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Previous estimates determined prevalence of hypothyroidism (HT) to be 4.6% of the US population. This study aimed to update estimates of HT prevalence in the United States by retrospective analysis of 2 datasets. Data on HT type (overt or subclinical HT) and treatment were collected from the 2009-2010 and 2011-2012 National Health and Nutrition Examination Survey (NHANES) cycles. From the Optum administrative claims database, medical and pharmacy claims were collected between January 1, 2012, and December 31, 2019. Patients were defined as having HT if, per given year, they had >1 prescription for HT treatment, >1 claim indicating an HT diagnosis, or thyroid-stimulating hormone levels >4.0 mIU/L (NHANES arm). For both studies, treatment was defined as any evidence of synthetic or natural thyroid hormone replacement, identified by pharmacy claims or patient surveys. Data are reported as percentage of patients with HT and treatments received. Between 2009 and 2012, HT prevalence remained around 9.6% of the US population. The administrative claims dataset showed that HT prevalence grew from 9.5% in 2012 to 11.7% in 2019 and that >78% of patients received thyroxine (T4) monotherapy. Similarly, the NHANES dataset showed that T4 replacement therapy was the most common treatment for HT. From 2012–2019, patients with untreated HT grew from 11.8% to 14.4%. The prevalence of HT in the United States has steadily increased since 2009. Likewise, the percentage of hypothyroid-diagnosed patients not receiving treatment also increased, suggesting that the increased prevalence may be due to increased cases of subclinical HT.

Introduction The new direct acting antiviral (DAA) therapies are able to effectively treat chronic hepatitis C (CHC). This study elicited the preferences of CHC patients for treatment attributes of new DAAs. Methods An online discrete choice experiment survey was designed to collect data from adult CHC patients in the USA, UK, France, Germany, Spain, and Italy. Patients were asked to choose from alternative hypothetical DAA options, defined by differing levels of nine attributes [i.e., treatment duration, tablet count and packaging, cure rate, required office visits when on treatment, modifications to statins or to proton pump inhibitors (PPIs), and risks of diarrhea, headache and nausea]. Logistic regression was used to assess preference for the treatment options. Results A total of 328 patients with CHC completed the survey (USA, n = 227; European countries, n = 101), with a mean age of 47.7 years (SD = 14.4) and an average 11.2 years since CHC diagnosis; 51% of patients were female. More than half (60%) of the patients had treatment for CHC. Patients significantly preferred a DAA regimen with higher cure rate, shorter treatment duration, lower risks of diarrhea, headache, and nausea (all p

Although direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug–drug interactions. Here, we report adherence, efficacy, safety and patient‐reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1‐6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co‐medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post‐treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2‐98.5) and 97.5% (1689/1733; 95% CI = 96.7‐98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co‐medication classes. Overall, most adverse events (AEs) were mild‐to‐moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well‐tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders.

Background & aims This study analyses health-related quality of life data from 8 randomized clinical trials using ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin to investigate: (i) the impact of the treatment vs placebo during treatment on health-related quality of life; (ii) the sustainability of such treatment effect after 12-week treatment period; and (iii) if results from (i) and (ii) differ in subgenotypes 1a vs 1b. Methods Six registration trials and 2 post-approval trials were pooled and analysed using longitudinal mixed models to estimate the effect of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin on health-related quality of life outcomes adjusting for baseline scores, as well as patient demographics and clinical characteristics. Results Patients treated with ribavirin-free ombitasvir/paritaprevir/ritonavir and dasabuvir regimen reported statistically significant increase in health-related quality of life outcomes as compared to placebo patients. While ombitasvir/paritaprevir/ritonavir and dasabuvir + ribavirin treatment saw statistically significant decline in health-related quality of life outcomes during treatment vs baseline and placebo, effect on health-related quality of life outcomes associated with ribavirin did not persist in the post-treatment period for ombitasvir/paritaprevir/ritonavir and dasabuvir patients followed for up to 52 weeks. The analysis also found Genotype 1b patients reported greater improvements in health-related quality of life as compared to genotype 1a patients. Conclusions During the active treatment period, small but statistically significant decrements in health-related quality of life outcomes were observed potentially driven by ribavirin, which were not sustained during the post-treatment follow-up period. Differences were observed by patient subgenotype, where health-related quality of life improvements were consistently higher for genotype 1b patients as compared to genotype 1a patients.

Treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin (OPrD ± RBV), was the first interferon-free direct-acting antiviral for hepatitis C virus (HCV) introduced to Israel's national basket of health services in February 2015. Patients with HCV genotype 1 (GT1) and advanced fibrosis (F3-F4) were eligible for treatment in 2015. This study aimed to characterize patients initiating OPrD ± RBV and assess sustained virological response (SVR). A retrospective cohort study was performed using the database of Maccabi Healthcare Services (MHS), a 2-million-member health plan in Israel. The study population included adults who initiated OPrD ± RBV through December 2015 per health basket criteria. A gap in medication fills (>14 days between a fill's run-out and the next fill) was used to estimate adherence. SVR was defined by the viral tests at least 12-week post-treatment. The study population consisted of 403 patients (56.3% male), with a mean age of 60.7 years (SD 11.0). Overall, 71.0% were naive to prior HCV treatment, and 95.6% were treated with a 12-week regimen. A total of 348 patients (86.4%) completed the regimen in the usual time frame (highly adherent), whereas 8.2% completed with a gap, and 4.7% purchased less than the recommended dose. SVR rates overall and among highly adherent patients were 395/403 (98.0%; 95% CI 96.1-99.1) and 346/348 (99.4%; 95% CI 97.9-99.9), respectively. GT1b patients on 12-week regimens attained SVR rates of 194/196 (fibrosis F3) and 170/176 (cirrhosis). After a first year of provision of OPrD ± RBV with good adherence, high SVR rates were achieved in various patient subgroups and comorbidities.

Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa.PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1:1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12.We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences.Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups. (Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and NCT01468233 for PIONEER I and PIONEER II, respectively.).

Background: Latin America has witnessed a marked increase in cardiovascular (CV) disease, the leading cause of death in many countries. The benefits of lipid-lowering therapy to reduce CVrelated events are widely accepted. Clinical evidence suggests that rosuvastatin is associated with slightly greater reductions in lowdensity lipoprotein cholesterol levels than is atorvastatin at comparable doses. Rosuvastatin, however, is often priced at a premium. Objective: Our objective was to examine the cost-effectiveness of using atorvastatin versus rosuvastatin in reducing CV events in Brazil and Colombia using real-world prices. Methods: A global Markov cohort model of primary and secondary CV prevention was developed and adapted to Brazilian and Colombian settings. The risks and costs of major CV events and efficacy, adherence, and costs of statins were considered. Total gains in life-years, quality-adjusted life-years, major CV events avoided, and costs over the lifetime horizon were estimated. Several dose comparisons were considered. Results: In the Colombian analyses, differences in drug costs between therapies were considerable while outcomes were similar. The incremental cost per quality-adjusted life-year gained for rosuvastatin versus atorvastatin was more than $700,000 and $200,000 in primary and secondary prevention, respectively. Brazilian analyses found lower incremental cost-effectiveness ratios for rosuvastatin at some dose comparisons due to similar pricing between statins. Sensitivity analyses revealed that changes in treatment efficacy and adherence had the largest impact on results. Conclusions: In primary and secondary CV prevention, the efficacy advantage of rosuvastatin was minimal, while its acquisition cost was higher, particularly in Colombia. The incremental cost-effectiveness ratios were, therefore, generally in favor of atorvastatin being the cost-effective option.

Diabetes accounts for almost 15% of all direct healthcare expenditures. Managed care organizations try to reduce costs and improve patient outcomes. Increasing patient persistence with antidiabetes treatment could help achieve these goals.A retrospective study was conducted using the Optum Research Database (Optum, Eden Prairie, MN) to analyze clinical and economic outcomes associated with initiation of insulin glargine via a disposable pen (GLA-P) or vial and syringe (GLA-V) among adult, insulin-naive patients with type 2 diabetes mellitus (T2DM). Propensity-matched patient cohorts were assessed for persistence with insulin therapy, glycated hemoglobin (A1C), hypoglycemic events (based on diagnosis codes), and healthcare costs (total paid amount of adjudicated claims) after follow-up at 1 year.In 1,308 matched patients, persistence was significantly higher (P=0.011) and longer (P=0.001) with GLA-P. Follow-up A1C values were significantly lower (P=0.038), and decreases in A1C from baseline significantly larger (P=0.043), in GLA-P than in GLA-V. Significantly fewer hypoglycemic events (P=0.042) were experienced, and a lower rate of diabetes-related inpatient admissions (P=0.008) was reported in GLA-P than GLA-V. Despite higher study drug costs with GLA-P than GLA-V, all-cause and diabetes-related healthcare costs were similar.In insulin-naive patients with T2DM, initiation of insulin glargine using the disposable pen rather than the vial and syringe is associated with higher persistence, better A1C control, and lower rates of hypoglycemia. The higher study drug costs associated with pen use do not increase total all-cause or diabetes-related healthcare costs. This may help treatment selection for patients with T2DM in a managed care setting.

