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.

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.

Collaborative practice model between cardiologists and clinical pharmacists for management of patients with cardiovascular disease in an outpatient clinic.

The increasing prevalence of cardiovascular disease (CVD) has prompted leading cardiovascular organizations to advocate utilization of a team approach to patient care that includes nonphysician providers. In spite of that, the American College of Cardiology reported that nonphysician providers are underutilized in the management of patients with CVD. A survey of cardiologists revealed that the underutilization is a result of lack of understanding of how best to involve nonphysician providers in the health care team. Clinical pharmacists are one category of nonphysician providers that have recognized effectiveness in managing patients with CVD. No example of a comprehensive model of collaboration between cardiologists and clinical pharmacists is described in the literature that could serve to close this gap in understanding. The objective of this report is to describe a model of cardiologist-clinical pharmacist collaboration in the longitudinal management of patients with CVD that has been successfully implemented in 2 diverse settings. The implementation, evolution, scope of practice, required pharmacist training, logistical elements needed for success, and implementation barriers are reviewed. A summary of the patients referred to the clinic are examined as well.

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.

Acetazolamide in critically ill neonates and children with metabolic alkalosis.

BACKGROUND: Acetazolamide is an option for hypochloremic metabolic alkalosis, but there are limited reports in children. OBJECTIVE: To describe the acetazolamide regimen and outcomes in critically ill children with metabolic alkalosis. METHODS: This was a descriptive, retrospective study of patients <18 years of age who received ≥3 doses of acetazolamide for metabolic alkalosis (ie, pH > 7.45 and bicarbonate [HCO3] > 26 mEq/L). Patients receiving other treatments for metabolic alkalosis within 24 hours of acetazolamide were excluded. The primary objective was to identify the mean dose and duration of acetazolamide. Secondary objectives were to determine the number of patients with treatment success (ie, serum HCO3 22-26 mEq/L) and occurrence of adverse events. RESULTS: Thirty-four patients were included for analysis, the median age was 0.25 years (range = 0.05-12 years). The acetazolamide regimen included a mean dose of 4.98 ± 1.14 mg/kg for a mean number of 6.1 ± 5.3 (range = 3-24) doses. The majority (70.6%) received acetazolamide every 8 hours. Treatment success was achieved in 10 (29.4%) patients. Statistically significant differences were noted between the pre-acetazolamide and post-acetazolamide pH and HCO3, 7.51 ± 0.05 versus 7.37 ± 0.05 (P < .001) and 39.4 ± 6.1 mEq/L versus 31.4 ± 7.5 mEq/L (P < .001), respectively. CONCLUSIONS: This is the first study to evaluate acetazolamide dosing for metabolic alkalosis in children with and without cardiac disease. Acetazolamide treatment resulted in improved HCO3, but the majority of patients did not achieve our definition of treatment success. Future studies should elucidate the optimal acetazolamide regimen.

Mental health treatment associated with community-based depression screening: considerations for planning multidisciplinary collaborative care.

BACKGROUND: Depression places a large economic burden on the US health care system. Routine screening has been recognized as a fundamental step in the effective treatment of depression, but should be undertaken only when support systems are available to ensure proper diagnosis, treatment, and follow-up. OBJECTIVE: To estimate differences in prescribing new antidepressants and referral to stress management, psychotherapy, and other mental health (OMH) counseling at physician visits when documented depression screening was and was not performed. METHODS: Cross-sectional physician visit data for adults from the 2005-2007 National Ambulatory Medical Care Survey were used. The final analytical sample included 55,143 visits, representing a national population estimate of 1,741,080,686 physician visits. Four dependent variables were considered: (1) order for new antidepressant(s), and referral to (2) stress management, (3) psycho therapy, or (4) OMH counseling. Bivariable and multivariable associations between depression screening and each measure of depression follow-up care were evaluated using the design-based F statistic and multivariable logistic regression models. RESULTS: New antidepressant prescribing increased significantly (2.12% of visits without depression screening vs 10.61% with depression screening resulted in a new prescription of an antidepressant). Referral to stress management was the behavioral treatment with the greatest absolute change (3.31% of visits without depression screening vs 33.10% of visits with depression screening resulted in a referral to stress management). After controlling for background sociodemographic characteristics, the adjusted odds ratio of a new antidepressant order remained significantly higher at visits involving depression screening (AOR 5.36; 99.9% CI 2.92-9.82), as did referrals for all behavioral health care services (ie, stress management, psychotherapy, and OMH counseling). CONCLUSIONS: At the national level, depression screening was associated with increased new antidepressant prescribing and referral for behavioral health care. It is critical for policy planners to recognize changes in follow-up depression care when implementing screening programs to ensure adequate capacity. Pharmacists are poised to assume a role in collaborative depression care, particularly with antidepressant medication therapy management.

