Dawn M. Bravata

Insulin resistance and risk for stroke.

Background and purpose Resistance to insulin-mediated glucose uptake by peripheral tissues is a cardinal defect in type 2 diabetes mellitus. Insulin resistance is also common among nondiabetic individuals, and may be an important risk factor for stroke in both populations. The authors review the definition, epidemiology, and treatment of insulin resistance. Methods The authors searched Medline (1977–2001) and reviewed bibliographies to identify pertinent English-language publications. Results Insulin resistance is present in most patients with type 2 diabetes. It is also common among elderly persons, certain ethnic groups, and persons with hypertension, obesity, physical deconditioning, and vascular disease. The principal pathophysiologic defect is impaired intracellular signaling in muscle tissue leading to defective glycogen synthesis. Insulin resistance is associated with numerous metabolic, hematologic, and cellular events that promote atherosclerosis and coagulation. The association between insulin resistance and risk for stroke has been examined in four case-control studies and five prospective observational cohort studies. Six of the nine studies are methodologically sound and provide evidence that insulin resistance is associated with risk for stroke. ConclusionInsulin resistance may be a prevalent risk factor for stroke. New drugs can safely reduce insulin resistance and may have a role in stroke prevention.

Impaired insulin sensitivity among nondiabetic patients with a recent TIA or ischemic stroke

Objectives: To determine the prevalence of impaired insulin sensitivity among nondiabetic patients with a recent TIA or nondisabling ischemic stroke. Methods: Eligible subjects were nondiabetic men and women over age 45 years who were hospitalized with a TIA or ischemic stroke. To measure insulin sensitivity, subjects underwent an oral glucose tolerance test between 2 and 6 months after their event. Impaired insulin sensitivity was defined by a value of ≤2.5 on the Composite Insulin Sensitivity Index derived from insulin and glucose values during the test. Results: Between July 2000 and June 2001, we identified 177 eligible patients, among whom 105 declined to participate and 72 enrolled. The median age of participants was 71 years and 46 (64%) were men. The baseline event was stroke for 57 subjects (79%). A history of myocardial infarction (MI) was reported by 14 subjects (19%), and 16 (22%) were obese (body mass index > 30). Fasting glucose was normal (<110 mg/dL) for 58 (80%) participants and impaired (110 to 125 mg/dL) for 14 (20%). Among 72 participants, the median insulin sensitivity index value was 2.6 (range 0.9 to 10.2). The prevalence of impaired insulin sensitivity was 36 of 72 (50%, 95% CI 38% to 62%). Impaired insulin sensitivity was more prevalent among younger patients and patients with obesity, lacunar stroke etiology, and disability (Rankin grade >1). Conclusion: Impaired insulin sensitivity is highly prevalent among nondiabetic patients with a recent TIA or nondisabling ischemic stroke. This finding has important therapeutic implications if treatment to improve insulin sensitivity is shown to reduce risk for subsequent stroke and heart disease.

BRIEF REPORT: Identification and Management of Overweight and Obesity by Internal Medicine Residents

AbstractBACKGROUND: Obesity is a major cause of morbidity and mortality in the United States. OBJECTIVE: To assess how frequently Internal Medicine residents identify and manage overweight and obese patients and to determine patient characteristics associated with identification and management of overweight compared with obesity. DESIGN: A cross-sectional medical record review. PATIENTS: Four hundred and twenty-four overweight or obese primary care patients from 2 Internal Medicine resident clinics in Connecticut. MEASUREMENTS: Measurements included the frequency with which obese and overweight patients were identified as such by their resident physicians, patient demographics, and co-morbid illnesses, as well as use of management strategies for excess weight. RESULTS: In this population of obese and overweight patients, obese patients were identified and treated more often compared with overweight patients (76/246%, 30.9% vs 12/178%, 7.3% for identification, P=.001, and 59/246%, 24.0% vs 11/178%, 6.2% for treatment, P=.001). Overall, only 70/424 (17%) of patients received any form of management. Only higher body mass index (BMI) (BMI ≥30 kg/m2 compared with BMI 25–29.9 kg/m2) was independently associated with identification of overweight or obesity (odds ratio 7.51%, 95% confidence interval [CI] 3.76 to 15.02] or with any management for excess weight (odds ratio 4.79%, 95% CI 2.44 to 9.42). CONCLUSIONS: Our results suggest that Internal Medicine residents markedly underrecognize and undertreat overweight and obesity.

The use of warfarin in veterans with atrial fibrillation

BackgroundWarfarin therapy is effective for the prevention of stroke in patients with atrial fibrillation. However, warfarin therapy is underutilized even among ideal anticoagulation candidates. The purpose of this study was to examine the use of warfarin in both inpatients and outpatients with atrial fibrillation within a Veterans Affairs (VA) hospital system.MethodsThis retrospective medical record review included outpatients and inpatients with atrial fibrillation. The outpatient cohort included all patients seen in the outpatient clinics of the VA Connecticut Healthcare System during June 2000 with a diagnosis of atrial fibrillation. The inpatient cohort included all patients discharged from the VA Connecticut Healthcare System West Haven Medical Center with a diagnosis of atrial fibrillation during October 1999 – March 2000. The outcome measure was the rate of warfarin prescription in patients with atrial fibrillation.ResultsA total of 538 outpatients had a diagnosis of atrial fibrillation and 73 of these had a documented contraindication to anticoagulation. Among the 465 eligible outpatients, 455 (98%) were prescribed warfarin. For the inpatients, a total of 212 individual patients were discharged with a diagnosis of atrial fibrillation and 97 were not eligible for warfarin therapy. Among the 115 eligible inpatients, 106 (92%) were discharged on warfarin.ConclusionsIdeal anticoagulation candidates with atrial fibrillation are being prescribed warfarin at very high rates within one VA system, in both the inpatient and outpatient settings; we found warfarin use within our VA was much higher than that observed for Medicare beneficiaries in our state.

