Donald L. Harrison

Effect of Oral Corticosteroids on Chronic Warfarin Therapy

Background: A potential drug interaction exists between oral corticosteroids and warfarin, but there is limited documentation. Objective: To evaluate the potential drug interaction between oral corticosteroids and long-term warfarin therapy. Methods: A retrospective review was conducted of 387 medical records for active patients within an anticoagulation clinic. Inclusion criteria were stable anticoagulation therapy, short-term oral corticosteroid therapy, international normalized ratio (INR) recorded within 30 days prior to corticosteroid initiation (pre-INR), and INR recorded during corticosteroid therapy or within 14 days of discontinuation (post-INR). Patients were excluded if they had been started on any antibiotic or other drug with a probable interaction with warfarin at the same time as corticosteroid initiation. Thirty-two patient encounters met the predetermined inclusion and exclusion criteria. The primary outcome assessed was the difference between pre- and post-INR values. Secondary endpoints included bleeding events, emergency department (ED) visits, hospitalizations, and warfarin dose modifications. Results: The mean difference between pre- and post-INR values was 1.24 (95% CI 0.86 to 1.62). Ninety-seven percent of the 32 patient encounters resulted in a change in their post-INR value, and 62.5% of patients had supratherapeutic INR values at the post-corticosteroid assessment. The majority of patients assessed had an elevation of their INR following concomitant use of warfarin and corticosteroids. The INR change was observed at a mean ± SD of 6.7 ± 3.3 days following the first dose of corticosteroid. Overall, 16 patients (50%) required a modification of their anticoagulation therapy during or following corticosteroid therapy. Only one adverse event of minor epistaxis was reported, and no ED visits or hospitalizations occurred as a consequence of the drug combination. Conclusions: Use of oral corticosteroids in patients on long-term warfarin therapy may result in a clinically significant interaction, which requires close INR monitoring and possible warfarin dose reduction.

Communicating non-steroidal anti-inflammatory drug risks: Verbal counseling, written medicine information, and patients’ risk awareness

OBJECTIVE To assess potential associations among physician counseling, pharmacist counseling, written medicine information (WMI) and patient awareness of non-steroidal anti-inflammatory drug (NSAID) risks. METHODS Three-hundred and eighty-two older, white and African American patients prescribed NSAIDs were surveyed regarding their NSAID risk awareness defined as an index score ranging from zero to four correctly identified risks (i.e., gastrointestinal bleeding, heart attack, hypertension, and kidney disease). Associations among NSAID risk awareness and patient-reported physician counseling, pharmacist counseling, and reading of WMI were evaluated in multivariable ordered logistic regression models and confirmed using path analysis. RESULTS Physician counseling was positively associated with reading WMI (p<0.001) and NSAID risk awareness (p<0.001). Pharmacist counseling was not associated with reading WMI (p=0.622) and neither pharmacist counseling (p=0.366) nor reading WMI (p=0.916) was associated with NSAID risk awareness. CONCLUSIONS Physicians play a prominent role in facilitating NSAID risk awareness whereas pharmacist counseling and WMI may have limited impact. PRACTICE IMPLICATIONS The lack of significant associations among pharmacist counseling and reading WMI with NSAID risk awareness suggests a missed opportunity to improve patient understanding. There is a need for coordinated and effective strategies to communicate risk information among physicians and pharmacists and to better integrate WMI into this process.

Vancomycin dosage in overweight and obese children

PURPOSE Vancomycin dosages in overweight and obese children were evaluated. METHODS This retrospective study evaluated data for children who were age 2-17 years, received i.v. vancomycin, and were admitted to a childrens hospital from September 1, 2007, through October 31, 2009. Patients were then stratified into two groups: normal-weight patients and overweight or obese patients. The primary objective was to compare the number of vancomycin regimens between groups with a trough concentration of 5-15 μg/mL. Secondary objectives included a comparison of dosage changes and toxicities. Multivariate, conditional logistic regression was performed to assess the relationship between attaining optimal vancomycin concentrations (5-15 μg/mL) and independent variables. RESULTS Data were collected for 232 courses of vancomycin, representing 187 patients. The mean ± S.D. initial dose for the normal-weight and overweight or obese groups differed significantly (461.3 ± 303.1 mg and 658.4 ± 389.6 mg, respectively; p < 0.01); the milligram-per-kilogram initial vancomycin dose did not. The multivariate analysis revealed that every-eight-hour regimens had increased odds of achieving therapeutic concentrations (p < 0.001), while obese children had decreased odds of achieving therapeutic concentrations (p = 0.037). CONCLUSION A study of prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses (in milligrams per kilogram) given to normal-weight children compared with overweight or obese children. Regimens using every-eight-hour dosing were significantly more likely than other regimens to result in a vancomycin trough concentration of 5-15 μg/mL, and regimens for obese children, compared with regimens for nonobese children, were less likely to produce trough concentrations in the same range of 5-15 μg/mL.

