Early-Life Social Determinants of SCA6 Age at Onset, Severity, and Progression.

SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) regressions were used to identify which early life factors are predictive of SCA6 AAO, severity, and progression. Multiple linear regression models were then used to assess the degree to which these determinants influence SCA6 health outcomes. A total of 105 participants with genetically confirmed SCA6 completed the assessments. SCA6 participants with maternal difficulty during pregnancy, active participation in school sports, and/or longer CAG repeats were determined to have earlier AAO. We found a 13.44-year earlier AAO for those with maternal difficulty in pregnancy than those without (p = 0.008) and a 12.31-year earlier AAO for those active in school sports than those who were not (p < 0.001). Higher education attainment was associated with decreased SCA6 severity and slower progression. Early life biological and social factors can have a strong influence on the SCA6 disease course, indicating that non-genetic factors can contribute significantly to SCA6 health outcomes.

Development and Validation of a Patient-Reported Outcome Measure of Ataxia.

BACKGROUND: Assessment of cerebellar ataxia has been confined to rating scales, gait laboratories, and wearable sensors agnostic to patient input. OBJECTIVES: The objective of this study was to develop a Patient-Reported Outcome Measure of Ataxia. METHODS: (1) The conceptual framework, item pool development, and domain selection were developed using online surveys completed by 147 ataxia patients. Responses generated the 70-item Patient-Reported Outcome Measure of Ataxia, scored on a 0-4 Likert scale. (2) Cognitive debrief in 17 patients grouped by ataxia severity assessed content validity, readability, and comprehension. (3) Psychometric validation by 78 anonymized ataxia patients included test-retest reliability, responsiveness to ataxia severity, internal consistency (Cronbach's alpha), and item-total score correlations. (4) Validation was tested against measures of ataxia and quality of life in 20 patients. (5) Items were rank-ordered to develop the Patient-Reported Outcome Measure of Ataxia Short Form. RESULTS: Three thousand eight hundred fifty-five symptoms were grouped into 3 domains (physical, activities of daily living, mental health) and 14 subdomains. The Patient-Reported Outcome Measure of Ataxia was comprehensible, important, and relevant. Internal consistency, reliability, and test-retest reliability were high. Scores were responsive to ataxia severity stages 1, 2, and 3: mean ± standard deviation 81.0 ± 37.0, 129.6 ± 32.0, and 151.1 ± 41.3, respectively (r = 0.58, P < 0.0001). The Patient-Reported Outcome Measure of Ataxia was validated against measures of motor ataxia, quality of life, and mental health. It had an R2 of 0.82 (P < 0.0001) with the preliminary Patient-Reported Outcome Measure of Ataxia Short Form. CONCLUSIONS: The Patient-Reported Outcome Measure of Ataxia is valid and reliable in cerebellar ataxia patients. It has the potential to improve patient care and natural history studies and quantify the efficacy of novel therapeutics in clinical trials. © 2021 International Parkinson and Movement Disorder Society.

Projecting long-term graft and patient survival after transplantation.

OBJECTIVE: In spite of increases in short-term kidney transplant survival rates and reductions in acute rejection rates, increasing long-term graft survival rates remains a major challenge. The objective here was to project long-term graft- and survival-related outcomes occurring among renal transplant recipients based on short-term outcomes including acute rejection and estimated glomerular filtration rates observed in randomized trials. METHODS: We developed a two-phase decision model including a trial phase and a Markov state transition phase to project long-term outcomes over the lifetimes of hypothetical renal graft recipients who survived the trial period with a functioning graft. Health states included functioning graft stratified by level of renal function, failed graft, functioning regraft, and death. Transitions between health states were predicted using statistical models that accounted for renal function, acute rejection, and new-onset diabetes after transplant and for donor and recipient predictors of long-term graft and patient survival. Models were estimated using data from 38,015 renal transplant recipients from the United States Renal Data System. The model was populated with data from a 3-year, randomized phase III trial comparing belatacept to cyclosporine. RESULTS: The decision model was well calibrated with data from the United States Renal Data System. Long-term extrapolation of Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial was projected to yield a 1.9-year increase in time alive with a functioning graft and a 1.2 life-year increase over a 20-year time horizon. CONCLUSIONS: This is the first long-term follow-up model of renal transplant patients to be based on renal function, acute rejection, and new-onset diabetes. It is a useful tool for undertaking comparative effectiveness and cost-effectiveness studies of immunosuppressive medications.

