Gabapentin, Concomitant Prescription of Opioids, and Benzodiazepines among Kidney Transplant Recipients.

BACKGROUND: Gabapentinoids, commonly used for treating neuropathic pain, may be misused and coprescribed with opioid and benzodiazepine, increasing the risk of mortality and dependency among kidney transplant recipients. METHODS: We identified adult kidney transplant recipients who enrolled in Medicare Part D in 2006-2017 using the United States Renal Data System/Medicare claims database. We characterized recipients' post-transplant concomitant prescription of gabapentinoids, opioids, and benzodiazepine stratified by transplant year and recipient factors (age, sex, race, and diabetes). We investigated whether concomitant prescriptions were associated with postkidney transplant mortality using Cox regression. Models incorporated inverse probability weighting to adjust for confounders. RESULTS: Among 63,359 eligible recipients, 13% of recipients filled at least one gabapentinoid prescription within 1 year after kidney transplant. The prevalence of gabapentinoid prescriptions increased by 70% over the study period (16% in 2017 versus 10% in 2006). Compared with nonusers, gabapentinoids users were more likely to have diabetes (55% versus 37%) and obesity (46% versus 34%). Of the 8509 recipients with gabapentinoid prescriptions, 45% were coprescribed opioids, 7% were coprescribed benzodiazepines, and 3% were coprescribed both opioids and benzodiazepines. Compared with no study prescriptions, gabapentinoid monotherapy (adjusted hazard ratio [aHR]=1.25; 95% confidence interval [CI], 1.16 to 1.32) and combination therapy (gabapentinoids and opioids [aHR=1.49; 95% CI, 1.39 to 1.60], gabapentinoids and benzodiazepines [aHR=1.46; 95% CI, 1.03 to 2.08], and coprescribing all three [aHR=1.88; 95% CI, 1.18 to 2.98]) were all associated with a higher risk of postkidney transplant mortality. CONCLUSIONS: Gabapentinoid coprescription with both benzodiazepines and opioids among kidney transplant recipients increased over time. Kidney transplant recipients prescribed gabapentinoids had a higher risk of post-transplant mortality, and the risk was higher with opioids or benzodiazepine coprescription.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications.

Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Resource utilization and costs among patients with heart failure with reduced ejection fraction following a worsening heart failure event.

AIMS: The aim of this study is to characterize healthcare resource utilization and costs in patients with heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event. METHODS AND RESULTS: This was a retrospective observational cohort analysis. Patients with HFrEF were identified from the PINNACLE Registry and linked to a nationwide pharmacy and medical claims database. Worsening heart failure was defined as stable heart failure with a subsequent hospitalization and/or intravenous diuretic therapy. Healthcare resource use and costs in 2015 US dollars were analysed for dispensed prescriptions, outpatient encounters, and hospital encounters. Among 11 064 patients with HFrEF, 3087 (27.9%) experienced a worsening heart failure event during an average follow-up of 973 days. During the first 30 days after the worsening event, 19.8% of patients had hospital readmissions with heart failure as the primary or secondary diagnosis. During that same time period, mean per patient heart failure-related healthcare resource use included 1.3 prescriptions, 0.5 practitioner visits, and 0.5 hospital encounters (admissions, observations, or emergency care), for an average total medical cost of $8779 per patient including $5359 in heart failure-related costs. During the first year following worsening heart failure onset, mean per patient total and heart failure-related costs were $62 615 and $35 329, respectively. CONCLUSIONS: The economic burden following a worsening heart failure event calls for further review of methods to prevent progressive disease, improve adherence to guideline-directed therapy, and develop novel treatments and care strategies to moderate further progression.

Hydroxychloroquine and maintenance immunosuppression use in kidney transplant recipients: Analysis of linked US registry and claims data.

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,1.12 1.963.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,1.00 1.813.29 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,1.02 1.542.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,1.03 1.311.68 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.

Induction immunosuppression and the risk of incident malignancies among older and younger kidney transplant recipients: A prospective cohort study.