Evaluation of Inpatient Admissions and Potential Antimicrobial and Analgesic Dosing Errors in Overweight Children

BACKGROUND The prevalence of overweight/obesity in US children has increased over the past several decades. Routine use of weight-based dosing of medications could potentially result in over- or underdosing in these children. OBJECTIVE To determine the percentage of admissions of children with a body mass index (BMI) greater than or equal to the 85th percentile for age and sex and the mean error rate per admission in the overweight versus control group. METHODS We performed a retrospective, preliminary study of children aged 5–12 years who were admitted to a childrens hospital over a period of 6 months. The overweight group included children with a BMI greater than or equal to the 85th percentile; the control group included children with a BMI less than the 85th percentile. Dose appropriateness was assessed, using 2 references. An overdose was defined as: (1) total mg/kg/day or mg/kg/dose greater than or equal to 110% of the maximum recommended pediatric dose, (2) total mg/day greater than the adult maximum recommended dose, or (3) greater than the recommended number of doses per day. An underdose was defined as: (1) total mg/kg/day or mg/kg/dose less than or equal to 90% of the minimum recommended pediatric dose, or (2) fewer than the recommended number of doses per day. Baseline comparisons between groups were done via Students t-tests and χ2 analysis, when appropriate, with an a priori α of p less than or equal to 0.05. RESULTS A total of 839 admissions representing 699 patients were included. The overweight group included 278 (33.1%) admissions. Comparison of overall mean error rate per admission revealed a statistically significant increase in dosing errors for overweight patients (0.4 ± 0.6 vs 0.3 ± 0.6; p = 0.030), with underdose errors occurring more frequently than overdose errors (0.3 ± 0.6 vs 0.2 ± 0.5; p = 0.010). CONCLUSIONS Overweight children accounted for one-third of admissions, and the results of this study suggest that these patients are at greater risk for errors in dosing than are children of age- and sex-appropriate weight. This study did not assess clinical outcomes; however, overweight children could be at increased risk for therapeutic failures or adverse effects.

Variations in the probability of depression screening at community-based physician practice visits.

BACKGROUND Despite depression screening being a US Preventive Services Task Force-recommended practice in primary care, little is known about the degree to which it is performed and the factors associated with its conduct. METHOD Using a nationally representative sample (National Ambulatory Medical Care Survey) of adult, community-based physician practice visits during the survey years 2005 to 2007 (total = 55,143; representing approximately 1.7 billion visits nationally), we estimated the probability of depression screening and variation by visit characteristics. RESULTS Depression screening occurred at 2.29% of adult, community-based physician practice visits. Visits with primary care physicians were more likely to include depression screening (AOR = 2.19; 95% CI, 1.31-3.65), as were visits for preventive (AOR = 4.09; 95% CI, 2.55-6.57) and chronic care (AOR = 2.00; 95% CI, 1.44-2.80) compared to visits for acute care. Compared to the Northeast, visits in the West were less likely to include depression screening (AOR = 0.27; 95% CI, 0.13-0.57), as were visits for patients having ≥ 6 visits within the past 12 months (AOR = 0.65; 95% CI, 0.42-1.00) when compared to visits for new patients. Depression screening was more common at visits for patients with ICD-9-diagnosed depression (AOR = 7.51; 95% CI, 5.38-10.50) and for females (AOR = 1.26; 95% CI, 1.00-1.57). Bivariate analyses revealed that depression screening was more common at visits for patients with hyperlipidemia (3.21% vs 2.09%, P = .0086), obesity (4.59% vs 2.08%, P < .0001), and osteoporosis (4.46% vs 2.21%, P = .0002) and less common at visits for patients with diabetes (1.58% vs 2.39%, P = .0102). CONCLUSIONS Depression screening at community-based physician practice visits in the United States appears to be low (2.29%) and may reflect an undefined optimal screening interval or strategy in published guidelines, lack of reimbursement incentives, or incomplete documentation in the medical record. Opportunities exist to improve depression screening in males, patients with chronic disease (especially diabetes), and the western region of the United States.

