Outcome of Flow Diverters with Surface Modifications in Treatment of Cerebral Aneurysms: Systematic Review and Meta-analysis.

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.

What factors influence weight loss in participants of commercial weight loss programmes? Implications for health policy.

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 ≥40kg/m2-<40kg/m2 and multiple referrals compared to only one referral. Linear mixed modelling was used to assess percentage weight change after adjusting for covariates. RESULTS: Participant's mean age was 48.5 years, 78.7% were of white ethnicity, 90.3% female and mean baseline BMI was 36.3kg/m2. There were no significant differences in percentage weight loss, between participants that self-referred and those that were referred by their general practitioner (GP) and no significant differences between baseline BMI categories. Referral to a weight loss programme more than once was associated with less weight loss at subsequent attendances (0.92%, 95% CI 0.70-1.14, p<0.001). CONCLUSION: Allowing self-referral to a weight loss programme widens access without compromising amount of weight lost. These programmes are beneficial for all categories of obesity, including those with a BMI ≥40kg/m2. Attending weight management programmes more than once results in less weight loss and that swapping to a different program may be advisable.

Feasibility and acceptability of regular weighing, setting weight gain limits and providing feedback by community midwives to prevent excess weight gain during pregnancy: randomised controlled trial and qualitative study.

BACKGROUND: Regular weighing in pregnant women is not currently recommended in many countries but has been suggested to prevent excessive gestational weight gain. This study aimed to establish the feasibility and acceptability of incorporating regular weighing, setting maximum weight gain targets and feedback by community midwives. METHODS: Low risk pregnant women cared for by eight community midwives were randomised to usual care or usual care plus the intervention at 10-14 weeks of pregnancy. The intervention involved community midwives weighing and plotting weight on a weight gain chart, setting weight gain limit targets, giving brief feedback at each antenatal appointment and encouraging women to weigh themselves weekly between antenatal appointments. Women and midwives were interviewed about their views of the intervention. The focus of the study was on process evaluation. RESULTS: Community midwives referred 123 women and 115 were scheduled for their dating scan within the study period. Of these, 84/115 were approached at their dating scan and 76/84 (90.5 %) randomised. Data showed a modest difference favouring the intervention group in the percentage of women gaining excessive gestational weight (23.5 % versus 29.4 %). The intervention group consistently reported smaller increases in depression and anxiety scores throughout pregnancy compared with usual care. Most women commented the intervention was useful in encouraging them to think about their weight and believed it should be part of routine antenatal care. Community midwives felt the intervention could be implemented within routine care without adding substantially to consultation length, thus not perceived as adding substantially to their workload. CONCLUSIONS: The intervention was feasible and acceptable to pregnant women and community midwives and was readily implemented in routine care. TRIAL REGISTRATION: ISRCTN81605162.

A pragmatic randomized controlled trial to evaluate the effectiveness of a facilitated exercise intervention as a treatment for postnatal depression: the PAM-PeRS trial.

BACKGROUND: Postnatal depression affects about 10-15% of women in the year after giving birth. Many women and healthcare professionals would like an effective and accessible non-pharmacological treatment for postnatal depression. METHOD: Women who fulfilled the International Classification of Diseases (ICD)-10 criteria for major depression in the first 6 months postnatally were randomized to receive usual care plus a facilitated exercise intervention or usual care only. The intervention involved two face-to-face consultations and two telephone support calls with a physical activity facilitator over 6 months to support participants to engage in regular exercise. The primary outcome was symptoms of depression using the Edinburgh Postnatal Depression Scale (EPDS) at 6 months post-randomization. Secondary outcomes included EPDS score as a binary variable (recovered and improved) at 6 and 12 months post-randomization. RESULTS: A total of 146 women were potentially eligible and 94 were randomized. Of these, 34% reported thoughts of self-harming at baseline. After adjusting for baseline EPDS, analyses revealed a -2.04 mean difference in EPDS score, favouring the exercise group [95% confidence interval (CI) -4.11 to 0.03, p = 0.05]. When also adjusting for pre-specified demographic variables the effect was larger and statistically significant (mean difference = -2.26, 95% CI -4.36 to -0.16, p = 0.03). Based on EPDS score a larger proportion of the intervention group was recovered (46.5% v. 23.8%, p = 0.03) compared with usual care at 6 months follow-up. CONCLUSIONS: This trial shows that an exercise intervention that involved encouragement to exercise and to seek out social support to exercise may be an effective treatment for women with postnatal depression, including those with thoughts of self-harming.