Background Community-acquired pneumonia (CAP) causes substantial clinical and economic burden. While several studies have reported the cost to treat CAP, there is little information on the cost to treat by age, risk profile, and hospitalization in US adults aged ≥50 years. Objective To quantify the cost, from a payer perspective, of treating CAP at the episode level, stratified by age, risk profile, and hospitalization. Methods A retrospective study of claims data from a large US health plan (1 January 2006–31 December 2008) was conducted. Patients aged ≥50 years having at least one medical claim with a primary diagnosis for pneumonia were identified. A CAP episode was defined as the period between the first and last pneumonia ICD-9 code with a chest X-ray claim. Episode-level variables included risk stratum based on presence of an immunocompromising/chronic condition, age group, number and length of inpatient and outpatient CAP episodes, and all-cause and CAP-related healthcare costs (adjusted to 2011 costs). Results Among the 27,659 study patients, 28,575 CAP episodes (20,454 outpatient; 8,121 inpatient) occurred. Mean age of patients with a CAP episode was 62.6. Low-risk patients accounted for 44.4 % of all CAP episodes. Mean CAP episode length was 31.8 days for an inpatient episode and 10.2 days for an outpatient episode. Mean all-cause total healthcare cost for an inpatient CAP episode ranged from $11,148 to $51,219 depending on risk stratum and age group. Mean outpatient episode-related costs were much lower than inpatient episode-related costs. Conclusions Cost to treat CAP requiring hospitalization is high regardless of age or the presence of underlying comorbidities. Given that almost half of the patients in this study did not have traditional risk factors for CAP, it is clear that better preventative strategies are needed. Electronic supplementary material The online version of this article (doi:10.1007/s40258-013-0026-0) contains supplementary material, which is available to authorized users.

To compare pharmacotherapy adherence, persistence, and healthcare utilization/costs among US patients with chronic hepatitis B (CHB) initiated on an oral antiviral monotherapy recommended as first-line treatment by current national (US) guidelines vs an oral antiviral not recommended as first-line monotherapy.In this retrospective cohort study, patients aged 18-64 with medical claims for CHB who initiated an oral antiviral monotherapy for CHB between 07/01/05 and 01/31/10 were identified from a large US commercial health insurance claims database. Patients were continuously enrolled for a 6-month baseline period and ≥90 days follow-up. They were assigned to 'currently recommended first-line therapy' (RT: entecavir or tenofovir) or 'not currently recommended first-line therapy' (NRT: lamivudine, telbivudine, or adefovir) cohorts.Multivariate analyses were conducted to compare treatment adherence, persistence, healthcare utilization, and costs for RT vs NRT cohorts.Baseline characteristics were similar between RT (n=825) and NRT (n=916) cohorts. In multivariate analyses, RT patients were twice as likely as NRT patients to be adherent (OR=2.09; p0.01) and persistent (mean: RT=361 days, NRT=298 days; p0.01) and half as likely to have an inpatient stay (OR=0.527; p0.01). Between the two oral antivirals recommended as first-line treatment, even though pharmacy cost was higher for entecavir, mean total healthcare costs for entecavir and tenofovir were similar ($1214 and $1332 per patient per month, respectively). Similar results were also observed with regard to adherence, persistence, and healthcare use for entecavir and tenofovir.A limitation associated with analysis of administrative claims data is that coding errors can be mitigated but are typically not fully eradicated by careful study design. Nevertheless, the current findings clearly indicate the benefits of initiating CHB treatment with an oral antiviral monotherapy recommended as first-line treatment by current guidelines.

Non-adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient-reported data were collected through a cross-sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs' beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy-seven RTRs were non-adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18-29 yr were more likely to be non-adherent than recipients 46-64 yr old (p ≤ 0.001). Non-adherent RTRs had greater adherence barriers than adherent RTRs (p < 0.001). Adherent RTRs believed their ISMs were more necessary than non-adherent RTRs (p < 0.001), while non-adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p < 0.001). Non-adherent RTRs had lower life satisfaction (p < 0.001). Non-adherence is significantly associated with patients' beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed.

Background & Aims Chronic kidney disease (CKD) can have a negative impact on the natural history of hepatitis C virus infection (HCV) infection; patients with HCV and CKD often have adverse outcomes. We evaluated a large and geographically diverse group of patients to determine whether HCV status has an independent effect on the risk of developing CKD. Methods We conducted a cohort study of 167,569 patients included in a national health care claims database from January 1, 2003–December 31, 2006, with a mean follow-up of 25.3 months. We used multivariable logistic regression analyses to measure the independent effect of HCV status on the baseline prevalence of and progression to CKD (estimated glomerular filtration rate, 2 ). Results The baseline prevalence of CKD was similar in patients with versus those without HCV (5.3% vs 5.1%, P = .3). Similarly, among patients with preserved renal function at baseline (n = 82,629), there was no difference in the overall progression to CKD in patients with versus those without HCV (3.8% vs 3.5%, P = .1). HCV status was not associated with progression to CKD, even after adjusting for patient demographics, comorbidities, and use of relevant medications (odds ratio, 0.92; 95% confidence interval, 0.79–1.08). Conclusions We found no association between HCV and risk of development of CKD. These data are relevant in counseling HCV patients regarding the impact of HCV on renal function.

