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Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.

Objective: To assess incidence of urinary tract infection (UTI) among patients with recent spinal cord injury (SCI) who initiated intermittent catheterization (IC). Design: Retrospective chart revi...

Background: Pulmonary arterial hypertension (PAH) is a disease characterized by dyspnea, fatigue, chest pain and syncope. As there is no known cure for PAH, the goal of treatment is to control symptoms and slow disease progression. Sildenafil, a phosphodiesterase-5 inhibitor, has been indicated to improve exercise capacity in PAH in both the United States and the European Union since 2005; since 2009, it also has been indicated in the United States to delay clinical worsening. Patterns of sildenafil use in PAH patients have not been reported. Objectives: To describe patterns of treatment with sildenafil among commercially insured patients in the United States with PAH. Methods: Using a large U.S. healthcare claims database, we identified all patients with evidence of PAH (International Classification of Disease, 9th Revision, Clinical Modification [ICD-9-CM] diagnosis codes 416.0, 416.8) and receipt of sildenafil between January 1, 2005 and September 30, 2008. The date of each patient’s earliest pharmacy claim for sildenafil was designated as his or her “index date”; patients with

CAR-T therapies represent a novel advance in oncology, albeit at list prices that exceed $373,000 (and that does not capture their total cost to the healthcare system). Since initial product approval in 2017, stakeholders and observers have attempted to investigate clinical and financial impacts of CAR-T therapies, and potential approaches to optimizing access and use by eligible patients. Most existing research is from a single stakeholder perspective - patients, providers, or payers - limiting the ability to draw broader conclusions on trends and offer prospective recommendations. To address this knowledge gap, we sought to identify and describe critical success factors for optimal delivery of CAR-T therapies. We undertook a qualitative study based on interviews with multiple US-based stakeholders including clinicians, financial and operations staff, and payer-insurers. Interviewees--which included oncologists (n=6), facility financial and operational personnel (n=4), and coverage and reimbursement decision-makers from US health plans (n=3)--completed structured, live, hour-long, interviews covering clinical, administrative, and general topics on patient access to CAR-T therapies. All clinicians had experience with ≥1 FDA-approved CAR-T therapies in both registered clinical trials and clinical practice; financial and operational personnel were affiliated with the same facilities as the clinicians, and also had real-world experience with these therapies; payer representatives were directors from a large national commercial plan, regional integrated delivery network, and a Medicare administrative contractor, respectively. Consensus facility feedback (i.e., clinicians, operational personnel) was that CAR-T is effective, and that their administrative processes had been optimized through care team coordination and experience-based efficiencies; in contrast, 2 of 3 payer interviewees expressed that, while CAR-T therapies have shown efficacy, their real-world benefits and applicability are less well-defined. Facility interviewees noted that: (1) reimbursement from commercial insurers is higher than from Medicare, with the latter associated with per-patient net-neutral or negative margins; (2) when possible, differential reimbursement between inpatient and outpatient settings may drive patient management towards outpatient care; and (3) negative-margin cases are currently deemed acceptable due to nonclinical factors (i.e., competitive pressure within a geographic region, anticipated branding/marketing value) and relatively small treated populations. From payer interviewees, CAR-T cost and perceived cost-to-value have made health plans more receptive to considering outcomes-based contracting, capitated provider payments, or other mitigation methods. Left unoptimized, these factors may adversely impact patient access to, and long-term provider attractiveness of, CAR-T therapies. All interviewees agreed that as the CAR-T marketplace grows, a strong preference exists for manufacturers to develop and communicate for their therapies durable outcomes data, clear and comprehensive reimbursement information, and competitive pricing. With the potential for many approved products in a single indication, and/or a single approval for indications with relatively large eligible patient populations, interviewees also conveyed interest in compelling health economic data. Facility interviewees also acknowledged that if it remains an overall net-negative margin service, new providers will be less able to start CAR-T programs and smaller programs may encounter sustainability issues, collectively jeopardizing patient access to these life-changing therapies. Overall, findings from this study suggest that during the continued maturation of the landscape, stakeholders will need to be proactive to ensure that CAR T-cell therapies can be maintained amidst financial and operational pressures. Several CAR-T therapy options for multiple myeloma are on the immediate horizon, likely increasing demand among eligible patients. Accordingly, the need to link real-world evidence of the clinical value and institutional investment burden of these therapies to reimbursement is imperative, both to insulate payers and enable clinicians to provide innovative therapies. Figure 1 Figure 1. Disclosures Faber: Amgen: Honoraria; Adaptive: Honoraria; Cardinal Health: Honoraria; Celgene: Honoraria; Astra Zeneca: Honoraria; GlaxoSmith Kline: Honoraria; Janssen: Honoraria; Juno: Honoraria; Karyopharm: Honoraria; Kite: Honoraria; Takeda: Honoraria; Sanofi Genzyme: Honoraria. Hunter: BMS: Consultancy, Honoraria; Kite: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria. Deol: Kite, a Gilead Company: Consultancy. Crivera: Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Riccobono: Legend Biotech: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Garrett: Legend Biotech USA: Current Employment. Jackson: Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Fowler: Amgen: Ended employment in the past 24 months; Janssen: Current Employment. Berger: Janssen Scientific Affairs: Consultancy, Research Funding. Lorden: Janssen Scientific Affairs: Consultancy, Research Funding. Stewart: Janssen Scientific Affairs: Consultancy, Research Funding.

