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.

The effectiveness of mood stabilizers and antiepileptic medication for the management of behaviour problems in adults with intellectual disability: a systematic review.

BACKGROUND: Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. METHOD: A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood stabilizers in the management of behaviour problems among adults with ID. Electronic searches of PsycInfo, Medline, Embase and Cinahl databases were conducted, as well as a thorough hand search for relevant literature. We reviewed primary trials relating to adults only that satisfied strict inclusion criteria. RESULTS: One randomized controlled trial (RCT) relating to lithium use and two non-RCTs, one on lithium and the other on carbamazepine, were revealed. In addition, one prospective non-controlled trial on sodium valproate and three retrospective case series studies were discovered, of which one considered the efficacy of lithium, one valproate and one topiramate. CONCLUSIONS: The current evidence lends some support for the use of lithium and some antiepileptic mood stabilizer medication for the management of behaviour problems in adults with ID. However, because most studies reviewed here are riddled with obvious methodological constrains, the findings have to be interpreted with caution.

The effectiveness of antidepressant medication in the management of behaviour problems in adults with intellectual disabilities: a systematic review.

BACKGROUND: A comprehensive systematic review was performed to establish the current evidence base regarding the effectiveness of antidepressant medication for the management of behaviour problems in adults with intellectual disabilities. METHOD: An electronic search of PsycInfo, Embase, Medline and Cinahl databases was conducted spanning the time period 1990 to October 2005 for primary trials. This was supplemented by hand searching and cross-referencing of relevant reviews. Strict scientific methodology requirements were formulated that the studies had to meet in order to merit inclusion in this review. RESULTS: One crossover randomized controlled trial in a small cohort, seven prospective uncontrolled trials and two retrospective studies were yielded in the search. Of these, one explored the effectiveness of the tricyclic antidepressant--clomipramine, and nine considered various selective serotonin reuptake inhibitors (SSRIs). CONCLUSION: Evidence based primarily on a small number of either prospective or retrospective case studies that included a small number of participants and often used non-validated outcome measures for a short period of follow-up, suggests that antidepressants, particularly SSRIs, show improvement of aggression and self-injurious behaviour on average in less than 50% of cases and the rest show either no improvement or deterioration. The effect is most pronounced in the presence of an underlying anxiety or an associated diagnosis of obsessive-compulsive disorder. Most studies have highlighted the concern regarding adverse effects.

The effectiveness of antipsychotic medication in the management of behaviour problems in adults with intellectual disabilities.

BACKGROUND: Psychopharmacological intervention in the management of behaviour problems in adults with intellectual disabilities (ID) has become a common treatment strategy. This has become a cause for concern, given that the evidence for its effectiveness is uncertain and most drugs are not licensed for this use. METHODS: A comprehensive systematic review of empirical research on the effectiveness of antipsychotic medication was conducted. Electronic and manual searches of literature were conducted. Stringent scientific methodology determined those primary trials that were worthy of inclusion. RESULTS: This review revealed one randomized controlled trial (RCT), one controlled, four uncontrolled prospective and three retrospective case series studies in adults. Additionally, two studies in both adults and children--one crossover RCT and one prospective controlled trial--were found. CONCLUSION: Presently, there is RCT-based evidence for risperidone to be effective in both adults and children; however, this treatment carries a certain amount of risk associated with adverse effects. There is also evidence to support the use of other antipsychotics, primarily atypicals, but the evidence is based on noncontrolled case studies. There is currently not enough evidence available to recommend specific medication for specific behaviour problems. Before prescribing medication, clinicians should carry out a thorough assessment of behaviour, including its causes and consequences, and draw up a formulation providing the rationale for the prescribed intervention after considering all medication- and nonmedication-based management options.

Prolonged metabolic recovery allows late identification of ischemia in the absence of electrocardiographic and perfusion changes in patients with exertional angina.

Regional myocardial perfusion and exogenous glucose uptake were assessed in 10 normal subjects and 10 patients with coronary artery disease and stable angina pectoris using 82Rubiduim and 18F-2-fluoro-2-deoxyglucose with positron emission tomography. At rest regional myocardial perfusion and glucose uptake in patients were comparable with those in normals. In 7 patients and 5 normals a supine bicycle exercise test was performed within the positron camera. In all 7 patients, exercise induced typical chest pain and ischemic electrocardiographic changes accompanied by regional abnormalities of myocardial perfusion which normalized 5 to 14 minutes after the end of exercise. In these patients 18F-2-fluoro-2-deoxyglucose was injected during recovery from exercise when all the parameters that were altered during the test, including myocardial perfusion, were back to control. In all 7, glucose uptake in the regions which showed abnormal perfusion during exercise was significantly higher than in the non ischemic regions (i.e. the ones with a normal increment of 82Rubidium uptake during exercise). In 2 patients the test was repeated on a different day and 18F-2-fluoro-2-deoxyglucose was injected during exercise in the presence of frank ischemia. In contrast to the injection following exercise, in both patients, glucose uptake in the ischemic region was found to be lower than in the non ischemic ones. In conclusion, in patients recovering from exercise-induced ischemia exogenous glucose utilization is enhanced in the previously ischemic myocardium. This occurs in the absence of symptoms and electrocardiographic changes and allows the identification and location of previous myocardial ischemia.