Effectiveness of regular weighing, weight target setting and feedback by community midwives within routine antenatal care in preventing excessive gestational weight gain: randomised controlled trial.

BACKGROUND: Many pregnant women gain excess weight during pregnancy which increases the health risks to the mother and her baby. Interventions to prevent excess weight gain need to be given to the whole population to prevent excess weight gain. The aim of this study was to assess the effectiveness of a simple and brief intervention embedded withinroutine antenatal care to prevent excessive gestation weight gain. METHODS: Six hundred and ten pregnant women (between 10-14 weeks gestation), aged ≥18 years with a body mass index (BMI) ≥18.5 kg/m2, planned to receive community midwife led care or shared care at the time of recruitment are eligible to take part in the study. Women will be recruited from four maternity centres in England. Community midwives complete a short training module before delivering the intervention. In the intervention, midwives weigh women, set maximum weight limits for weight gain at each antenatal appointment and ask women to monitor their weight at home. Themaximum weight limit is adjusted by the midwife at each antenatal appointment if women have exceeded their maximum weight gain limit set at their previous appointment. The intervention will be compared with usual antenatal care. The primary outcome is the proportion of women per group who exceed the Institute of Medicine guidelines for gestational weight gain at 38 weeks of pregnancy according to their early pregnancy BMI category. DISCUSSION: The proposed trial will test a brief intervention comprising regular weighing, target setting and monitoring ofweight during pregnancy that can be delivered at scale as part of routine antenatal care. Using the professional expertise of community midwives, but without specialist training in weight management, the intervention will incur minimal additionalhealthcare costs, and if effective at reducing excess weight gain, is likely to be very cost effective. TRIAL REGISTRATION: Current controlled trials ISRCTN67427351. Date assigned 29/10/2014.

The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of exercise as treatment for vasomotor menopausal symptoms. DESIGN: Three-group randomised controlled trial, two exercise interventions and a control group. SETTING: Primary Care, West Midlands UK. POPULATION: Perimenopausal and postmenopausal women experiencing at least five hot flushes/night sweats per day and not taken MHT in previous 3 months were recruited from 23 general practices. METHODS: Participants in both exercise interventions groups were offered two face-to-face consultations with a physical activity facilitator to support engagement in regular exercise. In addition, one exercise group received a menopause-specific information DVD and written materials to encourage regular exercise and the other exercise group was offered the opportunity to attend exercise social support groups in their communities. Interventions lasted 6 months. MAIN OUTCOME MEASURE: The primary outcome was frequency of hot flushes/night sweats at 6-month up. RESULTS: Two hundred and sixty-one women were randomised (n = 87 per group). Neither of the exercise intervention groups reported significantly less frequent hot flushes/night sweats per week than controls (exercise-DVD versus control: -8.9, 95% CI -20.0 to 2.2; exercise-social support versus control: -5.2, 95% CI -16.7 to 6.3). CONCLUSIONS: This trial indicates that exercise is not an effective treatment for hot flushes/night sweats. Contrary to current clinical guidance, women should not be advised that exercise will relieve their vasomotor menopausal symptoms.

The potential role of NT-proBNP in screening for and predicting prognosis in heart failure: a survival analysis.

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.

Pragmatic intervention for increasing self-directed exercise behaviour and improving important health outcomes in people with multiple sclerosis: a randomised controlled trial.

BACKGROUND: Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed for people with multiple sclerosis (PwMS). 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 PwMS to nine months of follow-up. METHODS: We conducted a parallel-arm, randomised controlled trial: 120 PwMS (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 PwMS.

Cost effectiveness of a pragmatic exercise intervention (EXIMS) for people with multiple sclerosis: economic evaluation of a randomised controlled trial.

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.

The feasibility and acceptability of regular weighing of pregnant women by community midwives to prevent excessive weight gain: RCT.

Pregnancy is a critical period for the development of later obesity. Regular weighing of pregnant women is not currently recommended in the UK. This study aimed to demonstrate the feasibility of regular weighing by community midwives (CMWs) as a potential intervention to prevent excessive gestational weight gain. Low risk healthy/overweight pregnant women cared for by eight CMWs were randomised to usual care or usual care plus the intervention at 10-14 weeks of pregnancy. The intervention involved CMWs weighing and charting weight gain on an IOM weight gain chart, setting a weight target and giving brief feedback at antenatal appointments. The focus of the study was on process evaluation outcomes. Data on other outcomes were also collected including gestational weight gain. We interviewed women and CMWs about their views of the intervention. CMWs referred 123 women, 95 agreed to participate and 76 were randomised. Over 90% of women were weighed at 38 weeks of pregnancy demonstrating high follow up. There was no evidence the intervention caused anxiety. Most women commented they had found the intervention useful in encouraging them to think about their weight and believed it should be part of routine antenatal care. CMW's felt the intervention could be implemented within antenatal care without adding substantially to consultation length. To conclude, pregnant women were keen to participate in the study and the intervention was acceptable to pregnant women and CMWs. An effectiveness trial is now planned.