Background Patients with nonvalvular atrial fibrillation (NVAF) are at increased risk for stroke and bleeding events, but bleeding as an outcome has not been extensively studied in this patient population. Objectives The goal of this study was to estimate the incidence of bleeding events among patients with NVAF enrolled in managed care, investigate the relationships between bleeding incidence and bleeding and stroke risks, and estimate health care costs for patients who had a major bleeding event. Methods Adults with commercial insurance or Medicare Advantage coverage and health care claims related to AF between January 2005 and June 2009 but with no evidence of valvular disease were included in this retrospective claims data analysis. Baseline stroke risk (CHADS 2 [Congestive Heart Failure, Hypertension, Age >75 Years, Diabetes Mellitus, and Prior Stroke or Transient Ischemic Attack]) and bleeding risk (HAS-BLED [Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratios, Elderly, Drugs/Alcohol]) were estimated. Bleeding events were identified during the variable follow-up period, which lasted from the date of the first qualifying AF visit until the earlier of death, disenrollment from the health plan, or June 30, 2010. Bleeding events were classified as major, serious nonmajor, or minor. Health care costs for patients with major bleeding events were calculated. Results Among 48,260 patients with NVAF (mean age, 67 years), 34% had an incident bleeding event during a mean (SD) follow-up period of 802 (540) days. Incidence rates for bleeding events of any severity and major events were 29.6 and 10.4 per 100 patient-years, respectively. Bleeding incidence rates increased with greater CHADS 2 and HAS-BLED risk scores. All-cause health care costs for patients during a major bleeding event averaged $16,830. Average costs per patient with a major event increased from approximately $52 per day in the prebleeding period to approximately $63 per day in the postbleeding period. Costs for patients who did not experience a major bleeding event averaged approximately $38 per day. Conclusions Bleeding incidence among patients with NVAF in a real-world setting was high and increased with greater stroke and bleeding risk scores. Health care costs for patients with major bleeding events were elevated. All rights reserved.

Background Stroke prevention is a goal of atrial fibrillation (AF) management, but discontinuation of warfarin anticoagulation therapy is common. Objective To investigate the association between warfarin discontinuation and hospitalization for stroke among nonvalvular AF (NVAF) patients enrolled in managed care. Methods Patients with NVAF who initiated warfarin therapy from January 2005 through June 2009 were included. Warfarin discontinuation was defined as a supply gap >60 days without evidence of International Normalized Ratio measurements. Follow-up, which was a variable time period from warfarin initiation until the earlier of death, disenrollment from the health plan, or June 30, 2010, was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis of stroke or transient ischemic attack. Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the previous warfarin treatment period. Results Among warfarin initiators with NVAF (N = 16,253), 51.4% discontinued warfarin therapy at least once during a mean follow-up of 668 days. Stroke risk was significantly greater during warfarin discontinuation periods compared with therapy periods (hazard ratio = 1.60; 95% CI, 1.35–1.90; P Conclusions More than half of patients on warfarin had treatment gaps or discontinued therapy. Therapy gaps were associated with increased stroke risk.

Introduction Stroke prevention among patients with nonvalvular atrial fibrillation (NVAF) requires careful assessment of both the risk of stroke and bleeding. Hypothesis We hypothesized that in a real-world managed care population of patients with NVAF, bleeding incidence increases with CHADS2 stroke risk. Methods Administrative claims data were used for this retrospective study. Adults with healthcare claims related to AF (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Patients were categorized based on CHADS2 scores of 0, 1, 2, or ≥3, with higher scores indicating more risk factors. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Results The mean (SD) age of the study sample (N=48,260) was 67±13 years and 62% of the patients were male. Mean follow-up duration was 802±540 days (median 673 days). Mean (SD) baseline CHADS2 score was 1.48±1.15. Event rates for each bleeding category increased with increasing CHADS2 scores (Table). Conclusions Patients with NVAF in a real-world managed care setting who had high stroke risk also had a high rate of bleeding events, including major events. Patients at high risk for stroke might require more careful selection of anticoagulation therapy to avoid bleeding events.