BACKGROUND: Older (≥65) KT recipients differ from their younger counterparts in their immune response to immunosuppression (IS) and may have a different risk of malignancy after receiving induction. METHODS: We identified 66 700 adult KT recipients treated with anti-thymocyte globulin (ATG) (n = 40 443) or interleukin-2 receptor antagonist (IL-2RA) (n = 26 327) induction (1/1/1999-12/31/2014) using USRDS/Medicare data. We estimated the risk of first-diagnosed post-KT malignancy associated with induction (ATG vs. IL-2RA) using Cox proportional hazard models. We then tested whether these risks differed between older and younger recipients (Wald test for interaction). Models incorporated inverse probability of treatment weights to adjust for confounders. RESULTS: The 3-year cumulative incidences of any diagnosed malignancy were 11.5%. ATG was associated with a higher malignancy risk (HR = 1.12, 95%CI:1.06-1.18). This association differed (pinteraction  = 0.04) between younger (HR = 1.12, 95%CI:1.06-1.18) and older recipients (HR = 1.03, 95%CI:0.96-1.09). ATG was also associated with higher risk of skin (HR = 1.18, 95%CI:1.08-1.29), lung (HR = 1.24, 95%CI:1.05-1.47), and ovary malignancies (HR = 1.94, 95%CI:1.08-3.48). However, only the association of ATG with post-KT skin malignancy differed (pinteraction  = 0.01) between younger (HR = 1.18; 95%CI:1.08-1.29) and older (HR = 1.01; 95%CI:0.93-1.09) recipients. CONCLUSIONS: Compared with IL-2RA induction, ATG was associated with elevated post-KT malignancy risk but only among younger recipients. Transplant centers may need to tailor induction IS for younger recipients to mitigate malignancy risk.

Prevalence of narcolepsy and other sleep disorders and frequency of diagnostic tests from 2013-2016 in insured patients actively seeking care.

STUDY OBJECTIVES: The primary objective was to describe trends in the 2-year limited duration prevalence of narcolepsy from 2013-2016 in a large insured population with claims activity. Secondary objectives were to assess the prevalence of other sleep disorders and the frequency of diagnostic sleep testing. METHODS: Nationwide medical/prescription claims (Symphony Health) were analyzed to estimate the annual prevalence per 100,000 persons of narcolepsy and other sleep disorders (obstructive sleep apnea, idiopathic hypersomnia, rapid eye movement sleep behavior disorder, periodic limb movement disorder) and the frequency of diagnostic sleep testing. Prevalence was adjusted to the age/sex distribution of the 2016 US census estimates. RESULTS: The prevalence of narcolepsy per 100,000 persons increased 14% from 38.9 in 2013 to 44.3 in 2016. Obstructive sleep apnea prevalence increased 41% over the study period from 2,429 to 3,420 per 100,000. Large increases in prevalence were also seen for idiopathic hypersomnia (32%), periodic limb movement disorder (30%), and rapid eye movement sleep behavior disorder (64%). For each sleep disorder, prevalence was higher for those with commercial insurance versus Medicare/Medicaid, and markedly lower prevalence was observed for the Northeast compared with the Midwest, South, and Western US regions. The frequency of multiple sleep latency/maintenance of wakefulness testing declined by 20%, and polysomnography declined by 15%. Conversely, home sleep apnea testing increased by 117%. CONCLUSIONS: The prevalence of narcolepsy, obstructive sleep apnea, and the other sleep disorders increased appreciably over the 2013-2016 period. It remains to be determined whether the trends seen in our analyses are due to increased incidence or increased awareness of these conditions.

Economic impacts of alternative kidney transplant immunosuppression: A national cohort study.

Understanding the economic implications of induction and maintenance immunosuppression (ISx) is important in developing personalized kidney transplant (KTx) care. Using data from a novel integrated data set including financial records from the University Health System Consortium, Medicare, and pharmacy claims (2007-2014), we estimated the differences in the impact of induction and maintenance ISx regimens on transplant hospitalization costs and Medicare payments from KTx to 3 years. Use of thymoglobulin (TMG) significantly increased transplant hospitalization costs ($12 006; P = .02), compared with alemtuzumab and basiliximab. TMG resulted in lower Medicare payments in posttransplant years 1 (-$2058; P = .05) and 2 (-$1784; P = .048). Patients on steroid-sparing ISx incurred relatively lower total Medicare spending (-$10 880; P = .01) compared with patients on triple therapy (tacrolimus, antimetabolite, and steroids). MPA/AZA-sparing, mammalian target of rapamycin inhibitors-based, and cyclosporine-based maintenance ISx regimens were associated with significantly higher payments. Alternative ISx regimens were associated with different KTx hospitalization costs and longer-term payments. Future studies of clinical efficacy should also consider cost impacts to define the economic effectiveness of alternative ISx regimens.