Evaluation of a diabetes management program using selected HEDIS measures.

OBJECTIVE: To evaluate the efficacy of a community-based, pharmacist-directed diabetes management program among managed care organization enrollees using National Committee for Quality Assurance (NCQA)-Healthcare Effectiveness Data and Information Set (HEDIS) performance measures. DESIGN: Randomized controlled trial. SETTING: Regional community pharmacy chain in Tulsa, OK, from November 2005 to July 2007. PATIENTS: 52 participants with diabetes and hypertension who were enrolled in a managed care organization. INTERVENTION: Diabetes management versus standard care. MAIN OUTCOME MEASURES: Comprehensive diabetes care measures of glycosylated hemoglobin (A1C <7.0%), blood pressure (<130/80 mm Hg), and low-density lipoprotein (LDL) cholesterol (<100 mg/dL). A composite research outcome of success was created by determining whether a participant achieved two of the three HEDIS goals at the end of 9 months. RESULTS: 46.7% of intervention group participants achieved the A1C goal, while 9.1% of control group participants achieved the goal ( P < 0.002). More than one-half (53.3%) of intervention participants achieved the blood pressure goal compared with 22.7% of control participants ( P < 0.02). Among control group participants, 50% achieved the LDL cholesterol goal compared with 46.67% of intervention group participants. The odds of the intervention group attaining the composite goal were 5.87 times greater than the control group. CONCLUSION: A community pharmacy-based diabetes management program was effective in achieving A1C and blood pressure goals measured by NCQA-HEDIS performance standards. Program participants were statistically significantly more likely to achieve two of three HEDIS standards during a 9-month period.

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 children's 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 Student's t-tests and chi2 analysis, when appropriate, with an a priori alpha 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.

Medication reconciliation in a community pharmacy setting.

OBJECTIVES: To describe the types and frequencies of medication discrepancies identified through medication reconciliation in a community pharmacy setting, to identify potential correlations between a patient's electronic medical record (EMR) and pharmacy medication list, and to determine the relationship between patients who use prescribers and/or pharmacies outside of the Family Medicine Center (FMC) and the occurrence of medication discrepancies. METHODS: Cross-sectional comparison of patients' EMR medication lists and pharmacy medication fill history for a sample of patients presenting to the Family Medicine Pharmacy (FMP), which is located in the FMC on the University of Oklahoma Health Sciences Center campus in Oklahoma City. Discrepancies identified were classified according to one of six categories that included therapeutic duplication, medication exclusion, medications that should be designated inactive in the EMR medication list, and differences in medication strength, dosage form, or dosing regimen. RESULTS: A total of 100 patients were included. Most patients reported having all of their medications dispensed from FMP (89%), and most patients had prescriptions prescribed by FMC physicians only (57%). Each patient had an average of six medication discrepancies. Most discrepancies belonged to the inactive medication category (41%). The correlation between patients' FMP medication lists and their EMR medication lists was 0.73. Patients with one or more non-FMC prescribers had a greater number of medication discrepancies than patients with FMC prescribers only, but this relationship was not identified for those who used pharmacies outside of FMP (P = 0.0264 and 0.2580, respectively). CONCLUSION: A variety of medication discrepancies were observed, signaling a need for medication reconciliation in the outpatient setting. Future research on this topic should focus on the implications of such discrepancies in the outpatient setting, interventions to reduce the number of discrepancies, and identifying patients at high risk for such discrepancies.

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 (chi(2) = 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.

Economic effect of an expansion of pharmacy benefits on total health care expenditures by a state Medicaid program.

