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IntroductionThe early stages of chronic progressive cardiovascular disease (CVD) generally cause non-specific symptoms that patients often do not spontaneously mention to their general practitioner, and are therefore easily missed. A proactive diagnostic strategy has the potential to uncover these frequently missed early stages, creating an opportunity for earlier intervention. This is of particular importance for chronic progressive CVDs with evidence-based therapies known to improve prognosis, such as ischaemic heart disease, atrial fibrillation and heart failure.Patients with type 2 diabetes or chronic obstructive pulmonary disease (COPD) are at particularly high risk of developing CVD. In the current study, we will demonstrate the feasibility and effectiveness of screening these high-risk patients with our early diagnosis strategy, using tools that are readily available in primary care, such as symptom questionnaires (to be filled out by the patients themselves), natriuretic peptide measurement and electrocardiography.Methods and analysisThe Reviving the Early Diagnosis-CVD trial is a multicentre, cluster randomised diagnostic trial performed in primary care practices across the Netherlands. We aim to include 1300 (2×650) patients who participate in a primary care disease management programme for COPD or type 2 diabetes. Practices will be randomised to the intervention arm (performing the early diagnosis strategy during the routine visits that are part of the disease management programmes) or the control arm (care as usual). The main outcome is the number of newly detected cases with CVDs in both arms, and the subsequent therapies they received. Secondary endpoints include quality of life, cost-effectiveness and the added diagnostic value of family and reproductive history questionnaires and three (novel) biomarkers (high-sensitive troponin-I, growth differentiation factor-15 and suppressor of tumourigenicity 2). Finally newly initiated treatments will be compared in both groups.Ethics and disseminationThe protocol was approved by the Medical Ethical Committee of the University Medical Center Utrecht, the Netherlands. Results are expected in 2022 and will be disseminated through international peer-reviewed publications.Trial registration numberNTR7360.

IntroductionClinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF). Frail elderly were under-represented in the landmark NOAC-trials, leaving a knowledge gap on the optimal anticoagulant management (VKA or NOAC) in this increasing population. The aim of the Frail-AF (FRAIL-AF) study is to assess whether switching from international normalised ratio (INR)-guided VKA-management to a NOAC-based treatment strategy compared with continuing VKA-management is safe in frail elderly patients with AF.Methods and analysisThe FRAIL-AF study is a pragmatic, multicentre, open-label, randomised controlled clinical trial. Frail elderly (age ≥75 years plus a Groningen Frailty Indicator score ≥3) who receive VKA-treatment for AF in the absence of a mechanical heart valve or severe mitral valve stenosis will be randomised to switch to a NOAC-based treatment strategy or to continue INR-guided VKA-management. Patients with severe renal impairment (estimated glomerular filtration rate 2) will be excluded from randomisation. Based on existing trial evidence in non-frail patients, we will aim to explore whether NOAC-treatment is superior to VKA-therapy in reducing major or clinically relevant non-major bleeding events. Secondary outcomes include minor bleeding, the composite of ischaemic and haemorrhagic stroke, health-related quality of life and cost-effectiveness. The follow-up period for all subjects is 12 months.Ethics and disseminationThe protocol was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, the Netherlands and by the Central Committee on Research Involving Human Subjects, the Netherlands. All patients are asked written informed consent. Results are expected in 2022 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences.Trial registration numberEudraCT: 2017-000393-11; The Netherlands Trial Registry: 6721 (FRAIL-AF study).

Aims To estimate the prevalence and clustering of major cardiovascular risk factors in adults in Northeast China. Methods In total, 37 141 individuals undergoing a health screening programme at the International Health Promotion Center at the 1st Hospital of Jilin University were enrolled. Height, weight, blood pressure, fasting serum glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein and low-density lipoprotein were recorded. Results Compared with women, the age-standardised prevalence of overweight (44.0% vs 25.0%) and obesity (20.2% vs 7.1%), hypertension (33.7% vs 19.3%), dyslipidaemia (63.8% vs 42.3%), impaired fasting glucose (5.1% vs 4.2%) and diabetes mellitus (8.1% vs 3.5%) was higher in men. Overall, 69.1%, 32.7% and 10.0% of participants had ≥1, ≥2 and ≥3 major cardiovascular risk factors, respectively (obesity, hypertension, dyslipidaemia, diabetes mellitus). For men, the figures were 79.2%, 41.1% and 13.3%, respectively, and for women 53.4%, 19.8% and 5.0%, respectively. With increasing age and increasing body mass index, the prevalence of clustering of cardiovascular risk factors increased in both men and women. Conclusions There is a high prevalence of cardiovascular risk factors in adults in Northeast China: one out of three has at least two risk factors. Prevalence was higher in men than in women. Clustering of risk factors is more common with increasing age and body mass index in both men and women. Prevention of the development of risk factors should be an extremely high priority in this region.