Video-Based Kinematic Analysis of Movement Quality in a Phase 3 Clinical Trial of Troriluzole in Adults with Spinocerebellar Ataxia: A Post Hoc Analysis.

INTRODUCTION: Traditional methods for assessing movement quality rely on subjective standardized scales and clinical expertise. This limitation creates challenges for assessing patients with spinocerebellar ataxia (SCA), in whom changes in mobility can be subtle and varied. We hypothesized that a machine learning analytic system might complement traditional clinician-rated measures of gait. Our objective was to use a video-based assessment of gait dispersion to compare the effects of troriluzole with placebo on gait quality in adults with SCA. METHODS: Participants with SCA underwent gait assessment in a phase 3, double-blind, placebo-controlled trial of troriluzole (NCT03701399). Videos were processed through a deep learning pose extraction algorithm, followed by the estimation of a novel gait stability measure, the Pose Dispersion Index, quantifying the frame-by-frame symmetry, balance, and stability during natural and tandem walk tasks. The effects of troriluzole treatment were assessed in mixed linear models, participant-level grouping, and treatment group-by-visit week interaction adjusted for age, sex, baseline modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA), and time since diagnosis. RESULTS: From 218 randomized participants, 67 and 56 participants had interpretable videos of a tandem and natural walk attempt, respectively. At Week 48, individuals assigned to troriluzole exhibited significant (p = 0.010) improvement in tandem walk Pose Dispersion Index versus placebo {adjusted interaction coefficient: 0.584 [95% confidence interval (CI) 0.137 to 1.031]}. A similar, nonsignificant trend was observed in the natural walk assessment [coefficient: 1.198 (95% CI - 1.067 to 3.462)]. Further, lower baseline Pose Dispersion Index during the natural walk was significantly (p = 0.041) associated with a higher risk of subsequent falls [adjusted Poisson coefficient: - 0.356 [95% CI - 0.697 to - 0.014)]. CONCLUSION: Using this novel approach, troriluzole-treated subjects demonstrated improvement in gait as compared to placebo for the tandem walk. Machine learning applied to video-captured gait parameters can complement clinician-reported motor assessment in adults with SCA. The Pose Dispersion Index may enhance assessment in future research. TRIAL REGISTRATION-CLINICALTRIALS. GOV IDENTIFIER: NCT03701399.

The burden of illness for patients with viral hepatitis C: evidence from a national survey in Japan.

OBJECTIVE: Viral hepatitis C (HCV) affects 170 million patients worldwide and 2 million patients in Japan. The objective of the current study was to examine the burden of HCV in Japan from a patient's perspective. METHODS: Using data from the 2008 and 2009 Japan National Health and Wellness Surveys, patients who reported an HCV diagnosis (n = 306) were compared with a propensity-score-matched control group (n = 306) on measures of quality of life (using the Medical Outcomes Study 12-Item Short Form Survey Instrument version 2), work productivity (using the Work Productivity and Activity Impairment questionnaire), and health-care resource use. All analyses applied sampling weights to project to the population. RESULTS: Prior to matching, patients with HCV had higher rates of hepatocellular carcinoma (4.88% vs. 0.02%) and cirrhosis (12.20% vs. 0.11%) than did subjects without HCV. The propensity-matching process eliminated differences between the two groups on demographics and patient characteristics. The postmatching analysis found significantly lower levels of quality of life for patients with HCV as measured by bodily pain (72.07 vs. 76.28), general health (44.64 vs. 48.61), and mental health (66.50 vs. 70.32) (all Ps < 0.05). Furthermore, compared with the matched group, the HCV group had significantly higher workplace absenteeism (8.59% vs. 4.12%), overall work impairment (26.08% vs. 17.32%), and health-care provider visits in the past 6 months (14.80 vs. 9.74). CONCLUSIONS: The results of this study suggest that HCV can be a substantial burden on patients in terms of quality of life in both physical and mental health measures. In addition, HCV can be a significant cost driver in terms of health-care use and lost productivity.

Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose?

BACKGROUND: The benefits of some second-generation antipsychotics (SGAs) must be weighed against the increased risk for diabetes mellitus. This study examines whether the association between SGAs and diabetes differs by dose. METHODS: Patients were ≥18 years of age from three US healthcare systems and exposed to an SGA for ≥45 days between November 1, 2002 and March 31, 2005. Patients had no evidence of diabetes before index date and no previous antipsychotic prescription filled within 3 months before index date.49,946 patients were exposed to SGAs during the study period. Person-time exposed to antipsychotic dose (categorized by tertiles for each drug) was calculated. Newly treated diabetes was identified using pharmacy data to determine patients exposed to anti-diabetic therapies. Adjusted hazard ratios for diabetes across dose tertiles of SGA were calculated using the lowest dose tertile as reference. RESULTS: Olanzapine exhibited a dose-dependent relationship for risk for diabetes, with elevated and progressive risk across intermediate (diabetes rate per 100 person-years = 1.9; adjusted Hazard Ratio (HR), 1.7, 95% confidence interval (CI), 1.0-3.1) and top tertile doses (diabetes rate per 100 person-years = 2.7; adjusted HR, 2.5, 95% CI, 1.4-4.5). Quetiapine and risperidone exhibited elevated risk at top dose tertile with no evidence of increased risk at intermediate dose tertile. Unlike olanzapine, quetiapine, and risperidone, neither aripiprazole nor ziprasidone were associated with risk of diabetes at any dose tertile. CONCLUSIONS: In this large multi-site epidemiologic study, within each drug-specific stratum, the risk of diabetes for persons exposed to olanzapine, risperidone, and quetiapine was dose-dependent and elevated at therapeutic doses. In contrast, in aripiprazole-specific and ziprasidone-specific stratum, these newer agents were not associated with an increased risk of diabetes and dose-dependent relationships were not apparent. Although, these estimates should be interpreted with caution as they are imprecise due to small numbers.

UK cost-consequence analysis of aripiprazole in schizophrenia: diabetes and coronary heart disease risk projections (STAR study).

Patients with schizophrenia experience elevated rates of morbidity and mortality, largely due to an increased incidence of cardiovascular disease and diabetes. There is increasing concern that some atypical antipsychotic therapies are associated with adverse metabolic symptoms, such as weight gain, dyslipidaemia and glucose dysregulation. These metabolic symptoms may further increase the risk of coronary heart disease (CHD) and diabetes in this population and, subsequently, the cost of treating these patients' physical health. The STAR study showed that the metabolic side effects of aripiprazole treatment are less than that experienced by those receiving standard-of-care (SOC). In a follow-up study the projected risks for diabetes or CHD, calculated using the Stern and Framingham models, were lower in the aripiprazole treatment group. Assuming the risk of diabetes onset/CHD events remained linear over 10 years, these risks were used to estimate the difference in direct and indirect cost consequences of diabetes and CHD in schizophrenia patients treated with aripiprazole or SOC over a 10-year period. Diabetes costs were estimated from the UKPDS and UK T(2)ARDIS studies, respectively, and CHD costs were estimated using prevalence data from the Health Survey of England and the published literature. All costs were inflated to 2007 costs using the NHS pay and prices index. The number of avoided diabetes cases (23.4 cases per 1,000 treated patients) in patients treated with aripiprazole compared with SOC was associated with estimated total (direct and indirect) cost savings of 37,261,293 pounds over 10 years for the UK population. Similarly, the number of avoided CHD events (3.7 events per 1,000 treated patients) was associated with estimated total cost savings of 7,506,770 pounds over 10 years. Compared with SOC, aripiprazole treatment may provide reductions in the health and economic burden to schizophrenia patients and health care services in the UK as a result of its favourable metabolic profile.

Risk of diabetes mellitus associated with atypical antipsychotic use among Medicaid patients with bipolar disorder: a nested case-control study.