Pragmatic exercise intervention for people with multiple sclerosis (ExIMS trial): study protocol for a randomised controlled trial.

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.

Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial.

OBJECTIVE: To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation. DESIGN: Comparative cohort study of eight risk stratification scores. SETTING: Trial of thromboprophylaxis in stroke, the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial. PARTICIPANTS: 665 patients aged 75 or over with atrial fibrillation based in the community who were randomised to the BAFTA trial and were not taking warfarin throughout or for part of the study period. MAIN OUTCOME MEASURES: Events rates of stroke and thromboembolism. RESULTS: 54 (8%) patients had an ischaemic stroke, four (0.6%) had a systemic embolism, and 13 (2%) had a transient ischaemic attack. The distribution of patients classified into the three risk categories (low, moderate, high) was similar across three of the risk stratification scores (revised CHADS(2), NICE, ACC/AHA/ESC), with most patients categorised as high risk (65-69%, n = 460-457) and the remaining classified as moderate risk. The original CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score identified the lowest number as high risk (27%, n = 180). The incremental risk scores of CHADS(2), Rietbrock modified CHADS(2), and CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex) failed to show an increase in risk at the upper range of scores. The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 (original CHADS(2)) to 0.62 (Rietbrock modified CHADS(2)), with all except the original CHADS(2) predicting better than chance. Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes. CONCLUSIONS: Based on this single trial population, current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke. Given the systematic undertreatment of older people with anticoagulation, and the relative safety of warfarin versus aspirin in those aged over 70, there could be a pragmatic rationale for classifying all patients over 75 as "high risk" until better tools are available.

WITHDRAWN: Eradication of Helicobacter pylori for non-ulcer dyspepsia.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Twenty one randomised controlled trials were included in the systematic review. Eighteen trials compared antisecretory dual or triple therapy with placebo antibiotics +/- antisecretory therapy, and evaluated dyspepsia at 3-12 months. Seventeen of these trials gave results as dichotomous outcomes evaluating 3566 patients and there was no significant heterogeneity between the studies. There was a 10% relative risk reduction in the H pylori eradication group (95% CI = 6% to 14%) compared to placebo. The number needed to treat to cure one case of dyspepsia = 14 (95% CI = 10 to 25). A further three trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. AUTHORS' CONCLUSIONS: H pylori eradication therapy has a small but statistically significant effect in H pylori positive non-ulcer dyspepsia. An economic model suggests this modest benefit may still be cost-effective but more research is needed.

Impact of study design on recruitment of patients to a primary care trial: an observational time series analysis of the Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study.

BACKGROUND: recruitment targets to randomized controlled trials (RCTs) are often not met. Many interventions are used to improve recruitment but there is little empirical evidence on whether these approaches work. OBJECTIVE: to examine whether changes to the design and conduct of a primary care-based RCT were associated with changes in patient recruitment. METHODS: an observational time series analysis of recruitment to a primary care-based multi-centre RCT of aspirin versus warfarin for stroke prevention, which involved 330 practices. Several changes to the trial protocol and procedures were made over the 4 years of patient recruitment. For each quarter throughout the recruitment period, the recruitment rate per 1000 total population in active practices was calculated. RESULTS: the recruitment target of 930 patients was exceeded. Fluctuations in recruitment rate occurred during the recruitment period. Following protocol changes aimed to reduce clinical workload, there was a significant increase in recruitment during the final 6 months of the study, during a period when there was not a similarly large increase in the total population available. CONCLUSIONS: these findings suggest that the conduct of a trial is an important consideration if studies are to recruit successfully. Expanding the number of centres may not be the most effective way to improve recruitment.

A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study.

