Correction: PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN74418480]

BACKGROUND: The Paracetamol (Acetaminophen) In Stroke (PAIS) study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever.The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS) may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. METHODS: Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. CONCLUSION: The protocol change was initiated becau

Hyperglycemia in bacterial meningitis: a prospective cohort study

ABSTRACT: BACKGROUND: Hyperglycemia has been associated with unfavorable outcome in several disorders, but few data are available in bacterial meningitis. We assessed the incidence and significance of hyperglycemia in adults with bacterial meningitis. METHODS: We collected data prospectively between October 1998 and April 2002, on 696 episodes of community-acquired bacterial meningitis, confirmed by culture of CSF in patients >16 years. Patients were dichotomized according to blood glucose level on admission. A cutoff random non-fasting blood glucose level of 7.8 mmol/L (140 mg/dL) was used to define hyperglycemia, and a cutoff random non-fasting blood glucose level of 11.1 mmol/L (200 mg/dL) was used to define severe hyperglycemia. Unfavorable outcome was defined on the Glasgow outcome scale as a score <5. We also evaluated characteristics of patients with a preadmission diagnosis of diabetes mellitus. RESULTS: 69% of patients were hyperglycemic and 25% severely hyperglycemic on admission. Compared with non-hyperglycemic patients, hyperglycemia was related with advanced age (median, 55 yrs vs. 44 yrs, P<0.0001), preadmission diagnosis of diabetes (9% vs. 3%, P=0.005), and distant focus of infection (37% vs. 28%, P=0.02). They were more often admitted in coma (16% vs. 8%; P=0.004) and with pneumococcal meningitis (55% vs. 42%, P=0.007). These differences remained significant after exclusion of patients with known diabetes. Hyperglycemia was related with unfavorable outcome (in a hockey stick-shaped curve) but this relation did not remain robust in a multivariate analysis. Factors predictive for neurologic compromise were related with higher blood glucose levels, whereas factors predictive for systemic compromise were related with lower blood glucose levels. Only a minority of severely hyperglycemic patients were known diabetics (19%). The vast majority of these known diabetic patients had meningitis due to Streptococcus pneumoniae (67%) or Listeria monocytogenes (13%) and they were at high risk for unfavorable outcome (52%). CONCLUSIONS: The majority of patients with bacterial meningitis have hyperglycemic blood glucose levels on admission. Hyperglycemia can be explained by a physical stress reaction, the central nervous system insult leading to disturbed blood-glucose regulation mechanisms, and preponderance of diabetics for pneumococcal meningitis. Patients with diabetes and bacterial meningitis are at high risk for unfavorable outcom

The Ischemic Stroke Genetics Study (ISGS) Protocol

BACKGROUND: The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. DISCUSSION: The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes

A rational model for assessing and evaluating complex interventions in health care

Background: understanding how new clinical techniques, technologies and other complex interventions become normalized in practice is important to researchers, clinicians, health service managers and policy-makers. This paper presents a model of the normalization of complex interventions.Methods: between 1995 and 2005 multiple qualitative studies were undertaken. These examined: professional-patient relationships; changing patterns of care; the development, evaluation and implementation of telemedicine and related informatics systems; and the production and utilization of evidence for practice. Data from these studies were subjected to (i) formative re-analysis, leading to sets of analytic propositions; and to (ii) a summative analysis that aimed to build a robust conceptual model of the normalization of complex interventions in health care.Results: a normalization process model that enables analysis of the conditions necessary to support the introduction of complex interventions is presented. The model is defined by four constructs: interactional workability; relational integration; skill set workability and contextual integration. This model can be used to understand the normalization potential of new techniques and technologies in healthcare settingsConclusion: the normalization process model has face validity in (i) assessing the potential for complex interventions to become routinely embedded in everyday clinical work, and (ii) evaluating the factors that promote or inhibit their success and failure in practic

Improving the prediction of outcome in severe acute closed head injury by using discriminant function analysis of normal auditory brainstem response latencies and amplitudes

Object. The auditory brainstem response (ABR) is a useful addition to standard medical measures for predicting outcome in patients with severe acute closed head injury (ACHI). Limiting this success, however, is the poor predictive value of a so-called "normal" ABR. In this study the authors used discriminant function analysis (DFA) of ABR Wave I, III, and V latencies and amplitudes to improve the predictive accuracy of the normal ABR, both as a single measure and in combination with other standard medical measures. Methods. The DFAs were conducted using the ABR and medical results in 68 patients with severe ACHI (30 who died [ACHI-died], and 38 who survived [ACHI-lived]) who presented with normal ABR responses in the neurosurgical intensive care unit of the authors' hospital in Johannesburg. All patients had undergone surgery to remove an intracranial hematoma. Correct predictions of outcome by ABR DFA measures were 83% for the ACHI-died group (48% at greater than or equal to 90% confidence level) and 87% for the ACHI-lived group (71% at greater than or equal to 90% confidence level); by medical DFA measures the correct predictions were 83% for the ACHI-died group (96% at greater than or equal to 90% confidence level) and 95% for the ACHI-lived group (94% at greater than or equal to 90% confidence level); and by combined ABR and medical DFA measures correct predictions were 100% for the ACHI-died group (100% at greater than or equal to 90% confidence level) and 97% for the ACHI-lived group (100% at greater than or equal to 90% confidence level). Conclusions. The DFA of ABR Wave I, III, and V latencies and amplitudes improved the predictive ability of normal ABR results to rates similar to those obtained using DFA for the medical measures, although at lower confidence levels. The DFA of the combined ABR and medical measures improved correct predictions to rates significantly higher than for either of the measures on its own