Background The relative contribution of antimicrobial resistance versus delayed appropriate treatment to the clinical and economic burden of Enterobacteriaceae infections is not well understood. Methods Using a large US hospital database, we identified all admissions between July 2011 and September 2014 with evidence of serious Enterobacteriaceae infection. The “index date” was the earliest date on which a culture positive for Enterobacteriaceae was drawn. Infections were classified as carbapenem-resistant (CRE) or carbapenem-susceptible (CSE). Receipt of antimicrobials with activity against all index pathogens on the index date or ≤2 days thereafter was deemed as “timely”; all other instances were “delayed.” Associations between CRE status and delayed appropriate therapy on outcomes were estimated using inverse probability weighting and multivariate regression models (ie, logistic model for discharge destination and composite mortality [in-hospital death or discharge to hospice] or generalized linear model for duration of antibiotic therapy, hospital length of stay [LOS], and costs). Results A total of 50 069 patients met selection criteria; 514 patients (1.0%) had CRE. Overall, 67.5% of CSE patients (vs 44.6%, CRE) received timely appropriate therapy (P < .01). Irrespective of CRE status, patients who received delayed appropriate therapy had longer durations of antibiotic therapy and LOS, higher costs, lower likelihood of discharge to home, and greater likelihood of the composite mortality outcome (P for trend < .01). Conclusions Delayed appropriate therapy is a more important driver of outcomes than CRE, although the 2 factors are somewhat synergistic. Better methods of early CRE identification may improve outcomes in this patient population., Although resistance and delayed appropriate therapy both are associated with worse clinical and economic outcomes, delayed therapy appears to be the more important factor. As these 2 measures are correlated, earlier identification of CRE may improve outcomes.

Background To examine the clinical and economic burdens associated with delayed receipt of appropriate therapy among patients with Gram-negative bacteria (GNB) infections, stratified by antibiotic resistance status. Materials and Methods Retrospective analysis using the Premier Hospital Database. Adult admissions (July 2011-September 2014) with evidence of complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, length of stay (LOS) ≥1 days and a positive GNB culture from a site consistent with infection type (culture draw date = index date) were identified and stratified by antibiotic susceptibility to index pathogens. Delayed appropriate therapy was defined as no receipt of antibiotic(s) with relevant microbiological activity on or within 2 days of index date. Inverse probability weighting and multivariate regression analyses were used to estimate the association between delayed appropriate therapy and outcomes. Generalized linear models were used to evaluate postindex duration of antibiotic therapy, LOS and total in-hospital costs. Logistic models were used to evaluate discharge destination and in-hospital mortality/discharge to hospice. Results A total of 56,357 patients with GNB infections were identified (resistant, n = 6,055; susceptible, n = 50,302). Delayed appropriate therapy was received by 2,800 (46.2%) patients with resistant and 16,585 (33.0%) patients with susceptible infections. Using multivariate analysis, delayed appropriate therapy was associated with worse outcomes including ∼70% increase in LOS, ∼65% increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality/discharge to hospice, regardless of susceptibility status. Conclusions Our results suggest that outcomes in patients with GNB infections, regardless of resistance status, significantly improve if timely appropriate therapy can be provided.

PURPOSE: To assess the cost-effectiveness of a ceramide-infused skin barrier (CIB) versus other skin barriers (standard of care) among patients who have undergone ostomy creation.DESIGN: Cost-effectiveness analysis, based on a decision-analytic model that was estimated using data from the ADVOCATE (A Study Determining Variances in Ostomy Skin Conditions And The Economic Impact) trial, which investigated stoma-related healthcare costs over 12 weeks among patients who recently underwent fecal ostomy, and from other sources.SUBJECTS AND SETTING: Analysis was based on a hypothetical cohort of 1000 patients who recently underwent fecal ostomy; over a 1-year period, 500 patients were assumed to use CIB and 500 were assumed to use standard of care.METHODS: We adapted a previous economic model to estimate expected 1-year costs and outcomes among persons with a new ostomy assumed to use CIB versus standard of care. Outcomes of interest included peristomal skin complications (PSCs) (up to 2 during the 1-year period of interest) and quality-adjusted life days (QALDs); QALDs vary from 1, indicating a day of perfect health to 0, indicating a day with the lowest possible health (deceased). Subjects were assigned QALDs on a daily basis, with the value of the QALD on any given day based on whether the patient was experiencing a PSC. Costs included those related to skin barriers, ostomy accessories, and care of PSCs. The incremental cost-effectiveness of CIB versus standard of care was estimated as the incremental cost per PSC averted and QALD gained, respectively; net monetary benefit of CIB was also estimated. All analyses were run using the perspective of an Australian payer.RESULTS: On a per-patient basis, use of CIB was expected over a 1-year period to result in 0.16 fewer PSCs, an additional 0.35 QALDs, and a savings of A$180 (Australian dollars, US $137) in healthcare costs all versus standard of care. Management with CIB provided a net monetary benefit (calculated as the product of maximum willingness to pay for 1 QALD times additional QALDs with CIB less the incremental cost of CIB) of A$228 (US $174). Probabilistic sensitivity analysis was also completed; it revealed that 97% of model runs resulted in fewer expected PSCs with CIB; 92% of these runs resulted in lower expected costs with CIB.CONCLUSIONS: Findings suggest that the CIB is a cost-effective skin barrier for persons living with an ostomy.