Intensive vs. conventional insulin management initiated at diagnosis in children with diabetes: Should payer source influence the choice of therapy?

Intensive insulin management (IIM) in type 1 diabetes facilitates improved glycemic control and a reduction in long‐term diabetes complications. We hypothesized that IIM can be started at diagnosis without deleterious effects on hemoglobin A1c (A1c), body mass index (BMI), and severe hypoglycemia regardless of payer source. Type 1 diabetes patients aged 0–18 yrs, in an academic endocrinology practice were identified for a retrospective chart review. Fifty‐four patients on conventional insulin management (CIM) were compared to 51 on IIM. Insulin regimens, payer, and A1c values were compared at baseline, 12, 15, and 18 months. Secondary analyses included BMI changes and hypoglycemia frequency. Overall mean A1c values for the IIM group (8.15 ± 1.41) were lower across all time periods compared to the CIM group (8.57 ± 1.52). Repeated measures anova revealed a significant treatment group effect (p = 0.01) with no time effect (p = 0.87) or interaction (group by time) effect (p = 0.65). Private insurance patients had lower mean A1C values than Medicaid patients (χ2 = 4.5186, p < 0.05), regardless of regimen. A1c values between IIM and CIM were not statistically different within the Medicaid group. BMI changes between groups were not different. Chi‐square analysis for severe hypoglycemia revealed no group differences. In conclusion, IIM had improved glycemic control. Private insurance vs. Medicaid patients had lower mean A1c values regardless of treatment group. Considering Medicaid patients only, IIM was not inferior, and for those with private insurance, IIM was superior. IIM, initiated at diagnosis, is a reasonable approach for newly diagnosed children with diabetes regardless of payer source.

Incidence of Transmitted Antiretroviral Drug Resistance in Treatment-Naive HIV-1-Infected Persons in a Large South Central United States Clinic

Background: Transmitted drug resistance (TDR) can limit effective treatment options to antiretroviral-naive HIV-infected persons and increase the risk of treatment failure. Limited estimates of TDR have been reported from the South Central United States. Objective: To describe the incidence of TDR in Oklahoma and to examine whether TDR rates have increased with time. Methods: This was a retrospective observational study of antiretroviral-naive patients at the Infectious Diseases Institute, a large infectious diseases clinic in Oklahoma City, Oklahoma, who had received baseline antiretroviral resistance testing. Mutations were screened using the 2011 International Antiviral Society-USA Drug Resistance Mutation (DRM) update, and categorized using the 2009 World Health Organization (WHO) Surveillance Drug Resistance Mutation (SDRM) list. Results: Genotypic sequences from 428 patients revealed a 6.0% to 13.6% incidence of SDRMs between 2007 and 2011, though no progression in the frequency was apparent during the study period. Primary DRMs were detected in 12.6% of the sampled patients, most commonly involving nonnucleoside reverse transcriptase inhibitors (NNRTIs; 8.2%), followed by protease inhibitors (PIs; 3.5%) and nucleoside reverse transcriptase inhibitors (NRTIs; 3.3%). The K103N/S and E138A reverse transcriptase mutations were the most common DRMs identified, both present in 3.5% of patients. The L90M mutation was the most frequently observed PI SDRM (1.6%), while the T215C/D/I mutation was the most common NRTI SDRM identified (1.9%). This study was limited by the fact that the WHO SDRM list was last updated in 2009. Conclusions: The frequency of DRMs in central and western Oklahoma is similar to recently reported rates in the United States which lack data from this region. However, the frequency of second-generation NNRTI DRMs (4.4%) suggests the need to closely monitor epidemiologic trends for increasing resistance rates to individual classes of ARVs in order to predict the impact of TDR on therapeutic options.

