Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Maintenance Regimens in Kidney Transplantation: Results from Discrete Event Simulation.

BACKGROUND: Corticosteroids used as immunosuppressants to prevent acute rejection (AR) and graft loss (GL) following kidney transplantation are associated with serious cardiovascular and other adverse events. Evidence from short-term randomized controlled trials suggests that many patients on a tacrolimus-based immunosuppressant regimen can withdraw from steroids without increased AR or GL risk. OBJECTIVES: To measure the long-term tradeoff between GL and adverse events for a heterogeneous-risk population and determine the optimal timing of steroid withdrawal. METHODS: A discrete event simulation was developed including, as events, AR, GL, myocardial infarction (MI), stroke, cytomegalovirus, and new onset diabetes mellitus (NODM), among others. Data from the United States Renal Data System were used to estimate event-specific parametric regressions, which accounted for steroid-sparing regimen (avoidance, early 7-d withdrawal, 6-mo withdrawal, 12-mo withdrawal, and maintenance) as well as patients' demographics, immunologic risks, and comorbidities. Regression-equation results were used to derive individual time-to-event Weibull distributions, used, in turn, to simulate the course of patients over 20 y. RESULTS: Patients on steroid avoidance or an early-withdrawal regimen were more likely to experience AR (45.9% to 55.0% v. 33.6%, P < 0.05) and GL (51.5% to 68.8% v. 37.8%, P < 0.05) compared to patients on steroid maintenance. Patients in 6-mo and 12-mo steroid withdrawal groups were less likely to experience MI (11.1% v. 13.3%, P < 0.05), NODM (30.7% to 34.4% v. 37.7%, P < 0.05), and cardiac death (29.9% to 30.5% v. 32.4%, P < 0.05), compared to steroid maintenance. CONCLUSIONS: Strategies of 6- and 12-mo steroid withdrawal post-kidney transplantation are expected to reduce the rates of adverse cardiovascular events and other outcomes with no worsening of AR or GL rates compared with steroid maintenance.

National Estimates of and Risk Factors for Inpatient Revision Surgeries for Orofacial Clefts.

OBJECTIVE: To provide national estimates of the number and cost of primary and revision cleft lip and palate surgeries in the U.S. and to determine patient and hospital characteristics associated with disproportionate use of revision surgery. DESIGN: Retrospective cross-sectional study using data obtained from the 2003, 2006, and 2009 Kids' Inpatient Database. SETTING: Inpatient. PATIENTS: Children with CL, CP, or CLP undergoing inpatient cleft lip and/or palate surgery. INTERVENTIONS: Inpatient cleft lip and/or palate surgery. MAIN OUTCOME MEASURES: Orofacial cleft surgery estimates, estimates of primary versus revision surgeries, and estimated inflation-adjusted hospitalization costs. RESULTS: In 2009, there were a total of 2824 and 5431 hospitalizations for cleft lip and palate surgeries, respectively. Revision surgery accounted for 24.2% of cleft lip surgeries and 36.8% of cleft palate surgeries. Children with CLP (OR 1.87, 95% CI: 1.48-2.38), a syndromic diagnosis (OR 1.47, 95% CI: 1.16-1.87), or private insurance (OR 1.71, 95% CI: 1.41-2.09) were more likely to undergo cleft lip revision surgery. Similar risk factors were found for children undergoing cleft palate revision. Mean cost per hospitalization ranged from $7564 to $8393 in 2009, depending on surgery type, and did not change significantly (in 2009 U.S. $) between 2003 and 2009. CONCLUSIONS: Interventions to reduce revision surgery by improving results of primary surgery should be targeted in the population of identified high-risk (e.g., syndromic) patients. In addition, the association of health insurance status with revision surgery highlights the need to understand and address the impact of economic disparities on cleft care delivery.

Sulfonylurea use and the risk of hospital readmission in patients with type 2 diabetes.