Introduction Warfarin discontinuation among real world nonvalvular atrial fibrillation (NVAF) patients is common. Hypothesis We hypothesized that in a managed care population, warfarin discontinuation is associated with increased stroke risk. Methods Patients who initiated warfarin therapy between Jan 2005 and Jun 2009 and had a healthcare claim related to AF within 30 days prior to the first warfarin claim, but no evidence of valvular disease, were included. Warfarin discontinuation was defined as a supply gap of >60 days without evidence of International Normalized Ratio (INR) measurements. Follow-up was divided into periods of warfarin treatment and discontinuation. Stroke events were identified based on claims for inpatient stays with a primary diagnosis for stroke or transient ischemic attack (TIA). Cox proportional hazards models were constructed to assess the relationship between warfarin discontinuation and incident stroke while adjusting for baseline demographics, stroke and bleeding risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and bleeding events in the prior warfarin treatment period. Results The mean (SD) age of the study sample (N=16,253) was 67±12 years; 64.8% was male. Mean CHADS2 score was 1.84±1.30; mean HAS-BLED score was 2.00±1.18. Half (51.4%) of patients discontinued warfarin therapy at least once and the overall sample had a mean of 1.87 warfarin treatment periods during a mean of 668 days follow-up. Approximately 1186 patients (7%) had a stroke or TIA at any site of service during follow-up. Risk of stroke significantly increased during warfarin discontinuation periods compared with therapy periods (HR 1.60; 95%CI 1.35-1.90; P Conclusions In the real world, over half of patients on anticoagulation therapy had treatment gaps or permanently discontinued therapy. These usage patterns, as well as prior bleeding, were associated with increased stroke risk.

Introduction Bleeding among patients with nonvalvular atrial fibrillation (NVAF) may prevent subsequent anticoagulation, and consequent inadequate stroke prophylaxis could extend the economic impact of bleeding beyond the acute event. Hypothesis We hypothesized that costs for NVAF patients rise acutely following a major bleed and stay elevated through extended follow-up compared with costs for NVAF patients without a major bleed. Methods Adults with healthcare claims related to AF between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Follow-up lasted until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, death, physician guided medical or surgical treatment, or intracranial bleed. Among patients with major bleeding events, average daily costs were calculated in the pre-bleed (from the index date until the event) and post-bleed (from the end of the event until the end of follow-up) periods, and during the event. Among patients without major bleeding events, the average daily cost during the entire follow-up period was calculated. Results Among 48,260 patients with NVAF (mean age 67±13 years; 62% male), 7908 (16%) had a major bleeding event during a mean (SD) follow-up of 802±540 days (median 673 days). Major bleeding events lasted a mean of 15±25 days and averaged $16,830 per event. Among patients who experienced a major event, average costs per patient increased from approximately $50 per day in the pre-bleed period to $63 per day in the post-bleed period, a difference of approximately $13 per day. Daily costs for NVAF patients who did not experience a major bleeding event averaged approximately $36 per day; thus, average daily costs for patients who had a major bleed were greater in both the pre- and post-bleed periods (by $14 per day and $27 per day, respectively) than for patients who did not have a major event. Cost differences persisted 2 years following incident major bleeding events. Conclusions Major bleeding events among NVAF patients are associated with substantial healthcare costs, both directly related to the event and in the post-event period.

Non-adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient-reported data were collected through a cross-sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs' beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy-seven RTRs were non-adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18-29 yr were more likely to be non-adherent than recipients 46-64 yr old (p ≤ 0.001). Non-adherent RTRs had greater adherence barriers than adherent RTRs (p0.001). Adherent RTRs believed their ISMs were more necessary than non-adherent RTRs (p0.001), while non-adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p0.001). Non-adherent RTRs had lower life satisfaction (p0.001). Non-adherence is significantly associated with patients' beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed.

Background Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function. Study Design Historical cohort study. Setting & Participants Study data were drawn from administrative records of a national private health insurer (2003-2006). We included all adult beneficiaries with concurrently measured serum creatinine and serum uric acid. Patients with acute kidney failure or undergoing renal replacement therapy at baseline were excluded. Predictors Serum uric acid concentration and estimated glomerular filtration rate (eGFR). Outcomes & Measurements Cardiovascular diagnoses (myocardial infarction, subacute coronary heart disease, heart failure, cerebrovascular disease, or peripheral arterial disease) ascertained from billing claims. Cox proportional hazard models were used to test the association of predictors with cardiovascular morbidity. Models were adjusted for sociodemographic characteristics, selected comorbid conditions, and laboratory results. Results In 148,217 eligible patients, mean eGFR was 84 mL/min/1.73 m 2 and the prevalence of CKD stages 3-5 was 6.0%. Hyperuricemia (serum uric acid >7 mg/dL) was found in 15.6% of patients. The 40-month cumulative incidence of cardiovascular events (mean follow-up, 15.3 months) was 8.1%. Cardiovascular risk was associated independently with uric acid level, and this association was stronger in patients with lower eGFRs. Limitations Observational design, lack of information for mortality and potential confounders, single creatinine and uric acid assessment. Conclusions Serum uric acid concentration was an independent correlate of cardiovascular morbidity, and this association was stronger in patients with severely decreased eGFR. This investigation provides a rationale for further study of serum uric acid–lowering interventions on cardiovascular risk in the general population and patients with CKD.