OBJECTIVES: To evaluate the economic effect of a pharmacy benefit expansion on a population of Oklahoma Medicaid recipients and to determine whether recipients who routinely maximized their monthly prescription limit (cap) before the benefit expansion benefited more from the expansion than the remainder of the study population. DESIGN: Retrospective study. SETTING: Oklahoma Medicaid claims data from January 1, 2003, to December 31, 2004. PATIENTS: Data from 15,936 Oklahoma Medicaid recipients. INTERVENTION: Retrospective administrative analysis using the Oklahoma Health Care Authority pharmacy and medical claims databases. MAIN OUTCOME MEASURES: Total health care expenditures per recipient per year, total medical expenditures per recipient per year, and total pharmacy expenditures per recipient per year. RESULTS: Total health care expenditures increased 17% after the benefit expansion (P < 0.0001). Of this increase, 65% was attributed to pharmacy expenditures and 35% to medical expenditures. However, a subpopulation of recipients who routinely reached their prescription limit before the expansion had a statistically significant increase in total and pharmacy expenditures; a statistically significant increase in medical expenditures was not observed. CONCLUSION: Although total health care expenditures increased after a monthly pharmacy benefit in a Medicaid population was expanded, a subpopulation of recipients identified as high pharmacy users before the expansion did not have a statistically significant increase in medical expenditures, whereas those who were non-high users experienced a significant increase. Additionally, this subpopulation experienced a nonsignificant decrease in hospital expenditures. These results could suggest that this subpopulation was affected differently than the overall population by the expansion of the Medicaid pharmacy benefit.

Effect of strategic planning education on attitudes and perceptions of independent community pharmacy owners/managers.

OBJECTIVE: To assess the impact of formal education program participation on the attitudes and perceptions of independent community pharmacy owners/managers toward strategic planning. DESIGN: Cross-sectional study. SETTING: United States; June 4-July 30, 2004. PARTICIPANTS: Nationwide random sample of 1,250 owners/managers of independent community pharmacies. INTERVENTION: Mailed survey. MAIN OUTCOME MEASURES: Strategic planning formal education program participation. Comprehensiveness of strategic planning. Attitudes and perceptions of owners/managers of independent community pharmacies toward strategic planning. RESULTS: A total of 527 (42.1%) usable questionnaires were returned. Only 124 (23.5%) respondents indicated that they participated in a formal strategic planning education program. However, of the 141 (26.85%) respondents who indicated that they had conducted strategic planning for their community pharmacy, 111 (89.5%) had participated in a formal strategic planning education program. A significant association was detected between formal education program participation and the conducting of strategic planning (P< or =0.0001). Significant differences were observed for all attitudes and perceptions of independent community pharmacy owners/managers toward strategic planning based on program participation (P< or =0.0001). Finally, respondents who indicated that they had participated in a formal education program had a significantly higher comprehensiveness of strategic planning rating than those respondents who did not participate in an educational program (P< or =0.0001). CONCLUSION: A significant association exists between formal strategic planning education program participation and the conducting of strategic planning by owner/managers of independent community pharmacies, and those participating in such programs have significantly different attitudes and perceptions toward the conducting of strategic planning and have a significantly higher comprehensiveness of strategic planning rating.

Disparities in the prevalence of medication therapy for hyperlipidemia in the elderly.

OBJECTIVE: To explore differences in the prevalence of therapy with antihyperlipidemic drugs in patients older than 75 years of age, as compared with patients between the ages of 55 to 74, and other variables. DESIGN: A cross-sectional study. SETTING: Two Oklahoma state-paid pharmacy drug-claims databases. PATIENTS, PARTICIPANTS: The first database contained 69,119 eligible patients 55 years of age and older. The second database contained 82,360 eligible patients 55 years of age and older. MAIN OUTCOME MEASURE(S): Comparison of the prevalence of therapy with antihyperlipidemic drugs in those 55 to 74 years of age with those older than 75 years of age in the data sets, and evaluation of the effect of gender, race, place of residence, and socioeconomic status. RESULTS: In the combined data sets, the group 55 to 74 years of age had a higher prevalence of therapy with antihyperlipidemics than those 75 years of age or older. Men had a higher prevalence of therapy than women, and those in higher socioeconomic status had a higher prevalence, but only in the group 75 years of age or older. Caucasians had a prevalence of therapy greater than African-Americans, but only in the group 55 to 74 years of age or older. CONCLUSIONS: We found that older people were prescribed therapy less frequently than younger people, that women were prescribed therapy less frequently than men, that Caucasians were prescribed therapy more frequently than African-Americans, and that those living in a nursing facility were prescribed therapy less frequently than those living in other settings. Regarding socioeconomic status, only in the younger age group was lower status associated with lower prevalence of prescribed therapy.

