Browsing by Author "Murray, Michael D."
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Item Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study(Springer, 2018-04) Murray, Michael D.; Hendrie, Hugh C.; Lane, Kathleen A.; Zheng, Mengjie; Ambuehl, Roberta; Li, Shanshan; Unverzagt, Frederick W.; Callahan, Christopher M.; Gao, Sujuan; Psychiatry, School of MedicineBACKGROUND: African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN: Prospective cohort. PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES: Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications.Item Association Between Medication Adherence and the Outcomes of Heart Failure(Wiley, 2018) Hood, Sarah R.; Giazzon, Anthony J.; Seamon, Gwen; Lane, Kathleen A.; Wang, Jane; Eckert, George J.; Tu, Wanzhu; Murray, Michael D.; Biostatistics, School of Public HealthBackground Previous studies of heart failure patients have demonstrated an association between cardiovascular medication adherence and hospitalizations or a composite end point of hospitalization and death. Few studies have assessed the impact of treatment adherence within large general medical populations that distinguish the health outcomes of emergency department visits, hospitalization, and death. Objective To determine the association of incremental cardiovascular medication adherence on emergency department visits, hospitalization, and death in adult heart failure patients in Indiana. Design Retrospective cohort study conducted using electronic health record data from the statewide Indiana Network for Patient Care (INPC) between 2004 and 2009. Methods Patients were at least 18 years of age with a diagnosis of heart failure and prescribed at least one cardiovascular medication for heart failure. Adherence was measured as the proportion of days covered (PDC) using pharmacy transaction data. Clinical end points included emergency department visits, hospital admissions, length of hospital stay, and mortality. Generalized linear models were used to determine the effect of a 10% increase in PDC on clinical end points adjusting for age, sex, race, Charlson comorbidity index, and medications. Results Electronic health records were available for 55,312 patients (mean age ± standard deviation [SD] 68 ± 16 years; 54% women; 65% white). Mean PDC for all heart failure medications was 63% ± 23%. For every 10% increase in PDC, emergency department visits decreased 11% (rate ratio [RR] 0.89; 95% confidence interval [CI] 0.89‐0.89), hospital admissions decreased 6% (RR 0.94; 95% CI 0.94‐0.94), total length of hospital stay decreased 1% (RR 0.99; 95% CI 0.99‐1.00), and all‐cause mortality decreased 9% (odds ratio 0.91; 95% CI 0.90‐0.92). Conclusion Incremental medication adherence was associated with reductions in emergency department visits, hospital admissions, length of hospital stay, and all‐cause mortality.Item Changes of glucose levels precede dementia in African Americans with diabetes but not in Caucasians(Elsevier, 2018-12) Hendrie, Hugh C.; Zheng, Mengjie; Lane, Kathleen A.; Ambuehl, Roberta; Purnell, Christianna; Li, Shanshan; Unverzagt, Frederick W.; Murray, Michael D.; Balasubramanyam, Ashok; Callahan, Chris M.; Gao, Sujuan; Psychiatry, School of MedicineINTRODUCTION Changes in glucose levels may represent a powerful metabolic indicator for dementia in African Americans with diabetes. It is unclear whether these changes also occur in Caucasians. METHODS A secondary data analysis using electronic medical records from 5228 African Americans and Caucasians 65 years and older. Mixed effects models with repeated serum glucose measurements were used to compare changes in glucose levels between African Americans and Caucasian patients with and without incident dementia. RESULTS African Americans and Caucasians with diabetes had significantly different changes in glucose levels by dementia status (p<0.0001). African Americans experienced a significant decline in glucose levels before the dementia diagnosis (estimated glucose decline 1.3421 mg/dL per year, p<0.0001) than those who did not develop dementia. Caucasians with and without dementia showed stable glucose levels over time (p=0.3071). DISCUSSION Significant changes in glucose levels precede dementia in African American patients with diabetes but not in Caucasians.Item Issues in Conducting Randomized Controlled Trials of Health Services Research Interventions in Nonacademic Practice Settings: The Case of Retail Pharmacies(2002-08) Weinberger, Morris; Murray, Michael D.; Marrero, David G.; Brewer, Nancy; Lykens, Michael; Harris, Lisa E.; Newell, A Jeffrey; Collins, Joyce; Tierney, William M.Objective. To describe unexpected challenges and strategies to overcome them when conducting randomized controlled trials (RCT) of health services research interventions in retail pharmacies. Study Setting. Thirty-six retail drug stores in Indianapolis. Study Design. We conducted an RCT to evaluate the effectiveness of an intervention to increase pharmacists’ involvement in caring for customers. We describe: (1) our RCT as originally designed, (2) unexpected challenges we faced; and (3) how we resolved those challenges. Data Collection/Extraction Methods. Randomized controlled trial. Principal Findings. Major modifications in research design were necessitated by factors such as corporate restructuring, heightened sensitivity to patient confidentiality, and difficulties altering employees’ behavior. We overcame these barriers by conducting research that is consistent with corporate goals, involving appropriate corporate administrators and technical personnel early in the process, and being flexible. Conclusions. Health services researchers should conduct RCTs in a variety of nonacademic practice settings to increase generalizability and better reflect the true impact of interventions. Pragmatic problems, although significant, can be successfully overcome.Item Memory and comprehension for health information among older adults: distinguishing the