BACKGROUND: Hospital inpatient care for patients with diabetes was estimated to cost $76 billion in 2012. Substantial expense resulted from those patients having multiple hospitalizations. The objective was to compare the risk for diabetes-related hospital readmission in patients with type 2 diabetes treated with sulfonylureas (SUs) compared to those treated with other oral antihyperglycemic agents (AHAs). METHODS: A retrospective cohort analysis was conducted using two-year panels, from 1999 to 2010, from the Medical Expenditure Panel Survey. The study included patients with type 2 diabetes taking an oral AHA who experienced a diabetes-related hospitalization. A Cox proportional hazard regression predicting time to readmission was used to estimate and compare the risks of readmission for SU-monotherapy versus other-AHA-monotherapy patients. Covariates included age, gender, marital status, cardiovascular disease, kidney disease, and eye disease, along with a propensity score to control for selection bias. The lack of clinical data on disease severity and progression limited our ability to estimate causal relationships between drug use and risk of hospital readmission. RESULTS: From 1999 to 2010, an estimated 13.5 million patients experienced a diabetes-related hospital admission and subsequent AHA treatment. While 23.2 % (n = 746,579) of patients in the SU monotherapy cohort had a readmission, only 16.1 % (n = 881,984) in the other-AHA monotherapy group were readmitted. Average readmission expenditure for readmitted SU users (in 2010 dollars) was $11,148 (±$1,558) compared to $7,673 (±$763) for users of other oral AHAs. The estimated readmission hazard ratio was 1.29 (95 % CI: 1.01-1.65; p-value = 0.04) for SU monotherapy users. If a patient's first hospital admission was during the time period 2008-2010, a readmission was significantly less likely (HR 0.49, 95 % CI: 0.31-0.78; p = 0.003) relative to 2004-2007. CONCLUSIONS: Among patients with type 2 diabetes, SU use was associated with an approximately 30 % increased risk for readmission compared to other-AHA use, while each readmission for an SU user cost on average 45 % more than one for an other-AHA patient. Because of the rapidly rising prevalence of diabetes in the U.S. and the large number of patients with prediabetes, preventing hospital readmissions will continue to be an important cost-saving strategy in the future.

Treatment of obesity: Pharmacotherapy trends in the United States from 1999 to 2010.

OBJECTIVE: To describe the antiobesity drug-prescribing patterns of US physicians over the past decade. METHODS: Data for adult patients were obtained from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. Obesity was identified using ICD-9 codes, BMI values, and a chronic-obesity-condition variable. For patients with obesity, a logistic-regression model was estimated to determine the odds of receiving pharmacotherapy. RESULTS: Of the 987 million visits by patients with obesity from 2005 to 2010, 2.0% mentioned an antiobesity drug. Additionally, there were 6.5 million visits by patients without obesity but with an antiobesity drug mention. Visits made by females (OR = 2.89; 95% CI: 2.08-4.03), by white patients (OR = 1.55; 95% CI: 1.08-2.24), by younger adults (OR = 1.71; 95% CI: 1.34-2.20), and in the South (OR = 3.39; 95% CI: 1.49-7.72) were more likely to involve an antiobesity drug prescription. CONCLUSIONS: Only 1 in 50 patients with obesity received a prescription for an antiobesity medication. Moreover, in contrast to what the 1998 Guidelines suggested, physicians tended to prescribe antiobesity medications to self-paying, young, white females, many of whom lived in the South, and not all of whom had obesity.

Comparative persistence on ß-blockers versus calcium channel blockers for ventricular rate control in nonelderly patients with atrial fibrillation.