Prostacyclins play an important role in the management of pulmonary arterial hypertension (PAH). Intravenous prostacyclin was the first disease-specific treatment for patients with PAH. Subcutaneous and nonparenteral (oral or inhaled) formulations have subsequently become available. However, data are lacking on how these different prostacyclin formulations are being used in clinical practice.To (a) conduct retrospective analyses of a large U.S. health care claims database to describe the characteristics of patients with PAH initiating prostacyclin therapy, and (b) evaluate their treatment patterns, health care resource use, and associated costs.Truven Commercial and Medicare databases were used to define annual cohorts of adults with PAH between January 1, 2010, and October 31, 2015. These patients were identified based on claims with ICD-9-CM diagnoses indicative of PAH (codes 416.0 or 416.8) and claims for PAH-specific medications and PAH-related procedures. Patients with evidence of receiving a prostacyclin were identified, and prostacyclin use was categorized as parenteral versus nonparenteral. Health care costs were assessed alternatively employing an all-cause and PAH-related perspective.Of 13,633 adults with identified PAH, 3,006 (22.0%) received a prostacyclin during at least 1 year of the study period, and annual prevalence of prostacyclin use ranged from 19.9% to 22.6%. Across calendar years, the median age of prostacyclin users ranged from 56 to 58 years, and 71.9%-75.8% were female. Among prostacyclin users, parenteral prostacyclin use declined from 63.2% in 2010 to 46.5% in 2015, while use of nonparenteral prostacyclins increased from 39.7% to 56.2% over the same period (both P0.001). Few patients (2.7%-4.1%) received both parenteral and nonparenteral formulations in a given calendar year. Among patients using prostacyclins, receipt of other PAH-specific medications increased from 62.1% in 2010 to 79.2% in 2015. Comparing the 6 months preceding the first prostacyclin prescription (any formulation) to the 6 months subsequent, mean overall health care costs rose from $61,243 to $119,283, and PAH-related health care costs increased from $58,815 to $116,661, driven mainly by PAH-specific medications, spending on which increased from $15,053 to $73,705 (all P0.001).While overall use of prostacyclins was relatively constant from 2010 to 2015, our findings revealed a shift from parenteral to nonparenteral formulations, coupled with increased prescribing of PAH-related medications from other drug classes. Further research is needed to better understand how these changes in patterns of prostacyclin use affect levels of health care resource utilization and costs and patients' overall quality of life.This research was funded by Actelion Pharmaceuticals US, a Janssen pharmaceutical company of JohnsonJohnson. Burger has received grant funding from Actelion, Gilead Sciences, and United Therapeutics; personal fees from Actelion and Gilead Sciences; and nonfinancial support from Actelion. Pruett, Lickert, and Drake are employees of Actelion. Pruett and Lickert own shares in Actelion. Berger and Murphy are employees of Evidera, a consultancy that received payment from Actelion to conduct this research. Pruett, Lickert, Berger, and Drake contributed to study conception and participated with Burger in study design. Lickert and Murphy performed the data analyses. Burger, Pruett, Lickert, Murphy, and Drake interpreted the data. All authors participated in manuscript drafting and/or critical revision, approved the final manuscript, and agree to be accountable for all aspects of the work.

Objectives: We estimated the total US hospital costs associated with acute bacterial skin and skin structure infection (ABSSSI) admissions as well as the admissions that may have been potential candidates for outpatient parenteral antimicrobial therapy (OPAT). Methods: We assessed inpatient admissions for ABSSSI from the Premier database (2011–2014), focusing on all admissions of adults with length of stay (LOS) ≥ 1 days and a primary diagnosis of erysipelas, cellulitis/abscess, or wound infection. We performed a detailed analysis of 2014 admissions for patient, treatment, hospital, and economic characteristic variables. Using published selection criteria, we identified a subset of patients admitted in 2014 who may have been potential candidates for OPAT. Results: We analyzed 277,971 admissions. In 2014, most admissions were for cellulitis without major complications or comorbidities; mean ± SD LOS was 4.0 ± 3.0 days, and total hospital cost per admission was $6400 ± $6874, 54% of which was attributable to room costs. Among 2014 admissions, 14% involved patients with clinical characteristics suggesting that they were consistent with guideline recommendations for exclusive treatment with OPAT. Compared with all admissions in the year, these admissions were of younger patients (aged 50 vs. 55 years), admitted more frequently for cellulitis (90% vs. 70%), with shorter LOS (2.8 ± 1.8 days), and lower mean total hospital cost per admission ($4080 ± $3066). Conclusions: Admissions for ABSSSI impose a substantial cost to US hospitals, with half of costs attributable to room costs. When extrapolated to all US patients admitted to the hospital for ABSSSI during 2014, had OPAT guidelines been universally followed, admissions may have been reduced by 14%, thereby saving US hospitals $161 million.

Based in part on the pivotal COMPASS trial, “vascular dose” rivaroxaban (2.5 mg twice/day) (+ aspirin [ASA]) was recently approved to reduce risk of cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral arterial disease (PAD). As patients in clinical

Background Patients with serious GNB infections who receive DAT have worse outcomes. Most studies that have examined this issue include both antibiotic-resistant and susceptible pathogens. It is difficult to assign causality as DAT is correlated with resistance, which is associated with poorer prognosis. Our objective was to assess association between DAT and outcomes among patients with GNB infection, stratified by antibiotic susceptibility status. Methods Hospitalized adults between 7/2011–9/2014 were identified from Premier Hospital Database. Patients were diagnosed with complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, and had a positive culture for GNB from a site consistent with infection type (date of culture draw was index date). Patients were required to receive antibiotics on this date or ≤2 days after. Delayed therapy was defined as no receipt of an antibiotic with microbiologic activity during this period. Patients were stratified by antibiotic-resistant GNB (Third-generation cephalosporin-resistant Enterobacteriaceae, carbapenem‐resistant (CR) Enterobacteriaceae, CR Pseudomonas sp., or multi‐drug-resistant Pseudomonas sp.) vs. antibiotic-susceptible GNB counterparts. Inverse probability weighting and multivariate regression analyses were used to estimate the association between DAT and outcomes. Logistic models were used for composite mortality (in-hospital death or discharge to hospice) and discharge to home. Generalized linear models were used for post-index duration of antibiotic therapy, hospital length of stay (LOS), and costs. Results A total of 6,055 resistant and 50,302 susceptible infections were identified; 2,800 and 16,585, respectively, received DAT. In multivariate analyses, DAT was associated with worse outcomes, including a 20% increased risk of composite mortality and an approximate 70% increase in LOS and total costs, respectively. The relative impact of DAT was nearly identical by antibiotic-resistant status (Figure). Conclusion Our study indicates that DAT is independently associated with poorer outcomes in serious infections due to GNB, irrespective of resistance status. Disclosures N. G. Bonine, Allergan plc: Employee, Salary. A. Berger, Allergan plc: Consultant, Consulting fee. R. Wang, Evidera: Employee, Salary. T. Bhagnani, Allergan plc: Consultant, Consulting fee. P. Gillard, Allergan plc: Employee, Salary. T. Lodise, Allergan plc: Consultant and Scientific Advisor, Consulting fee and Speaker honorarium.