STUDY OBJECTIVE: To quantify the risk of diabetes mellitus associated with atypical antipsychotics compared with conventional antipsychotics in managed care Medicaid patients with bipolar disorder. DESIGN: Retrospective nested case-control study. DATA SOURCE: Integrated seven-state Medicaid managed care claims database from January 1, 1998-December 31, 2002. PATIENTS: Two hundred eighty-three patients with diabetes (cases) and 1134 controls matched by age, sex, and the index date on which bipolar disorder was diagnosed. MEASUREMENTS AND MAIN RESULTS: Cases were defined as those having an International Classification of Diseases, Ninth Revision diagnosis of diabetes or those receiving treatment with antidiabetic drugs. Both case and control patients had at least a 3-month exposure to either conventional or atypical antipsychotic agents or three filled prescriptions related to treatment for bipolar disorder. Of the 283 cases, 139 (49%) received atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, and clozapine) and 133 (47%) were prescribed conventional antipsychotics. To compare the risk for new-onset diabetes associated with atypical versus conventional antipsychotics, we conducted a Cox proportional hazard regression, in which we controlled for age; sex; duration of bipolar disorder follow-up; use of lithium, anticonvulsants, antidepressants, and other drugs; and psychiatric and medical comorbidities. Compared with patients receiving conventional antipsychotics, the risk of diabetes was greatest among patients taking risperidone (hazard ratio [HR] 3.8, 95% confidence interval [CI] 2.7-5.3), olanzapine (3.7, 95% CI 2.5-5.3), and quetiapine (2.5, 95% CI 1.4-4.3). The risk for developing diabetes was also associated with weight gain (HR 2.5, 95% CI 1.9-3.4), hypertension (HR 1.6, 95% CI 1.2-2.2), and substance abuse (HR 1.5, 95% CI 1.0-2.2). CONCLUSION: Olanzapine, risperidone, and quetiapine are all associated with development or exacerbation of diabetes mellitus in patients with bipolar disorder. When prescribing therapy for this patient population, metabolic complications such as diabetes, weight gain, and hypertension need to be considered.

Hyperlipidemia following treatment with antipsychotic medications.

OBJECTIVE: This study attempted to estimate the relative risk of developing hyperlipidemia after treatment with antipsychotics in relation to no antipsychotic treatment. METHOD: A matched case-control analysis was performed with pharmacy and claims data from California Medicaid (Medi-Cal). Patients were excluded if they were treated for medical disorders or prescribed medications known to increase their risk of hyperlipidemia. Cases were ages 18 to 64 years with schizophrenia, major depression, bipolar disorder, or other affective psychoses and incident hyperlipidemia. Cases were matched to up to six control subjects by age, sex, race, and psychiatric diagnosis. Both groups were prescribed either no antipsychotic medication or had two or more prescriptions for one and only one antipsychotic medication during the 60 days prior to the first indication of hyperlipidemia (cases) or matched index date (controls) in the billing record. Conditional logistic regressions were used to derive odds ratios and 95% confidence intervals (95% CIs) of each antipsychotic medication in relation to no antipsychotic medication. RESULTS: A total of 13,133 incident cases of hyperlipidemia were matched to 72,140 control subjects. As compared with no antipsychotic medication, treatment with clozapine (odds ratio: 1.82, 95% CI: 1.61-2.05), risperidone (odds ratio: 1.53, 95% CI: 1.43-1.64), quetiapine (odds ratio: 1.52, 95% CI: 1.40-1.65), olanzapine (odds ratio: 1.56, 95% CI: 1.47-1.67), ziprasidone (odds ratio: 1.40, 95% CI: 1.19-1.65), and first-generation antipsychotics (odds ratio: 1.26, 95% CI: 1.14-1.39), but not aripiprazole (odds ratio: 1.19, 95% CI: 0.94-1.52) was associated with a significant increase in risk of incident hyperlipidemia. CONCLUSIONS: These findings suggest that most commonly prescribed antipsychotic medications increase the risk of developing hyperlipidemia in patients with schizophrenia or mood disorders.

Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: A retrospective, population-based, case-control study.

