Glenn K. Goodrich

Impairment of executive cognitive functioning in males with fragile X-associated tremor/ataxia syndrome

The fragile X‐associated tremor/ataxia syndrome (FXTAS) is a recently identified phenotype associated with trinucleotide repeat expansions in the premutation range of the fragile X mental retardation 1 (FMR1) gene. In addition to progressive gait ataxia, action tremor, peripheral neuropathy, and parkinsonism, FXTAS involves impaired cognition. Our preliminary research suggests that executive cognitive functioning (ECF) is especially affected. In this study, a brief neuropsychological exam was administered to 33 men with FXTAS and 27 healthy controls. Compared with controls, individuals with FXTAS showed statistically significant impairments on measures from the Wechsler Adult Intelligence Scale, third edition (WAIS‐III; verbal IQ, performance [nonverbal] IQ, verbal comprehension, perceptual organization, and processing speed). FXTAS subjects scored significantly lower on three of four measures of ECF and on two tests of information processing speed. The results provide evidence that FXTAS involves impairment of general intellectual functioning, with marked impairment of executive cognitive abilities. The pattern of cognitive performance is somewhat similar to that observed in the frontal variant of frontotemporal dementia and several of the spinocerebellar ataxias, but differs from the deficits observed in dementia of the Alzheimer type.

The primary cognitive deficit among males with fragile X-associated tremor/ataxia syndrome (FXTAS) is a dysexecutive syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with a premutation trinucleotide repeat expansion in the fragile X mental retardation 1 gene. Symptoms include gait ataxia, action tremor, and cognitive impairment. The objectives of the study were to clarify the nature of the dysexecutive syndrome observed in FXTAS and to assess the contribution of executive impairment to deficits in nonexecutive cognitive functions. Compared to controls, men with FXTAS demonstrated significant executive impairment, which was found to mediate group differences in most other cognitive abilities. Asymptomatic premutation carriers performed similarly to controls on all but two measures of executive functioning. These findings suggest that the impairment of nonexecutive cognitive skills in FXTAS is in large part secondary to executive dysfunction.

Construction of a Multisite DataLink Using Electronic Health Records for the Identification, Surveillance, Prevention, and Management of Diabetes Mellitus: The SUPREME-DM Project

Introduction Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. Methods We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. Results The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. Conclusion The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.

Geographic variation in cardiovascular procedure use among medicare fee-for-service vs medicare advantage beneficiaries

IMPORTANCE Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. OBJECTIVE To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. MAIN OUTCOMES AND MEASURES Rates of coronary angiography, PCI, and CABG surgery. RESULTS We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. CONCLUSIONS AND RELEVANCE Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.

Pragmatic Trial of Health Care Technologies to Improve Adherence to Pediatric Asthma Treatment: A Randomized Clinical Trial

IMPORTANCE Most patients with asthma take fewer than half of prescribed doses of controller medication. Interventions to improve adherence have typically been costly, impractical, and at best only minimally successful. OBJECTIVE To test a speech recognition (SR) intervention to improve adherence to pediatric asthma controller medication. DESIGN, SETTING, AND PARTICIPANTS The Breathe Well study was a 24-month pragmatic randomized clinical trial. The study was conducted within Kaiser Permanente Colorado, a large, group-model health maintenance organization. A total of 1187 children aged 3 to 12 years with a persistent asthma diagnosis and prescription for an inhaled corticosteroid were randomized to the computerized SR intervention or usual care condition and followed up for 24 months between October 2009 and February 2013. INTERVENTIONS Speech recognition telephone calls to parents in the intervention condition were triggered when an inhaled corticosteroid refill was due or overdue. Calls were automatically tailored with medical and demographic information from the electronic health record and from parent answers to questions in the call regarding recent refills or a desire to receive help refilling, learn more about asthma control, or speak with an asthma nurse or pharmacy staff member. MAIN OUTCOMES AND MEASURES Adherence to pediatric asthma controller medication, measured as the medication possession ratio over 24 months. RESULTS In the intention-to-treat analysis, inhaled corticosteroid adherence was 25.4% higher in the intervention group than in the usual care group (24-month mean [SE] adherence, 44.5% [1.2%] vs 35.5% [1.1%], respectively; P < .001). Asthma-related urgent care events did not differ between the 2 groups. The intervention effect was consistent in subgroups stratified by age, sex, race/ethnicity, body mass index, and disease-related characteristics. CONCLUSIONS AND RELEVANCE The interventions significant impact on adherence demonstrates strong potential for low-cost SR adherence programs integrated with an electronic health record. The absence of change in urgent care visits may be attributable to the already low number of asthma urgent care visits within Kaiser Permanente Colorado. Application of electronic health record-leveraged SR interventions may reduce health care utilization when applied in a population with less-controlled asthma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00958932.

Preventable Major Cardiovascular Events Associated With Uncontrolled Glucose, Blood Pressure, and Lipids and Active Smoking in Adults With Diabetes With and Without Cardiovascular Disease: A Contemporary Analysis