Objective To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). Methods Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with

Coronary artery disease (CAD) and peripheral artery disease (PAD) increase risk of cardiovascular (CV) and limb events. We ascertained “real-world” rates and economic impact of these events. We identified adults in a US database containing claims and medical records between 1/1/2009 - 9/30/2015

Summary Purpose: To examine the characteristics and healthcare costs of fibromyalgia syndrome (FMS) patients in clinical practice.

We developed a decision-analytic model to examine the economic impact of shifting the locus of care for patients with painful neuropathies from specialists to GPs. The impetus for such a shift was assumed to be a formal education program, focusing on the recognition and treatment of neuropathic pain, conducted for GPs. In the model, all patients with neuropathic pain were assumed to initiate care with their GPs and then be referred to specialists and, ultimately, pain clinics as required for adequate pain control. Two alternative scenarios were examined--the "current" arrangement in which most patients were assumed to be referred for treatment by specialists and pain clinics and a "hypothetical" arrangement in which GPs were assumed to play an expanded role in the treatment of neuropathic pain and which, therefore, often precluded the need for referral. The model was populated with clinical, epidemiologic, and economic data from Norway. A total of 34,951 persons in Norway were estimated to seek care for painful neuropathies each year. The formal education program was assumed to cost 1.5 million Kroner (NOK). Shifting the locus of care from specialists to GPs would result in 4,715 additional GP visits, but 12,123 fewer specialist visits and 7,967 fewer visits to pain clinics. This change would result in estimated savings to the Norwegian health-care system in 2004 of 74.1 million NOK (approx. US $11.9 million). A partial shift in the locus of care of painful neuropathies from specialists to GPs may result in substantial cost savings to the Norwegian health-care system.

Using a large US health insurance claims database, we identified all persons aged 18 years or older with 2 or more medical encounters in calendar year 2000 for painful neuropathic disorders (PNDs). We also identified an age- and gender-matched group of patients without PNDs (matched control subjects). We then compared the clinical characteristics and economic costs of PND patients with those of matched control subjects. There were a total of 55,686 patients with PNDs in the study database. The most frequently noted PNDs were back and neck pain with neuropathic involvement (62.3% of PND patients), causalgia (12.1%), and diabetic neuropathy (10.8%). In comparison with matched control subjects, PND patients were more likely to have other pain-related conditions, including fibromyalgia (6.0% vs 0.6% for control subjects), osteoarthritis (13.6% vs 3.6%), and other chronic comorbidities, such as coronary heart disease (13.6% vs 6.5%) and depression (6.4% vs 2.3%). Total calendar year 2000 health care charges were 3-fold higher for PND patients than matched control subjects ($17,355 vs $5,715, respectively). Our results suggest that patients with PNDs are generally in poorer health and have higher health care costs than their peers without these conditions. Perspective Use of nonsteroidal anti-inflammatory agents and opioids was widespread in patients with PNDs, while relatively few received antiepileptic drugs and tricyclic antidepressants, both of which are often more effective against neuropathic pain. Our study raises questions about the optimality of PND treatment in clinical practice.

Background While CRE and DAT are both associated with worse outcomes, their relative impact to the clinical and economic burden among patients with infections due to Enterobacteriaceae is not well understood. This study assessed the independent and combined effect of these two items on selected outcomes among patients with these infections. Methods Hospitalized adults between July 2011 and September 2014 were identified from Premier Hospital Database. Patients were diagnosed with complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, and had a positive culture for Enterobacteriaceae from a site consistent with infection type (date of culture draw was index date). Patients were required to receive antibiotics on this date or ≤2 days after. Delayed therapy was defined as no receipt of an antibiotic with microbiologic activity during this period. CRE was defined as resistant to ≥1 carbapenems. Inverse probability weighting and multivariate regression analyses were used to estimate the associations between CRE status, DAT and outcomes. Logistic models were used for composite mortality (in-hospital death or discharge to hospice), in-hospital mortality, and discharge to home (reference group was timely therapy plus non-CRE); generalized linear models, for post-index duration of antibiotic therapy, hospital length of stay (LOS), and costs. Results A total of 50,069 patients were included in the analyses; 514 had CRE and 16,414 received DAT. A gradient effect was observed across strata as the burden of serious infections was least among the reference group, and greatest among patients with CRE infection who received DAT (Figure). For example, as compared with the reference group, the risk of composite mortality increased nearly fourfold in patients with CRE infection who received DAT; total in-hospital costs more than doubled. Conclusion DAT has a stronger association than CRE on outcomes, and their effects are synergistic. Given these findings, better methods of early pathogen identification (especially organisms such as CRE) should reduce time to appropriate therapy, thereby improving outcomes in this patient population. Disclosures T. Lodise, Allergan plc: Consultant, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; A. Berger, Allergan plc: Consultant, Consulting fee; A. Altincatal, Evidera: Consultant, Salary; R. Wang, Evidera: Employee, Salary; T. Bhagnani, Allergan plc: Consultant, Consulting fee; P. Gillard, Allergan plc: Employee, Salary; N. G. Bonine, Allergan plc: Employee, Salary