Transplant recipients are vulnerable to coverage denial under Medicare Part D.

Transplant immunosuppressants are often used off-label because of insufficient randomized prospective trial data to achieve organ-specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off-label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)-approved compendia. An integrated dataset including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off-label and not supported by CMS-approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off-label and off-compendia immunosuppression regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at-risk medications exceeds $30 million. This population-based study of transplant immunosuppressants vulnerable to claim denials under Medicare Part D coverage demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life-saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication nonadherence.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapy: Payer Approvals and Rejections, and Patient Characteristics for Successful Prescribing.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are a novel class of medications for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease requiring additional lipid lowering beyond dietary measures and statin use. Because of the drugs' high cost, rates of prescription approval by payers may be low. We aimed to identify payer approval and rejection rates for PCSK9i prescriptions and the potential factors influencing these rates. METHODS: This is a retrospective, descriptive cohort study using nationwide pharmacy claims linked to electronic medical records from a nationwide data warehouse. The data set includes >220 million patients from all 50 states and all payer types with 5140 distinct health plans. PCSK9i prescriptions were submitted for 51 466 patients in the pharmacy data set. The main outcome was approval or rejection of PCSK9i prescription claims. Factors associated with approval and rejection of these medications in the United States were assessed. RESULTS: Among patients who were prescribed a PCSK9i, 47.0% were approved for coverage by the payer. Variables that were associated with PCSK9i approval included age >65 years (P<0.01), history of atherosclerotic cardiovascular disease (P<0.01), prescription by a cardiologist or nonprimary care provider (P<0.01), statin intolerance (P=0.03), longer statin duration (P=0.01), and noncommercial payers (P<0.01). Higher low-density lipoprotein cholesterol levels were not associated with higher approval rates. Commercial third-party payers had the lowest approval rates (24.4%) and Medicare had the highest (60.9%). CONCLUSIONS: Rates of approval for PCSK9i therapy are low, even for patients who appear to meet labeled indications. Although a combination of clinical characteristics increases the likelihood of approval, payer type is the most significant factor.

Identifying Health Information Technology Needs of Oncologists to Facilitate the Adoption of Genomic Medicine: Recommendations From the 2016 American Society of Clinical Oncology Omics and Precision Oncology Workshop.

At the ASCO Data Standards and Interoperability Summit held in May 2016, it was unanimously decided that four areas of current oncology clinical practice have serious, unmet health information technology needs. The following areas of need were identified: 1) omics and precision oncology, 2) advancing interoperability, 3) patient engagement, and 4) value-based oncology. To begin to address these issues, ASCO convened two complementary workshops: the Omics and Precision Oncology Workshop in October 2016 and the Advancing Interoperability Workshop in December 2016. A common goal was to address the complexity, enormity, and rapidly changing nature of genomic information, which existing electronic health records are ill equipped to manage. The subject matter experts invited to the Omics and Precision Oncology Workgroup were tasked with the responsibility of determining a specific, limited need that could be addressed by a software application (app) in the short-term future, using currently available genomic knowledge bases. Hence, the scope of this workshop was to determine the basic functionality of one app that could serve as a test case for app development. The goal of the second workshop, described separately, was to identify the specifications for such an app. This approach was chosen both to facilitate the development of a useful app and to help ASCO and oncologists better understand the mechanics, difficulties, and gaps in genomic clinical decision support tool development. In this article, we discuss the key challenges and recommendations identified by the workshop participants. Our hope is to narrow the gap between the practicing oncologist and ongoing national efforts to provide precision oncology and value-based care to cancer patients.

Diabetes Mellitus in Living Pancreas Donors: Use of Integrated National Registry and Pharmacy Claims Data to Characterize Donation-Related Health Outcomes.