BACKGROUND: Drug-induced diabetes onset has not been adequately quantified in patients with bipolar disorder, although atypical antipsychotics have been widely used as new mood stabilizers. OBJECTIVES: To quantify the association between atypical antipsychotics and diabetes mellitus. METHOD: A retrospective, population-based, case-control study was conducted using the medical claims database from U.S. managed care organizations from January 1, 1998, to December 31, 2002. Nine hundred twenty incident cases of diabetes were matched with 5258 controls by age, sex, and bipolar index month and year. Diabetes cases were identified by either diagnosis of ICD-9 codes or diabetic medications. Patients with diabetes had a minimum 3-month exposure to any medications or at least 3 prescriptions for their bipolar or comorbidity treatment. Cox proportional hazard regression was conducted to assess the risk of diabetes associated with antipsychotic use. RESULTS: Of 920 cases, 41% received atypical antipsychotics (e.g., olanzapine, risperidone, quetiapine, ziprasidone, clozapine) and 34% received conventional antipsychotics. Compared to patients receiving conventional antipsychotics, the risk of diabetes was greatest among patients taking clozapine (hazard ratio [HR] = 7.0, 95% confidence interval [CI] = 1.7 to 28.9), risperidone (HR = 3.4, 95% CI = 2.8 to 4.2), olanzapine (HR = 3.2, 95% CI = 2.7 to 3.8), and quetiapine (HR = 1.8, 95% CI =1.4 to 2.4), with controlling covariates of age; sex; duration of follow-up; use of lithium, anticonvulsants, antidepressants, or concomitant drugs; and psychiatric and medical comorbidities. CONCLUSION: Development or exacerbation of diabetes mellitus is associated with antipsychotic use in bipolar patients. Metabolic complications are a major issue in patients receiving antipsychotic therapy. Thus, the propensity of an antipsychotic to induce diabetes should be a consideration when selecting an agent for patients with bipolar disorder.

New National Cholesterol Education Program III guidelines for primary prevention lipid-lowering drug therapy: projected impact on the size, sex, and age distribution of the treatment-eligible population.

BACKGROUND: The guidelines in the Third Report of the National Cholesterol Education Program (NCEP III) include absolute risk and lower LDL cholesterol (LDL-C) levels to assess eligibility for lipid-lowering drug therapy. We studied the impact of these changes on the size, sex, and age distribution of the target US population using data from the Third Annual National Health and Nutrition Survey (NHANES III) (1988 to 1994). METHODS AND RESULTS: A subsample of NHANES III participants aged 20 to 79 years with known cardiovascular risk factors and LDL-C levels was identified (n=13 589). We assessed their eligibility for drug therapy first using NCEP II guidelines and then using the new NCEP III criteria. We also calculated the number eligible for LDL-C lowering to <100 mg/dL. An estimated 15 million individuals aged 20 to 79 years are eligible for drug therapy under NCEP II; 51% are males, 49% are females, 26% are <45 years old, and 28% are > or =65 years old. Under NCEP III, 36 million would be eligible for treatment; 55% are males, 45% are females, 32% are <45 years old, and 27% are > or =65 years old. This represents a 140% increase in eligibility overall, a 157% increase among males, a 122% increase among females, a 131% increase among those > or =65 years old, and a 201% increase among those < 45 years old. Of treatment-eligible individuals, 26% of males, 24% of females, 39% of elderly, and 14% of those <45 years old are targeted for LDL-C lowering to <100 mg/dL. CONCLUSIONS: The NCEP III guidelines will alter the age and sex distributions of the treatment-eligible population, targeting many more younger (<45 years old) and greater numbers of elderly (> or =65 years) individuals, particularly for aggressive intervention.

Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults.