Background: Allogeneic HCT is a potentially curative procedure for many hematologic malignancies, but is associated with several complications. Acute GvHD is a condition that affects 35-50% of allogeneic HCT recipients, typically occurs within 100 days after transplant, and can be life-threatening. Existing treatments are poorly tolerated and frequently ineffective. While the clinical consequences of acute GvHD are understood, the economic burden of the condition has not been well characterized. Methods: Using a large US healthcare claims database (Truven MarketScan® Commercial Claims and Encounters Database), patients aged ≥2 years old were identified who underwent allogeneic HCT between October 2009 and March 2013. Patients without continuous health plan enrollment or evidence of hematologic malignancy in the 6-month period prior to the "Index Admission" (hospital admission during which HCT was performed) were excluded. Patients were followed from the first day of the Index Admission until death, plan disenrollment, or one year; whichever occurred first ("Follow-Up"). Patients were classified into two cohorts: "Acute GvHD" based on ICD-9 CM diagnosis codes within first 100 days of Follow Up, or "No Acute GvHD". Total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) at discharge from Index Admission, the 100th day of Follow-Up, and the 365th day of Follow-Up were determined. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. Total healthcare costs and LOS between the two cohorts were compared for each of the three evaluation periods using Student's t-tests (unadjusted analyses), and analyses of covariance (ANCOVA; adjusting for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, Charlson Comorbidity Index score, and pre-admission healthcare cost). Results: 1,635 patients underwent HCT and met all selection criteria (mean age was 48 years, 56% were men, acute myeloid leukemia was the most common malignancy); 42% met the criteria for inclusion in the Acute GvHD cohort. Univariate mean total healthcare costs for the Acute GvHD cohort (vs No Acute GvHD) were $36,651 greater during Index Admission, $83,322 greater at the 100th day of Follow-Up, and $123,220 greater at the end of the 1-year Follow-Up (all p Conclusions: Over the one-year period following allogeneic HCT, patients who develop Acute GvHD experience over $100,000 more in total healthcare costs-and nearly three additional weeks in hospital-relative to those who do not. While healthcare claims appear to represent a good source with which to assess the impact of complications of HCT, confirmation with prospective clinical studies is recommended. Given that nearly one-half of patients develop Acute GvHD, our findings suggest that therapeutic strategies that prevent this complication may confer substantial savings to the healthcare system. Disclosures Grubb: Fate Therapeutics: Employment, Equity Ownership. Huse:Evidera: Employment; Fate Therapeutics: Consultancy. Alam:Evidera: Employment; Fate Therapeutics: Consultancy. Dychter:Fate Therapeutics: Employment, Equity Ownership. Wingard:Merck: Consultancy; Ansun: Consultancy; Fate Therapeutics: Consultancy; Gilead: Consultancy; Astellas: Consultancy. Berger:Evidera: Employment; Fate Therapeutics: Consultancy.

Background Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and benzodiazepine anxiolytics are used in the US to treat generalized anxiety disorder (GAD). While benzodiazepines typically provide rapid symptomatic relief, long-term use is not recommended due to risks of dependency, sedation, falls, and accidents. Methods Using a US health insurance database, we identified all persons with GAD (ICD-9-CM diagnosis code 300.02) who began a long-term course of treatment (≥90 days) with a benzodiazepine anxiolytic between 1/1/2003 and 12/31/2007, We compared healthcare utilization and costs over the six-month periods preceding and following the date of treatment initiation (“pretreatment” and “post-treatment”, respectively), and focused attention on accident-related encounters (e.g., for treatment of fractures) and care received for other reasons possibly related benzodiazepine use (e.g., sedation, dizziness). Results A total of 866 patients met all study entry criteria; 25% of patients began treatment on an add-on basis (i.e., adjunctive to escitalopram, paroxetine, sertraline, or venlafaxine), while 75% of patients did not receive concomitant therapy. Mean total healthcare costs increased by $2334 between the pretreatment and post-treatment periods (from $4637 [SD=$9840] to $6971 [$17,002]; p Conclusions Healthcare costs increase in patients with GAD beginning long-term (≥90 days) treatment with a benzodiazepine anxiolytic; a substantial proportion of this increase is attributable to care associated with accidents and other known sequelae of long-term benzodiazepine use.

Background Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders (PNDs) who are under the care of general practitioners (GPs) in the UK are not well understood. Methods Using a large electronic UK database, we identified all adults (age ≥ 18 years) with any GP encounters between 1 January 2006 - 31 December 2006 at which a diagnosis of PND was noted ("PND patients"). An age-and gender-matched comparison group also was constituted consisting of randomly selected patients with one or more GP encounters-but no mention of PNDs-during this period. Characteristics and patterns of healthcare utilization of patients in the two groups were then examined over the one-year study period. Results The study sample consisted of 31,688 patients with mention of PNDs and an equal number of matched comparators; mean age was 56 years, and 62% were women. The prevalence of various comorbidities was higher among patients in the PND group, including digestive disorders (31% vs. 17% for comparison group), circulatory disorders (29% vs. 22%), and depression (4% vs. 3%) (all p < 0.01). Receipt of prescriptions for pain-related pharmacotherapy also was higher among PND patients, including nonsteroidal anti-inflammatory drugs (56% of PND patients had one or more such prescriptions vs. only 22% in the comparison group), opioids (49% vs. 12%), tricyclic antidepressants (20% vs. 1%), and antiepileptics (12% vs. 1%) (all p < 0.01). PND patients also averaged significantly more GP visits (22.8 vs. 14.2) and referrals to specialists (2.8 vs. 1.4) over one year (both comparisons p < 0.01). Conclusions Patients with PNDs under the care of GPs in the UK have relatively high levels of use of healthcare services and pain-related pharmacotherapy.

Invasive meningococcal disease (IMD) is under-reported in countries that do not employ polymerase-chain reaction for surveillance because culture-negative cases are omitted. To evaluate a clinically based, case-finding method, we developed case definitions for "probable," "compatible with," and "possible, but unlikely" IMD, respectively, based on supportive documentation (e.g., discharge diagnosis of meningococcal infection, culture-negative bacterial meningitis, petechiae/purpura, Gram-negative diplococci on Gram stain) and weight of clinical evidence, which we then applied to electronic health records for all children aged ≤5 y who were admitted to approximately 100 US hospitals between January 2000 and June 2009. Among 47,863 qualifying admissions, 16 children had culture-positive IMD, 5 had "probable" IMD, and 5 had illness "compatible with" IMD. Five additional children had disease considered "possible but unlikely" IMD. Our case-finding methods suggest that culture-based ascertainment may underestimate the number of IMD cases by 31-63%, supporting findings in other nations that culture-based reporting provides incomplete information on disease incidence and therefore underestimates the potential benefits of routine vaccination of young children against meningococcal disease.