Background Diagnosing early stages of heart failure with mild symptoms is difficult. B-type natriuretic peptide (BNP) has promising biochemical test characteristics, but its diagnostic yield on top of readily available diagnostic knowledge has not been sufficiently quantified in early stages of heart failure. Objectives To quantify the added diagnostic value of BNP for the diagnosis of heart failure in a population relevant to GPs and validate the findings in an independent primary care patient population. Design Individual patient data meta-analysis followed by external validation. The additional diagnostic yield of BNP above standard clinical information was compared with ECG and chest x-ray results. Patients and methods Derivation was performed on two existing datasets from Hillingdon (n=127) and Rotterdam (n=149) while the UK Natriuretic Peptide Study (n=306) served as validation dataset. Included were patients with suspected heart failure referred to a rapid-access diagnostic outpatient clinic. Case definition was according to the ESC guideline. Logistic regression was used to assess discrimination (with the c-statistic) and calibration. Results Of the 276 patients in the derivation set, 30.8% had heart failure. The clinical model (encompassing age, gender, known coronary artery disease, diabetes, orthopnoea, elevated jugular venous pressure, crackles, pitting oedema and S3 gallop) had a c-statistic of 0.79. Adding, respectively, chest x-ray results, ECG results or BNP to the clinical model increased the c-statistic to 0.84, 0.85 and 0.92. Neither ECG nor chest x-ray added significantly to the ‘clinical plus BNP’ model. All models had adequate calibration. The ‘clinical plus BNP’ diagnostic model performed well in an independent cohort with comparable inclusion criteria (c-statistic=0.91 and adequate calibration). Using separate cut-off values for ‘ruling in’ (typically implying referral for echocardiography) and for ‘ruling out’ heart failure—creating a grey zone—resulted in insufficient proportions of patients with a correct diagnosis. Conclusion BNP has considerable diagnostic value in addition to signs and symptoms in patients suspected of heart failure in primary care. However, using BNP alone with the currently recommended cut-off levels is not sufficient to make a reliable diagnosis of heart failure.

Objective To determine the accuracy of heart-type fatty acid-binding protein (H-FABP) as a new and early cardiac biomarker in the early diagnosis of acute myocardial infarction (AMI). The introduction of early and safe biomarkers could lead to (a) a large reduction in unnecessary hospital referrals of patients suspected of, but not, having AMI and (b) an earlier start of treatment in patients with AMI. Design Diagnostic meta-analysis. Setting Hospital and pre-hospital. Patients Consecutive patients suspected of having AMI. Main outcome measures A summary estimate for sensitivity and specificity was calculated using the bivariate random-effects approach, and covariate analysis was used to examine sources of heterogeneity between studies. Results A systematic search yielded 16 studies (3709 patients, prevalence of AMI 13e74%, male gender 49e84%, median age 64e76 years). The summary estimate was 84% (95% CI 76% to 90%) for sensitivity and 84% (95% CI 76% to 89%) for specificity. Covariate analyses revealed that the use of troponin in the reference standard for AMI (as opposed to creatine kinase or creatine kinase-myocardial band) had a significant impact on sensitivity. Conclusion H-FABP does not fulfil the requirements needed for a safe and early diagnosis of AMI when used as a stand-alone test. Sound diagnostic studies examining the additional role of H-FABP combined with clinical findings and other diagnostic tests are needed to further clarify a potential future role for this cardiac biomarker.