BACKGROUND: Living donor pancreas transplant is a potential treatment for diabetic patients with end-organ complications. Although early surgical risks of donation have been reported, long-term medical outcomes in living pancreas donors are not known. METHODS: We integrated national Scientific Registry of Transplant Recipients data (1987-2015) with records from a nationwide pharmacy claims warehouse (2005-2015) to examine prescriptions for diabetes medications and supplies as a measure of postdonation diabetes mellitus. To compare outcomes in controls with baseline good health, we matched living pancreas donors to living kidney donors (1:3) by demographic traits and year of donation. RESULTS: Among 73 pancreas donors in the study period, 45 were identified in the pharmacy database: 62% women, 84% white, and 80% relatives of the recipient. Over a mean postdonation follow-up period of 16.3 years, 26.7% of pancreas donors filled prescriptions for diabetes treatments, compared with 5.9% of kidney donors (odds ratio, 4.13; 95% confidence interval, 1.91-8.93; P = 0.0003). Use of insulin (11.1% vs 0%) and oral agents (20.0% vs 5.9%; odds ratio, 4.50, 95% confidence interval, 2.09-9.68; P = 0.0001) was also higher in pancreas donors. CONCLUSIONS: Diabetes is more common after living pancreas donation than after living kidney donation, supporting clinical consequences from reduced endocrine reserve.

Hospital Admissions, Costs, and 30-Day Readmissions Among Newly Diagnosed Nonvalvular Atrial Fibrillation Patients Treated with Dabigatran Etexilate or Warfarin.

BACKGROUND: Oral anticoagulation such as warfarin and dabigatran is indicated for atrial fibrillation (AF) patients at risk of ischemic stroke. Dabigatran etexilate was developed to address the limitations of warfarin, including the need for regular blood monitoring, which has the potential to lead to higher health care resource use, particularly in hospitalized patients. OBJECTIVE: To evaluate whether hospitalization cost, length of hospital stay (LOS), likelihood of readmission within 30 days, and cost of readmissions differed across inpatient encounters among nonvalvular atrial fibrillation (NVAF) patients that were newly diagnosed and newly treated with either dabigatran or warfarin. METHODS: A retrospective cohort study was conducted using IMS Health's Charge Detail Master (CDM) database. Hospitalizations were identified based on a primary or secondary AF diagnosis, dabigatran or warfarin use, and a discharge date from January 2011 through March 2012. The identified patients without valvular procedures and transient AF were required to have a minimum of 12 months of pharmacy and private practitioner records prior to the inpatient encounter to ensure that they were newly treated on dabigatran or warfarin. Propensity score matching was used to balance baseline characteristics between treatment cohorts. Outcomes assessed were LOS, 30-day readmissions, and costs. Because individual patients could have more than 1 hospital observation, generalized estimating equations (GEE) with a gamma distribution (log link) were used for the analysis of continuous outcome measures (e.g., LOS and costs) and a binominal distribution for dichotomous outcomes (hospital readmissions). RESULTS: Two cohorts were propensity score matched (1:2) on demographic and clinical characteristics. The dabigatran cohort included 646 hospitalizations, and the warfarin cohort included 1,292 hospitalizations. Hospitalizations were on average 13% shorter (4.8 vs. 5.5 days, P less than 0.001) and cost 12% less ($14,794 vs. $16,826, P = 0.007) when dabigatran was used versus warfarin. No differences in 30-day readmissions were observed. CONCLUSIONS: Hospital encounters among newly diagnosed NVAF patients during which warfarin was initiated had longer lengths of stay and incurred higher costs than those during which dabigatran was initiated.

Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders.

Pharmacogenetic/pharmacogenomic (PGx) testing is currently available for a wide range of health problems including cardiovascular disease, cancer, diabetes, autoimmune disorders, mental health disorders and infectious diseases. PGx contributes important information to the field of precision medicine by clarifying appropriate treatments for specific disease subtypes. Tangible benefits to patients including improved outcomes and reduced total health care costs have been observed. However, PGx-guided therapy faces many barriers to full integration into clinical practice and acceptance by stakeholders, whether practitioner, patient or payer. Each stakeholder has a unique perspective on the role of PGx testing, although all are similarly challenged with demonstrating or appraising its cost-to-benefit value. Coverage by insurers is a critical step in achieving widespread adoption of PGx testing. The acceleration of adoption of precision medicine in general and for PGx testing in particular will be determined by how quickly robust evidence can be accumulated that shows a return on investment for payers in terms of real dollars, for clinicians in terms of patient clinical responses, and for patients in terms of economic, health and quality of life outcomes. Trends in PGx testing utilization and uptake by payers in real-world practice are discussed; the role of pharmacoeconomics in assessing cost-effectiveness is highlighted using a case study in psychiatric care, and several issues that will affect adoption of PGx testing in the United States (US) over the next few years are reviewed.