CONTEXT: Subclinical hypothyroidism (SCH) and cognitive dysfunction are both common in the elderly and have been linked. It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit. OBJECTIVE: Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function. DESIGN AND SETTING: We conducted a double-blind placebo-controlled randomized controlled trial in the context of United Kingdom primary care. PATIENTS: Ninety-four subjects aged 65 yr and over (57 females, 37 males) with SCH were recruited from a population of 147 identified by screening. INTERVENTION: T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 microg T4 per day for 12 months. Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm. Fifty-two subjects received T4 (31 females, 21 males; mean age 73.5 yr, range 65-94 yr); 42 subjects received placebo (26 females, 16 males; mean age 74.2 yr, 66-84 yr). MAIN OUTCOME MEASURES: Mini-Mental State Examination, Middlesex Elderly Assessment of Mental State (covering orientation, learning, memory, numeracy, perception, attention, and language skills), and Trail-Making A and B were administered. RESULTS: Eighty-two percent and 84% in the T4 group achieved euthyroidism at 6- and 12-month intervals, respectively. Cognitive function scores at baseline and 6 and 12 months were as follows: Mini-Mental State Examination T4 group, 28.26, 28.9, and 28.28, and placebo group, 28.17, 27.82, and 28.25 [not significant (NS)]; Middlesex Elderly Assessment of Mental State T4 group, 11.72, 11.67, and 11.78, and placebo group, 11.21, 11.47, and 11.44 (NS); Trail-Making A T4 group, 45.72, 47.65, and 44.52, and placebo group, 50.29, 49.00, and 46.97 (NS); and Trail-Making B T4 group, 110.57, 106.61, and 96.67, and placebo group, 131.46, 119.13, and 108.38 (NS). Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months. CONCLUSIONS: This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function.

Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care.

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 pro-B-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.

Factors affecting attitudes toward colorectal cancer screening in the primary care population.

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.

The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial.

While it seems intuitively appealing to promote participation in regular exercise in the management of irritable bowel syndrome, limited randomised controlled trial evidence exists to support this recommendation. We examined the feasibility and effects of an exercise intervention upon quality of life and irritable bowel symptoms using a randomised controlled trial methodology. Patients with a clinically confirmed diagnosis of irritable bowel syndrome according to Rome II criteria were randomised to either an exercise consultation intervention or usual care for 12 weeks. Outcomes included irritable bowel specific quality of life, symptoms (total symptoms, constipation, diarrhoea and pain) and exercise participation. The recruitment rate of eligible patients identified from hospital records was 18.3% (56/305). Analyses revealed no differences in quality life scores between groups at 12-week follow-up. The exercise group reported significantly improved symptoms of constipation (mean difference=10.9, 95 % CI= -20.1, -1.6) compared to usual care at follow-up. The intervention group participated in significantly more exercise than usual care at follow-up (mean difference=21.6, 95% CI=9.4, 33.8). Recruitment of eligible patients into this study was possible but rates were low. Findings highlight the possibility that exercise may be an effective intervention for symptom management in patients with irritable bowel syndrome; this may be particularly the case for constipation predominant patients.

Factors associated with the use of complementary medicine and non-pharmacological interventions in symptomatic menopausal women.

BACKGROUND: Hormone replacement therapy is now thought to have serious adverse effects; consequently, many menopausal women are seeking to use complementary and alternative medicine (CAM), including non-pharmacological interventions (NPI), to alleviate symptoms. The prevalence and perceived effectiveness of CAM and NPI for ameliorating menopausal symptoms are not widely known and factors likely to predict CAM and NPI utilization for menopausal symptom management have not been comprehensively documented. OBJECTIVES: The objectives of this study were to (1) determine the prevalence of using CAM and NPI for menopausal symptoms; (2) describe the perceived effectiveness of CAM and NPI for symptom management; and (3) investigate lifestyle and demographic factors associated with CAM/NPI use among menopausal women with vasomotor symptoms. METHODS: Women aged 46-55 years were recruited via six socioeconomically diverse general practices. Participants completed a postal questionnaire that contained items relating to demographics, lifestyle factors, weight, height, exercise behavior, menopausal status, vasomotor symptoms and utilization and perceived effectiveness of a range of CAM/NPI for symptom management. RESULTS: Of 1,206 women who responded, 563 (47%) were symptomatic. The most commonly used CAM/NPI for symptom management were diet/nutrition (44.3%), exercise/yoga (41.5%), relaxation/stress management (27.4%) and homeopathic/naturopathic remedies (25.4%). Of women who used these interventions, large proportions reported them to be helpful. The characteristics that were independently associated with use of CAM/NPI were White ethnicity, being physically active, and not smoking. CONCLUSIONS: Many menopausal symptomatic women are using a wide range of CAM/NPI and report these to be effective, particularly those who are white, physically active and do not smoke.