ObjectivesPatients with atrial fibrillation (AF) are at increased risk of many adverse events, notably stroke. To prevent all adverse outcomes, integrated AF care is advocated though the potential domain for such multidisciplinary management is still unclear. Therefore, insight in the systemic nature of AF and identifying patients at risk of adverse events after oral anticoagulation is needed. The aim of this study is to first describe the risk of hospitalisation and mortality in community-dwelling older patients with AF using anticoagulants, and second to assess the association between traditional cardiac risk factors and these outcomes.DesignA prospective cohort.SettingGeneral practice.Participants2068 patients with AF using oral anticoagulants.Outcome measuresWe calculated incidence rates (IRs) of ischaemic stroke, bleeding, hospitalisations and mortality, and compared risk factors using Cox regression between those with and without an adverse event, both for cardiac and non-cardiac causes.ResultsDuring a median follow-up of 2.7 (IQR 2.2–3.0) years, the IR per 100 person-years was 22.1 for hospitalisations and 6.7 for mortality. Non-cardiac events outnumbered cardiac events (IRs 15.7 vs 7.6 per 100 person-years for hospitalisation, pConclusionsIn anticoagulated community-dwelling patients with AF, stroke risk is effectively reduced and thus fairly low, whereas risks of hospitalisation and mortality remain high, importantly mainly for non-cardiac causes. Notably high age, heart failure and vascular disease are predictive for such outcomes and may be of value in identifying high-risk patients in the future.Trial registration numberNTR3741.

Context Early recognition of acute coronary syndrome (ACS) is essential. Cardiac troponins are not consistently elevated within the first hours after symptom onset. Objective Review current guidelines recommendations regarding biomarkers in the early assessment of ACS and review the evidence for using established and specific new diagnostic biomarkers. Data sources MEDLINE and EMBASE. Study selection Articles on diagnostic accuracy of ACS biomarkers. Data extraction Relevance of clinical domain, adequacy of measures of clinical utility and outcome assessment. Results The 73 articles identified on early biochemical markers CK-MB, myoglobin, heart-type fatty acid binding protein (H-FABP), ischemia modified albumin (IMA), pregnancy-associated plasma protein A, glycogen phosphorylase isoenzyme BB and myeloid-related protein 8/14 often did not quantify clinical utility correctly. Conclusions IMA and H-FABP seem to be promising biomarkers in the early assessment of ACS. There is an urgent need for adequately designed diagnostic studies of (novel) ACS markers against contemporary troponin assays.

ObjectiveHeart failure (HF) often coexists in atrial fibrillation (AF) but is frequently unrecognised due to overlapping symptomatology. Furthermore, AF can cause elevated natriuretic peptide levels, impairing its diagnostic value for HF detection. We aimed to assess the prevalence of previously unknown HF in community-dwelling patients with AF, and to determine the diagnostic value of the amino-terminal pro B-type natriuretic peptide (NTproBNP) for HF screening in patients with AF.MethodsIndividual participant data from four HF-screening studies in older community-dwelling persons were combined. Presence or absence of HF was in each study established by an expert panel following the criteria of the European Society of Cardiology. We performed a two-stage patient-level meta-analysis to calculate traditional diagnostic indices.ResultsOf the 1941 individuals included in the four studies, 196 (10.1%) had AF at baseline. HF was uncovered in 83 (43%) of these 196 patients with AF, versus 381 (19.7%) in those without AF at baseline. Median NTproBNP levels of patients with AF with and without HF were 744 pg/mL and 211 pg/mL, respectively. At the cut-point of 125 pg/mL, sensitivity was 93%, specificity 35%, and positive and negative predictive values 51% and 86%, respectively. Only 23% of all patients with AF had an NTproBNP level below the 125 pg/mL cut-point, with still a 13% prevalence of HF in this group.ConclusionsWith a prevalence of nearly 50%, unrecognised HF is common among community-dwelling patients with AF. Given the high prior change, natriuretic peptides are diagnostically not helpful, and straightforward echocardiography seems to be the preferred strategy for HF screening in patients with AF.

The aim of this paper is to review the clinical epidemiology of heart failure. The last paper comprehensively addressing the epidemiology of heart failure in Heart appeared in 2000. Despite an increase in manuscripts describing epidemiological aspects of heart failure since the 1990s, additional information is still needed, as indicated by various editorials.

Randomised allocation of vaccine or placebo is the preferred method to assess the effects of the vaccine on clinical outcomes relevant to the individual patient. In the absence of phase 3 trials using clinical end points, notably post-influenza complications, alternative non-experimental designs to evaluate vaccine effects or safety are often used. The application of these designs may, however, lead to invalid estimates of vaccine effectiveness or safety. As patients with poor prognosis are more likely to be immunised, selection for vaccination is confounded by patient factors that are also related to clinical end points. This paper describes several design and analytical methods aimed at limiting or preventing this confounding by indication in non-experimental studies. In short, comparison of study groups with similar prognosis, restriction of the study population, and statistical adjustment for dissimilarities in prognosis are important tools and should be considered. Only if the investigator is able to show that confounding by indication is sufficiently controlled for, results of a non-experimental study may be of use to direct an evidence based vaccine policy.

