Characteristics and outcomes of patients with type 2 diabetes mellitus treated with canagliflozin: a real-world analysis.

BACKGROUND: Canagliflozin, an oral agent that inhibits sodium glucose co-transporter 2, improves glycemic control, body weight, and blood pressure and is generally well tolerated in patients with type 2 diabetes mellitus (T2DM). This study extends the scope of previous analyses by evaluating outcomes associated with the use of canagliflozin over a 6-month period in a real-world setting. METHODS: This retrospective cohort study used data obtained from a large health plan database for patients (≥18 years) with a diagnosis of T2DM who filled at least one canagliflozin prescription between April 1, 2013 and October 30, 2013 (first 7 months canagliflozin was commercially available in the USA) and were continuously enrolled in the health plan for 6 months prior to (baseline) and 6 months following the first canagliflozin prescription claim (follow-up). Changes in glycemic control were evaluated, along with characteristics of enrolled patients and changes in treatment patterns. RESULTS: 4017 patients (mean age 56 years, 43 % female) met the study inclusion criteria. Of these, at the time of first canagliflozin claim, 21 % used canagliflozin concomitantly with three or more other antihyperglycemic agents (AHAs), 29 % with two other AHAs, 30 % with one other AHA, and 20 % without other AHAs. During follow-up, patients received 3.4 (average) canagliflozin prescription fills and a mean of 148 total days of supply; median adherence (interquartile range [IQR]) was 86 % (66-98 %) for patients with ≥2 fills. Among patients with available glycated hemoglobin (A1C) measurements at baseline and follow-up (n = 826, baseline A1C 8.59 %), mean A1C reduction was 0.81 % (P < 0.001). Mean A1C reduction during the follow-up period was greatest in patients with the highest baseline A1C levels. Of the patients who used canagliflozin concomitantly with other AHAs, 20 % were observed to discontinue one or more other AHAs during follow-up. The most commonly discontinued baseline AHAs were: glucagon-like peptide-1 receptor agonists (16 %), dipeptidyl peptidase-4 inhibitors (15 %), insulin (13 %), sulfonylureas (13 %), and metformin (11 %). CONCLUSIONS: This real-world study on canagliflozin use in a range of patients with T2DM demonstrated significant improvements in mean A1C from baseline following the first canagliflozin prescription. In patients concomitantly using one or more additional AHAs at baseline, there appears to be a trend toward lower other AHA use after canagliflozin initiation.

Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients.

BACKGROUND: Inadequate surgical hemostasis may lead to transfusion and/or other bleeding-related complications. This study examines the incidence and costs of bleeding-related complications and/or blood product transfusions occurring as a consequence of surgery in various inpatient surgical cohorts. METHODS: A retrospective analysis was conducted using Premier's Perspective™ hospital database. Patients who had an inpatient procedure within a specialty of interest (cardiac, vascular, non-cardiac thoracic, solid organ, general, reproductive organ, knee/hip replacement, or spinal surgery) during 2006-2007 were identified. For each specialty, the rate of bleeding-related complications (including bleeding event, intervention to control for bleeding, and blood product transfusions) was examined, and hospital costs and length of stay (LOS) were compared between surgeries with and without bleeding-related complications. Incremental costs and ratios of average total hospital costs for patients with bleeding-related complications vs. those without complications were estimated using ordinary least squares (OLS) regression, adjusting for demographics, hospital characteristics, and other baseline characteristics. Models using generalized estimating equations (GEE) were also used to measure the impact of bleeding-related complications on costs while accounting for the effects related to the clustering of patients receiving care from the same hospitals. RESULTS: A total of 103,829 cardiac, 216,199 vascular, 142,562 non-cardiac thoracic, 45,687 solid organ, 362,512 general, 384,132 reproductive organ, 246,815 knee/hip replacement, and 107,187 spinal surgeries were identified. Overall, the rate of bleeding-related complications was 29.9% and ranged from 7.5% to 47.4% for reproductive organ and cardiac, respectively. Overall, incremental LOS associated with bleeding-related complications or transfusions (unadjusted for covariates) was 6.0 days and ranged from 1.3 to 9.6 days for knee/hip replacement and non-cardiac thoracic, respectively. The incremental cost per hospitalization associated with bleeding-related complications and adjusted for covariates was highest for spinal surgery ($17,279) followed by vascular ($15,123), solid organ ($13,210), non-cardiac thoracic ($13,473), cardiac ($10,279), general ($4,354), knee/hip replacement ($3,005), and reproductive organ ($2,805). CONCLUSIONS: This study characterizes the increased hospital LOS and cost associated with bleeding-related complications and/or transfusions occurring as a consequence of surgery, and supports implementation of blood-conservation strategies.

