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Fort Washington, PA, United States

Shaya F.T.,ReSearch Pharmaceutical Services | McPherson M.L.,University of Maryland, Baltimore | Snitker S.,University of Maryland Baltimore County
Journal of Managed Care Pharmacy

Background: Medicaid covers a high-risk population typically underrepresented in clinical trial data and largely absent in observational studies of real-world cardiovascular risks associated with thiazolidinediones (TZDs), such as pioglitazone and rosiglitazone, which are used to manage type 2 diabetes. In November 2013, the FDA removed prescribing restrictions for rosiglitazone in light of new evidence that rosiglitazone did not increase the risk of heart attack compared with standard type 2 diabetes medications. Further investigation is needed to elucidate whether the risk of heart failure (HF) associated with TZDs may be exacerbated in the Medicaid population. Objective: To determine the relative risk of incident HF in patients initiating rosiglitazone, pioglitazone, and metformin therapy in a Medicaid population. Methods: We retrospectively examined claims data for patients with type 2 diabetes enrolled in Maryland State Medicaid and managed care or feefor- service programs between July 2005 and June 2010. Patients initiated on metformin, pioglitazone, or rosiglitazone treatments were extracted for analysis. Relative risks of incident HF after initiating treatment were compared using survival analysis, adjusting for switching or adding antidiabetic therapies during follow-up and other baseline risk factors for HF. Results: Of 6,271 patients meeting inclusion criteria, 88% were started on metformin; 7% were started on pioglitazone; and 5% were started on rosiglitazone. Patients who initiated rosiglitazone had higher risk of HF than patients who initiated metformin using either univariate (HR = 1.81, 95% CI = 1.37-2.39), multivariate (HR = 1.57, 95% CI = 1.15-2.15), or propensity score-matched (HR = 1.79, 95% CI = 1.16-2.76) analysis. There was no significant difference in risk between patients who initiated pioglitazone and metformin therapy. Conclusions: Compared with metformin, there may be higher risk of developing HF in Medicaid patients started on rosiglitazone but not pioglitazone. While pioglitazone was associated with a lower risk of developing HF compared with rosiglitazone, health care professionals should continue to work closely with their patients to determine the treatment options most appropriate. © 2014, Academy of Managed Care Pharmacy. Source

Khokhar B.,ReSearch Pharmaceutical Services
Journal of Head Trauma Rehabilitation

OBJECTIVE:: To estimate the risk of stroke associated with new antidepressant use among older adults with traumatic brain injury (TBI). PARTICIPANTS:: A total of 64 214 Medicare beneficiaries aged 65 years or older meeting inclusion criteria and hospitalized with a TBI during 2006 to 2010. DESIGN:: New user design. Generalized estimating equations were used to estimate the relative risks (RRs) of stroke. MAIN MEASURES:: Primary exposure was new antidepressant use following TBI identified through Medicare part D claims. The primary outcome was stroke following TBI. Ischemic and hemorrhagic strokes were secondary outcomes. RESULTS:: A total of 20 859 (32%) beneficiaries used an antidepressant at least once following TBI. Selective serotonin reuptake inhibitors accounted for the majority of antidepressant use. Selective serotonin reuptake inhibitor use was associated with an increased risk of hemorrhagic stroke (RR, 1.26; 95% confidence interval [CI], 1.06-1.50) but not ischemic stroke (RR, 1.04; 95% CI, 0.94-1.15). The selective serotonin reuptake inhibitors escitalopram (RR, 1.33; 95% CI, 1.02-1.74) and sertraline (RR, 1.46; 95% CI, 1.10-1.94) were associated with an increase in the risk of hemorrhagic stroke. CONCLUSION:: Findings from this study will aid prescribers in choosing appropriate antidepressants to treat depression in older adults with TBI. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

An extractable survey is one of several studies performed on a pharmaceutical storage/delivery system as part of the process of demonstrating that the system is suitable for its intended use. In this paper, a solid phase extraction method for the preparation of aqueous extracts generated during an extractable survey is presented. The method offers a convenient means to isolate semi-volatile organic extractable compounds from aqueous extraction solvents for analysis by gas chromatography/mass spectrometry. Following the solid phase extraction procedure, derivatization is performed to convert problematic functionalities (such as amines and acids) into appropriate chromatographically friendly derivatives. Demonstration of method performance is achieved in three ways using a set of 31 commonly observed extractable substances as model compounds. First, a breakthrough experiment was performed with a 2 solvent system consisting of water and 10/90 isopropanol/water over a range of 6. mL to 100. mL. Results from this experiment show only caprolactam possessed a significant level of breakthrough in either solvent over the range of volumes evaluated. Second, a formal accuracy/precision study was conducted using a three solvent system consisting of water, 10/90 isopropanol/water and 1% polysorbate 80. This experiment demonstrates the quantitative ability of the method at levels ranging from 20. ng/mL to 50. μg/mL. Recovery values of 70% to 130% of the theoretical concentration, with relative standard deviation values of less than 15% for replicate preparations, are obtained for a majority of the compounds evaluated. Finally, a case study involving the extraction of an intravenous drug delivery bag with multiple aqueous solvent systems further demonstrates the viability of solid phase extraction for use in an extractables survey. © 2015 Elsevier B.V. Source