effects of domain-general and domain-specific knowledge(Informa UK (Taylor & Francis), 2015) Chin, Jessie; Payne, Brennan; Gao, Xuefei; Conner-Garcia, Thembi; Graumlich, James F.; Murray, Michael D.; Morrow, Daniel G.; Stine-Morrow, Elizabeth A. L.; Department of Medicine, IU School of MedicineWhile there is evidence that knowledge influences understanding of health information, less is known about the processing mechanisms underlying this effect and its impact on memory. We used the moving window paradigm to examine how older adults varying in domain-general crystallised ability (verbal ability) and health knowledge allocate attention to understand health and domain-general texts. Participants (n = 107, age: 60-88 years) read and recalled single sentences about hypertension and about non-health topics. Mixed-effects modelling of word-by-word reading times suggested that domain-general crystallised ability increased conceptual integration regardless of text domain, while health knowledge selectively increased resource allocation to conceptual integration at clause boundaries in health texts. These patterns of attentional allocation were related to subsequent recall performance. Although older adults with lower levels of crystallised ability were less likely to engage in integrative processing, when they did, this strategy had a compensatory effect in improving recall. These findings suggest that semantic integration during reading is an important comprehension process that supports the construction of the memory representation and is engendered by knowledge. Implications of the findings for theories of text processing and memory as well as for designing patient education materials are discussed.Item Ondansetron blocks wild-type and p.F503L variant small-conductance Ca2+-activated K+ channels(American Physiological Society, 2018-08-01) Ko, Jum-Suk; Guo, Shuai; Hassel, Jonathan; Celestino-Soper, Patricia; Lynnes, Ty C.; Tisdale, James E.; Zheng, James J.; Taylor, Stanley E.; Foroud, Tatiana; Murray, Michael D.; Kovacs, Richard J.; Li, Xiaochun; Lin, Shien-Fong; Chen, Zhenhui; Vatta, Matteo; Chen, Peng-Sheng; Rubart, Michael; Medicine, School of MedicineApamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.Item Optimization of Drug Prescription and Medication Management in Older Adults with Cardiovascular Disease(Springer, 2017-11) Wenger, Nanette K.; Doherty, Caroline Lloyd; Gurwitz, Jerry H.; Hirsch, Glenn A.; Holmes, Holly M.; Maurer, Matthew S.; Murray, Michael D.; Medicine, School of MedicineCardiovascular disease increases incrementally with age and elderly patients concomitantly sustain multimorbidities, with resultant prescription of multiple medications. Despite conforming with disease-specific cardiovascular clinical practice guidelines, this polypharmacy predisposes many elderly individuals with cardiovascular disease to adverse drug events and non-adherence. Patient-centered care requires that the clinician explore with each patient his or her goals of care and that this shared decision-making constitutes the basis for optimization of medication management. This approach to aligning therapies with patient preferences is likely to promote patient satisfaction, to limit morbidity, and to favorably affect healthcare costs.Item Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension(Springer, 2016-01) Tu, Wanzhu; Decker, Brian S.; He, Zangdong; Erdel, Blake L.; Eckert, George J.; Hellman, Richard N.; Murray, Michael D.; Oates, John A.; Pratt, J. Howard; Department of Biostatistics, Richard M. Fairbanks School of Public HealthBACKGROUND: Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. OBJECTIVE: To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. DESIGN: We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. MAIN MEASURES: BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. KEY RESULTS: The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. CONCLUSIONS: In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.Item Utilizing an integrated infrastructure for outcomes research: a systematic review.(Health Libraries Group, 2016-03) Dixon, Brian E.; Whipple, Elizabeth C.; Lajiness, John M; Murray, Michael D.OBJECTIVE: To explore the ability of an integrated health information infrastructure to support outcomes research. METHODS: A systematic review of articles published from 1983 to 2012 by Regenstrief Institute investigators using data from an integrated electronic health record infrastructure involving multiple provider organisations was performed. Articles were independently assessed and classified by study design, disease and other metadata including bibliometrics. RESULTS: A total of 190 articles were identified. Diseases included cognitive, (16) cardiovascular, (16) infectious, (15) chronic illness (14) and cancer (12). Publications grew steadily (26 in the first decade vs. 100 in the last) as did the number of investigators (from 15 in 1983 to 62 in 2012). The proportion of articles involving non-Regenstrief authors also expanded from 54% in the first decade to 72% in the last decade. During this period, the infrastructure grew from a single health system into a health information exchange network covering more than 6 million patients. Analysis of journal and article metrics reveals high impact for clinical trials and comparative effectiveness research studies that utilised data available in the integrated infrastructure. DISCUSSION: Integrated information infrastructures support growth in high quality observational studies and diverse collaboration consistent with the goals for the learning health system. More recent publications demonstrate growing external collaborations facilitated by greater access to the infrastructure and improved opportunities to study broader disease and health outcomes. CONCLUSIONS: Integrated information infrastructures can stimulate learning from electronic data captured during routine clinical care but require time and collaboration to reach full potential.