Electronic medical records as a research tool: evaluating topiramate use at a headache center.

BACKGROUND: Electronic medical records (EMRs) are used in large healthcare centers to increase efficiency and accuracy of documentation. These databases may be utilized for clinical research or to describe clinical practices such as medication usage. METHODS: We conducted a retrospective analysis of EMR data from a headache clinic to evaluate clinician prescription use and dosing patterns of topiramate. The study cohort comprised 4833 unique de-identified records, which were used to determine topiramate dose and persistence of treatment. RESULTS: Within the cohort, migraine was the most common headache diagnosis (n = 3753, 77.7%), followed by tension-type headache (n = 338, 7.0%) and cluster or trigeminal autonomic cephalalgias (n = 287, 5.9%). Physicians prescribed topiramate more often for subjects with migraine and idiopathic intracranial hypertension (P < .0001) than for those with other conditions, and more often for subjects with coexisting conditions including obesity, bipolar disorder, and depression. The most common maintenance dose of topiramate was 100 mg/day; however, approximately 15% of subjects received either less than 100 mg/day or more than 200 mg/day. More than a third of subjects were prescribed topiramate for more than 1 year, and subjects with a diagnosis of migraine were prescribed topiramate for a longer period of time than those without migraine. CONCLUSIONS: Findings from our study using EMR demonstrate that physicians use topiramate at many different doses and for many off-label indications. This analysis provided important insight into our patient populations and treatment patterns.

Cost-effectiveness of a potential prophylactic Helicobacter pylori vaccine in the United States.

BACKGROUND: Helicobacter pylori vaccines are under development to prevent infection. We quantified the cost-effectiveness of such a vaccine in the United States, using a dynamic transmission model. METHODS: We compartmentalized the population by age, infection status, and clinical disease state and measured effectiveness in quality-adjusted life years (QALYs). We simulated no intervention, vaccination of infants, and vaccination of school-age children. Variables included costs of vaccine, vaccine administration, and gastric cancer treatment (in 2007 US dollars), vaccine efficacy, quality adjustment due to gastric cancer, and discount rate. We evaluated possible outcomes for periods of 10-75 years. RESULTS: H. pylori vaccination of infants would cost $2.9 billion over 10 years; savings from cancer prevention would be realized decades later. Over a long time horizon (75 years), incremental costs of H. pylori vaccination would be $1.8 billion, and incremental QALYs would be 0.5 million, yielding a cost-effectiveness ratio of $3871/QALY. With school-age vaccination, the cost-effectiveness ratio would be $22,137/QALY. With time limited to <40 years, the cost-effectiveness ratio exceeded $50,000/QALY. CONCLUSION: When evaluated with a time horizon beyond 40 years, the use of a prophylactic H. pylori vaccine was cost-effective in the United States, especially with infant vaccination.

Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs.

OBJECTIVE: The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache. METHODS: This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment. RESULTS: The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains of the MSQ (P = 0.012, P = 0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline. Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction, whereas the amitriptyline group reported an overall deterioration in weight satisfaction (P < 0.001, topiramate vs amitriptyline). TEAEs of mild or moderate severity were reported in 118 subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the amitriptyline group. Among the most common TEAEs (reported in +/-5% of subjects during the double-blind phase) in the topiramate group were paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%). The most commonly reported TEAEs in the amitriptyline group were dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%). CONCLUSIONS: In this noninferiority study, topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points. Topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.

