diabetes control deteriorates temporarily during the first year after quitting. We examined whether or not quitting smoking was associated with altered diabetes control in a population study, for how long this association persisted, and whether or not this association was mediated by weight change. Methods We did a retrospective cohort study (Jan 1, 2005, to Dec 31, 2010) of adult smokers with type 2 diabetes using The Health Improvement Network (THIN), a large UK primary care database. We developed adjusted multilevel regression models to investigate the association between a quit event, smoking abstinence duration, change in HbA1c, and the mediating effect of weight change. Findings 10 692 adult smokers with type 2 diabetes were included. 3131 (29%) quit smoking and remained abstinent for at least 1 year. After adjustment for potential confounders, HbA1c increased by 0·21% (95% CI 0·17–0·25; p Interpretation In type 2 diabetes, smoking cessation is associated with deterioration in glycaemic control that lasts for 3 years and is unrelated to weight gain. At a population level, this temporary rise could increase microvascular complications.

BACKGROUND: Although obesity causes many adverse health consequences, modest weight loss reduces the incidence. There are effective interventions that help people to lose weight but weight regain is common and long term maintenance remains a critical challenge. As a high proportion of the population of most high and middle income countries are overweight, there are many people who would benefit from weight loss and its maintenance. Therefore, we need to find effective low cost scalable interventions to help people achieve this. One such intervention that has shown promise is regular self-weighing, to check progress against a target, however there is no trial that has tested this using a randomised controlled design (RCT). The aim of this RCT is to evaluate the effectiveness and cost effectiveness of a brief behavioural intervention delivered by non-specialist staff to promote regular self-weighing to prevent weight regain after intentional weight loss.METHODS: A randomised trial of 560 adults who have lost ≥ 5 % of their initial body weight through a 12 week weight loss programme. The comparator group receive a weight maintenance leaflet, a diagram representing healthy diet composition, and a list of websites for weight control. The intervention group receive the same plus minimally trained telephonists will ask participants to set a weight target and encourage them to weigh themselves daily, and provide support materials such as a weight record card. The primary outcome is the difference between groups in weight change from baseline to 12 months.DISCUSSION: If effective, this study will provide public health agencies with a simple, low cost maintenance intervention that could be implemented immediately.TRIAL REGISTRATION: ISRCTN52341938 Date Registered: 31/03/2014.

Streptococcus pneumoniaeserotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3S. pneumoniaeserotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%,P< 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P< 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

OBJECTIVE. We conducted a proof-of-concept, randomized, controlled trial to investigate the effects of a supervised exercise therapy intervention on psychopathologic outcomes in obese adolescents. METHODS. The participant sample consisted of 81 adolescents (age: 11–16 years) who had been referred to a children's hospital for evaluation of obesity or who responded to a community advertisement. Participants were assigned randomly to exercise therapy, an equal-contact exercise placebo intervention, or usual care. Intervention participants attended 3 one-on-one sessions per week for 8 weeks and then completed a home program for another 6 weeks. Outcomes included self-perceptions (self-esteem), depression, affect, physical activity, aerobic fitness, and BMI. RESULTS. A total of 18 of 81 participants were categorized as morbidly obese (BMI SD score: >3.5; adult equivalent BMI: ≥40). At baseline, 30.3% of participants had a Children's Depression Inventory score of ≥13, and 27% reported recent suicidal ideation. Repeated-measures mixed analysis of covariance (controlling for baseline scores) revealed significant changes in physical self-worth, associated measures of self-esteem, and physical activity over time, consistently favoring exercise therapy. There were no significant changes in BMI. CONCLUSIONS. Findings confirmed psychopathologic conditions as a serious health concern in obese and morbidly obese adolescents. Our study is the first randomized, controlled trial to demonstrate that a brief supervised exercise therapy intervention has the potential to improve psychopathologic outcomes significantly and to increase physical activity in obese adolescents, relative to usual care.