Pharmacogenetic-guided psychiatric intervention associated with increased adherence and cost savings.

OBJECTIVES: Pharmacogenetic testing as a means of guiding treatment decisions is beginning to see wider clinical use in psychiatry. The utility of this genetic information as it pertains to clinical decision making, treatment effectiveness, cost savings, and patient perception has not been fully characterized. STUDY DESIGN: In this retrospective study, we examined health claims data in order to assess medication adherence rates and healthcare costs for psychiatric patients. METHODS: Individuals for whom pharmacogenetic testing was ordered (cases) were contrasted with those who did not undergo such testing (controls). Cases and controls were propensity score matched in order to minimize risk of confounding in this nonrandomized study. An initial analysis of 111 cases and 222 controls examined both adherence and healthcare costs. A replication study of 116 cases and 232 controls examined adherence alone, as cost data was not available for this latter cohort. RESULTS: Overall, individuals with assay-guided treatment were significantly more medication adherent (P = 1.56 3 10­3; Cohen's d = 0.511) than patients with standard treatment and demonstrated a relative cost savings of 9.5% in outpatient costs over a 4-month follow-up period, or $562 in total savings. CONCLUSIONS: The data show the utility of pharmacogenetic testing in everyday psychiatric clinical practice, as it can lead to improved patient adherence and decreased healthcare costs.

Healthcare use and costs before and after parathyroidectomy in patients on dialysis.

BACKGROUND: Parathyroidectomy (PTX) is often performed in dialysis patients when medical treatment fails to control secondary hyperparathyroidism (SHPT). PTX is viewed by many as a cost-containing measure for patients who have been treated with vitamin D analogs and calcimimetics. Yet, information about health resource utilization and costs before and after PTX is limited. METHODS: This retrospective cohort study used professional service and pharmacy claims to identify subjects on dialysis undergoing PTX from 1/1/2008-12/31/2010. Only subjects with at least six months of information before and after PTX were considered. Subjects with primary hyperparathyroidism or kidney transplant were excluded. Prescription use, physician encounters, and surgical complications were compared during the six months immediately before and after PTX. RESULTS: The mean (SD) age of the 181 study subjects was 51 (15) years; 59% female; and 80% insured by Medicare. Overall, the percentage of patients receiving medications to manage altered mineral metabolism increased from 67% before to 79% after PTX. Specifically, oral vitamin D use increased, while the utilization of cinacalcet decreased resulting in mean (SD) monthly medication charges decreasing from $486 (507) to $226 (288) (p < 0.01). The mean (SD) number of physician encounters rose from 15 (14) before to 21 (22) per 6 months after PTX (p < 0.01) resulting in the corresponding increase in mean (SD) monthly charges from $1531 (2150) to $1965 (3317) (p = 0.08). Hypocalcemia was the predominant diagnosis recorded for post-surgical physician encounters occurring in 31% of all subjects; 84% of hypocalcemic episodes were managed in acute care facilities. CONCLUSIONS: The cost of medications to manage SHPT decreased after PTX largely due to reduction in cinacalcet use, whereas vitamin D use increased likely to manage hypocalcemia. The frequency and cost of physician encounters, especially in acute care settings, were higher in the 6 months after PTX attributable largely to episodes of severe hypocalcemia. Overall, the reduction in prescription costs during the 6 months after PTX is outweighed by the higher costs associated with physician care.

The disease burden of pertussis in adults 50 years old and older in the United States: a retrospective study.