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.

Applicability of the Schwartz Equation and the Chronic Kidney Disease in Children Bedside Equation for Estimating Glomerular Filtration Rate in Overweight Children.

STUDY OBJECTIVE: To determine if significant correlations exist between glomerular filtration rate (GFR) prediction equation values, derived by using the original Schwartz equation and the Chronic Kidney Disease in Children (CKiD) bedside equation with a 24-hour urine creatinine clearance (Clcr ) value normalized to a body surface area of 1.73 m(2) in overweight and obese children. DESIGN: Prospective analysis (20 patients) and retrospective analysis (43 patients). SETTING: Pediatric inpatient ward and pediatric nephrology clinic at a comprehensive academic medical center. PATIENTS: Sixty-three pediatric patients (aged 5-17 years), of whom 27 were overweight (body mass index [BMI] at the 85th percentile or higher) and 36 were not overweight (BMI lower than the 85th percentile [controls]) between 2007 and 2012. METHODS AND MAIN RESULTS: Data from the overweight patients were compared with nonoverweight controls. GFR values were calculated by using the original Schwartz equation and the CKiD bedside equation. Each patient's 24-hour urine Clcr value normalized to a body surface area of 1.73 m(2) served as the index value. A Pearson correlation coefficient model was used to determine association between the 24-hour urine Clcr value (index value) with the Schwartz and CKiD GFR estimations. Significant correlation was found to exist between the Schwartz and CKiD bedside GFR estimations relative to the 24-hour urine Clcr in the control subjects (r = 0.85, p<0.0001, and r = 0.85, p<0.0001, respectively). Significant correlation was also found to exist between the Schwartz and CKiD bedside GFR values with the 24-hour urine Clcr value in overweight subjects (r = 0.86, p<0.0001, and r = 0.86, p<0.0001, respectively). The Schwartz equation estimated average GFR 21.75 ml/minute/1.73 m(2) higher than 24-hour urine Clcr (p<0.0001) in overweight children with a kidney disorder. The CKiD bedside GFR estimations were not significantly different compared with 24-hour urine Clcr values for the overweight group with kidney disorder (p=0.85). CONCLUSION: The Schwartz and CKiD bedside estimations of GFR correlated with 24-hour urine Clcr values in both overweight and nonoverweight children. Compared with the Schwartz equation, which tended to overestimate renal function, the CKiD bedside equation appeared to approximate 24-hour urine Clcr more closely in overweight children with kidney disorder.

An evaluation of three statistical estimation methods for assessing health policy effects on prescription drug claims.

BACKGROUND: While the choice of analytical approach affects study results and their interpretation, there is no consensus to guide the choice of statistical approaches to evaluate public health policy change. OBJECTIVES: This study compared and contrasted three statistical estimation procedures in the assessment of a U.S. Food and Drug Administration (FDA) suicidality warning, communicated in January 2008 and implemented in May 2009, on antiepileptic drug (AED) prescription claims. METHODS: Longitudinal designs were utilized to evaluate Oklahoma (U.S. State) Medicaid claim data from January 2006 through December 2009. The study included 9289 continuously eligible individuals with prevalent diagnoses of epilepsy and/or psychiatric disorder. Segmented regression models using three estimation procedures [i.e., generalized linear models (GLM), generalized estimation equations (GEE), and generalized linear mixed models (GLMM)] were used to estimate trends of AED prescription claims across three time periods: before (January 2006-January 2008); during (February 2008-May 2009); and after (June 2009-December 2009) the FDA warning. RESULTS: All three statistical procedures estimated an increasing trend (P < 0.0001) in AED prescription claims before the FDA warning period. No procedures detected a significant change in trend during (GLM: -30.0%, 99% CI: -60.0% to 10.0%; GEE: -20.0%, 99% CI: -70.0% to 30.0%; GLMM: -23.5%, 99% CI: -58.8% to 1.2%) and after (GLM: 50.0%, 99% CI: -70.0% to 160.0%; GEE: 80.0%, 99% CI: -20.0% to 200.0%; GLMM: 47.1%, 99% CI: -41.2% to 135.3%) the FDA warning when compared to pre-warning period. CONCLUSIONS: Although the three procedures provided consistent inferences, the GEE and GLMM approaches accounted appropriately for correlation. Further, marginal models estimated using GEE produced more robust and valid population-level estimations.

