Migraine-related healthcare resource use and costs for subjects prescribed fixed-dose combination sumatriptan/naproxen sodium vs. single-entity oral triptans in a managed care population in the USA.

BACKGROUND: Randomized clinical trials have demonstrated that the efficacy of a fixed-dose single-tablet combination containing sumatriptan and naproxen sodium (S/NS) was greater than either of its individual components. Simplifying drug regimens (e.g., via a fixed-dose combination) has been shown to improve "real-world" outcomes by reducing pill burden and treatment regimen complexity, improving adherence, and reducing healthcare resource use and associated costs; however, no studies assessing such outcomes have been conducted to date for the acute treatment of migraine. OBJECTIVE: To assess migraine-related healthcare resource use and associated costs for subjects prescribed S/NS vs. subjects prescribed single-entity oral triptans (SOTs) within a managed care population in the USA. METHODS: In this retrospective analysis of administrative claims data from July 1, 2008 to December 31, 2009 (IMS LifeLink), subjects meeting the following criteria were selected: one or more pharmacy claim(s) for either S/NS or SOT (index date), aged 18-64 years; at least one migraine diagnosis, and continuous enrollment in the 6 months prior to and post the index date. The study population was subsequently stratified for two analyses: triptan-naïve (triptan naïve in the 6-month period prior to the index date) and triptan-switch (triptan user in the 6-month period prior to the index date and switching to another triptan). Subjects prescribed S/NS were propensity-score matched with subjects prescribed SOT (triptan-naïve analysis: 1:3; triptan-switch analysis: 1:1) to assess differences in healthcare resource use and associated costs (2009 US$) between the S/NS and SOT groups. RESULTS: Results from the triptan-naïve and triptan-switch analyses suggest that subjects prescribed S/NS are likely to have similar healthcare resource use patterns as those either newly initiated on an SOT or switching SOTs, as measured by migraine medication use, migraine-related healthcare resource use, and all-cause healthcare resource use. One exception was the observed increased use of opioids in the SOT group compared with the S/NS group (change in mean number of tablets pre-index vs. post-index, S/NS vs. SOT; triptan-naïve analysis: 8.6 vs.18.3, p = 0.045; triptan-switch analysis: -8.2 vs. 17.7; p = 0.120). Total costs from the triptan-naïve analysis indicated that the S/NS group had lower migraine-related (US$744 vs. US$820; p = 0.067) and all-cause healthcare costs (US$4,391 vs. US$4,870; p = 0.040) when compared with the SOT group, driven by savings in medical costs (migraine-related: US$252 vs. US$380; p = 0.001; all-cause: US$3,023 vs. US$3,599; p = 0.014). However, no significant differences were observed for total costs from the triptan-switch analysis (migraine-related healthcare costs, S/NS vs. SOT: US$1,159 vs. US$1,117; p = 0.929; all-cause healthcare costs: US$5,128 vs. US$4,788; p = 0.381). CONCLUSION: Study results suggest similar healthcare resource use patterns and associated costs when comparing S/NS and SOT across a triptan-naïve and triptan-experienced population. While the current study focuses on direct medical costs, future studies should extend beyond such a perspective to explore functional status, productivity, and health-related quality of life and satisfaction, attributes not captured in administrative claims data, but nonetheless important treatment goals.

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

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 = $12,258 [$10,482-$14,083]; employer = $14,582 [$12,019-$17,097]) vs well-controlled patients. Privately insured employees with uncontrolled epilepsy lost 2.5 times more work days, with associated indirect costs of $2,857 (95% CI $1,042-$4,581). CONCLUSIONS: Uncontrolled epilepsy in patients requiring ED visit or hospitalization was associated with significantly greater health care resource utilization and increased direct and indirect costs compared to well-controlled epilepsy in both publicly and privately insured settings.

Development and psychometric evaluation of a new patient-reported outcome instrument measuring the functional impact of insomnia.

PURPOSE: The objective of this study was to develop and validate a patient-reported outcome instrument to comprehensively assess the consequences of inadequate sleep for use in insomnia-related studies. METHODS: To inform item development, relevant constructs were identified through patient focus groups, literature review, and expert input. Following a translatability assessment for United States (US) English, US Spanish, and French, the draft items were refined through iterative sets of patient interviews in the United States and France. Psychometric properties were evaluated using patient responses from a validation study including 432 participants with either a diagnosis of primary insomnia or no history of insomnia. RESULTS: Psychometric analyses supported item reduction from 38 to 26 items, yielding a unidimensional scale and preserving the original content (mood, tiredness/energy, memory/concentration, motivation, daily performance, social interaction, sexual functioning). Evidence of internal consistency (coefficient α = 0.97), convergent validity, and known-groups validity also was documented. CONCLUSIONS: The Sleep Functional Impact Scale (SFIS) is a psychometrically sound measure targeting the impact of insomnia on patient functioning. When administered with a sleep diary, this instrument has the ability to provide a more comprehensive assessment of treatment response in clinical studies.

Sarcoidosis in World Trade Center rescue workers presenting with rheumatologic manifestations.