Background The purpose of this study was to compare pre- and post-surgical healthcare costs in commercially insured total joint arthroplasty (TJA) patients with osteoarthritis (OA) in the United States (U.S.). Methods Using a large healthcare claims database, we identified patients over age 39 with hip or knee OA who underwent unilateral primary TJA (hip or knee) between 1/1/2006 and 9/30/2007. Utilization of healthcare services and costs were aggregated into three periods: 12 months "pre-surgery," 91 days "peri-operative," and 3 to 15 month "follow-up," Mean total pre-surgery costs were compared with follow-up costs using Wilcoxon signed-rank test. Results 14,912 patients met inclusion criteria for the study. The mean total number of outpatient visits declined from pre-surgery to follow-up (18.0 visits vs 17.1), while the percentage of patients hospitalized increased (from 7.5% to 9.8%) (both p < 0.01). Mean total costs during the follow-up period were 18% higher than during pre-surgery ($11,043 vs. $9,632, p < 0.01), largely due to an increase in the costs of inpatient care associated with hospital readmissions ($3,300 vs. $1,817, p < 0.01). Pharmacotherapy costs were similar for both periods ($2013 [follow-up] vs. $1922 [pre-surgery], p = 0.33); outpatient care costs were slightly lower in the follow-up period ($4338 vs. $4571, p < 0.01). Mean total costs for the peri-operative period were $36,553. Conclusions Mean total utilization of outpatient healthcare services declined slightly in the first year following TJA (exclusive of the peri-operative period), while mean total healthcare costs increased during the same time period, largely due to increased costs associated with hospital readmissions. Further study is necessary to determine whether healthcare costs decrease in subsequent years.

To compare healthcare utilization and costs in the year preceding and following initial diagnosis of fibromyalgia (FM).Using a large US health insurance claims database, we identified all persons with newly diagnosed FM (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 729.1) between January 1, 2003, and December 31, 2005 ("FM patients"). Each patient's first-noted claim with a diagnosis of FM was designated the "index date," and all pharmacy, outpatient, and inpatient claims were compiled over the 12-month periods preceding and following this date ("prediagnosis" and "postdiagnosis," respectively). Patients with incomplete pre- or postdiagnosis data were excluded. Healthcare utilization and costs were compared between the 2 periods.A total of 1803 patients met all study inclusion criteria; mean (SD) age was 50.4 (9.4) years; 91% were women. Comorbidities were common, including arthritis (21% of study subjects), back pain (20%), and painful neuropathic disorders (16%). The percentage of study subjects receiving various pain-related medications increased from pre- to postdiagnosis, including opioids (51.3% vs 55.9%), antiepileptics (22.6% vs 28.6%), and tricyclic antidepressants (15.5% vs 21.2%) (all P.01). Mean total healthcare costs also increased by $1725 between these periods (mean [95% confidence interval]: $9324 [$8655, $10,092] vs $11,049 [$10,245, $11,973], respectively; P.01).Patients with FM are often seen for other medical problems prior to initial diagnosis. Levels of healthcare utilization and costs are high during both the pre- and postdiagnosis periods.

To compare healthcare utilization and costs in patients with end-stage renal disease (ESRD) beginning peritoneal dialysis (PD) or hemodialysis (HD).Retrospective cohort study.Using a US health insurance database, we identified all patients with ESRD who began dialysis between January 1, 2004, and December 31, 2006. Patients were designated as PD patients or as HD patients based on first-noted treatment. Patients with less than 6 months of pretreatment data and those with less than 12 months of data following initiation of dialysis ("pretreatment" and "follow-up," respectively) were dropped from the study sample. The PD patients were matched to HD patients using propensity scoring to control for differences in pretreatment characteristics. Healthcare utilization and costs were then compared over 12 months between propensity-matched PD patients and HD patients using paired t tests and Wilcoxon signed rank tests for continuous variables and using Bowker and McNemar tests for categorical variables, as appropriate.A total of 463 patients met all study entrance criteria; 56 (12%) began treatment with PD, and 407 (88%) began treatment with HD. Fifty PD patients could be propensity matched to an equal number of HD patients. The HD patients were more than twice as likely as matched PD patients to be hospitalized over the subsequent 12 months (hazard ratio, 2.17; 95% confidence interval, 1.34-3.51; P.01). Their median healthcare costs over the 12-month follow-up period were $43,510 higher ($173,507 vs $129,997 for PD patients, P = .03).Among patients with ESRD, PD patients are less likely than HD patients to be hospitalized in the year following initiation of dialysis. They also have significantly lower total healthcare costs.

Background Several medications commonly used to treat generalized anxiety disorder (GAD) have been designated "potentially inappropriate" for use in patients aged ≥65 years because their risks may outweigh their potential benefits. The actual extent of use of these agents in clinical practice is unknown, however. Methods Using a database with information from encounters with general practitioners (GP) in Germany, we identified all patients, aged ≥65 years, with any GP office visits or dispensed prescriptions with a diagnosis of GAD (ICD-10 diagnosis code F41.1) between 10/1/2003 and 9/30/2004 ("GAD patients"). Among GAD-related medications (including benzodiazepines, tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors, venlafaxine, hydroxyzine, buspirone, pregabalin, and trifluoperazine), long-acting benzodiazepines, selected short-acting benzodiazepines at relatively high dosages, selected TCAs, and hydroxyzine were designated "potentially inappropriate" for use in patients aged ≥ 65 years, based on published criteria. Results A total of 975 elderly patients with GAD were identified. Mean age was 75 years, and 72% were women; 29% had diagnoses of comorbid depression. Forty percent of study subjects received potentially inappropriate agents – most commonly, bromazepam (10% of all subjects), diazepam (9%), doxepin (7%), amitriptyline (5%), and lorazepam (5%). Twenty-three percent of study subjects received long-acting benzodiazepines, 10% received short-acting benzodiazepines at relatively high doses, and 12% received TCAs designated as potentially inappropriate. Conclusion GPs in Germany often prescribe medications that have been designated as potentially inappropriate to their elderly patients with GAD – especially those with comorbid depressive disorders. Further research is needed to ascertain whether there are specific subgoups of elderly patients with GAD for whom the benefits of these medications outweigh their risks.