BACKGROUND: Mortality resulting from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in persons with diabetes and pre-existing CVD is high; however, these risks compared with those with metabolic syndrome (MetS) are unclear. We examined the impact of MetS on CHD, CVD, and overall mortality among US adults. METHODS AND RESULTS: In a prospective cohort study, 6255 subjects 30 to 75 years of age (54% female) (representative of 64 million adults in the United States) from the Second National Health and Nutrition Examination Survey were followed for a mean+/-SD of 13.3+/-3.8 years. MetS was defined by modified National Cholesterol Education Program criteria. From sample-weighted multivariable Cox proportional-hazards regression, compared with those with neither MetS nor prior CVD, age-, gender-, and risk factor-adjusted hazard ratios (HRs) for CHD mortality were 2.02 (95% CI, 1.42 to 2.89) for those with MetS and 4.19 (95% CI, 3.04 to 5.79) for those with pre-existing CVD. For CVD mortality, HRs were 1.82 (95% CI, 1.40 to 2.37) and 3.14 (95% CI, 2.49 to 3.96), respectively; for overall mortality, HRs were 1.40 (95% CI, 1.19 to 1.66) and 1.87 (95% CI, 1.60 to 2.17), respectively. In persons with MetS but without diabetes, risks of CHD and CVD mortality remained elevated. Diabetes predicted all mortality end points. Those with even 1 to 2 MetS risk factors were at increased risk for mortality from CHD and CVD. Moreover, MetS more strongly predicts CHD, CVD, and total mortality than its individual components. CONCLUSIONS: CHD, CVD, and total mortality are significantly higher in US adults with than in those without MetS.

An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients.

BACKGROUND: The newer antipsychotic agents exhibit a superior safety profile compared with conventional antipsychotic agents in terms of extrapyramidal symptoms. Previous studies have suggested an association between olanzapine treatment and hyperlipidemia. We evaluated this association using a large health care database. METHODS: The study was derived from the England and Wales-based General Practice Research Database, composed of 3.5 million subjects followed up between June 1, 1987, and September 24, 2000. A total of 18 309 individuals diagnosed as having schizophrenia were identified. A 6:1 matched nested case-control design was used. Conditional logistic regression was used to derive adjusted odds ratios (ORs), controlling for sex, age, and other medications and disease conditions influencing lipid levels. Antipsychotic drug exposure was defined as the receipt of at least 1 prescription for an antipsychotic medication within the 3 months before the date of diagnosis of hyperlipidemia. RESULTS: There were 1268 incident cases of hyperlipidemia in the cohort, matched to 7598 control subjects. Olanzapine use was associated with nearly a 5-fold increase in the odds of developing hyperlipidemia compared with no antipsychotic exposure (OR, 4.65; 95% confidence interval [CI], 2.44-8.85) (P<.001) and more than a 3-fold increase compared with those receiving conventional agents (OR, 3.36; 95% CI, 1.77-6.39) (P<.001). Risperidone was not associated with increased odds of hyperlipidemia compared with no antipsychotic exposure (OR, 1.12; 95% CI, 0.60-2.11) (P =.72) or conventional antipsychotic exposure (OR, 0.81; 95% CI, 0.44-1.52) (P =.52). CONCLUSIONS: We observed a strong association between olanzapine exposure and hyperlipidemia in schizophrenic patients. The possible metabolic consequences of olanzapine use should be given serious consideration by treating physicians.

Prevalence and control of dyslipidemia among persons with diabetes in the United States.

OBJECTIVE: We assessed the prevalence, treatment, and control of dyslipidemia among United States (U.S.) adults with diabetes. METHODS: Among 498 adults (projected to 13.4 million) aged >or=18 years with diabetes representative of the U.S. population and surveyed within the cross-sectional National Health and Nutrition Examination Survey 1999-2000, control of lipids was classified according to American Diabetes Association criteria. The extent of low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) control was examined by gender and ethnicity, in comparison to those without diabetes, and according to lipid-lowering treatment. Analyses were weighted to the U.S. population. RESULTS: Less than one-third of men and only one-fifth of women with diabetes are in control for LDL-C, defined as <2.6 mmol/l (<100mg/dl); over 70% are not at goal. Over half of men and over two-thirds of women have low levels of HDL-C (or=1.7 mmol/l [150 mg/dl]). Low HDL-C was more common in Caucasians (70.1%) than in Hispanics (58.8%) or African-Americans (41.5%) (p<0.001). 28.2% of subjects with diabetes were on lipid-lowering treatment. Control of LDL-C did not differ by treatment status and only 3% of subjects were controlled to target levels for all lipids. CONCLUSION: Many persons with diabetes remain uncontrolled for dyslipidemia. Intensified efforts at screening and treatment according to current guidelines are warranted.