BACKGROUND: For patients with atrial fibrillation (AF), early treatment is essential to prevent serious complications such as stroke. Several randomized clinical trials have shown that rate-control may be as effective as rhythm-control medications, whereas the latter have serious side effects. Little evidence exists, however, about which class of rate-control medication-ß-blockers (BBs) or calcium channel blockers (CCBs)-may be superior. OBJECTIVE: The objective was to compare the long-term persistence on BBs versus CCBs in nonelderly adult patients with AF. METHODS: A longitudinal retrospective cohort study for patients 40 to 60 years old with newly diagnosed AF (identified by ICD-9 code 427.31) was performed using data from Ohio Medicaid physician, institutional, and pharmacy claims from January 2006 through June 2011. A Cox proportional hazard regression, with time to change out of rate-control therapy as the dependent variable, was estimated to compare persistence on (proxy for effectiveness of) rate-control medication across drug classes. A propensity-score analysis was used to control for selection bias. Additional covariates included age, development of heart failure, and medication adherence. RESULTS: Out of 1239 patients included in the cohort, 1016 received a BB; 223 received a CCB. Over time, patients on CCBs were significantly more likely to switch out of rate-control therapy (hazard ratio = 1.89; 95% CI = 1.14-3.09) than patients on BBs. CONCLUSIONS: Evidence suggests that nonelderly AF patients, when prescribed rate-control therapy, persist longer on BBs than CCBs. Because this is the first long-term study comparing the 2 drug classes in the nonelderly population, further research is suggested.

Trends in the outpatient treatment of atrial fibrillation in the USA from 2001 to 2010.

PURPOSE: Several clinical trials have shown that rhythm-control drugs have serious adverse events and no survival advantage over rate-control drugs in patients with atrial fibrillation. The objectives were to determine and explain the recent trends in outpatient prescribing of both drug classes. METHODS: Data were obtained over 10 years from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. Visits by patients with atrial fibrillation were identified by ICD-9 diagnosis code 427.31. Trend lines were estimated for drug prescribing and comorbidities. A multinomial logistic model was estimated to predict treatment on the basis of visit characteristics. RESULTS: The percentage of visits mentioning only a rate-control medication trended upward (p = 0.07) from 41.9% in 2001 to 47.3% in 2010; the percentage mentioning both rhythm-control and rate-control drugs also had an upward trend (p < 0.05) from 3.1% to 12.5%; finally, the percentage mentioning rhythm-control drugs alone remained steady (p = 0.37). Consistent with the increase (p = 0.10) in the percentage of visits mentioning hypertension, there was a statistically significant (p < 0.01) rise in the prescribing of ß-blockers from 20.5% to 43.4%. The odds that a patient aged 65 years or younger was prescribed a rhythm-control medication were significantly higher (p < 0.01) than those for a patient older than 65 years. The estimated odds that a diabetic patient was prescribed both rhythm-control and rate-control medications was only 0.269 (p < 0.05). CONCLUSIONS: This study documents change in the outpatient treatment of atrial fibrillation in the USA from 2001-2010. In clinical practice, there has been a growing reliance on rate-control medications.

Firm- and drug-specific patterns of generic drug payments by US medicaid programs: 1991-2008.

BACKGROUND: The entry of generic drugs into markets previously monopolized by patented, branded drugs often represents large potential savings for healthcare payers in the USA. OBJECTIVES: Our objectives were to describe and explain the trends in drug reimbursement by public Medicaid programmes post-generic entry for as many drug markets and for as long a time period as possible. METHODS: The data were the Medicaid State Drug Utilization Data maintained by the Centers for Medicare and Medicaid Services. Quarterly utilization and expenditure data from 1991 to 2008 were extracted for 83 drugs, produced by 229 firms, that experienced initial generic entry between 1992 and 2004. A relative 'price' for a specific drug, firm and quarter was constructed as Medicaid reimbursement per unit (e.g. tablet, capsule or vial) divided by average reimbursement per unit for the branded drug the year before entry. Fixed-effects models controlling for time-, firm- and drug-specific differences were estimated to explain reimbursement. RESULTS: Twelve quarters after generic entry, 18 % of drugs had average per-unit reimbursement less than 50 % of the original branded-drug reimbursement. For each additional firm manufacturing the drug, reimbursement per unit, relative to the pre-generic-entry branded-drug reimbursement, was estimated to fall by 17 (p < 0.01) and 3 (p < 0.01) percentage points for generic and branded-drug companies, respectively. Each additional quarter post-generic entry brought a 2 (p < 0.01) percentage point drop in relative reimbursement. CONCLUSIONS: State Medicaid programmes generally have been able to obtain relief from high drug prices following patent expirations for many branded-drug medications by adjusting reimbursement following the expanded competition in the pharmaceutical market.