BACKGROUND: While the incidence of pertussis has increased in adolescents and adults in recent years in the U.S., little is known about the incidence and economic burden of pertussis in older adults. This study provides evidence of the incidence of pertussis and direct medical charges associated with pertussis episodes of care (PEOCs) in adults aged 50 years and older in the U.S. METHODS: PEOCs were divided into periods before and after the initial pertussis diagnosis was made (i.e., the index date) to capture any conditions immediately preceding the pertussis diagnosis that may have represented misdiagnoses and subsequent conditions that may have represented sequelae. Data were extracted from IMS's recently acquired SDI databases of longitudinal, patient-level practitioner claims and hospital operational billing records collected from private practitioners and hospitals, respectively, across the U.S. Patients 50 years and older with one or more ICD-9-CM diagnoses for pertussis/whooping cough and/or a laboratory test positive for Bordetella pertussis between 1/1/2006 and 10/31/2010 were eligible for study inclusion. Resource utilization and charges (i.e., unadjudicated claims) associated with the patient's physician and hospital care were analyzed. The nationally projected incidence of pertussis was estimated using a subsample of patients with the required data necessary for projection. RESULTS: Estimated incidence of diagnosed pertussis ranged from 2.1-4.6 cases per 100,000 people across the two age groups (50-64 and [greater than or equal to] 65) during the years 2006 to 2010. The analysis of charges included 5,748 patients [greater than or equal to] 50 years of age with pertussis. Average charges across the entire episode of care were $1,835 and $14,428 per patient in the outpatient and inpatient settings, respectively. The average number of outpatient (i.e., private practitioner) visits was 2 per patient in both the pre-index and post-index periods. CONCLUSIONS: In the U.S., the incidence of diagnosed pertussis in adults 50 years and older has increased between 2006 and 2010. Healthcare utilization and charges associated with pertussis are substantial, suggesting the need for additional prevention and control strategies and a higher degree of clinical awareness on the part of health care providers. Additional research regarding pertussis in older populations is needed to substantiate these findings.

Cost of palliative radiation to the bone for patients with bone metastases secondary to breast or prostate cancer.

BACKGROUND: To estimate the costs (paid amounts) of palliative radiation episodes of care (REOCs) to the bone for patients with bone metastases secondary to breast or prostate cancer. METHODS: Claims-linked medical records from patients at 98 cancer treatment centers in 16 US states were analyzed. Inclusion criteria included a primary neoplasm of breast or prostate cancer with a secondary neoplasm of bone metastases; ≥2 visits to ≥1 radiation center during the study period (1 July 2008 through 31 December 2009) on or after the metastatic cancer diagnosis date; radiation therapy to ≥1 bone site; and ≥1 complete REOC as evidenced by a >30-day gap pre- and post-radiation therapy. RESULTS: The total number of REOCs was 220 for 207 breast cancer patients and 233 for 213 prostate cancer patients. In the main analysis (which excluded records with unpopulated costs) the median number of fractions per a REOC for treatment of metastases was 10. Mean total radiation costs (i.e., radiation direct cost + cost of radiation-related procedures and visits) per REOC were $7457 for patients with breast cancer and $7553 for patients with prostate cancer. Results were consistent in sensitivity analyses excluding patients with unpopulated costs. CONCLUSIONS: In the US, current use of radiation therapy for bone metastases is relatively costly and the use of multi-fraction schedules remains prevalent.

Clinical burden of illness in patients with neuroendocrine tumors.

OBJECTIVE: The objective of this study was to evaluate the incremental risk of morbidities affecting the cardiovascular, hepatic, gastrointestinal, skeletal, and neuropsychiatric systems in patients with neuroendocrine tumors (NETs) compared with a noncancer cohort. METHODS: In a retrospective, matched-control study using US claims databases, noncancer control subjects (n = 3524) were matched 2:1 with patients with newly diagnosed NET (n = 1762) on age, sex, region, hospital data availability, and index year. Rates of select morbidities were compared between patients with NET and control subjects. Incremental risks were analyzed using logistic regressions adjusting for baseline characteristics. RESULTS: In the first 3 years after diagnosis in patients with NET versus matched control subjects without cancer, (1) the adjusted risk of cardiovascular morbidities was higher (odds ratio [OR], 1.26; P = 0.0206); (2) the adjusted risk of hepatic or gastrointestinal morbidities was higher (OR, 1.95, P < 0.0001); (3) the adjusted risk of osteoporosis/osteopenia was higher among those 50 years or younger (OR, 3.24; P = 0.0081); and (4) the adjusted risk of anxiety/depression was higher among those 65 years or younger (OR, 1.48; P = 0.0210). CONCLUSIONS: Patients with NET have greater clinical burden of disease than matched control subjects with respect to conditions affecting the cardiovascular, hepatic, and gastrointestinal systems. Excess clinical burden of disease with respect to anxiety, depression, osteoporosis, and osteopenia was observed in patients with NET in the younger age groups.