We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19-24 years were more likely to be persistently noncompliant compared to patients aged 24-44 years (aOR 1.49 [1.06-2.10]). Poor (aHR 1.80 [1.52-2.13]) and fair (aHR 1.63[1.37-1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3-year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.

Background Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. Methods We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching. Results All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. Conclusions Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.

OBJECTIVE To quantify the incremental survival benefit of the pancreas allograft in simultaneous pancreas-kidney (SPK) transplant recipients. RESEARCH DESIGN AND METHODS Data from the national transplant database from 2000 to 2007 were analyzed. SPK recipients who had functioning allografts to 1-year post transplant (n = 3,304) were compared with those who had failure of the renal (n = 233) or pancreatic (n = 112) graft. The main outcome was a projection of 10 life-years of patient survival beyond the first transplant anniversary. RESULTS Recipients with function of both organs accrued 9.4 life-years following transplantation. Projected survival in patients with kidney failure was reduced to 2.5 life-years. Pancreas failure reduced predicted survival to 8 life-years. Renal allograft failure impacts life expectancy significantly (adjusted hazard ratio [aHR] 12.13). However, pancreas allograft failure was also associated with reduced survival (aHR 2.62). CONCLUSIONS Although the majority of the survival benefit of SPK transplant is due to the renal transplant, pancreas allograft function does contribute to patient survival.

To determine the accuracy of personal breast cancer risk estimation, interviews were conducted of 110 women between November 2004 and May 2005 during primary care visits. The average age of the women was 39 years. Considering their lifetime breast cancer risk, 49% of women perceived their risk to be low, 35% average, and 11% high. Compared to Gail-model lifetime risk scores, 62% of women were inaccurate and underestimated or overestimated risk. Factors affecting accuracy of risk prediction were race, family history of cancer, alcohol use and exercise. Our study highlights the need for personalized breast cancer education between an individual woman and her health care provider.

Background. Gastrointestinal complications are common in patients who undergo kidney transplantation and may affect posttransplant outcomes. We examined the incidence and predictors of gastroesophageal reflux disease (GERD) and dyspepsia and their associations with graft survival and mortality after transplant. Methods. We examined United States Renal Data System data and Medicare billing claims to identify diagnoses of dyspepsia and GERD among Medicare beneficiaries transplanted in 1995-2002 (n=42,257). Among GERD cases, we identified patients with reflux esophagitis (RE). We determined independent predictors of upper gastrointestinal complications and modeled these conditions as time-dependent outcomes predictors with Cox regression. Results. The 3-year cumulative incidences of GERD, RE, and dyspepsia were 20%, 5%, and 6%, respectively. Overall, 23% of transplant recipients received a diagnosis of at least one of these complications by 3 years after transplant. Female gender and a pretransplant upper gastrointestinal disease diagnosis predicted posttransplant gastrointestinal complications. Older age, obesity, Caucasian, and African-American race were associated to increased risk of developing GERD. Patients diagnosed with any of the examined upper gastrointestinal complications experienced an increased risk of graft-failure (hazard ratio 1.58; 95% confidence interval 1.48-1.69) and death (hazard ratio 1.61; 95% confidence interval 1.46-1.77). Conclusions. Upper gastrointestinal complications are relatively common after kidney transplantation and are associated with a significantly increased risk of graft loss and death. Further research is needed to elucidate mechanisms underlying the observed adverse prognoses conferred by diagnosis of upper gastrointestinal complications after kidney transplant.

We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome. Medicare claims for MMF in 7062 deceased donor renal recipients with at least 1 year of graft function were used to calculate compliance and dose reductions. Compliance was modeled using medication possession ratio to define quartiles for poor, low, medium and high compliance. The relative impact of compliance, dose reduction and discontinuation on graft outcome was assessed with Cox proportional hazards. Pediatric (Age 0-18, Odds ratio = 1.71, 95% CI 1.11-2.63, p = 0.014) and adolescent recipients (19-24, 1.57, 1.23-2.00, p0.001) were more likely poorly compliant compared to adults age 25-44. Poor compliance was also associated with physical limitations, hypertension, delayed graft function, rejection, infection and GI conditions. Poor (1.43, 1.11-1.84, p = 0.005) and low (1.46, 1.13-1.88, p = 0.004) compliance was associated with an increased hazard of graft loss as was50% dose reduction (1.69, 1.15-2.50, p = 0.008) and discontinuation (8.34, 6.85-10.2, p0.001). Medication possession ratios lower than the 3-year mean were associated with an increased risk of graft loss. These results may indicate that interventions to improve compliance among kidney transplant recipients should strive for high rather than discourage low compliance.