State Medicaid programs missed $220 million in uncaptured savings as generic fluoxetine came to market, 2001-05.

Patent expiration of brand-name pharmaceuticals creates opportunities for large savings for state Medicaid programs because generic versions of medications frequently represent a lower-cost alternative. State Medicaid programs that quickly recognize the availability of generics and adjust their drug payments in response to falling market prices can obtain the greatest benefit. We examined one such case: the movement to generic fluoxetine following patent expiration for Prozac, a widely prescribed antidepressant and an expensive drug for Medicaid. We found large differences in states' responses to generic availability. States took between two and ten calendar quarters to reach 90 percent use of generic rather than brand-name fluoxetine and four to eight quarters to achieve a 50 percent decrease in reimbursement per pill. We estimated that states failed to realize $220 million in uncaptured savings during 2001-05. By coordinating their efforts, perhaps with federal help, states could gain access in a more timely way to market prices for generic drugs and, hence, take greater advantage of the savings that those drugs offer.

Frequencies, costs, and complications of catheter ablation for tachyarrhythmias in children: 2000-2009.

BACKGROUND: Over the past two decades, catheter ablation (CA) has revolutionized the treatment of tachyarrhythmias in children by providing a relatively safe and effective alternative to open heart surgery or lifelong pharmacotherapy. This study (1) described national trends in pediatric CAs and their associated costs and complications and (2) predicted the likelihood of major complications based on patient and hospital characteristics. METHODS: Inpatient data were obtained from the Kids' Inpatient Database for the years 2000, 2003, 2006, and 2009. Outpatient data were obtained from the California, Maryland, and New Jersey State Ambulatory Surgery Databases for the years 2006 and 2009. Logistic regression was used to predict the odds of major complications from CA. RESULTS: There was a 20% increase (4,134-4,967) in the number of pediatric CAs performed from 2006 to 2009 that was concomitant with a decrease in the percentage of those procedures being performed as inpatient procedures (2,254-1,846). In 2009, a complication rate of 4.81% was estimated. For inpatient CAs, higher risk patients (with congenital heart disease, congestive heart failure, or heart transplant), ablations for ventricular tachycardias, and low-CA-volume hospitals were associated with increased risk of complications. In 2009, the mean cost of a hospitalization involving CA, but no cardiac surgery, was $17,204 (standard error = $1,015). CONCLUSIONS: CA has increasingly been used over the past decade for pediatric patients with a multitude of tachycardia mechanisms. There continues to be a small risk of major complications, especially for higher risk children and in hospitals with more limited experience with the procedure.

Adaptation and application of the Agency for Healthcare Research and Quality's asthma admission rate pediatric quality indicator to Ohio Medicaid claims data.

BACKGROUND: The U.S. Agency for Healthcare Research and Quality (AHRQ) developed, in the context of a national pediatric discharge database, 18 pediatric quality indicators (PDIs) for assessing pediatric care. These measures have not yet been adapted for and applied to claims databases. OBJECTIVES: The objectives of this study were to (1) adapt the asthma admission rate (AAR) PDI methodology for claims data; (2) calculate AARs for Ohio Medicaid beneficiaries for 2007-2009, overall as well as by patient and regional characteristics; (3) determine the cost and length of stay associated with these hospitalizations; (4) describe medication use for 90 days before the hospitalizations; and (5) estimate the effect of asthma prevalence rates on AARs across Ohio counties. METHODS: A retrospective study was performed using Ohio Medicaid claims data. After adapting the AHRQ methodology for a claims database, AARs were computed for the pediatric asthma population (aged 2-17 years). Total and mean costs and days spent in the hospital were calculated. A Poisson regression model was developed to estimate the effect of asthma prevalence on the AAR. RESULTS: Between 2007 and 2009, the Ohio Medicaid AAR rose from 182 to 258 per 100,000 children. Costs (in 2009$) rose from $1,069,783 to $1,470,918, whereas hospital days increased from 672 to 815. Close to 70% of patients had no claims for a maintenance medication for 90 days before their hospitalization. The asthma prevalence rate was significantly associated with the AAR. CONCLUSIONS: The remaining 17 PDIs could also be adapted for claims data to assess the quality of pediatric care.