IntroductionIn our ageing society, we are at the merge of an expected epidemic of atrial fibrillation (AF). AF management requires an integrated approach, including rate or rhythm control, stroke prevention with anticoagulation and treatment of comorbidities such as heart failure or type 2 diabetes. As such, primary care seems to be the logical healthcare setting for the chronic management of patients with AF. However, primary care has not yet played a dominant role in AF management, which has been in fact more fragmented between different healthcare providers. This fragmentation might have contributed to high healthcare costs. To demonstrate the feasibility of managing AF in primary care, studies are needed that evaluate the safety and (cost-)effectiveness of integrated AF management in primary care.Methods and analysisThe ALL-IN trial is a multicentre, pragmatic, cluster randomised, non-inferiority trial performed in primary care practices in a suburban region in the Netherlands. We aim to include a minimum of 1000 patients with AF aged 65 years or more from around 18 to 30 practices. Duration of the study is 2 years. Practices will be randomised to either the intervention arm (providing integrated AF management, involving a trained practice nurse and collaboration with secondary care) or the control arm (care as usual). The primary endpoint is all-cause mortality. Secondary endpoints are cardiovascular mortality, (non)-cardiovascular hospitalisation, major adverse cardiac events, stroke, major bleeding, clinically relevant non-major bleeding, quality of life and cost-effectiveness.Ethics and disseminationThe protocol was approved by the Medical Ethical Committee of the Isala Hospital Zwolle, the Netherlands. Patients in the intervention arm will be asked informed consent for participating in the intervention. Results are expected in 2019 and will be disseminated through both national and international journals and conferences.Trial registration numberThis trial is registered at the Netherlands Trial Register (NTR5532).

Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43 family practices in the Netherlands. Participants 561 patients, aged 15›60 years, with sore throat for less than seven days and at least three of the four Centor criteria—that is, history of fever, absence of cough, swollen tender anterior cervical lymph nodes, and tonsillar exudate. 142 patients were excluded for medical reasons and 73 needed penicillin. Interventions Patients were randomly assigned to penicillin V for seven days, penicillin V for three days followed by placebo for four days, or placebo for seven days. Main outcome measures Resolution of symptoms in the first week, eradication of bacteria after two weeks, and recurrences of sore throat after two, four, and six months. Results Symptoms resolved 1.9 and 1.7 days earlier in patients taking penicillin for seven days than in those taking penicillin for three days or placebo respectively. Symptoms resolved 2.5 days earlier in patients with group A streptococci and 1.3 days earlier in patients with high colony counts of non›group A streptococci. 23 (13%) of the placebo group had to be given antibiotics later in the week because of clinical deterioration; three developed a peritonsillar abscess. The eradication rate for group A streptococci was 72% in the seven day penicillin group, 41% in the three day penicillin group, and 7% in the placebo group. Sore throat recurred more often in the three day penicillin group than in the seven day penicillin or placebo groups. Conclusion Penicillin treatment for seven days was superior to treatment for three days or placebo in resolving symptoms of sore throat in patients with group A streptococcal pharyngitis and, possibly, in those with non›group A streptococcal pharyngitis.

Relapse of congestive heart failure (CHF) frequently occurs and has serious consequences in terms of morbidity, mortality, and health care expenditure. Many studies have investigated the aetiological and prognostic factors of CHF, but there are only limited data on the role of precipitating factors that trigger relapse of CHF. Knowledge of potential precipitating factors may help to optimise treatment and provide guidance for patients with CHF. The literature was reviewed to identify factors that may influence haemodynamic homeostasis in CHF. Precipitating factors that may offer opportunities for preventing relapse of CHF were selected. Potential precipitating factors are discussed in relation to the pathophysiology of CHF: alcohol, smoking, psychological stress, uncontrolled hypertension, cardiac arrhythmias, myocardial ischaemia, poor treatment compliance, and inappropriate medical treatment. Poor treatment compliance in particular is frequently encountered in patients with CHF. Furthermore, studies of medical treatment under everyday circumstances indicate that some aspects of the management of CHF can be improved. In conclusion, the identification of precipitating factors for relapse of CHF may strongly contribute to optimal treatment. Improvement of treatment compliance and optimalisation of medical treatment may offer important possibilities to clinicians to reduce the number of relapses in patients with CHF. Keywords: congestive heart failure; precipitating factors; prevention