The health consequences of the World Trade Center collapse are unknown, but likely to be significant and may take years to fully appreciate. Sarcoidosis is a multisystem inflammatory disorder of unknown etiology characterized pathologically by noncaseating granulomas. Inciting events, such as infectious agents or possible environmental exposures, have been postulated as the source of antigen exposure initiating an inflammatory cascade. We describe 2 cases of sarcoidosis in rescue workers with significant exposure from the World Trade Center collapse, who presented with extrapulmonary rheumatologic manifestations. Our first case involved a 33-year-old white New York City man detective found to have sarcoidosis following an evaluation of diffuse joint pain. The second case involved a 40-year-old African American man, New York City officer, who presented with uveitis, and was subsequently diagnosed with sarcoidosis. These 2 cases extend the spectrum of disorders resulting from the World Trade Center disaster and illustrate the need for clinicians to be aware of the diverse presentations of sarcoidosis in this patient population.

Exophthalmos as a presenting manifestation of limited Wegener's granulomatosis in a patient with prior graves' disease.

Wegener's granulomatosis is a granulomatous necrotizing vasculitis characterized by its predilection to affect the upper and lower respiratory tracts and kidneys. Ocular manifestations such as keratitis, conjunctivitis, scleritis, episcleritis, nasolacrimal duct obstruction, uveitis, retroorbital pseudotumor with proptosis retinal vessel occlusion, and optic neuritis have all been described. We present a case of limited Wegener's granulomatosis presenting with proptosis. A 57 year old woman with a history of Graves' disease 20 yrs ago, presented to her ophthalmologist with new onset of exophthalmos of right eye. An MRI of the brain and orbits revealed a soft tissue mass behind the right orbit. The biopsy of the mass revealed transmural inflammation with fibrinoid necrosis consistent with necrotizing vasculitis. She was diagnosed with Wegener's granulomatosis limited to the eye and was treated with oral cyclophosphamide and prednisone followed by weekly methotrexate with good response. Though ocular manifestations of Wegener's granulomatosis are well described, a review of the literature revealed that exophthalmos as the lone presenting manifestation is quite rare. Only two cases have been reported in the English literature since 1977. This case illustrates the importance of considering a diagnosis of limited Wegener's granulomatosis presenting with proptosis of the orbit.

Successful remission of thrombotic thrombocytopenic purpura with rituximab in a patient with undifferentiated connective tissue disorder.

Thrombotic thrombocytopenic purpura (TTP) is rarely associated with undifferentiated connective tissue disorder. We present a patient with TTP, undifferentiated connective tissue disorder, and very high titer of anti-ribonucleoprotein antibodies. Her TTP did not respond to intravenous methylprednisolone and cyclophosphamide requiring her to remain dependent on plasmapheresis. Her disease remitted successfully after 4 doses of rituximab given at weekly intervals and she remained in continuous remission 6 months after therapy. We propose early and aggressive use of B-cell depletion therapy in TTP associated with autoimmune disorders.

Fluticasone propionate/salmeterol combination compared with montelukast for the treatment of persistent asthma.

BACKGROUND: Asthma is a chronic disease characterized by inflammation and bronchoconstriction. Medications that are able to effectively treat both components are advantageous. OBJECTIVE: To compare the efficacy of an inhaled corticosteroid and a long-acting beta2-agonist combination product with a leukotriene antagonist for initial maintenance therapy in patients who were symptomatic while receiving short-acting beta2-agonists alone. METHODS: A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 432 patients 15 years of age and older with persistent asthma who were symptomatic on short-acting beta2-agonists alone. Fluticasone propionate 100 microg and salmeterol 50 microg combination product (FSC) twice daily or montelukast 10 mg once daily was administered. RESULTS: At endpoint, compared with montelukast, FSC significantly increased morning predose forced expiratory volume in 1 second (0.61 +/- 0.03 L vs 0.32 +/- 0.03 L), morning peak expiratory flow rate (peak expiratory flow rate; 81.4 +/- 5.9 L/minute vs 41.9 +/- 4.8 L/minute), evening peak expiratory flow rate (64.6 +/- 5.3 L/minute vs 38.8 +/- 4.7 L/minute), the percentage of symptom-free days (40.3 +/- 2.9% vs 27.0 +/- 2.7%), the percentage of rescue-free days (53.4 +/- 2.8% vs 26.7 +/- 2.5%), and the percentage of nights with no awakenings (29.8 +/- 2.5% vs 19.6 +/- 2.1%) (P < or = 0.011, all comparisons). At endpoint, FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs -0.7 +/- 0.1) and rescue albuterol use (-3.6 +/- 0.2 puffs/day vs -2.2 +/- 0.2 puffs/day) compared with montelukast (P < 0.001). At endpoint, patients treated with FSC also had a significantly greater improvement in quality of life scores and were more satisfied with their treatment compared with montelukast-treated patients (P < or = 0.001). Both treatments were well tolerated. CONCLUSIONS: Initial maintenance therapy with FSC provides greater improvement in asthma control and patient satisfaction than montelukast.