The burden of migraine in the United States: current and emerging perspectives on disease management and economic analysis.

OBJECTIVES: Migraine is often perceived as a low-impact condition that imposes a limited burden to society and the health-care system. This study reviews the current understanding of the burden of migraine in the U.S., the history of economic understanding of migraine treatment and identifies emergent trends for future studies evaluating clinical and economic outcomes of migraine treatment. METHODS: This study traced the history of economic articles published on migraine by performing a literature search using PubMed MEDLINE database and ancestral searches of relevant articles. The intention was not to provide an exhaustive review of every article or adjudicate between studies with different findings. RESULTS: Migraine affects millions of individuals worldwide, generally during the most productive years of a person's life. Studies show that migraineurs are underdiagnosed, undertreated, and experience substantial decreases in functioning and productivity, which in turn translates into diminished quality of life for individuals, and financial burdens to both health-care systems and employers. Economic evaluations of migraine therapies have evolved with new clinical developments beginning with cognitive-behavioral therapy, introduction of triptans, concern over medication overuse, and emergence of migraine prophylaxis. Now recent clinical studies suggest that migraine may be a progressive disease with cardiovascular, cerebrovascular, and long-term neurologic effects. CONCLUSIONS: Migraine imposes a substantial burden on patients, families, employers and societies. The economic standards by which migraine and treatment are evaluated have evolved in response to clinical developments. Emerging evidence suggests that migraine is a chronic and progressive disease. If confirmed, approaches to acute and prophylactic treatments and economic evaluations of migraine treatment may require major reconsideration.

Economic burden of transformed migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study.

OBJECTIVE: To evaluate the impact of incident transformed migraine on health care resource utilization, medication use, and productivity loss. In addition, the study estimates the total direct and indirect costs associated with transformed migraine. BACKGROUND: Emerging evidence indicates that migraine may be a chronic progressive disorder characterized by escalating frequency of headache attacks, often termed transformed migraine. Little is known about the economic impact of transformed migraine. METHODS: AMPP is a 5-year, national, longitudinal survey study of headache in the US. The study utilized data from the 2006 follow-up survey based on an initial sample of 14,544 adults identified as having migraine in either the 2004 screening or 2005 baseline survey. A diagnosis of migraine was assigned based on criteria proposed by the International Classification of Headache Disorders, 2nd Edition. Participants completed self-administered, validated questionnaires on headache features, frequency, impairment, resource use, medication use, and productivity loss. Direct and indirect headache-related costs were estimated using unit cost assumptions from the PharMetrics Patient-Centric database, wholesale acquisition costs (Red Book), and wage data from the US Bureau of Labor Statistics. Those who developed transformed migraine were compared with those who did not develop transformed migraine in the 1-2 year interval between screening/baseline and follow-up. RESULTS: A total of 7796 (54%) identified migraine cases completed the 2006 follow-up survey. Of those cases, 359 (4.6%) developed transformed migraine. Participants who developed transformed migraine reported significantly more primary care visits, neurologist or headache specialist visits, pain clinic visits, and emergency room visits compared with participants whose migraine remained episodic. Hospital nights and urgent care visits did not reach statistical significance. Transformed migraine participants reported significantly more time missed at work or school because of headaches and more time where work or school productivity was reduced by >50% in the previous 3 months because of headaches. Average per-person annual total costs, including direct and indirect costs, were 4.4-fold greater for those who developed transformed migraine ($7750) compared with those who remained episodic ($1757). CONCLUSION: Transformed migraine exacts a significantly higher economic toll on patients and health care systems compared with other forms of migraine. Our findings support the need to prevent migraine progression and to provide appropriate management and treatment of transformed migraine.

Persistence with migraine prophylactic treatment and acute migraine medication utilization in the managed care setting.