Background and Objectives: To describe patterns of healthcare utilization among patients with generalized anxiety disorder (GAD) in general practitioner (GP) settings in Germany. Methods: Using a large computerized database with information from GP practices across Germany, we identified all patients, aged > 18 years, with diagnoses of, or prescriptions for, GAD (ICD-10 diagnosis code F41.1) between October 1, 2003 and September 30, 2004 ("GAD patients"). We also constituted an age- and sex-matched comparison group, consisting of randomly selected patients without any GP encounters or prescriptions for anxiety or depression (a common comorbidity in GAD) during the same period. GAD patients were then compared to those in the matched comparison group over the one-year study period. Results: The study sample consisted of 3340 GAD patients and an equal number of matched comparators. Mean age was 53.2 years; 66.3% were women. Over the 12-month study period, GAD patients were more likely than matched comparators to have encounters for various comorbidities, including sleep disorders (odds ratio [OR] = 6.75 [95% CI = 5.31, 8.57]), substance abuse disorders (3.91 [2.89, 5.28]), and digestive system disorders (2.62 [2.36, 2.91]) (all p < 0.01). GAD patients averaged 5.6 more GP encounters (10.5 [SD = 8.8] vs 4.9 [5.7] for comparison group) and 1.4 more specialist referrals (2.3 [2.9] vs 0.9 [1.7]) (both p < 0.01). Only 58.3% of GAD patients received some type of psychotropic medication (i.e., benzodiazepines, antidepressants, and/or sedatives/hypnotics). Conclusions: Patients with GAD in GP practices in Germany have more clinically recognized comorbidities and higher levels of healthcare utilization than patients without anxiety or depression.

Objective.To estimate the consequences of failure of initial antibiotic therapy for patients with complicated skin and skin-structure infections.Design.Retrospective cohort study.Setting.Large US multihospital database.Patients.We identified a total of 47,219 patients (age 18 years or older) who were admitted to the hospital for complicated skin and skin-structure infections from April 1, 2003, through March 31, 2004, and who received intravenous antibiotics during the first 2 hospital-days (ie, initial antibiotic therapy). Failure of therapy was defined as drainage, debridement, or receipt of other intravenous antibiotics at any subsequent time (except for changes to narrower-spectrum agents or any therapy change immediately before discharge). Predictors of failure of antibiotic therapy and mortality were examined using multivariate logistic regression. Analysis of covariance was used to estimate the impact of treatment failure on duration of intravenous antibiotic therapy, length of stay, and total inpatient charges.Results.For 10,782 admitted patients (22.8%), there was evidence of failure of initial antibiotic therapy. In multivariate analyses, treatment failure was associated with receipt of vasoactive medications during the first 2 hospital-days (odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.19-2.31]), initiation of antibiotic therapy in the intensive care unit (OR, 1.53 [95% CI, 1.28-1.84]), and the patient's Charlson comorbidity index (OR per 1-point increase, 1.06 [95% CI, 1.04-1.08]); treatment failure was also was associated with a 3-fold increase in mortality (OR, 2.91 [95% CI, 2.34-3.62]). Compared with patients for whom initial treatment was successful, patients who experienced treatment failure received intravenous antibiotic therapy for a mean of 5.7 additional days, were hospitalized for a mean of 5.4 additional days, and incurred a mean of $5,285 (in 2003 dollars) in additional inpatient charges (all P Conclusion.Failure of initial antibiotic therapy in the treatment of complicated skin and skin-structure infections is associated with significantly worse clinical and economic outcomes.

Background: Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option for many hematologic malignancies, but is associated with numerous complications, including infection. While the clinical consequences of infection post-HCT have been well characterized, details of their economic burden have not. Methods: Using a large US healthcare claims database, we identified patients aged ≥2 years who underwent allogeneic HCT between October 2009 and March 2013. The hospital admission during which HCT was performed was deemed the "Index Admission". We excluded patients without continuous health plan enrollment and evidence of a hematologic malignancy in the 6-month period prior to the Index Admission. Patients were followed from discharge of the Index Admission until death, plan disenrollment, or one year, whichever occurred first ("Follow-Up"). We ascertained the incidence of infections during the Index Admission through 100 days after discharge ("Early Infections"), and examined by etiology (bacterial, viral, fungal, other/unknown) using relevant ICD-9-CM diagnosis codes. We then ascertained total healthcare costs (inpatient care, outpatient care, outpatient pharmacy) and hospital length of stay (LOS) during the Index Admission and Follow-Up. Reimbursed amounts (plan payment plus patient liability) were used as a proxy for healthcare costs. We compared total healthcare costs and LOS during the Index Admission, Follow-Up, and Overall (Index Admission + Follow-Up) between patients who did versus did not experience an Early Infection using Student's t-tests (unadjusted analyses), and analyses of covariance (ANCOVA) to adjust for differences in age, sex, plan type, geography, year of Index Admission, type of malignancy, and comorbidities. Results: A total of 1,635 patients were identified who underwent allogeneic HCT and met all selection criteria; mean age was 48.4 years, 55.6% were men, and acute myeloid leukemia was the most common malignancy (41.8%). A total of 77.7% of patients (n=1,270) experienced ≥1 Early Infections: bacterial (45.5%), viral (33.2%), fungal (19.5%), and other/unknown (54.1%). Univariate findings are presented in the table. Compared to patients without Early Infections, multivariate-adjusted mean total healthcare costs among patients with Early Infection were $69,044 greater during Index Admission, $74,307 greater during Follow-Up, and $143,351 greater Overall; corresponding increases in LOS were 8 days, 10 days, and 18 days, respectively (all p Conclusions: Nearly four-in-five patients who undergo allogeneic HCT experience Early Infections. These infections are associated with significant increases in healthcare costs and hospital LOS. Our findings suggest new therapies capable of preventing infection - especially across etiologies- could be impactful from an economic perspective. Table 1. Mean (SD) Total LOS and Healthcare Costs, by Time Since Allogeneic HCT and Early Infection Status Type of Infection Overall Index Admission Follow-Up Period WITHInfection WITHOUT Infection p-value WITH Infection WITHOUT Infection p-value WITH Infection WITHOUT Infection p-value Total LOS, days Any Infection 56.9 (41.8) 38.0 (25.2) Disclosures Berger: Evidera: Employment; Fate Therapeutics, Inc: Research Funding. Grubb:Fate Therapeutics, Inc: Employment, Equity Ownership. Huse:Fate Therapeutics, Inc: Research Funding; Evidera: Employment. Mohanty:Evidera: Employment; Fate Therapeutics, Inc: Research Funding. Ferraro:Fate Therapeutics, Inc: Employment, Equity Ownership. Daniels:Fate Therapeutics, Inc: Employment, Equity Ownership. Levin:Fate Therapeutics, Inc: Employment, Equity Ownership.