In research on the effectiveness of treatments, the randomised controlled trial is considered the best study design because it enables several sources of bias to be removed from the observation. The most important advantage of such a trial is that the baseline prognoses of patient groups are comparable so that unbiased estimates of the effects of a particular intervention can be obtained. In non-experimental (observational) studies allocation to drug treatment is, by definition, not random. This usually means that the prognoses of the patient groups are not comparable and any inferences drawn about the relative effects of treatment are therefore invalid.1 2 In studies of patients who are not randomly allocated to a treatment arm but receive treatment when their doctor decides to prescribe it, the onus is on the investigator to achieve comparability. We discuss the pitfalls of non-randomised comparisons of treatment effects. The results of a recently published study which suggested that hypertension should not be lowered too far by treatment and the subsequent debate provide an example of problems that may arise in validating the conclusions of such studies. A sensible doctor prescribes drugs only to patients who need them—those who have indications that this treatment is required. Moreover, he or she will give priority to treating the most needy patients. When two patients seem to have indications but only one is being treated, the treated patient probably has more compelling indications than the second. The prognosis in any given group of treated patients will be different from that in untreated subjects because the latter will not generally have any indications for treatment. Furthermore, although many drugs can affect the course of a disease positively, the outcome in people with that disease compared with those who do not have it or have a less severe form …

OBJECTIVES: About 20% of elderly people use long-term diuretic medication, but there is doubt whether prolonged diuretic medication on such a large scale is necessary. We performed a study to assess what proportion may successfully be withdrawn from diuretic therapy. DESIGN: Double blind randomised controlled trial with six month follow up. SETTING: General practice. SUBJECTS: 202 patients taking long-term diuretics without manifest heart failure or hypertension. INTERVENTIONS: Patients were allocated to either placebo (withdrawal group, n = 102) or continuation of diuretic treatment (control group, n = 100). MAIN OUTCOME MEASURE: Occurrence of clinical conditions requiring diuretic therapy based on fixed criteria. RESULTS: During follow up diuretic therapy was required in 50 patients in the withdrawal group and 13 in the control group (risk difference 36%; 95% confidence interval 22% to 50%). Heart failure was the most frequent cause of prescribing diuretic therapy (n = 25). Cessation of diuretic therapy caused a mean increase in systolic blood pressure of 13.5 (9.2 to 17.8) mm Hg and in diastolic pressure of 4.6 (1.9 to 7.3) mm Hg. CONCLUSION: Withdrawal of long-term diuretic treatment in elderly patients leads to symptoms of heart failure or increase in blood pressure to hypertensive values in most cases. Any attempt to withdraw diuretic therapy requires careful monitoring conditions, notably during the initial four weeks.

ObjectivesEvidence-based medicine (EBM) is an important element in the general practice (GP) specialty training. Studies show that integrating EBM training into clinical practice brings larger benefits than stand-alone modules. However, these studies have neither been performed in GP nor assessed EBM behaviour of former trainees in daily clinical practice. SettingGP specialty training in the Netherlands.ParticipantsAll 82 third year GP trainees who started their final third year in 2011 were approached for inclusion, of whom 79 (96%) participated: 39 in the intervention group and 40 in the control group.InterventionIntegrated EBM training, in which EBM is embedded closely within the clinical context by joint assignments for the trainee and supervisor in daily practice, and teaching sessions based on dilemmas from actual patient consultations.ComparisonStand-alone EBM training at the institute only.Primary and secondary outcomesOur primary outcome was EBM behaviour, assessed by measuring guideline adherence (incorporating rational, motivated deviation) and information-seeking behaviour. Our secondary outcomes were EBM attitude and EBM knowledge. Data were acquired using logbooks and questionnaires, respectively. Analyses were performed using mixed models.ResultsLogbook data were available from 76 (96%) of the participating trainees at baseline (7614 consultations), 60 (76%) at the end of the third year (T1, 4973 consultations) and 53 (67%) 1 year after graduation (T2, 3307 consultations). We found no significant differences in outcomes between the 2 groups, with relative risks for guideline adherence varying between 0.96 and 0.99 (95% CI 0.86 to 1.11) at T1, and 0.99 and 1.10 (95% CI 0.92 to 1.25) at T2, and for information-seeking behaviour between 0.97 and 1.16 (95% CI 0.70 to 1.91) and 0.90 and 1.10 (95% CI 0.70 to 1.32), respectively.ConclusionsIntegrated EBM training compared with stand-alone EBM training does not improve EBM behaviour, attitude or knowledge of (future) GPs.