The effect of electronic medical record system sophistication on preventive healthcare for women.

OBJECTIVE: To observe the effect of electronic medical record (EMR) system sophistication on preventive women's healthcare. MATERIALS AND METHODS: Providers in the National Ambulatory Medical Care Survey (NAMCS), 2007-8, were included if they had at least one visit by a woman at least 21 years old. Based on 16 questions from NAMCS, the level of a provider's EMR system sophistication was classified as non-existent, minimal, basic, or fully functional. A two-stage residual-inclusion method was used with ordered probit regression to model the level of EMR system sophistication, and outcome-specific Poisson regressions to predict the number of examinations or tests ordered or performed. RESULTS: Across the providers, 29.23%, 49.34%, 15.97%, and 5.46% had no, minimal, basic, and fully functional EMR systems, respectively. The breast examination rate was 20.27%, 34.96%, 37.21%, and 44.98% for providers without or with minimal, basic, and fully functional EMR systems, respectively. For breast examinations, pelvic examinations, Pap tests, chlamydia tests, cholesterol tests, mammograms, and bone mineral density (BMD) tests, an EMR system increased the number of these tests and examinations. Furthermore, the level of sophistication increased the number of breast examinations and Pap, chlamydia, cholesterol, and BMD tests. DISCUSSION: The use of advanced EMR systems in obstetrics and gynecology was limited. Given the positive results of this study, specialists in women's health should consider investing in more sophisticated systems. CONCLUSIONS: The presence of an EMR system has a positive impact on preventive women's healthcare; the more functions that the system has, the greater the number of examinations and tests given or prescribed.

Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma.

The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration.

Trends in the utilization of, spending on, and prices for outpatient antifungal agents in US Medicaid programs: 1991-2009.

BACKGROUND: The incidence of invasive fungal infections (IFIs) has increased substantially in the recent past. Advances in medical technology, including broad-spectrum antibiotics, may increase the risk for fungal infections. Moreover, immunocompromised patients with cancer, HIV/AIDS, and/or transplants are susceptible to IFIs. Meanwhile, superficial fungal infections (SFIs) are common and can be difficult to cure. OBJECTIVE: To provide a historical perspective on a dynamic market with expensive medications, this study describes trends in the utilization of, spending on, and average per-prescription spending on outpatient antifungal medications individually, in classes (for IFIs or SFIs), and overall, by the US Medicaid programs from 1991 to 2009. METHODS: The publicly available Medicaid State Drug Utilization Data, maintained by the Centers for Medicare & Medicaid Services, were used. Annual prescription counts and reimbursement amounts were calculated for each of the antifungals reimbursed by Medicaid. Average per-prescription spending as a proxy for drug price was calculated by dividing reimbursement by the number of prescriptions. RESULTS: Overall utilization for Medicaid beneficiaries remained steady, with 4.56 million prescriptions in 1991 and 4.51 million in 2009. Expenditures rose from $93.87 million to $143.76 million (in current-year US$) over the same time period. The drop in the utilization of first-generation azoles over the last 5 years of the study period can be explained in part by the movement of dual-eligibles from Medicaid to Medicare Part D and in part to a rise in fungal infections better treated with second-generation azoles or echinocandins. Whereas the average per-prescription price for generic (oral) fluconazole was $8 in 2009, the price per prescription of branded (intravenous) voriconazole was $2178. CONCLUSIONS: Overall spending by Medicaid on outpatient antifungal medications increased more slowly than did the growth of the Medicaid programs from 1991 to 2009. However, the utilization of antifungal agents for IFIs increased almost 10-fold over this period, far outpacing the rise in the number of Medicaid beneficiaries.