Background: Gastrointestinal complications after kidney transplantation are associated with inferior graft outcomes. We examined the incidence, risk factors, and outcomes of posttransplantation diarrhea. Study Design: Historic cohort study. Setting & Participants: We examined first kidney transplant recipients in the United States from 1995 to 2002, with follow-up through December 2002. Recipients of multiple organs were excluded. We limited our study population to Medicare beneficiaries. Predictors: Recipient, donor, and transplant characteristics were ascertained by means of US Renal Data System database inquiry. Outcomes: Incidence of diarrhea, graft loss, and death after transplantation. First episodes of diarrhea after transplantation were ascertained by using International Classification of Disease, Ninth Revision, Clinical Modification codes using Medicare billing data. Cause of diarrhea was classified as infectious or not and according to specific cause. Graft loss and death were ascertained from the date of the first diarrhea episode. Results: We enrolled 41,442 patients. Mean follow-up was 758 399 days. We observed 7,103 diarrhea cases and 8,104 graft losses (4,201 deaths). The 3-year cumulative incidence of diarrhea was 22%, with 18% diagnosed as noninfectious diarrhea with an unspecified cause. Using multivariate Cox proportional hazards analysis, factors associated with increased risk of unspecified noninfectious diarrhea were female sex (hazard ratio [HR], 1.40; 95% confidence interval, 1.33 to 1.48), type 1 diabetes (HR, 1.20; 95% confidence interval, 1.06 to 1.37), and regimens containing tacrolimus and mycophenolate mofetil (HR, 1.37; 95% confidence interval, 1.28 to 1.46). Unspecified noninfectious diarrhea was associated with increased risk of graft failure (HR, 2.13; 95% confidence interval, 1.98 to 2.28) and patient death (HR, 2.04; 95% confidence interval, 1.85 to 2.24). Limitations: Use of claims data to ascertain patient characteristics and events; inability to make causal inference based on retrospective designs. Conclusions: Regimens containing tacrolimus and mycophenolate mofetil were associated with increased risk of noninfectious diarrhea. Episodes of noninfectious diarrhea doubled the hazard of graft loss and patient death. Am J Kidney Dis 51:478-486. © 2008 by the National Kidney Foundation, Inc.

ICD-9-CM diagnoses for hospitalizations occurring during the first 6 post-transplant months were summarized into Clinical Classifications System (CCS) categories. Of the 28,900 patients examined, 54% had at least one hospitalization. There were 2.39 hospitalizations per patient-year at risk. The total Medicare inpatient costs were $339 million and mean length of stay was 8.3 days. The most common and costly CCS diagnosis was complications of a kidney transplant followed by infections, circulatory system disease, gastrointestinal disease and endocrine complications. The CCS is a useful tool to summarize the complexity of claims information in the USRDS and could prove useful in further claims research.

Background. Mycophenolate mofetil (MMF) use in renal transplantation has steadily increased since 1995 because of its ability to lower the risks of rejection and chronic allograft nephropathy. However, significant gastrointestinal (GI) complications may lead to MMF dose reductions and discontinuations. Little is known of the association between MMF dose reductions and discontinuations following GI complications and graft survival. Methods. Using the United States Renal Data System, we identified 3,675 adult recipients (age ≥18) with a diagnosed GI complication who were prescribed MMF at the time of first GI diagnosis and had Medicare as their primary insurer. MMF doses were ascertained from Medicare payment records. We estimated risk of graft loss associated with MMF dose adjustments after GI diagnosis: dosage unchanged (reference), reduced

Background Palivizumab has been shown to decrease the incidence of hospitalization due to respiratory syncytial virus (RSV) in infants at risk of severe RSV disease. We examined the association between compliance with palivizumab dosing throughout the RSV season and risk of RSV-related hospitalization in clinical practice. Methods Subjects who were born and discharged from the hospital before the RSV season and received ≥1 palivizumab dose during their first RSV season were identified from a large US commercial health insurance database between 01/01/03 and 12/31/09. Subjects were deemed compliant if they received ≥5 palivizumab doses without gaps (>35 days) and their first dose was received by November 30. RSV-related hospitalizations were identified using ICD-9-CM diagnosis codes and examined over 2 observation periods: post-index dose and RSV season. A Cox proportional hazard model was used to evaluate the association between non-compliance and RSV-related hospitalization. Results Of the 5,003 subjects who received palivizumab, 62% were deemed non-compliant. Non-compliant subjects had significantly higher unadjusted rates of RSV-related hospitalizations compared to compliant subjects during both observation periods (post-index: 6.1 vs. 2.8 per 100 infant seasons, p

Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF) due to the need for stroke prevention through anticoagulation. Older patients may be at risk for more frequent or more severe bleeding events. Objective: To describe the incidence of bleeding events in various age groups of patients with NVAF. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims data related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were categorized as major, serious non-major, or minor. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Patients were grouped based on their age as of the first atrial fibrillation diagnosis: younger than 65 years or 65 years and older; bleeding events in the subgroup of patients aged 75 years and older were also examined. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Event rates for major bleeds were 5.2 events per 100 patient-years for patients aged younger than 65 years and 13.9 major bleeds per 100 patient-years for patients aged 65 years and older. Patients aged 75 and older had 15.6 major bleeds per 100 patient-years. Approximately 38.9% of all bleeding events experienced by patients aged 65 years and older were major. Approximately 23.3%, 33.6%, and 35.8% of major bleeds among patients younger than 65 years, 65 years and older, and 75 years and older, respectively, were associated with a hospitalization. Corresponding event rates for incident bleeds associated with an inpatient stay were 4.7 bleeding events per 100 patient-years for patients aged younger than 65 years, 12.0 events per 100 patient-years for patients aged 65 years and older, and 13.6 events per 100 patient-years for patients aged 75 years and older. Conclusions: Increasing age was associated with increased rate of any type of bleeding. The increase in rate with increasing age was particularly notable for major bleeds. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Jing:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

Abstract 2073 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF), and different anatomical sites may carry greater risk for bleeding. Objective: To describe the incidence of critical anatomical site bleeding events among patients with NVAF in the pre-NOAC (novel oral anticoagulation) era. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were considered major if they were associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Anatomical bleeding sites were identified based on diagnosis codes. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Over 105,419 patient-years, the critical site with the highest rate of major bleeding events was the gastrointestinal tract, followed by intracranial bleeding (TABLE). Conclusions: Gastrointestinal, intracranial, and pericardial bleedings were the most frequently observed major bleedings in the pre-NOAC era. Patients with NVAF have a high rate of major gastrointestinal bleedings. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Makenbaeva:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

The ability to accurately predict a population′s long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population′s long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and com-pared with the population′s actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted sur-vival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population′s long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Abstract 1366 Poster Board I-388 Background: Multiple myeloma (MM) is a complex disease that places a significant burden on patients and their caregivers. Novel agents have different administration methods (oral versus intravenous [IV]) and differ in terms of patient convenience (such as number of visits) and costs. This study compared the burden of patient visits and out-of-pocket costs for MM patients treated with bortezomib (BOR; Velcade®; IV administration), lenalidomide (LEN; Revlimid®; oral), thalidomide (THAL; Thalomid®; oral), or other unspecified chemotherapies or radiation therapy. Methods: This retrospective cohort study used claims data from a large national US commercial health plan representing approximately 14 million members. Patients aged 318 yrs, diagnosed with MM between January 1 2005 and September 30 2007, and treated with BOR, LEN, THAL, or other unspecified chemotherapies or radiation therapy during this period were included in the study. Patient costs and resource utilization data were analyzed at the treatment level. Treatment episodes (defined as each course of therapy) were identified from records for each patient; some patients had multiple episodes. Health care utilization (according to number of ambulatory patient visits) and inflation-adjusted patient out-of-pocket costs, including co-pays and deductibles, were examined for 1 yr from the beginning of each treatment episode. An ambulatory visit was defined as any visit with a unique day and a unique provider ID in an outpatient or office setting. Descriptive analyses were supplemented with multivariate regression analyses to control for patient characteristics, comorbidities, and line of treatment (more prior lines of therapy are indicative of more advanced disease). Results: A total of 2,642 treatment episodes were identified for the 1,900 MM patients included in the study. The majority of episodes were classified as “other chemotherapy or radiation therapy” (n=1,759, 66.6%). The second most common treatment episode was THAL (n=549, 20.8%), followed by BOR (n=244, 9.2%) and LEN (n=90, 3.4%). There were no differences among treatment groups in terms of inpatient or emergency room visits in the year following treatment initiation. As expected, patients treated with BOR appeared to have more ambulatory visits compared with patients treated with LEN, which is administered orally; however, this difference was not significant after adjustment for patient characteristics, line of treatment, and comorbidities by multivariate analysis (Table). The total adjusted patient out-of-pocket costs for the year after treatment initiation were significantly less for patients treated with BOR ($3,504) than for those treated with THAL ($4,443, p Conclusions: In this study, the perceived advantage of orally administered drugs (THAL, LEN) in terms of fewer patient visits was not significant. In addition, direct out-of-pocket costs were significantly higher for patients treated with the oral drugs THAL and LEN compared with the IV drug BOR, especially for Medicare patients, likely due to the Coverage Gap, commonly known as the “donut hole”, in Medicare Part D. Disclosures: Huang: Milllennium: Employment, Equity Ownership. Teitelbaum: Spectrum Pharmaceuticals: Consultancy; EGEN: Consultancy, Honoraria; CV Therapeutics: Consultancy. Esseltine: Milllennium: Employment, Equity Ownership.