STUDY OBJECTIVE--Dutch public health services are charged with collective preventive care for the population--care that should, by law, be based on epidemiological data. General practices potentially offer important data for this purpose, particularly since more and more use a computer. This study aimed to assess whether it is possible to obtain useful epidemiological data from this source. DESIGN--In 1990, the Rotterdam Municipal Health Service, in collaboration with the Erasmus University Rotterdam, started a computerised sentinel practice network. The main features of this and a specific small investigation are described. SETTING--The following institutions cooperate in the network: Municipal Health Service Rotterdam Area; Departments of General Practice and of Medical Informatics, Erasmus University Rotterdam; Rotterdam District Association of General Practitioners. PATIENTS--Data are currently collected from 20 general practitioners and > 40,000 patients. In a specific project, the distribution of cardiovascular risk factors in different ethnic groups was compared. MAIN RESULTS--It was possible to build up a regional epidemiological registration system in this manner. In the cardiovascular project we found striking differences between ethnic groups. The risk profile for Turkish men, in particular, was less favourable. The health service also uses the system to improve cooperation between public health and primary health care (for example, in cervical screening, influenza vaccination). CONCLUSION--Computerised general practices offer great possibilities for research and for preventive activities in which public health care and general practitioners can cooperate.

Aim The aim of the EUROACTION PLUS trial was to determine if the nurse-led preventive cardiology programme in primary care, with an intensive smoking intervention including the optional use of Varenicline, could achieve more effective smoking abstinence among persistent smokers with either established vascular disease, or at high risk of developing cardiovascular disease and to reduce overall cardiovascular risk compared to usual care (UC). Methods EUROACTION PLUS (EA PLUS) was a randomised controlled intervention trial carried out in general practices across 4 European countries: Italy, The Netherlands, Spain and the UK. Vascular patients and people at high risk of developing cardiovascular disease who were current smokers were individually randomised to receive either a professional smoking cessation intervention, which included the optional use of Varenicline, delivered in the context of the nurse-led EUROACTION preventive cardiology programme, or their usual care. The primary outcome was the proportion of non-smokers (7-day prevalence of non-smoking) validated by breath CO ( Results 696 patients were recruited: 350 randomised to EA PLUS and 346 to UC. 85% EA PLUS and 83% UC returned at 16 weeks. For the primary endpoint 51% of patients in the EA PLUS arm were abstinent compared to 19% in UC at 16 weeks; OR 4.52 (95% CI 3.20 to 6.39, p Conclusion This European trial has demonstrated that the EUROACTION nurse-led preventive cardiology programme, with an intensive smoking cessation intervention including optional Varenicline, helps more vascular and high risk patients, together with their partners, to stop smoking and better achieve the other European lifestyle and blood pressure targets for cardiovascular disease prevention than usual medical care.

Objective Heart failure (HF) is an important public health problem. Detailed information on prognosis following hospital admission is crucial for cost-effectiveness analysis and determination of the burden of HF on the health care system. However, such data are scarce. Therefore, the objective of this study was to provide mortality risk following hospital admission stratified by age- and gender. Design Hospital based follow-up study. Setting and Participants A nationwide cohort of patients hospitalised for the first time for heart failure was identified through linkage of national registers in 1997 and 2000. The total population of the Netherlands in 1997 and 2000 was 15 567 107 (men 7 696 803, women 7 870 304) and 15 863 950 (men 7 846 317, women 8 017 633), respectively. Main Outcome Measure The crude short-term (28 day), 1-year and long-term (5-year) mortality was computed by age and gender according to the actuarial life table method and expressed as percentages. The mortality rate in men was compared to mortality rate in women by calculating RR (with 95% CI). Results 14 529 men, mean age 74±11 years and 14 524 women, mean age 78±11 years were identified. Mortality risk after admission for HF increased with age from 35–44 years to 75–84 years (men: 28-day mortality from 7.5% to 32.9%, 1-year mortality from 17.2% to 58.6% and 5-year mortality from 34.2% to 87.1%; and women: 28-day mortality from 6.9% to 27.2%, 1-year mortality from 14.9% to 49.9% and 5-year mortality from 27.6% to 84.1%). The risk of death was higher among man than women of the same age. Conclusions There are clear age and gender differences in short- and long-term risk of death after first hospitalisation for heart failure. This information is helpful for clinicians, policymakers and service planners. Findings will also be useful for the development of models that evaluate cost-effectiveness and impact on outcomes of heart failure management programmes, and for predicting the future health care burden of heart failure.