Long-term Medicaid excess payments from alleged price manipulation of generic lorazepam.

BACKGROUND: Cost savings from the use of generic drugs versus brand-name drugs are well known. Both private and public prescription drug plans encourage the use of generic drugs through a variety of mechanisms. The magnitude of cost savings for a given generic drug is dependent on the degree to which the generic market is competitive. Should the competitive structure become compromised, higher prices and reduced cost savings may result. An alleged conspiracy between Mylan Laboratories and its active-ingredient suppliers in 1997 was associated with an increase in seller concentration in the generic lorazepam market. The Federal Trade Commission (FTC) alleged that Mylan raised costs to consumers by $120 million because of price increases for generic lorazepam from March through December 1998 and for generic clorazepate from January through December 1998. In November 2002, a settlement with Mylan was approved by the FTC, and a federal district court required Mylan to pay $147 million, including $28.2 million to state agencies including Medicaid. OBJECTIVES: To (a) describe the seller concentration in the national Medicaid generic lorazepam market over a 19-year period from January 1991 through December 2009, (b) estimate the excess payments for generic lorazepam by Medicaid between 1998 and 2009, and (c) investigate potentially increased utilization and prices of 2 substitute pharmaceuticals: branded lorazepam (Ativan) and generic alprazolam (another widely used intermediate-acting benzodiazepine). METHODS: Using Medicaid State Drug Utilization Data from the Centers for Medicare Medicaid Services, we calculated the 4-firm concentration ratio (CR4) and the Herfindahl-Hirschman Index (HHI) for the Medicaid generic lorazepam market, along with pre-rebate reimbursement for pharmacy claims, number of claims (utilization), and average pre-rebate reimbursement per claim (average "price") for generic lorazepam, from 1991 through 2009. Medicaid's excess payments were estimated under 2 different assumptions regarding what the average generic lorazepam price would have been in the absence of the alleged conspiracy. To find counterfactual prices, the average per-claim reimbursement for lorazepam for the 4 quarters prior to the alleged conspiracy, $6.80, was inflated using (a) the quarterly change in the average per-claim reimbursement for generic alprazolam and (b) the Consumer Price Index (CPI) for all urban consumers, all goods. Potential impact of the alleged conspiracy on the branded lorazepam and generic alprazolam markets was investigated. RESULTS: The average pre-rebate reimbursements per claim for generic lorazepam were $10.25, $23.12, and $8.48 in 1991, 1998, and 2009, respectively. For the same 3 years, CR4 = 52.80, 76.02, and 86.74, while HHI = 905.71, 2,166.25, and 2,233.36. Medicaid's excess payments from 1998-2009 were estimated at approximately $625-$657 million. The data also suggest the possibility of small impacts on the utilization of branded lorazepam and the price of generic alprazolam. CONCLUSIONS: Prior to the alleged conspiracy in 1997, average pre-rebate reimbursement per claim for generic lorazepam was declining, while seller concentration was rising. After a jump in average payment per claim in the years immediately following the alleged conspiracy, prices have gradually returned to their pre-1998 levels. However, the generic lorazepam market was more concentrated in 2009 than prior to the alleged conspiracy.

Exposure to potentially dangerous drug-drug interactions involving antipsychotics.