This study documents the use of oral and transdermal opioids among patients with metastatic cancer during their final year of life. Using a large, integrated health-insurance claims database, we identified all patients who had metastatic lung, breast, colorectal, prostate, or breast cancer and who also died in 1998 or 1999. We then examined all pharmacy claims for these patients over their final 12 months of life. A total of 2,132 patients were identified who met study entrance criteria. Among patients with bone metastases (n=717), 86.9% received opioids at some point during their final year of life; 71.2% of those without bone metastases (n=1,415) received them. Corresponding figures for long-acting opioids were 52.9% and 23.5%. Coverage ratios (total days supplied/total noninstitutionalized days) for any opioids and long-acting opioids were 25.1% and 12.5%, respectively, among patients with bone metastases, and 13.9% and 4.2% for those without bone metastases. During the final month of life, these ratios were 50.8% and 31.3%, and 28.7% and 13.1%. These relatively low rates of opioid use among patients with metastatic cancer in their final year of life suggest that pain in many cases may be suboptimally treated.

Introduction The efficacy and safety of the novel agents, lenalidomide and bortezomib, in previously untreated MM has been demonstrated in several randomized controlled trials (Online-OnlyTs). In this study, we examine the cost-effectiveness of lenalidomide-melphalan–prednisone induction followed by lenalidomide maintenance (MPR-R), and bortezomib-melphalan-prednisone (VMP), respectively, versus melphalan-prednisone (MP), in patients with previously untreated MM. Methods We developed a partitioned-survival model to estimate expected clinical outcomes and costs in newly diagnosed MM patients receiving MPR-R, VMP, or MP as first-line therapy. The model had 3 mutually exclusive health states: (1) “progression-free, alive”; (2) “post-progression, alive”; and (3) “death.” Progression-free survival (PFS) for MP was estimated by aggregating data across five Online-OnlyTs (Palumbo 2012, San Miguel 2008, Facon 2007, Hulin 2009, Palumbo 2006). Estimates of PFS for MPR-R and VMP were based on an adjusted indirect treatment comparison with MP, using data from MM-015 for MPR-R (Palumbo 2012) and VISTA for VMP (San Miguel 2008). Since many MP patients in both MM-015 and VISTA “crossed over” to lenalidomide and bortezomib following disease progression in these trials, we estimated post-progression survival (PPS) for MPR-R and VMP based on a review of novel agents in MM (Messori 2011), which reported mean PPS of 30.9 months. Costs of MPR-R and VMP were estimated based on actual use of study drug in Online-OnlyTs; costs of adverse events as well as other disease-related costs were estimated based on published data. Health-state utilities also were estimated using published data. All costs were expressed in 2012 US$. Cost-effectiveness of MPR-R and VMP versus MP was examined in terms of cost per life-year (LY) gained, cost per quality-adjusted life-year (QALY) gained, and cost per progression-free life-year gained. Future costs and benefits were discounted at 3% annually. Results Mean estimated PFS was 3.4 years for MPR-R, 2.6 years for VMP, and 1.7 years for MP; corresponding estimates for OS were 6.0 years, 5.2 years, and 4.3 years, respectively (Table 1). Mean total expected lifetime costs (discounted) are reported in the Table. The incremental cost per life-year (LY) gained versus MP was $75,392 for MPR-R and $86,213 for VMP; corresponding estimates of the incremental cost per QALY gained were $91,794 and $106,211, respectively (Figure 1). The incremental cost per progression-free LY (PFLY) gained versus MP was $70,666 for MPR-R and $80,565 for VMP. Conclusions In patients with previously untreated MM, cost-effectiveness ratios for MPR-R and VMP are well within the range reported for other well-accepted novel therapies in oncology. $/LY: Incremental cost per life-year gained; $/QALY: Incremental cost per quality-adjusted life-year gained; $/PFLY: Incremental cost per progression-free life-year gained Support Funded by Celgene Corporation Disclosures: Oster: Celgene: Research Funding. Off Label Use: Lenalidomide (immunomodulatory agent), bortezomib (proteosome inhibitor), melphalan (alkylator), and prednisone (steroid), are all treatments for multiple myeloma. Berger:Celgene: Research Funding. Bornheimer:Celgene: Research Funding. Binder:Celgene: Employment, Equity Ownership. Nagarwala:Celgene: Employment, Equity Ownership.