Effect of reimbursement changes on erythropoiesis-stimulating agent utilization and transfusions.

Cancer patients frequently develop chemotherapy-induced anemia, which can be treated with erythropoiesis-stimulating agents. These agents have shifted the standard of chemotherapy-induced anemia treatment away from the previous mainstay of red blood cell transfusions. In July 2007, the Centers for Medicare and Medicaid Services issued a National Coverage Decision restricting reimbursement for erythropoiesis-stimulating agents to those chemotherapy patients who have hemoglobin levels <10 g/dL at initiation of therapy. This decision was hypothesized to place a greater reliance on transfusions for chemotherapy-induced anemia treatment. This observational study examined transfusions and erythropoiesis-stimulating agent utilization rates within defined episodes of chemotherapy care using electronic medical records from seven practices consisting of 39 sites of care across seven states. We compared the frequency of myelosuppressive chemotherapy treatment, erythropoiesis-stimulating agent administrations, and red blood cell transfusions before and after the National Coverage Decision in oncology patients with chemotherapy-induced anemia. Although exposure to myelosuppressive chemotherapy was not different, erythropoiesis-stimulating agent administrations significantly decreased and blood transfusions significantly increased after implementation of the National Coverage Decision. The 31% increase in transfusions for patients aged 65 years and older was significant (P = 0.007) and higher than the 8% increase for patients younger than 65 years (P = 0.358). Changes in practice patterns for chemotherapy-induced anemia treatment that followed the Centers for Medicare and Medicaid Services reimbursement decision for erythropoiesis-stimulating agents seem to be impacting practice patterns. Further research is necessary to determine whether these changes represent a widespread and durable shift in patient treatment.

Comparative antibiotic failure rates in the treatment of community-acquired pneumonia: Results from a claims analysis.

INTRODUCTION: Antibiotic treatment failure contributes to the economic and humanistic burdens of community-acquired pneumonia (CAP) by increasing morbidity, mortality, and healthcare costs. This study compared treatment failure rates of levofloxacin with those of other antibiotics in a large US sample. METHODS: Medical and pharmacy claims in the nationally representative SDI database were used to identify adults with a new outpatient diagnosis of CAP receiving a study antibiotic (levofloxacin, amoxicillin/clavulanate, azithromycin, moxifloxacin) between September 1, 2005 and March 31, 2008. Treatment failure was defined as ≥1 of the following events ≤30 days after index date: a refill for the index antibiotic after completed days of therapy, a different antibiotic dispensed >1 day after the index prescription, or hospitalization with a pneumonia diagnosis or emergency department visit >3 days postindex. Cohorts were propensity score matched for demographic and clinical characteristics. Treatment failure rates were compared between pairs of cohorts for the full sample and for high-risk patients (age ≥65 and/or on Medicaid). RESULTS: Among the 3994 study patients, the numbers of dispensed index prescriptions were 268 for amoxicillin/clavulanate, 1609 for azithromycin, 1460 for levofloxacin, and 657 for moxifloxacin. Unadjusted treatment failure rates for the sample were 20.8% for levofloxacin, 23.9% for amoxicillin/clavulanate, 23.9% for azithromycin, and 19.9% for moxifloxacin. For high-risk patients, unadjusted treatment failure rates were 19.1% for levofloxacin, 26.1% for amoxicillin/clavulanate, 26.3% for azithromycin, and 24.3% for moxifloxacin. Propensity score-matched treatment failure rates were significantly lower with levofloxacin than azithromycin (19.8% vs. 24.5%, odds ratio [OR] comparator vs. levofloxacin 1.38; 95% CI: 1.14, 1.67), a difference amplified in high-risk patients (19.0% vs. 26.4%, OR 1.61; 95% CI: 1.22, 2.13). No significant differences were observed for other paired comparisons. CONCLUSION: In a large US sample, treatment failure in CAP appeared to be less likely with quinolones (such as levofloxacin) than azithromycin, an effect particularly marked in high-risk patients (age ≥65 and/or on Medicaid).