OBJECTIVE: The aim of this study was to describe persistence with migraine prophylactic treatment and acute migraine medication utilization in patients prescribed migraine prophylaxis. METHODS: For this retrospective cohort study, the Health Core Integrated Research Database provided pharmacy/medical claims data from 5 commercial health insurance plans (ie, excluding Medicare and Medicaid) on adult patients with migraine. Eligible patients had >or=1 pharmacy claim for a migraine prophylactic medication between July 1, 2000, and May 31, 2005, and >or=12 U of any combination of acute treatment (serotonin receptor agonist [triptan], ergotamine, or ergotamine combination) dispensed during the 180-day period preceding a first pharmacy claim for a prophylactic medication (index date). The prophylactic medication identified at index date was used for categorizing patients into 1 of 4 cohorts: amitriptyline, propranolol/timolol, divalproex sodium, or topiramate (reference). Kaplan-Meier curves were used for evaluating unadjusted risk for discontinuation over time, and a multivariate Cox proportional hazards model was developed to analyze factors associated with discontinuation of prophylactic medication. RESULTS: A total of 12,783 patients met the inclusion criteria and were included in the analysis (amitriptyline, 3749; propranolol/timolol, 2718; divalproex sodium, 1644; and topiramate, 4672). The mean (SD) ages were not significantly different across cohorts (43.9 [11.3], 42.0 [11.1], 43.1 [11.3], and 43.9 [10.6] years, respectively). The mean duration of treatment was significantly longer (131 [184] days) with topiramate compared with amitriptyline (94 [152] days), propranolol/ timolol (119 [180] days), and divalproex sodium (109 [158] days) (P < 0.001, P = 0.005, and P<0.001,respectively). The risks for discontinuing prophylactic treatment were 23%, 6%, and 11% higher with amitriptyline, propranolol/timolol, and divalproex sodium, respectively, compared with topiramate (P<0.001, P = 0.024, and P <0.001). Patients prescribed topiramate had a higher mean consumption rate of triptans preindex; postindex, decreases in triptan use were observed in all cohorts, although the magnitude of the decrease was greatest in patients prescribed topiramate compared with the other cohorts. CONCLUSIONS: In this study, prescription of topiramate was associated with greater persistence with prophylactic treatment than the other prophylactic drugs. Furthermore, greater reductions in acute treatment utilization, particularly triptans, were observed among patients prescribed topiramate compared with the other prophylactic cohorts.

Residential care/assisted living staff may detect undiagnosed dementia using the minimum data set cognition scale.

OBJECTIVES: To estimate the sensitivity, specificity, and reliability of the Minimum Data Set Cognition Scale (MDS-COGS) in screening for undetected dementia when completed by direct care staff in residential care/assisted living (RC/AL) facilities and secondarily to determine the prevalence of dementia in the sample. DESIGN: A cross-sectional study in which staff were trained to complete the MDS-COGS. Research interviewers and a neuropsychologist obtained information on each participant. Two neurologists reviewed the data and examined the participant, rendering a probable diagnosis of dementia/non-dementia diagnosis. MDS-COGS results were compared with the neurologists' determination. SETTING: Fourteen RC/AL facilities in North Carolina. PARTICIPANTS: Data were collected from 50 staff on 166 residents without a diagnosis of dementia. MEASUREMENTS: In addition to the MDS-COGS, measures included a comprehensive neuropsychological battery. Depression and other neuropsychiatric symptoms were also assessed. RESULTS: Neurologists determined that 38% of participants had probable dementia. An MDS-COGS cutpoint of 2 was highly specific (0.97) but not very sensitive (0.49) for dementia. Test-retest and interrater agreement for a negative screen were high (88% and 93%, respectively). CONCLUSION: The MDS-COGS is a simple, brief screen that RC/AL staff can complete. It will identify with high specificity a subset of residents with undetected dementia, allowing rapid identification of those likely to need dementia care. Caution needs to be exercised in light of its low sensitivity, because some with milder dementia will not be detected. Further work is needed to determine whether staff can and will use the MDS-COGS as a trigger for more-thorough assessment and to guide care and improve outcomes.

Topiramate prescribing patterns among medicaid patients: diagnosis, comorbidities, and dosing.