To investigate the efficacy of water preloading before meals as a weight loss strategy for adults with obesity.A two-group randomized controlled trial was conducted in Birmingham, England. Eighty-four adults with obesity were recruited from general practices. All participants were given a face-to-face weight management consultation at baseline (30 min) and a follow-up telephone consultation at 2 weeks (10 min). At baseline, participants were randomized to either drinking 500 ml of water 30 min before their main meals or an attention control group where participants were asked to imagine their stomach was full before meals. The primary outcome was weight change at 12-week follow-up. Several measures of adherence were also used, including 24 h total urine collections.41 participants were randomized to the intervention group and 43 to the comparator group. The water preloading group lost -1.3 kg (95% CI -2.4 to -0.1, P = 0.028) more than comparators at follow up. Adjusting for ethnicity, deprivation, age, and gender resulted in the intervention group losing -1.2 kg (95% CI -2.4 to 0.07, P = 0.063) more than the comparator.There is preliminary evidence that water preloading before main meals leads to a moderate weight loss at follow up. ISRCTN33238158.

Background: Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed for people with multiple sclerosis (P wMS). Objective: The objective of this study was to assess the effects of a practically implemented exercise programme on self-directed exercise behaviour and important health outcomes in P wMS to nine months of follow-up. Methods: We conducted a parallel-arm, randomised controlled trial: 120 P wMS (Expanded Disability Status Scale (EDSS) 1.0–6.5) randomised to a three-month exercise intervention plus usual care, or usual care only. Two supervised plus one home-exercise session (weeks 1–6) were followed by one supervised and two home-exercise sessions (weeks 7–12). Cognitive-behavioural techniques promoted long-term exercise behaviour change. Outcomes were blindly assessed at baseline and at three and nine months after randomisation. The primary outcome was self-reported exercise behaviour (Godin Leisure Time Exercise Questionnaire (GLTEQ)). Secondary outcomes included fatigue and health-related quality of life (HRQoL). Results: The intervention increased self-reported exercise (9.6 points; 95% CI: 2.0 to 17.3 points; p = 0.01) and improved fatigue ( p < 0.0001) and many HRQoL domains ( p ≤ 0.03) at three months. The improvements in emotional well-being ( p = 0.01), social function ( p = 0.004) and overall quality of life ( p = 0.001) were sustained for nine months. Conclusion: This pragmatic approach to implementing exercise increases self-reported exercise behaviour, improves fatigue and leads to a sustained enhancement of HRQoL domains in P wMS.

BACKGROUND: Accurate data for prevalence rates for heart failure due to various causes, and for left-ventricular systolic dysfunction in all adults are unavailable. Our aim was to assess prevalence of left-ventricular systolic dysfunction and heart failure in a large representative adult population in England. METHODS: Of 6286 randomly selected patients aged 45 years and older, 3960 (63%) participated in the study. They came from 16 randomly selected general practices. We assessed patients by history and examination, electrocardiography, and echocardiography. Prevalence of left-ventricular systolic dysfunction (defined as ejection fraction

Increasing attention is being given to the role of active commuting to school as a means of promoting active lifestyles in young people. A recent study highlighted that school children who actively commute to school may be at lower risk of being overweight than their inactive counterparts.1 Whilst programmes/ interventions that promote active commuting to school have been implemented,2,3 a paucity of research has related this to objectively determined health outcomes. Most previous studies have focused on primary school children who are potentially less involved in the decision-making process about the mode of transport taken to school compared with adolescents. In addition, children from ethnic minority groups and those living in deprived communities have been under-represented in previous research of this type. This is important as ethnic minority children have been found to be less active and more likely to be overweight/obese than White children.4 This study aimed to document the prevalence of active commuting to/from school in children of different ethnicities living in deprived communities, and to investigate the association between ethnicity, physical activity during the school day, weight status and mode of transportation to school. Two single sex (one boy and one girls) and one mixed sex urban state schools in Birmingham that comprised a high proportion of children from ethnic minority groups without walk-to-school schemes were purposefully recruited. All children aged 11–14 years in each school were invited to participate. Participants were asked to indicate their age and postcode. Ethnicity was determined using questions from the England and Wales 2001 Census. Participants