Physician-related barriers to the effective management of uncontrolled hypertension.

BACKGROUND: Primary care physicians may not be aggressive enough with the management of hypertension. The purpose of this study was to identify barriers to primary care physicians' willingness to increase the intensity of treatment among patients with uncontrolled hypertension. METHODS: Descriptive survey study. We sampled patient visits in a large midwestern health system to identify patients with uncontrolled hypertension. The treating primary care physicians were asked to complete a survey about the patient visit with a copy of the office notes attached to the survey (patient visits, n = 270; response rate, 86%). RESULTS: Pharmacologic therapy was initiated or changed at only 38% of visits, despite documented hypertension for at least 6 months before the patients' most recent visit. The most frequently cited reason for no initiation or change in therapy was related to the primary care physicians being satisfied with the blood pressure (BP) value (satisfactory BP response, 30%; satisfactory diastolic BP response, 16%; only borderline hypertension, 10%). At 93% of these visits, systolic BP values were 140 mm Hg or higher, which is above the cut point recommended by Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, and 35% were 150 mm Hg or higher. On average, physicians reported that 150 mm Hg was the lowest systolic BP at which they would recommend pharmacologic treatment to patients, compared with 91 mm Hg for diastolic BP. CONCLUSIONS: Our findings suggest that an important reason why physicians do not treat hypertension more aggressively is that they are willing to accept an elevated systolic BP in their patients. This has an important impact on public health because of the positive association between systolic BP and cardiovascular disease.

Skin reactions in patients with influenza treated with oseltamivir: a retrospective cohort study.

Oseltamivir phosphate is an FDA-approved treatment for influenza that has been available for prescription use in the USA since 1999. The present report describes findings from a post-marketing safety study of skin reactions associated with oseltamivir use. All patients in the claims-derived Ingenix Research Database with a physician diagnosis of influenza and/or a dispensing of oseltamivir between 1 December 1999 and 31 March 2002 were identified. Cohort eligibility criteria included minimum baseline enrolment duration of 3 months, age of at least 1 year and no influenza vaccination on the date of influenza diagnosis or oseltamivir dispensing. Patients were classified into two primary cohorts, influenza diagnosis and oseltamivir dispensing on the same day, and influenza diagnosis but no oseltamivir at any time, and a cohort included for secondary analyses comprising patients who received an oseltamivir dispensing without an influenza diagnosis on the same day. Outcomes included general skin reactions and several specific skin reactions. Events occurring during the 30 days following the date of influenza diagnosis or oseltamivir dispensing were examined using Cox proportional hazards models. Model covariates included age, use of another influenza drug, month and year of index date, and use of antitussives. Adjusted rate ratios for the general class of skin reactions among the primary cohort of oseltamivir users versus non-users were 1.05 (95% CI: 0.88-1.24) for incident cases and 0.98 (95% CI: 0.77-1.24) among patients with a history of a skin reaction. Similar results were seen for the other skin reaction categories, and secondary analyses investigating the oseltamivir users without influenza revealed no elevation in risk. It is concluded that oseltamivir use does not appear to be associated with an increased risk of skin reactions.

The expanding national burden of heart failure in the United States: the influence of heart failure in women.

