Marsha A. Raebel

Adherence with urate-lowering therapies for the treatment of gout.

IntroductionAdherence to urate-lowering drugs (ULDs) has not been well evaluated among those with gout. Our aim was to assess the level and determinants of non-adherence with ULDs prescribed for gout.MethodsWe identified persons using two integrated delivery systems aged 18 years or older with a diagnosis of gout who initiated use of allopurinol, probenecid or sulfinpyrazone from 1 January 2000 to 30 June 2006. Non-adherence was measured using the medication possession ratio (MPR) over the first year of therapy and defined as an MPR < 0.8. Descriptive statistics were calculated and logistic regression was used to estimate the strength of the association between patient characteristics and non-adherence.ResultsA total of 4,166 gout patients initiated ULDs; 97% received allopurinol. Median MPR for any ULD use was 0.68 (interquartile range (IQR) 0.64). Over half of the patients (56%) were non-adherent (MPR < 0.8). In adjusted analyses, predictors of poor adherence included younger age (odds ratio (OR) 2.43, 95% confidence interval (CI) 1.86 to 3.18 for ages <45 and OR 1.44, 95% CI 1.08 to 1.93 for ages 45 to 49), fewer comorbid conditions (OR 1.46, 95% CI 1.20 to 1.77), no provider visits for gout prior to urate-lowering drug initiation (OR 1.28, 95% CI 1.05 to 1.55), and use of non-steroidal anti-inflammatory drugs in the year prior to urate-lowering drug initiation (OR 1.15, 95% CI 1.00 to 1.31).ConclusionsNon-adherence amongst gout patients initiating ULDs is exceedingly common, particularly in younger patients with less comorbidity and no provider visits for gout prior to ULD initiation. Providers should be aware of the magnitude of non-adherence with ULDs.

Recent Trends in Outpatient Antibiotic Use in Children

OBJECTIVE: The goal of this study was to determine changes in antibiotic-dispensing rates among children in 3 health plans located in New England [A], the Mountain West [B], and the Midwest [C] regions of the United States. METHODS: Pharmacy and outpatient claims from September 2000 to August 2010 were used to calculate rates of antibiotic dispensing per person-year for children aged 3 months to 18 years. Differences in rates by year, diagnosis, and health plan were tested by using Poisson regression. The data were analyzed to determine whether there was a change in the rate of decline over time. RESULTS: Antibiotic use in the 3- to <24-month age group varied at baseline according to health plan (A: 2.27, B: 1.40, C: 2.23 antibiotics per person-year; P < .001). The downward trend in antibiotic dispensing slowed, stabilized, or reversed during this 10-year period. In the 3- to <24-month age group, we observed 5.0%, 9.3%, and 7.2% annual declines early in the decade in the 3 plans, respectively. These dropped to 2.4%, 2.1%, and 0.5% annual declines by the end of the decade. Third-generation cephalosporin use for otitis media increased 1.6-, 15-, and 5.5-fold in plans A, B, and C in young children. Similar attenuation of decline in antibiotic use and increases in use of broad-spectrum agents were seen in other age groups. CONCLUSIONS: Antibiotic dispensing for children may have reached a new plateau. Along with identifying best practices in low-prescribing areas, decreasing broad-spectrum use for particular conditions should be a continuing focus of intervention efforts.

Importance of Including Early Nonadherence in Estimations of Medication Adherence

Background Many medication adherence metrics are based on refill rates determined from pharmacy claims databases. However, these methods do not incorporate assessment of nonadherence to new prescriptions when those prescriptions are never dispensed (primary nonadherence), or dispensed only once (early nonpersistence). As a result, published studies may overestimate adherence, but the extent of overestimation posed by not considering patients with primary nonadherence and early nonpersistence has not been assessed. Objective: To estimate the magnitude of misestimation in adherence estimates that results from not including patients with primary nonadherence and early nonpersistence, Methods: We conducted a retrospective cohort study of 15,417 patients enrolled in an integrated health care delivery system who were newly prescribed an antihypertensive, antidiabetic, or antihyperlipidemic medication. We linked prescription orders to medication dispensings. Based on dispensing and refill rates, we stratified patients into primary nonadherent, early nonpersistent, and ongoing dispensings groups. Adherence was estimated using the proportion of days covered (PDC). Standardized observation periods were applied across all groups. Results: A total of 1142 (7.4%) patients were primarily nonadherent, 3356 (21.8%) demonstrated early nonpersistence, and 10,919 (70.8%) patients received ongoing dispensings, with a mean PDC of 84%. Not including primarily nonadherent and early nonpersistent patients in calculations resulted in adherence estimates overestimated by 9-18%. Conclusions: When medication adherence is estimated from pharmacy claims databases, adherence estimates are substantially inflated because primarily nonadherent and early nonpersistent patients are not included in the estimations. An implication of this incorrect estimation is potential distortion of the true relationship between medication adherence and clinical outcomes.