BACKGROUND: Routine clinical practice data are useful for payers and formulary decision makers to make sound decisions regarding coverage policy. Based on a literature search, there has been scant research into topiramate prescribing patterns among Medicaid patients. OBJECTIVE: The aim of this study was to describe diagnoses, demographic characteristics, additional co-existing diagnoses, and dosing among Medicaid patients prescribed topiramate. METHODS: This descriptive, retrospective database analysis used data from South Carolina (SC) and Texas (TX) ambulatory Medicaid claims dated October 1, 2003, to December 31, 2004. Patients whose data were eligible for inclusion in the study were enrolled in Medicaid during the study period, had >or=2 topiramate prescriptions, were aged <65 years, and had evidence of a topiramate treatment-related diagnosis (possible diagnoses were identified through literature search and drug compendiums). Four cohorts were defined: (1) epilepsy only; (2) migraine only; (3) epilepsy and migraine; and (4) nonepilepsy/nonmigraine. Demographic characteristics, diagnoses, comorbidities, and daily dose of topiramate were summarized using descriptive statistics. The initial study analysis (period 1) was a 180-day window comprising the 90 days before and after the first available topiramate prescription claim was filed. A second, 360-day analysis (period 2) was completed comprising the 180 days before and after the index topiramate prescription date. RESULTS: In the 180-day analysis, 2216 SC and 4766 TX Medicaid patients met the selection criteria. Cohort classification percentages were 32.3% and 39.6% (epilepsy only), 29.7% and 16.4% (migraine only), 10.7% and 9.2% (epilepsy and migraine), and 27.3% and 34.9% (nonepilepsy/nonmigraine) for SC and TX, respectively. Mean (SD) ages were 29.9 (15.9) (SC) and 27.1 (16.1) (TX) years. In the nonepilepsy/nonmigraine cohort, the most common diagnoses were bipolar disorder and depression. The median daily doses in the epilepsy-only cohort were 175 mg/d in the SC group and 200 mg/d in the TX group. In the migraine-only cohort, the median daily dose was 100 mg/d in SC and TX. Results for the 360-day analysis were similar. CONCLUSIONS: In this descriptive study using data from 2 Medicaid populations, the majority of patients using topiramate had a diagnosis of epilepsy and/or migraine. Median dosages ranged from 175 to 200 mg/d in patients with epilepsy and 100 mg/d in those with migraine. Depression was a common comorbidity in the migraine cohort and the nonepilepsy/nonmigraine cohort.

The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials.

BACKGROUND: Topiramate is approved for the prophylaxis (prevention) of migraine headache in adults. The most common adverse events in the three pivotal, randomized, double-blind, placebo-controlled trials were paresthesia, fatigue, cognitive impairment, anorexia, nausea, and taste alteration. In these trials, topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) scores versus placebo (p < 0.001). The MSQ measures how much migraine limits/interrupts daily performance. Pooled analyses of pivotal trial data were conducted to further assess how topiramate 100 mg/d affects daily activities and patient functioning. METHODS: Mean MSQ and Medical Outcome Study Short Form 36 (SF-36) change scores (baseline to each double-blind assessment point) were calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT patients receiving topiramate 100 mg/d or placebo were combined and divided into two responder groups according to percent reduction in monthly migraine frequency: < 50% responders or >or= 50% responders. Between-group differences were assessed using analysis of covariance. RESULTS: Of 756 patients (mean age 39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo. Topiramate significantly improved all three MSQ domains throughout the double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and 26] for role prevention; p < 0.001 for role restriction and emotional function [all time points]). Topiramate 100 mg/d significantly improved SF-36 physical component scores (PCS) throughout the double-blind phase versus placebo (p < 0.001, all time points) and significantly improved mental component scores (MCS) at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 subscales were seen for bodily pain and general health perceptions (p < 0.05; weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and social functioning (p < 0.05; weeks 16 and 26). Significantly greater improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were observed for >or= 50% responders versus < 50% responders (p < 0.001). Significantly greater percentages of topiramate-treated patients were >or= 50% responders versus placebo (46% versus 23%; p < 0.001). CONCLUSION: Topiramate 100 mg/d significantly improved daily activities and patient functioning at all time points throughout the double-blind phase. Daily function and health status significantly improved for those achieving a >or= 50% migraine frequency reduction.