BACKGROUND: Although some studies have shown that hospital admissions for heart failure doubled between 1973 and 1995, other data suggest that the heart failure hospitalization epidemic has stabilized in the United States. We sought to describe trends in heart failure hospitalizations over the past decade using data from the National Hospital Discharge Survey (NHDS). METHODS: The NHDS provides annual estimates of hospitalization discharges from a sample of hospitals in the United States. We combined the heart failure hospitalization frequencies with census estimates to calculate age and gender-specific annual hospitalization rates. RESULTS: Hospitalizations with a primary diagnosis of heart failure among adults (age > or =35) increased from 810,624 in 1990 to 989,500 in 1995 (annual increase 36,088, R2 = 0.816, P =.014), and to 1,088,349 in 1999 (annual increase 31,091, R2 = 0.780, P =.047). The age-adjusted hospitalization rate (per 1000 persons) increased from 7.186 in 1990 to 8.554 in 1999 for women (annual increase 0.14/year, R2 = 0.731, P =.002) and from 6.892 in 1990 to 7.372 in 1999 for men (annual increase 0.011/year, R2 = 0.008, P = 0.80). For women, the annual hospitalization rate increased from 1990 to 1999 in each age group (35-64, 65-74, 75-84, and > or =85), while the age-specific rates did not change in men. CONCLUSIONS: Heart failure hospitalizations have continued to increase from 1990 to 1999. Although aging and growth of the US population contribute to this trend, the increases are substantially influenced by changes in hospitalization rates in women.

Regional variation in health care utilization and outcomes in ischemic stroke.

Little information is available about regional variation in health care utilization and the effect of utilization on outcomes after ischemic stroke. The goal of this study was to investigate the effect of regional variation in outpatient health care use on mortality after ischemic stroke. We performed a retrospective cohort study of 55,094 veterans hospitalized for ischemic stroke at any US Veterans Affairs Medical Center between October 1, 1990, and September 30, 1997. We extracted administrative data on patient demographics, coexisting medical conditions, site of hospitalization, inpatient and outpatient health care utilization, and all-cause mortality during hospitalization and after stroke discharge. Predictors of long-term mortality in patients surviving at least 60 days post-stroke were modeled using Cox regression. Patients in the Northeast part of the country had higher comorbidity scores, a longer median length of stay, and higher in-hospital mortality than patients in other regions. However, Northeast and West patients had lower all-cause mortality after stroke than those in the Midwest or South. Patients in the Northeast (28%) and West (32%) were also more likely than those in the South (21%) or Midwest (22%) to have a neurology and/or general medicine visit within 60 days of discharge (P < .001). Adjusted mortality (HR, 95% CI) was lower in the Northeast (0.84, 0.80-0.88) and West (0.93, 95% CI 0.89, 0.97), and in patients with neurology (0.72, 0.67-0.77) or general medicine (0.85, 0.81-0.89) follow-up within 60 days of stroke discharge. We concluded that regional variation exists in patient outcomes and patterns of care following stroke. Mortality is lower in regions where more patients have early outpatient care after stroke. Prospective studies evaluating the cause and impact of these variations are needed to identify optimal stroke care practices.

Cost of Heart Failure in Patients Receiving beta-Blockers and Angiotensin-Converting Enzyme Inhibitors.

OBJECTIVE: Numerous studies support the benefit of beta-blockers and angiotensin-converting enzyme inhibition (ACE-I) in the management of heart failure. However, the real-world cost of heart failure in patients who take these medications is not well documented; furthermore, it is unclear if heart failure costs remain significant when current, appropriately aggressive care is delivered. DESIGN: This study describes 1-year medical costs in patients hospitalised for heart failure who received these therapies, alone or in combination. METHODS: The study population was derived from 2.5 million patients with at least 3 years' continuous eligibility in Pharmetrics((R)), an integrated claims and pharmacy database on approximately 25 million covered lives from 40 US health plans. The enrolment period was from 1 January 1996 to 31 December 2000. Costs included all recorded payments over a 1-year period. A total of 3073 patients (age >18 years) hospitalised with heart failure were identified (mean [+/- SD] age 72 +/- 13 years; 46% female). RESULTS: The 1-year cost was $US16 786 in patients who received neither ACE inhibitors nor beta-blockers as compared with $US19 567, $US22 785 and $US27 078 in patients who received ACE inhibitors, beta-blockers or both drugs at maximum dosage, respectively (p < 0.001) [year of costing 2000]. Follow-up costs were substantial, representing almost twice the initial hospitalisation cost. Adjusted for age, sex, diabetes mellitus, coronary disease, hypertension and renal failure, costs remained significant in heart failure patients who received ACE inhibitors and/or beta-blockers. CONCLUSIONS: The 1-year cost of therapy for patients with heart failure is substantial, and there remains considerable need for more effective therapy to reduce the societal economic burden.