Evaluation of Dabigatran Exposures Reported to Poison Control Centers

Background: Dabigatran is a novel oral anticoagulant for which a well-defined range of toxicity and proven antidote has not been established. Objective: The primary objective of this study was to characterize dabigatran exposures reported to poison centers by dose ingested, clinical effects, treatments used, and managment sites to gain a better understanding of patient outcomes. Methods: A retrospective database review was conducted for dabigatran exposures reported to the National Poison Data System for the American Association of Poison Control Centers (AAPCC) over the period October 2010 to December 2012. Results: There were 802 human dabigatran exposures involving adults predominantly (91% of cases). Exposure chronicity was acute in 43%, acute-on-chronic in 46%, and chronic in 11%, with the most common reason for an exposure call being an unintentional therapeutic error (70.6%). The most common management sites were on-site in 72% of cases and within a health care facility for 26%. Bleeding events and coagulopathies were the most commonly observed clinical effects. Treatments administered included activated charcoal, blood and coagulation products, hemodialysis, and supportive measures. Confirmed outcomes included death in 13 patients (1.6%), major effects in 23 (2.9%), and moderate effects in 50 (6.2%). More severe outcomes were significantly associated with adverse drug reactions, patients ≥65 years of age, those treated with blood and coagulation products and/or dialysis, and renal dysfunction (P < .05). Children experienced few moderate effects and no major effects or deaths. Conclusions: Severe outcomes from dabigatran exposures were not common, occurring in approximately 5% of cases.

Integration of an Introductory Pharmacy Practice Experience With an Advanced Pharmacy Practice Experience in Adult Internal Medicine

Objective. To describe the development, implementation, and assessment of an internal medicine introductory pharmacy practice experience (IPPE) that was integrated with an existing advanced pharmacy practice experience (APPE) in internal medicine. Design. A structured IPPE was designed for first-, second-, and third-year pharmacy (P1, P2, and P3) students. Activities for the IPPE were based on the established APPE and the individual learners educational level. Assessment. Students reported a greater understanding of clinical pharmacists’ roles, increased confidence in their clinical skills, and better preparation for APPEs. Peers viewed the approach as innovative and transferable to other practice settings. Participating faculty members provided a greater number of contact hours compared to traditional one-time site visits. Conclusions. Integrating an IPPE with an existing APPE is an effective and efficient way to provide patient care experiences for students in the P1-P3 years in accordance with accreditation standards.

Have antiepileptic drug prescription claims changed following the FDA suicidality warning? An evaluation in a state Medicaid program

OBJECTIVE In January 2008, the Food and Drug Administration (FDA) communicated concerns and, in May 2009, issued a warning about an increased risk of suicidality for all antiepileptic drugs (AEDs). This research evaluated the association between the FDA suicidality communications and the AED prescription claims among members with epilepsy and/or psychiatric disorder. METHODS A longitudinal interrupted time-series design was utilized to evaluate Oklahoma Medicaid claims data from January 2006 through December 2009. The study included 9289 continuously eligible members with prevalent diagnoses of epilepsy and/or psychiatric disorder and at least one AED prescription claim. Trends, expressed as monthly changes in the log odds of AED prescription claims, were compared across three time periods: before (January 2006 to January 2008), during (February 2008 to May 2009), and after (June 2009 to December 2009) the FDA warning. RESULTS Before the FDA warning period, a significant upward trend of AED prescription claims of 0.01% per month (99% CI: 0.008% to 0.013%, p<0.0001) was estimated. In comparison to the prewarning period, no significant change in trend was detected during (-20.0%, 99% CI: -70.0% to 30.0%, p=0.34) or after (80.0%, 99% CI: -20.0% to 200.0%, p=0.03) the FDA warning period. After stratification, no diagnostic group (i.e., epilepsy alone, epilepsy and comorbid psychiatric disorder, and psychiatric disorder alone) experienced a significant change in trend during the entire study period (p>0.01). CONCLUSIONS During the time period considered, the FDA AED-related suicidality warning does not appear to have significantly affected prescription claims of AED medications for the study population.