Observed clinical and health services outcomes in pediatric inpatients treated with atypical antipsychotics: 1999-2003.

OBJECTIVE: The aim of this study was to compare clinical and health services outcomes in pediatric inpatients prescribed an atypical antipsychotic (AA) to those not prescribed an AA at discharge. METHODS: Descriptive statistics, analysis of variance (ANOVA), and, where necessary, analysis of covariance (ANCOVA) were used to compare differences between and within an inpatient group prescribed risperidone, olanzapine, or quetiapine (n=1,131) with an inpatient group not prescribed an antipsychotic at discharge (n=1,741). RESULTS: The AA treatment group showed greater psychiatric symptom difficulty at admission as measured by the Brief Psychiatric Rating Scale for Children (Mean BPRS-C) than the group not prescribed AAs (40.3 [n=433] vs. 35.2 [n=452], respectively, p<0.001). AA-treated inpatients also had a higher number of mental health outpatient visits during the 6 months prior to admission. Patients receiving AAs (n=1,050) had significantly longer adjusted length of stay (LOS) than those not receiving antipsychotics (n=1,664): 26.4 days versus 22.4 days, respectively (p<0.04). CONCLUSIONS: The findings suggested pediatric inpatients presenting with greater psychiatric symptom difficulty at hospital admission were more likely to be prescribed an AA. Choice of AA may influence certain clinical and health services outcomes. Additional prospective controlled studies evaluating AA efficacy and safety, including head-to-head comparisons, in pediatric inpatients are warranted.

Indirect cost burden of migraine in the United States.

OBJECTIVE: The purpose of this study was to determine the indirect cost burden associated with migraine. METHODS: Data were obtained from Thomson-Medstat's Health and Productivity Management (HPM) database for the 2002 through 2003 calendar years. The migraine cohort was composed of patients who had a diagnosis of migraine or migraine-specific abortive prescription medication, or both. A control cohort of patients without migraine was matched to patients in the migraine cohort. The average annual indirect burden of illness (BOI) of migraine and a national indirect BOI were estimated. RESULTS: Annual indirect expenditures were significantly higher in the migraine group compared with the control group ($4453 vs $1619; P<0.001). The national annual indirect BOI, excluding presenteeism, was estimated to be $12 billion (mostly attributed to absenteeism). CONCLUSIONS: Migraine imparts a substantial indirect cost burden. Projected to a national level, this amounts to an annual cost to US employers of approximately $12 billion.

Impact of topiramate migraine prophylaxis on workplace productivity: results from two US randomized, double-blind, placebo-controlled, multicenter trials.

OBJECTIVE: We conducted this study to determine whether topiramate at 100 mg/d for the treatment of migraine headache is associated with improved productivity in the workplace. METHODS: Results were derived from two randomized, double-blind, placebo-controlled trials among migraineurs. The number of hours of absenteeism (A), presenteeism (P), and total lost productivity (TLP) (A + P) were calculated. Results were not adjusted for multiplicity. RESULTS: A total of 325 (162 in the topiramate group and 163 in the placebo group) of 449 subjects were included. Per person mean monthly A rate was only significantly less for individuals within the topiramate group (1.0 hours per person) versus those in the placebo group (1.5 hours per person) for month 3 (P < 0.05). Per person mean P and TLP rates were significantly lower for individuals in the topiramate group versus those in the placebo group for months 1 through 5 (P < 0.05). CONCLUSIONS: Findings suggest that topiramate, compared with placebo, is associated with decreased workplace presenteeism and TLP.

Assessing the ability of topiramate to improve the daily activities of patients with migraine.