Intravenous thrombolysis in acute ischaemic stroke: optimising its use in routine clinical practice.

Stroke is a common and important medical problem. Intravenous thrombolysis with alteplase (recombinant tissue plasminogen activator; rtPA) is the only available direct treatment that reduces neurological injury following ischaemic stroke. Strong efficacy data from randomised, controlled trials support the use of intravenous thrombolysis to improve outcomes for patients with acute ischaemic stroke. Numerous studies have provided effectiveness data that demonstrate that intravenous thrombolytic therapy can be given safely outside clinical trial settings. However, effectiveness studies have demonstrated that intravenous thrombolytic therapy is often given despite protocol violations when it is prescribed in routine clinical practice. Protocol violations must be avoided because they are associated with adverse events including higher mortality and increased haemorrhagic complications. Although thrombolytic therapy with alteplase is currently being used in only <10% of patients with acute ischaemic stroke, recent studies demonstrate that quality management efforts can improve both the absolute rate of use as well as the proficiency with which alteplase is administered. Given the complexities inherent in prescribing thrombolysis for patients with acute ischaemic stroke, alteplase should be used by clinicians who are experienced in the diagnosis and management of stroke, working in medical centres that have systems in place to ensure that alteplase is given without protocol violations.

Incidence of and factors associated with achieving target lipid levels in patients with peripheral arterial disease

AbstractBACKGROUND: Patients with peripheral arterial disease (PAD) have increased mortality compared with patients without PAD. Coronary artery disease (CAD) accounts for almost 75% of deaths in PAD patients. Studies suggest that PAD is underdiagnosed and atherosclerotic risk factors undertreated when compared with CAD. OBJECTIVE: To determine whether cholesterol guidelines are being met in patients with PAD and to determine whether any independent factors increase the likelihood of reaching goal low-density lipoprotein (LDL). DESIGN: A retrospective chart review of subjects diagnosed with PAD in 2001 at 2 Veterans Affairs Medical Centers. MEASUREMENTS: Univariate analysis compares baseline characteristics between those reaching goal and those who do not. Multivariate logistic regression analysis identified predictors of meeting LDL goal among PAD patients. RESULTS: Of 315 patients, 62% reached goal LDL. Those more likely to reach goal were older, had hypertension, and a history of CAD and stroke. Positive predictors of LDL goal were age and CAD, while smoking was a negative predictor. CONCLUSION: The majority of veterans with PAD received lipid-lowering medication and achieve goal LDL, but they are more likely to do so if they are older than 70 and have a history of CAD.

Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs).

Objective: Our purpose was to develop a geographically localized, multi-institution strategy for improving enrolment in a trial of secondary stroke prevention. Methods: We invited 11 Connecticut hospitals to participate in a project named the Local Identification and Outreach Network (LION). Each hospital provided the names of patients with stroke or TIA, identified from electronic admission or discharge logs, to researchers at a central coordinating center. After obtaining permission from personal physicians, researchers contacted each patient to describe the study, screen for eligibility, and set up a home visit for consent. Researchers traveled throughout the state to enroll and follow participants. Outside the LION, investigators identified trial participants using conventional recruitment strategies. We compared recruitment success for the LION and other sites using data from January 1, 2005, through June 30, 2007. Results: The average monthly randomization rate from the LION was 4.0 participants, compared with 0.46 at 104 other Insulin Resistance Intervention after Stroke (IRIS) sites. The LION randomized on average 1.52/1,000 beds/month, compared with 0.76/1,000 beds/month at other IRIS sites (p = 0.03). The average cost to randomize and follow one participant was

Thrombocytopenia and In-hospital Mortality Risk among Ischemic Stroke Patients

8,697 for the LION, compared with

Arterial Compliance in Elderly Men with Chronic Kidney Disease

7,198 for other sites. Conclusion: A geographically based network of institutions, served by a central coordinating center, randomized substantially more patients per month compared with sites outside of the network. The high enrollment rate was a result of surveillance at multiple institutions and greater productivity at each institution. Although the cost per patient was higher for the network, compared with nonnetwork sites, cost savings could result from more rapid completion of research.

An Organizational Innovation: The Yale Primary Care Residency Program's Experience With a Firm System

BACKGROUND Thrombocytopenia has been associated with increased mortality in nonstroke conditions. Because its role in acute ischemic stroke is less well understood, we sought to determine whether thrombocytopenia at admission for acute ischemic stroke was associated with in-hospital mortality. METHODS We used data from a retrospective cohort of stroke patients (1998-2003) at 5 U.S. hospitals. Risk factors considered included conditions that can lead to thrombocytopenia (e.g., liver disease), increase bleeding risk (e.g., hemophilia), medications with antiplatelet effects (e.g., aspirin), and known predictors of mortality (e.g., National Institutes of Health Stroke Scale and Charlson Comorbidity Index scores). Logistic regression modeling evaluated the adjusted association between thrombocytopenia, defined as platelets <100,000/μL, and in-hospital mortality. RESULTS Among 1233 acute ischemic stroke patients, thrombocytopenia was present in 2.3% (n = 28). A total of 6.1% (n = 75) of patients died in the hospital. In unadjusted analyses, thrombocytopenia was associated with higher mortality (8/28 [28.6%] v 67/1205 [5.6%]; P < .0001). Thrombocytopenia was also independently associated with in-hospital mortality after adjustment for National Institutes of Health Stroke Scale score and comorbidities, with an odds ratio of 6.6 (95% confidence interval 2.3-18.6). CONCLUSIONS Admission thrombocytopenia among patients presenting with acute ischemic stroke predicts in-hospital mortality.