OBJECTIVE: Antipsychotic drug therapy is the cornerstone of treatment of persons with schizophrenia. Because most antipsychotics are metabolized by the hepatic cytochrome P450 system, concomitant use of an antipsychotic and medications that are competitively metabolized by the same system may cause a potentially harmful drug-drug interaction. This study used a large state's Medicaid claims database to examine the proportion of patients exposed to such interactions and the risk factors associated with exposure. METHODS: Claims from January 2000 through December 2003 for adult patients with a diagnosis of schizophrenia and at least one prescription for an antipsychotic (N=27,909) were examined for pairs of medications identified as potentially causing moderate or severe adverse drug effects. Logistic regression models were estimated to determine potential risk factors associated with exposure to the interaction pairs. RESULTS: A total of 6,417 (23%) patients were exposed to 14,213 potentially harmful interactions; 4,725 patients had at least one exposure from the same pharmacy, and 4,032 patients were exposed by the same physician. The greatest number of exposures (N=1,353) to potentially harmful combinations involved olanzapine and haloperidol. Patients prescribed risperidone were most likely to be exposed to an interaction (13.1%), followed by patients prescribed olanzapine (10.3%), quetiapine (3.3%), and clozapine (3.2%). A higher risk of exposure was associated with being female (odds ratio [OR]=.94), being white (OR=1.43), having depression (OR=1.21), or having impulse-control disorder (OR=1.98). CONCLUSIONS: Interventions by physicians and pharmacies to reduce the prescribing and dispensing of potentially harmful pairs of medications to patients with schizophrenia are recommended.

Utilization, spending, and price trends for benzodiazepines in the US Medicaid program: 1991-2009.

BACKGROUND: Although it is well-known that drug costs in the US have risen precipitously over the last 25 years, what is much less appreciated is how this rise in cost has occurred across so many seemingly distinct drug markets. OBJECTIVE: To describe trends in the utilization, spending, and average per-prescription cost of benzodiazepines individually, in subgroups, and overall, in the Medicaid program. Medicaid has been the primary public payer for benzodiazepines over the past 2 decades. METHODS: A retrospective, descriptive analysis was performed for the years 1991-2009 using the publicly available national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services. Quarterly prescription counts and reimbursement amounts were calculated for all benzodiazepines reimbursed by Medicaid. Average per-prescription spending as a proxy for drug price was found by dividing reimbursement by the number of prescriptions. RESULTS: Prescriptions for benzodiazepines among Medicaid beneficiaries increased from 8.0 million in 1991 to 17.1 million in 2009. Expenditures rose from $131.6 million to $171.1 million over the same time period. The average per-prescription price was a little over $10 in 2009. Whereas utilization of intermediate- and long-acting agents increased over time, prescriptions for short-acting drugs fell from 1.1 million to 0.3 million (1991-2009). The percentage rise in Medicaid spending on benzodiazepines since 1991 (30.0%) was less than the general rate of inflation (57.5%), as measured by the percentage change in the consumer price index over the same time period. CONCLUSIONS: Relative to the rise in the number of Medicaid beneficiaries (more than doubled over the study period), there is no evidence of an extraordinary rise in the utilization of benzodiazepines. Moreover, both nominal and real average prices of benzodiazepines have fallen, primarily because of generic entry over the last 2 decades.

Impact of the Food and Drug Administration's antipsychotic black box warning on psychotropic drug prescribing in elderly patients with dementia in outpatient and office-based settings.

BACKGROUND: Most patients with dementia also suffer from behavioral and psychological symptoms of dementia, for which there is no Food and Drug Administration-approved treatment. OBJECTIVES: To determine whether the Food and Drug Administration's black box warning in April 2005 has led to a decline in prescriptions of atypical antipsychotics for behavioral and psychological symptoms of dementia, as well as whether prescriptions for other psychotropic drugs, including antidepressants, anxiolytics, and antiepileptics, as substitutes, have increased. METHODS: Data on outpatient visits by elderly dementia patients were obtained from two large national surveys from 2003 to 2008. Any psychotropic drug mentions were identified. Percentage utilization statistics were calculated. RESULTS: The percentage of visits mentioning an atypical antipsychotic decreased from 12.5% prewarning to 11.5% postwarning. Postwarning, 34.4% of patients were taking none of the study medications, as opposed to 26.1% prewarning. CONCLUSIONS: After the warning, there was a small decline in the use of atypical antipsychotics and no evidence of substitution of other psychotropic medications.