Association between anti-TNF-alpha therapy and all-cause mortality

To compare mortality among patients with selected autoimmune diseases treated with anti‐tumor necrosis factor alpha (TNF‐α) agents with similar patients treated with non‐biologic therapies.

Prevalence, Trends, and Patterns of Use of Antidiabetic Medications Among Pregnant Women, 2001-2007

OBJECTIVE: To describe the prevalence, trends, and patterns in use of antidiabetic medications to treat hyperglycemia and insulin resistance before and during pregnancy in a large U.S. cohort of insured pregnant women. METHODS: Pregnancies resulting in live births were identified (N=437,950) from 2001 to 2007 among 372,543 females 12–50 years of age at delivery from 10 health maintenance organizations participating in the Medication Exposure in Pregnancy Risk Evaluation Program. Information for these descriptive analyses, including all antidiabetic medications dispensed during this period, was extracted from electronic health records and newborn birth certificates. RESULTS: A little more than 1% (1.21%) of deliveries were to women dispensed antidiabetic medication in the 120 days before pregnancy. Use of antidiabetic medications before pregnancy increased from 0.66% of deliveries in 2001 to 1.66% of deliveries in 2007 (P<.001) because of an increase in metformin use. Most women using metformin before pregnancy had a diagnosis code for polycystic ovaries or female infertility (67.2%), whereas only 13.6% had a diagnosis code for diabetes. The use of antidiabetic medications during the second or third trimester of pregnancy increased from 2.8% of deliveries in 2001 to 3.6% in 2007 (P<.001). Approximately two thirds (68%) of women using metformin before pregnancy did not use any antidiabetic medications during pregnancy. CONCLUSIONS: Antidiabetic medication use before and during pregnancy increased from 2001 to 2007, possibly because of increasing prevalence of gestational diabetes mellitus, type 1 and type 2 diabetes, and other conditions associated with insulin resistance. LEVEL OF EVIDENCE: III

Ambulatory Management of Chemotherapy-Induced Fever and Neutropenia in Adult Cancer Patients

OBJECTIVE: To review the literature on the management of low-risk adults with chemotherapy-induced fever and neutropenia (CIFN). Included in the review are methods to identify these patients, management options, and economic impact associated with nontraditional treatment options. DATA SOURCES: A MEDLINE and bibliographic search (January 1966–December 1997) for all English-language studies evaluating the identification and treatment of adult, low-risk CIFN patients was completed. Reference lists from identified articles also served as literature sources. STUDY SELECTION AND DATA EXTRACTION: All human studies identified from the data sources were evaluated. Pertinent information, excluding pediatric studies, was selected and critically evaluated for discussion. DATA SYNTHESIS: Alterations in prominent bacterial isolates in CIFN, newer antibiotic choices, enhanced focus on patient comfort, and cost-containment directives have promoted recent research identifying adult cancer patients with low-risk CIFN. Using this information to select low-risk CIFN patients, several investigators have completed trials using antibiotic therapy applicable to the ambulatory setting. Additionally, some investigators have included the use of an oral outpatient antibiotic regimen. Limited data indicate that this approach is a reasonable treatment option for selected patients. CONCLUSIONS: A subset of adult patients with CIFN are at low risk for serious morbidity and mortality when treated with broad-spectrum antibiotics in the ambulatory setting. Managing these patients with this approach requires close patient selection, intense follow-up, data collection, and ongoing evaluation to determine efficacy and patient safety. Currently, ambulatory treatment with oral antibiotics for CIFN is not considered standard of care. Further studies of larger size designed to confirm low-risk patient characteristics and optimal antibiotic selection are required.

Interventions aimed at improving performance on medication adherence metrics

Background medication adherence is one determining factor of treatment success. Poor medication adherence mitigates optimum clinical benefits and increases total health care costs. Current evidence suggests that for population-based adherence interventions to be effective, a multidisciplinary, multifactorial approach that can be tailored for each individual should be adopted. In the United States, national organizations such as the National Committee for Quality Assurance and the Centers for Medicare and Medicaid Services include medication adherence as a metric of health care system performance Aim of the Commentary This article provides an overview of efforts at Kaiser Permanente Colorado to impact medication adherence-related metrics. Described interventions are supported by electronic data gathering processes with an emphasis on the role of pharmacists.

Implications of different laboratory-based incident diabetic kidney disease definitions on comparative effectiveness studies

BACKGROUND Comparative effectiveness studies using electronic health records (EHRs) often define chronic kidney disease (CKD) outcomes using laboratory-based definitions. Recommendations for defining CKD require multiple longitudinal measurements. The implications of applying these definitions to EHR data are poorly understood. METHODS Using a cohort of 36,025 individuals with diabetes from three health systems who initiated a new glucose-lowering medication, we compared concordance and CKD incidence rates and rate ratios for glucose-lowering medication classes for laboratory-based CKD definitions requiring one versus multiple abnormal tests. RESULTS & CONCLUSION CKD incidence rates differed more than twofold based on the definition. Reassuring for CER, incidence rate ratios for glucose-lowering medication classes on risk of developing CKD were relatively unaffected by CKD definition.