Objective To determine the effectiveness of increasing the dietary content of soluble fibre (psyllium) or insoluble fibre (bran) in patients with irritable bowel syndrome. Design Randomised controlled trial. Setting General practice. Participants 275 patients aged 18-65 years with irritable bowel syndrome. Interventions 12 weeks of treatment with 10 g psyllium (n=85), 10 g bran (n=97), or 10 g placebo (rice flour) (n=93). Main outcome measures The primary end point was adequate symptom relief during at least two weeks in the previous month, analysed after one, two, and three months of treatment to assess both short term and sustained effectiveness. Secondary end points included irritable bowel syndrome symptom severity score, severity of abdominal pain, and irritable bowel syndrome quality of life scale. Results The proportion of responders was significantly greater in the psyllium group than in the placebo group during the first month (57% v 35%; relative risk 1.60, 95% confidence interval 1.13 to 2.26) and the second month of treatment (59% v 41%; 1.44, 1.02 to 2.06). Bran was more effective than placebo during the third month of treatment only (57% v 32%; 1.70, 1.12 to 2.57), but this was not statistically significant in the worst case analysis (1.45, 0.97 to 2.16). After three months of treatment, symptom severity in the psyllium group was reduced by 90 points, compared with 49 points in the placebo group (P=0.03) and 58 points in the bran group (P=0.61 versus placebo). No differences were found with respect to quality of life. Fifty four (64%) of the patients allocated to psyllium, 54 (56%) in the bran group, and 56 (60%) in the placebo group completed the three month treatment period. Early dropout was most common in the bran group; the main reason was that the symptoms of irritable bowel syndrome worsened. Conclusions Psyllium offers benefits in patients with irritable bowel syndrome in primary care. Trial registration Clinical trials NCT00189033.

Objective To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy. Design Open, randomised controlled trial. Setting 21 general hospitals and three academic centres in the Netherlands. Participants 300 children aged 2-8 years requiring adenotonsillectomy. Intervention Adenotonsillectomy compared with watchful waiting. Main outcome measures Episodes of fever, throat infections, upper respiratory tract infections, and health related quality of life. Results During the median follow up period of 22 months, children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group (difference -0.21, 95% confidence interval -0.54 to 0.12), 0.56 throat infections per person year compared with 0.77 (-0.21, -0.36 to -0.06), and 5.47 upper respiratory tract infections per person year compared with 6.00 (-0.53, -0.97 to -0.08). No clinically relevant differences were found for health related quality of life. Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two. 12 children had complications related to surgery. Conclusion Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy.

Objective To assess the effectiveness of penicillin for three days and treatment for seven days compared with placebo in resolving symptoms in children with sore throat. Design Randomised, double blind, placebo controlled trial. Setting 43 family practices in the Netherlands. Participants 156 children aged 4-15 who had a sore throat for less than seven days and at least two of the four Centor criteria (history of fever, absence of cough, swollen tender anterior cervical lymph nodes, and tonsillar exudate). Interventions Patients were randomly assigned to penicillin for seven days, penicillin for three days followed by placebo for four days, or placebo for seven days. Main outcome measures Duration of symptoms, mean consumption of analgesics, number of days of absence from school, occurrence of streptococcal sequelae, eradication of the initial pathogen, and recurrences of sore throat after six months. Results Penicillin treatment was not more beneficial than placebo in resolving symptoms of sore throat, neither in the total group nor in the 96 children with group A streptococci. In the groups randomised to seven days of penicillin, three days of penicillin, or placebo, one, two, and eight children, respectively, experienced a streptococcal sequela. Conclusion Penicillin treatment had no beneficial effect in children with sore throat on the average duration of symptoms. Penicillin may, however, reduce streptococcal sequelae.