OBJECTIVE: To assess the impact of topiramate on the daily activities of patients with migraine. PATIENTS AND METHODS: We performed a randomized, double-blind, placebo-controlled multicenter trial Initiated on March 1, 2001, and completed on April 4, 2002. Patient-reported data from the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) were collected at baseline and at weeks 8, 16, and 26 from an intent-to-treat population receiving either topiramate, 50, 100, or 200 mg/d, or placebo. Two activity-related MSQ domains (role restrictive [MSQ-RR] and role prevention [MSQ-RP]) and 2 activity-related SF-36 domains (role physical [SF36-RP] and vitality [SF36-VT]) were the prospectively designated secondary outcome measures. The changes in MSQ and SF-36 scores for each treatment group were calculated by measuring the area under the curve from week 8 (the beginning of the maintenance period) through week 26 of the double-blind phase, relative to the prospective baseline. A mixed-effect piecewise linear regression model was used to estimate average domain score over time. RESULTS: Patients receiving topiramate, 100 or 200 mg/d, had significantly reduced mean monthly (28-day) migraine frequency (P = .008 and P < .001, respectively) compared with placebo, but not patients receiving topiramate, 50 mg/d (P = .48). Topiramate significantly improved mean MSQ-RR domain scores (50 mg/d [P = .02], 100 mg/d [P< .001], and 200 mg/d [P < .001]) and mean MSQ-RP domain scores (50 mg/d [P = .007], 100 mg/d [P = .001], and 200 mg/d [P= .002]) vs placebo. Topiramate, 100 and 200 mg/d, significantly improved mean SF36-RP domain scores vs placebo (P = .02). Topiramate (all doses) improved SF36-VT domain scores, although not significantly vs placebo. Changes in prospectively designated domain scores were significantly correlated with changes in mean monthly migraine frequency (P < or = .001 [MSQ domains], P < or = .002 [SF-36 domains]). CONCLUSION: Patient-reported migraine-specific outcomes measured by the MSQ-RR and MSQ-RP domains improved significantly for those receiving topiramate (all doses) vs placebo. The SF36-RP domain scores improved significantly for patients receiving 100 or 200 mg/d of topiramate. Improvements in all 4 prospectively selected MSQ and SF-36 domains were significantly correlated with decreases in mean monthly migraine frequency.

A double-blind comparison of risperidone, quetiapine and placebo in patients with schizophrenia experiencing an acute exacerbation requiring hospitalization.

OBJECTIVE: This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization. METHODS: This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications. RESULTS: Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain. CONCLUSION: While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.

A taxonomy and economic consequences of nursing home falls.

BACKGROUND: Falls are a primary cause of injury and disability in the nursing home environment and can be costly to treat. We propose a taxonomy of nursing home falls that accounts for both the severity of fall consequences and the duration of the treatment episode. No other systematic approach of this kind has been previously described. METHODS: We defined a 9-level taxonomy of fall types and outcomes. Components of each fall category include resource use during the acute, convalescent, and long-term phases of treatment. Three variants of each category describe typical, best-case and worst-case fall episodes. Treatment costs were estimated for each fall category by applying unit costs from national databases and published sources to projected medical resource utilisation. Long-term costs reflect adjustment in Medicare per diem reimbursement rates associated with change in patient status subsequent to the fall. RESULTS: The most common and least costly fall category was category 1 -- non-injurious, which accounted for 30% of falls and a 1-year cost of US dollars 319 per event (range US dollars 71-550). The least common and most costly was fall category 9 -- multiple injuries, which accounted for 1% of falls and a 1-year cost of US dollars 22,368 (range US dollars 9,969-64,382). CONCLUSIONS: The falls taxonomy represents a unique approach to estimating the cost of nursing home falls and offers a tool for evaluating the cost-effectiveness of fall prevention strategies. A validation study should be performed to confirm the magnitude of fall frequency and cost estimates.

Reduction in psychotic symptoms as a predictor of patient satisfaction with antipsychotic medication in schizophrenia: data from a randomized double-blind trial.

