Ranjani Manjunath

The impact of inadequately controlled asthma in urban children on quality of life and productivity

BACKGROUND The burden of inadequately controlled pediatric asthma on education and other daily activities is not well described. OBJECTIVE To evaluate asthma-related activity limitations and productivity losses among children and caregivers. METHODS Surveys were mailed to caregivers of children with asthma. Caregivers provided demographics, health-related quality of life (HRQL), workplace productivity, and asthma-related costs. Adolescents (aged 12-18 years) provided HRQL, asthma control, and school-based productivity, and young children (aged 4-11 years) completed an asthma control questionnaire with help from a caregiver. RESULTS Among the 239 respondents, the mean age was 10.1 years; 49% were girls. More than half were inadequately controlled as measured using the Asthma Control Test. Both HRQL and productivity were significantly lower in patients with inadequately controlled asthma compared with those with controlled asthma. In the previous year, caregivers reported missing 1.4 days of work due to their childs asthma, with the child missing an average of 4.1 school days. Fewer adolescents with controlled asthma reported missing 1 or more school days in the previous week compared with adolescents with inadequately controlled asthma (3.5% vs 34.0%; P < .001). There were similar differences in caregiver workdays missed and health care resource use: both were significantly higher in children with inadequately controlled asthma. CONCLUSIONS Inadequately controlled asthma has a significant impact on asthma-specific HRQL, school productivity and attendance, and work productivity of children and their caregivers.

Prevalence and cost of nonadherence to antiepileptic drugs in elderly patients with epilepsy

Retrospective insurance claims from the United States were analyzed to assess nonadherence to antiepileptic drugs (AEDs) and the association between AED nonadherence, seizures, and health care costs in elderly persons with epilepsy. Inclusion criteria were: age 65, epilepsy diagnosis between 1 January 2000 and 31 June 2006, 2 AED prescriptions, and insurance enrollment for 6 months pre- and 12 months post-AED initiation. Adherence was evaluated using the medication possession ratio (MPR), with MPR<0.8 defining nonadherence. Per-patient outcomes were evaluated over 12 months post-AED initiation. Of 1278 patients identified, 41% were nonadherent. Seizure, defined by epilepsy-related inpatient or emergency department admission, occurred in 12.1% of nonadherers versus 8.2% of adherers (P=0.0212). Nonadherers had higher inpatient (+

Clinical consequences of generic substitution of lamotrigine for patients with epilepsy

872, P=0.001), emergency department (+

Association of antiepileptic drug nonadherence with risk of seizures in adults with epilepsy.

143, P=0.0008), other outpatient ancillary (+

Stated Preferences of Patients with Cancer for Health-related Quality-of-life (HRQOL) Domains During Treatment

1741, P=0.0081), and total health care (+

Burden of uncontrolled epilepsy in patients requiring an emergency room visit or hospitalization

2674, P=0.0059) costs. AED adherence among elderly patients with epilepsy is suboptimal and associated with increased seizures and health care costs.

The relationship of depression to antiepileptic drug adherence and quality of life in epilepsy

CLINICAL CONSEQUENCES OF GENERIC SUBSTITUTION OF LAMOTRIGINE FOR PATIENTS WITH EPILEPSY To the Editor: LeLorier et al.1 studied the risks associated with patients switching to and from generic antiepileptic drugs (AEDs) in Quebec. The authors did not consider that such changes could be attributed to promotionally driven doctor and patient preferences. Industry representatives vigorously promote the idea that generics are less potent (“up to 20% less effective”) than their brand name equivalents despite Food and Drug Administration (FDA) assertions to the contrary.2 Study patients taking generics underwent dose escalations. The authors suggest that dose escalations were in response to increased side effects, but this is counterintuitive. More plausibly, anxietyinduced dose escalations contributed to side effects and, in turn, switch-backs. The unspoken hypothesis that switches to generic led to more seizures is unaddressed by the presented data, which blur psychiatric and neurologic indications for lamotrigine (LTG). LTG is used heavily in psychiatry and most recent growth in sales is driven by the psychiatric market.3 A single claim submitted with a code for epilepsy is considered sufficient evidence that LTG is being prescribed as an AED, but this is unlikely. The leading outpatient diagnostic code as well as four of five diagnostic codes for outpatient visits and two of three diagnostic codes for inpatient hospitalizations were not for epilepsy. By contrast, all comparator non-AED drugs in this study lent themselves to readily available objective efficacy assessment (blood pressure and lipid levels). There is no such equivalent for any LTG indication. FDA standards for generic bioequivalence are the same standards applied to branded medication for between-batch variability.2 Bioequivalence is complex.4 For example, the area under the curve and maximum concentration but not time to maximum (tmax) concentration are used by the FDA in determining bioequivalence. Manufacturer disclosures of bioequivalence data indicate that branded LTG tmax varies from half an hour to 6 hours for various formulations of the 100 mg tablets.5 Clinical relevance of FDA-permitted variance within a brand or between brand and generic medication is unclear. Millions of doses of generic medications have been dispensed with no well-documented instances of therapeutic failures for medications produced in accordance with existing FDA standards.4 It is clear that promotional activity influences prescribing behavior. Furthermore, under experimental conditions, expensive placebos are more effective.6 Not only patients but neurologists are anxious about generic medications encouraged in this regard by controversial American Academy of Neurology (AAN) policies on generic substitution of AEDs.7 The authors should compare switches to and from generics by specialty of the prescriber (neurologist, psychiatrist, primary care) and by first indication for which the medication was prescribed, stratifying by promotional dollars spent per indication and specialty.

Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting.

This study evaluated the potential effect of antiepileptic drug (AED) nonadherence on the risk of subsequent seizure. Retrospective insurance claims from the United States were analyzed. Inclusion criteria were: age 21-64 years, diagnosis of epilepsy or nonfebrile convulsions, 2 AED prescriptions, and insurance enrollment for 6 months pre- and 60 days post-AED initiation. Seizure was defined as a hospital or emergency admission associated with epilepsy or nonfebrile convulsions. Observation began 7 days post-drug initiation, ending with the first of the following: seizure, insurance disenrollment, or 365 days post-drug initiation. Adherence was measured using the medication possession ratio (MPR), with MPR <0.8 defining nonadherence. Seizure risk was assessed using an extended Cox proportional hazards model. Of 18,073 subjects identified, 2467 (14%) had 1 seizure. Mean follow-up was 133 days among subjects with event and 305 days for patients without event. Seizure risk was 21% higher among nonadherers (hazard ratio=1.205, P=0.0002) than adherers.

Patient characteristics and costs associated with dyslipidaemia and related conditions in HIV-infected patients: a retrospective cohort study

Objectives: It is postulated that patients with different cancer diagnoses, stages of disease and treatments will exhibit different individual preferences for health-related quality-of-life (HRQOL) functional domains and symptoms. Methods: A stated-preference (SP) instrument incorporating all functional domains and symptoms of the EORTC Quality of Life Questionnaire (QLQ-C30) was administered to 400 patients with either breast (n=150); colorectal (n=150) or non-small cell lung cancer (n=100) who had previously experienced chemotherapy. The SP survey asked patients to make choices between a series of hypothetical functional/symptom pairs defined by combinations of HRQOL attributes, and depicted by levels of functioning and symptomatology. Results: In the 400 patients, considered as one group, role, cognitive, and social functioning, fatigue, nausea/vomiting, pain, appetite loss, diarrhea and financial difficulties were most important, whereas physical and emotional functioning, dyspnea, constipation and insomnia were less important. The four effects that patients with breast cancer most wished to avoid were nausea and vomiting, pain, and decreases in emotional and role functioning. Patients with colorectal cancer listed diarrhea as the second most important effect to avoid (after nausea/vomiting, but before pain and role functioning), whereas those with non-small cell lung cancer listed dyspnea as the fourth most important effect to avoid. Conclusion: These results provide more precise information regarding patient treatment concerns than that provided by the usual measurement of HRQOL. This information can be used by clinical trial investigators to design more precise interventions to improve HRQOL in the domains of greatest importance to patients and by all health care professionals to improve counseling of patients.

Economic burden associated with the use of generic antiepileptic drugs in the United States

Objective: To quantify the clinical and economic burden of uncontrolled epilepsy in patients requiring emergency department (ED) visit or hospitalization. Methods: Health insurance claims from a 5-state Medicaid database (1997Q1–2009Q2) and 55 self-insured US companies (“employer,” 1999Q1 and 2008Q4) were analyzed. Adult patients with epilepsy receiving antiepileptic drugs (AED) were selected. Using a retrospective matched-cohort design, patients were categorized into cohorts of “uncontrolled” (≥2 changes in AED therapy, then ≥1 epilepsy-related ED visit/hospitalization within 1 year) and “well-controlled” (no AED change, no epilepsy-related ED visit/hospitalization) epilepsy. Matched cohorts were compared for health care resource utilization and costs using multivariate conditional regression models and nonparametric methods. Results: From 110,312 (Medicaid) and 36,529 (employer) eligible patients, 3,454 and 602 with uncontrolled epilepsy were matched 1:1 to patients with well-controlled epilepsy, respectively. In both populations, uncontrolled epilepsy cohorts presented about 2 times more fractures and head injuries (all p values < 0.0001) and higher health care resource utilization (ranges of adjusted incidence rate ratios [IRRs] [all-cause utilization]: AEDs = 1.8–1.9, non-AEDs = 1.3–1.5, hospitalizations = 5.4–6.7, length of hospital stays = 7.3–7.7, ED visits = 3.7–5.0, outpatient visits = 1.4–1.7, neurologist visits = 2.3–3.1; all p values < 0.0001) than well-controlled groups. Total direct health care costs were higher in patients with uncontrolled epilepsy (adjusted cost difference [95% confidence interval (CI)] Medicaid =