Evidence-based prediction of statin use with lipid-panel data from the National Health and Nutrition Examination Survey.

OBJECTIVES: This study compared actual use of individual statin drugs to expected use based on their efficacy and safety profiles. METHODS: Five panels covering the years 1999 to 2008 from the National Health and Nutrition Examination Survey provided interview, demographic, and laboratory data for 8769 (365,503,838 weighted) people aged 20 years or older who were not taking a statin medication. An individual's risk for coronary heart disease and low-density lipoprotein (LDL) cholesterol goal were determined, following the Adult Treatment Panel III Cholesterol Guidelines. The percentage LDL cholesterol lowering required to reach his/her LDL cholesterol level goal was calculated. Depending on the amount of LDL cholesterol lowering needed and on if the individual had a liver condition (i.e., enhanced risk of rhabdomyolysis) statins were hypothetically prescribed. Predicted use was compared to actual use by U.S. Medicaid beneficiaries in the third quarter of 2009, obtained from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare and Medicaid Services. RESULTS: Results showed that 72.34% of the population was in the lowest coronary heart disease risk group and that 86.30% required no statin therapy. Among the people who did require LDL cholesterol lowering, a significant majority (37.3 million or 10.22% of the population) needed 30% lowering or less. Only 314,784 (0.09%) required LDL cholesterol lowering of greater than 60%. Utilization shares based on safety and efficacy were estimated at 19.26% (rosuvastatin), 18.67% (atorvastatin), 16.48% (simvastatin), 16.30% (lovastatin), 14.93% (pravastatin), and 14.36% (fluvastatin). CONCLUSIONS: Actual statin use differed substantially from predicted use. It may be appropriate to develop and maintain policies that encourage use of less costly products that have essentially equivalent safety profiles and efficacy.

National burden of pediatric hospitalizations for inflammatory bowel disease: results from the 2006 Kids' Inpatient Database.

OBJECTIVES: : The objective of the present study was to quantify the national pediatric inpatient inflammatory bowel disease (IBD) burden in terms of the number of IBD-related hospitalizations, the number of days spent in the hospital, and hospitalization costs. METHODS: : Hospitalizations for children and adolescents 20 years and younger with a primary diagnosis of either Crohn disease (CD) or ulcerative colitis (UC) were selected from the 2006 Kids' Inpatient Database (KID). Length of the hospital stay in days (LOS) and charges for the hospitalization were found directly in the Kids' Inpatient Database, and cost was calculated using the hospital's cost-to-charge ratio. Predictor variables included patient characteristics, such as age and severity of illness, and hospital characteristics. Ordinary-least-squares regressions were developed and estimated to explain hospitalization costs. RESULTS: : In 2006, there were 10,777 IBD-related hospitalizations. The total and mean costs for CD were $66.3 million and $10,176 (95% confidence interval [CI] $9647-$10,705), and for UC were $48.6 million and $11,836 (95% CI $10,760-$12,912). For CD, 0- to 5-year-old patients had the highest mean LOS (8.10, 95% CI 5.53-10.67, days) and mean cost ($13,894, 95% CI $9053-$18,735), whereas, for UC, 11- to 15-year-old patients had the highest mean LOS (7.49, 95% CI 6.88-8.10, 95% CI 5.53-10.67, days) and mean cost ($13,407, 95% CI $11,704-$15,110). CONCLUSIONS: : For a pediatric disease with a rather low prevalence rate, the estimated annual inpatient pediatric burden of IBD is a sizeable $152.4 million (2010 US$) and 64,985 days spent in the hospital. As medications and outpatient treatments improve for the treatment of IBD, there is an opportunity for significant reduction in inpatient burden.