Background: Exercise is a safe, non-pharmacological adjunctive treatment for people with multiple sclerosis but cost-effective approaches to implementing exercise within health care settings are needed. Objective: The objective of this paper is to assess the cost effectiveness of a pragmatic exercise intervention in conjunction with usual care compared to usual care only in people with mild to moderate multiple sclerosis. Methods: A cost-utility analysis of a pragmatic randomised controlled trial over nine months of follow-up was conducted. A total of 120 people with multiple sclerosis were randomised (1:1) to the intervention or usual care. Exercising participants received 18 supervised and 18 home exercise sessions over 12 weeks. The primary outcome for the cost utility analysis was the incremental cost per quality-adjusted life year (QALY) gained, calculated using utilities measured by the EQ-5D questionnaire. Results: The incremental cost per QALY of the intervention was £10,137 per QALY gained compared to usual care. The probability of being cost effective at a £20,000 per QALY threshold was 0.75, rising to 0.78 at a £30,000 per QALY threshold. Conclusion: The pragmatic exercise intervention is highly likely to be cost effective at current established thresholds, and there is scope for it to be tailored to particular sub-groups of patients or services to reduce its cost impact.

AimsTo establish the prevalence of atrial fibrillation (AF) in the general population in the UK, and in those with risk factors.Methods and resultsThe prevalence of AF on electrocardiography was established in prospectively selected groups: 3960 randomly selected from the population, aged 45; 782 with a previous diagnosis of heart failure; and 1062 with a record of myocardial infarction, hypertension, angina, or diabetes. Patients were also assessed clinically and with echocardiography. Mortality was tracked for 8 years. Atrial fibrillation was found in 78 of the random population sample (2.0). Prevalence was 1.6 in women and 2.4 in men, rising with age from 0.2 in those aged 45-54 to 8.0 in those aged 75 and older. Half of all cases were in patients aged 75 and older. Only 23 of the 78 (29.5) of those in AF took warfarin. Of the 782 patients, 175 (22.4) with a diagnosis of heart failure were in AF, with normal left ventricular function in 95 (54.3) of these. Atrial fibrillation was found in 14 of the 244 (5.7) of those with a history of myocardial infarction, 15 of the 388 (3.9) of those with hypertension, 15 of the 321 (4.7) of those with angina, and 11 of the 208 (5.3) of diabetics. Adjusting for age and sex, mortality was 1.57 times higher for those in AF.ConclusionAtrial fibrillation is common in the elderly and those with clinical risk factors. Screening these groups would identify many with AF. Use of anticoagulation was low at the time of the initial assessments in the late 1990s; practice may have changed recently. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: journals.permissionsoup.com.

There is increased demand for emergency healthcare by the public when abroad. This study aimed to investigate adults' reported level of knowledge about how to contact emergency healthcare services while abroad. A street survey was administered at various times, over several days, to 554 members of the general public who had been abroad in the previous 18 months. Only 33.6% [95% confidence interval (29.6%-37.7%)] of respondents reported that they knew the emergency medical number for the country last visited. This did not differ by sex (34.2% males vs. 33% females). Those fluent in the language of the country last visited were more likely to report knowing the emergency number for that country (54%), compared with those who were not (24.8%) (P

Exercise is an effective intervention for improving function, mobility and health-related quality of life in people with multiple sclerosis (PwMS). Questions remain however, regarding the effectiveness of pragmatic exercise interventions for evoking tangible and sustained increases in physical activity and long-term impact on important health outcomes in PwMS. Furthermore, dose-response relationships between exercise and health outcomes have not previously been reported in PwMS. These issues, and improved knowledge of cost effectiveness, are likely to influence key decisions of health policy makers regarding the implementation of exercise therapy as part of the patient care pathway for PwMS. Hence, the primary aim of this study is to investigate whether a 12-week tapered programme of supervised exercise, incorporating cognitive-behavioural techniques to facilitate sustained behaviour change, is effective for evoking improvements in physical activity and key health outcomes in PwMS over 9 months of follow-up. A total of 120 PwMS will be randomised (1:1) to either a 12-week pragmatic exercise therapy intervention or usual care control group. Participants will be included on the basis of a clinical diagnosis of MS, with an expanded disability status score (EDSS) between 1 and 6.5. Outcome measures, to be assessed before and after the intervention and 6 months later, will include physical activity, clinical and functional measures and health-related quality of life. In addition, the cost effectiveness of the intervention will be evaluated and dose-response relationships between physical activity and the primary/secondary outcomes in those with mild and more severe disease will be explored.

AimsTo 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 resultsThe 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