BACKGROUND: Patient satisfaction with antipsychotic treatment is important. Limited evidence suggests that satisfaction is associated with symptom improvement and compliance. Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia. METHODS: Data are from a randomized, double-blind trial comparing risperidone (n = 152), quetiapine (n = 156), and placebo (n = 73). Medication Satisfaction Questionnaire (MSQ) was completed after 14 days of treatment and after 6 weeks at last study visit. RESULTS: Medication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale (PANSS) factor scores (positive symptoms p < .01; uncontrolled hostility/excitement, p < .0005; anxiety/depression, p < .04) and treatment with risperidone (p < .03); at day 14, significant association was also found with older age (p = .01). At both time points, predictor variables explained over 30% of the variance in medication satisfaction. Change in Hamilton Depression Scale, prolactin levels, sex, and reported adverse events of extrapyramidal symptoms, sedation, and movement disorders were not significant predictors of satisfaction. Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point. A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude: lower levels of (a) uncontrolled hostility/excitement, (b) positive symptoms, and (c) negative symptoms, disorganized thoughts, and anxiety/depression. CONCLUSION: Results give further support that treatment satisfaction is positively associated with symptom improvement, particularly psychotic symptoms, and suggest that satisfaction may also be related to compliance, as those who were more satisfied remained in the trial for a longer period of time.

Cost effectiveness of topiramate in the prevention of migraines in the United States: an update.

A previously published decision-analytic model assessing the clinical and economic consequences of topiramate versus no preventive treatment in migraineurs was updated with new published literature and unpublished clinical trial data. The model captured baseline migraine days, treatment discontinuation, treatment response (i.e., > or = 75%, 50%-74%, and < 50% reduction in migraine frequency), hours of disability, cost of preventive therapy, cost of acute treatment (pharmacy and medical service), and wages. Topiramate was associated with 29 fewer migraine-days and 78 fewer hours of disability per year, compared with no preventive treatment. The incremental cost per migraine-day averted for topiramate versus no preventive treatment was dollar 29 when only direct medical costs were considered and dollar 2 when total costs were included. Model results were sensitive to baseline migraine-days, response probability, and probability of an attack being treated with a triptan. Topiramate may be a cost-effective treatment for the prevention of migraine.

Canagliflozin treatment of Hispanic and non-Hispanic patients with type 2 diabetes in a US managed care setting.

BACKGROUND: Hispanic/Latino (H/L) ethnicity is associated with higher prevalence of type 2 diabetes mellitus (T2DM) and more complications and comorbidities. Few studies of antihyperglycemic agents (AHAs) have compared H/L with non-H/L patients. Randomized controlled trials and observational studies have shown canagliflozin (CANA) is effective at lowering hemoglobin A1C (A1C). OBJECTIVE: To describe characteristics and compare glycemic control between H/L and non-H/L patients with T2DM filling their first prescription for CANA. METHODS: This retrospective cohort study examined healthcare claims for diabetic patients who filled ≥1 prescription for CANA between 1 April 2013 and 31 October 2013. We captured available demographic data; ethnicity was imputed as previously published. Clinical data included the Diabetes Complications Severity Index (DCSI), A1C values, and claims for any AHA, with 6 months of follow-up. RESULTS: Our sample included 438 (11.4%) H/L individuals and 3408 (88.6%) non-H/L individuals; each cohort had 43% females. The H/L patients were younger (53 vs. 56 years, p < 0.001) with higher mean baseline A1C (8.9% vs. 8.5%, respectively; p = 0.028) compared to non-H/L patients. Mean DCSI was similar (H/L 0.92 vs. non-H/L 0.84, p = 0.289) between cohorts. More H/L patients (25%) were taking ≥3 AHAs at the first CANA prescription fill (vs. 21% for non-H/L; p = 0.044), most commonly metformin, followed by sulfonylureas, dipeptidyl peptidase-4 inhibitors, and basal insulin. Among patients with ≥2 fills for CANA, mean adherence (proportion of days covered) was slightly lower for H/L than non-H/L patients (0.77 vs. 0.80, p = 0.003). From their respective baseline A1C values, reduction in A1C was significantly greater for H/L than non-H/L patients (1.1% vs. 0.8%; p = 0.043). CONCLUSION: Compared with non-H/L patients, our H/L patients were younger and had higher mean baseline A1C. Significant improvement in glycemic control was observed for both cohorts, with greater improvement for H/L patients. Additional research is warranted, including longer follow-up and adjusting for possible confounding factors.