OBJECTIVE The objective of this study was to assess the incidence of major cardiovascular (CV) hospitalization events and all-cause deaths among adults with diabetes with or without CV disease (CVD) associated with inadequately controlled glycated hemoglobin (A1C), high LDL cholesterol (LDL-C), high blood pressure (BP), and current smoking. RESEARCH DESIGN AND METHODS Study subjects included 859,617 adults with diabetes enrolled for more than 6 months during 2005–2011 in a network of 11 U.S. integrated health care organizations. Inadequate risk factor control was classified as LDL-C ≥100 mg/dL, A1C ≥7% (53 mmol/mol), BP ≥140/90 mm Hg, or smoking. Major CV events were based on primary hospital discharge diagnoses for myocardial infarction (MI) and acute coronary syndrome (ACS), stroke, or heart failure (HF). Five-year incidence rates, rate ratios, and average attributable fractions were estimated using multivariable Poisson regression models. RESULTS Mean (SD) age at baseline was 59 (14) years; 48% of subjects were female, 45% were white, and 31% had CVD. Mean follow-up was 59 months. Event rates per 100 person-years for adults with diabetes and CVD versus those without CVD were 6.0 vs. 1.7 for MI/ACS, 5.3 vs. 1.5 for stroke, 8.4 vs. 1.2 for HF, 18.1 vs. 40 for all CV events, and 23.5 vs. 5.0 for all-cause mortality. The percentages of CV events and deaths associated with inadequate risk factor control were 11% and 3%, respectively, for those with CVD and 34% and 7%, respectively, for those without CVD. CONCLUSIONS Additional attention to traditional CV risk factors could yield further substantive reductions in CV events and mortality in adults with diabetes.

Intensification of antihyperglycemic therapy among patients with incident diabetes: a Surveillance Prevention and Management of Diabetes Mellitus (SUPREME-DM) study

Antihyperglycemic medication intensification practices among patients with incident diabetes are incompletely understood. We characterized the first intensification the year after oral antihyperglycemic medication initiation among incident diabetes patients.

Initial Antihyperglycemic Drug Therapy Among 241 327 Adults With Newly Identified Diabetes From 2005 Through 2010: A Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) Study

Background: Among adults with incident diabetes, data are lacking about first antihyperglycemic initiation and whether medication choice aligns with recommendations. Objective: To identify predictors of initiating any antihyperglycemic, and specifically sulfonylurea versus metformin. Methods: This retrospective cohort study included 241 327 patients from 11 US health systems, 2005 through 2010. Assessments included antihyperglycemic initiation within 6 months of diabetes identification, first medication initiated, and initiation predictors. Results: Only 40.3% (n = 97 350) started any antihyperglycemic; 75.2% (n = 73 221) started metformin. Glycosylated hemoglobin (HbA1c) predicted initiating any antihyperglycemic (HbA1c >9%, relative risk [RR] = 3.94, 95% CI = 3.82, 4.07, vs HbA1c >6.5%-7%). Age modified the HbA1c effect: at higher HbA1c, likelihood of starting antihyperglycemics differed little across ages; at lower HbA1c, older patients were less likely to start antihyperglycemics (P < .001). Individuals with elevated serum creatinine (SCr) were more likely to started on sulfonylurea (SCr = 1.4-2, RR = 2.21 [2.05, 2.39]; SCr >2, RR = 2.75 [2.30, 3.29] vs normal SCr), particularly as HbA1c increased: patients with HbA1c 8%-9% and SCr >2 were 5.59 times (2.94, 10.65) more likely to start sulfonylurea versus those with HbA1c >6.5%-7% and normal SCr. Age predicted sulfonylurea initiation (20-39 years, RR = 0.87 [0.79, 0.95]; ≥80 years, RR = 2.41 [2.20, 2.65] vs 50-59 years). Conclusions: Among adults with incident diabetes, metformin was generally the first antihyperglycemic initiated. However, 59.7% did not start any antihyperglycemic at diabetes identification. HbA1c and age predict antihyperglycemic initiation; SCr and age predict sulfonylurea initiation.

Racial and Ethnic Disparities in the Outcomes of Elderly Home Care Recipients

ABSTRACT The purpose of this study was to examine racial/ethnic disparities in functional outcomes of elderly home health care recipients. Analyses were conducted using Outcome and Assessment Information Set (OASIS) data for a nationally representative sample of home health care episodes for patients aged 65 and older. Risk-adjusted regression analyses examined the association between race/ethnicity and functional outcomes. Fourteen outcome measures reflected improvement in specific functional areas (e.g., ambulation) and two reflected overall functional change. Non-Hispanic Whites (“Whites”) experienced substantially better functional outcomes than did home health care recipients of other racial/ethnic backgrounds. The disparity in outcomes was most pronounced between Whites and African Americans.

Adherence to Guidelines for Glucose Assessment in Starting Second-Generation Antipsychotics

OBJECTIVES: In 2003, the US Food and Drug Administration issued warnings about hyperglycemia and diabetes with second-generation antipsychotics (SGAs); guidelines have recommended metabolic screening since 2004. However, little is known of contemporary practices of glucose screening among youth initiating SGAs. Our objective was to evaluate baseline glucose assessment among youth in the Mini-Sentinel Distributed Database starting an SGA. METHODS: The cohort included youth ages 2 through 18 newly initiating SGAs January 1, 2006, through December 31, 2011, across 10 sites. Baseline glucose was defined as fasting/random glucose or hemoglobin A1c (GLU) measurement occurring relative to first SGA dispensing. Differences in GLU assessment were evaluated with χ2 tests and logistic regression. RESULTS: The cohort included 16 304 youth; 60% boys; mean age 12.8 years. Risperidone was most commonly started (43%). Eleven percent (n = 1858) had GLU assessed between 90 days before and 3 days after first dispensing. Assessment varied across SGAs (olanzapine highest), sites (integrated health care systems higher), ages (16–18 highest), years (2007 highest), and gender (female higher; all P < .001). GLU assessment among those starting olanzapine was more likely than among those starting quetiapine (odds ratio [OR]: 1.72 [95% confidence interval (CI): 1.37–2.18]), aripiprazole (OR: 1.49 [95% CI: 1.18–1.87]), or risperidone (OR: 1.61 [95% CI: 1.28–2.03]). CONCLUSIONS: Few children and adolescents starting SGA have baseline glucose assessed. This is concerning because those at high diabetes risk may not be identified. Further, lack of screening impedes determining the contribution of SGAs to hyperglycemia development.