Ginsberg J.S.,University of Maryland, Baltimore | Zhan M.,University of Maryland, Baltimore | Diamantidis C.J.,University of Maryland, Baltimore | Woods C.,ReSearch Pharmaceutical Services | And 2 more authors.
Journal of the American Society of Nephrology

Patients with CKD are at high risk for adverse safety events because of the complexity of their care and impaired renal function. Using data fromour observational study of predialysis patients with CKD enrolled in the Safe Kidney Care study, we estimated the baseline frequency of adverse safety events and determined to what extent these events co-occur. We examined patient-reported adverse safety incidents (class I) and actionable safety findings (class II), conditioned on participant use of drugs that might cause such an event, and we used association analysis as a data-mining technique to identify co-occurrences of these events. Of 267 participants, 185 (69.3%) had at least one class I or II event, 102 (38.2%) had more than one event, and 48 (18.0%) had at least one event from both classes. The adjusted conditional rates of class I and class II events ranged from 2.9 to 57.6 per 100 patients and from 2.2 to 8.3 per 100 patients, respectively. The most common conditional class I and II events were patient-reported hypoglycemia and hyperkalemia (serum potassium >5.5 mEq/L), respectively. Reporting of hypoglycemia (in patients with diabetes) and falling or severe dizziness (in patients without diabetes) were most frequently paired with other adverse safety events. We conclude that adverse safety events are common and varied in CKD, with frequent association between disparate events. Further work is needed to define the CKD "safety phenotype" and identify patients at highest risk for adverse safety events. Copyright © 2014 by the American Society of Nephrology. Source

Badawi O.,Philips | Badawi O.,University of Maryland, Baltimore | Waite M.D.,Riverside Methodist Hospital | Fuhrman S.A.,Sentara Healthcare System | Zuckerman I.H.,ReSearch Pharmaceutical Services
Critical Care Medicine

Objective:: Our Objective was to quantify the association between intensive care unit-acquired dysglycemia (hyperglycemia, hypoglycemia, and high variability) and in-hospital mortality. DESIGN:: Retrospective, observational study. SETTING:: eICU Research Institute participating hospitals with an active tele-ICU program between January 1, 2008, and September 30, 2010, representing 784,392 adult intensive care unit patients. PATIENTS:: A total of 194,772 patients met inclusion criteria with an intensive care unit length of stay >48 hrs. INTERVENTIONS:: None. MEASUREMENTS AND MAIN Results:: Acute Physiology and Chronic Health Evaluation IV standardized mortality ratios were calculated for dysglycemia present at admission and acquired in the intensive care unit. Intensive care unit-acquired dysglycemia was modeled using multivariable modified Poisson regression to account for confounding not incorporated in Acute Physiology and Chronic Health Evaluation. Dysglycemia severity was assessed by the relative risk of in-hospital mortality associated with the maximum, time-weighted average daily glucose; lowest glucose value throughout the intensive care unit stay; and quintiles of variability (coefficient of variation). The association of duration beyond thresholds of dysglycemia on mortality was also modeled. The adjusted relative risk (95% confidence interval) of mortality for the maximum intensive care unit average daily glucose was 1.13 (1.04-1.58), 1.43 (1.30-1.58), 1.63 (1.47-1.81), 1.76 (1.55-1.99), and 1.89 (1.62-2.19) for 110-150 mg/dL, 151-180 mg/dL, 180-240 mg/dL, 240-300 mg/dL, and >300 mg/dL, respectively, compared to patients whose highest average daily glucose was 80-110 mg/dL. The relative risk of mortality for the lowest glucose value was 1.67 (1.37-2.03), 1.53 (1.37-1.70), 1.12 (1.04-1.21), and 1.06 (1.01-1.11) for <20 mg/dL, 20-40 mg/dL, 40-60 mg/dL, and 60-80 mg/dL, respectively, compared to patients whose lowest value was 80-110 mg/dL. The relative risk of mortality increased with greater duration of hyperglycemia and with increased variability. The relative risk for the highest compared to lowest quintile of variability was 1.61 (1.47-1.78). The association of duration of hyperglycemia on mortality was more pronounced with more severe hyperglycemia. Conclusions:: The risk of mortality progressively increased with severity and duration of deviation from euglycemia and with increased variability. These data suggest that severe intensive care unit-acquired hyperglycemia, hypoglycemia, and variability are associated with similar risks of mortality. © 2012 by the Society of Critical Care Medicine and Lippincott Williams and Wilkins. Source

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