National antidepressant prescribing in children and adolescents with mental health disorders after an FDA boxed warning.

BACKGROUND: In October 2004, the U.S. Food and Drug Administration (FDA) issued a boxed warning about an increased risk of suicidality (i.e., suicidal ideation, behavior, or attempts) related to all antidepressants in children and adolescents. OBJECTIVE: To describe national antidepressant prescribing patterns in children and adolescents before, during, and after the introduction of the FDA boxed warning. METHODS: Cross-sectional data from the 2002-2009 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to describe antidepressant prescribing patterns within a nationally-representative sample of 4035 physician visits for children and adolescents diagnosed with depression or other psychiatric disorder(s) [i.e., anxiety disorders or attention deficit/hyperactivity disorder (ADHD)]. RESULTS: In 2002-2003, antidepressants were prescribed in 4.1 million (36.1%) visits, followed by 3.2 million (28.8%) visits in 2004-2005 and 2.8 million (26.8%) visits in 2006-2007. However, antidepressant prescribing patterns reversed during 2008-2009, with an increase to 3.6 million (32.5%) visits. Compared to the period preceding the FDA boxed warning (2002-2003), a significant decline in visits related to antidepressant prescribing detected in the immediate post-FDA boxed warning period (2006-2007) (AOR = 0.67, 95% CI: 0.47-0.96). No association between the FDA boxed warning and antidepressant prescribing visits was detected during the FDA boxed warning period (2004-2005) (AOR = 0.80, 95% CI: 0.53-1.21) and in the late post-FDA boxed warning period (2008-2009) (AOR = 1.01, 95% CI: 0.63-1.60). CONCLUSIONS: After a 2-year lag period, antidepressant prescribing for visits of children and adolescents diagnosed with depression or other psychiatric disorder(s) in community-based and outpatient clinic settings declined when compared to the period preceding the FDA boxed warning. This decline was not sustained in the period of five years after implementation of the FDA boxed warning.

Ethacrynic Acid continuous infusions in critically ill pediatric patients.

OBJECTIVES: The purpose of this study was to describe dosage regimens and treatment outcomes in critically ill children receiving ethacrynic acid continuous infusions (CI). METHODS: This retrospective cross-sectional study evaluated patients less than 18 years of age who received ethacrynic acid CI with a duration exceeding 12 hours, from January 1, 2007, through January 31, 2012. The primary objective was to determine the mean/median doses of ethacrynic acid CI. Secondary objectives were to assess surrogate efficacy markers (e.g., urine output [UOP], fluid balance) and the number of patients with electrolyte abnormalities or metabolic alkalosis. Descriptive statistics were used. A series of repeated measures analyses of variance were conducted to assess differences in surrogate efficacy markers and in adverse events that occurred pre-, mid-, and posttherapy. RESULTS: Nine patients were included. The mean ± SD initial and maximum doses (mg/kg/hr) were 0.13 ± 0.07 (median 0.1; range, 0.08-0.3) and 0.17 ± 0.08 (median, 0.16; range 0.09-0.3), respectively. The median UOP (mL/kg/hr) pre-, mid-, and postinfusions (interquartile range [IQR]) were 2.4 (1.8-3.2), 4.2 (3.5-6), and 4 (3.4-5.3), respectively. The median fluid balance (mL; IQR) was 189 (90-526), -258 (-411.7 to 249) and -113.5 (-212.5 to 80.2), respectively. There were statistically significant differences in UOP and fluid balance pre- versus mid-therapy (0.014) and pre- versus posttherapy (p=0.010). No significant differences were noted with magnesium and potassium. Five children (55.6%) developed metabolic alkalosis. CONCLUSIONS: This study provides preliminary evidence for ethacrynic acid CI in children. The median initial dose and maximum dose in this cohort were 0.13 mg/kg/hr and 0.17 mg/kg/hr, respectively. Larger prospective studies are needed to confirm these findings.