Impact of Elexacaftor/Tezacaftor/Ivacaftor on Healthcare Resource Utilization and Associated Costs Among People With Cystic Fibrosis in the US: A Retrospective Claims Analysis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2 years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12 years in the US. METHODS: We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12 years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis. RESULTS: In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic. CONCLUSIONS: These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

Pediatric Vaccines and Cost-Effectiveness Thresholds: How Much is Too Much to Pay for Prevention?

Cost-effectiveness evaluations play an important role in recommendations for use of pediatric vaccines that are set forth by the US Advisory Committee on Immunization Practices (ACIP). The fact that these evaluations are undertaken and accorded weight suggests that a critical value for designating pediatric vaccines as cost-effective (or not) must exist. For recommended pediatric vaccines, however, reported incremental cost-effectiveness ratios (ICERs) have varied greatly, and there does not appear to be an explicit threshold used by the ACIP to define how much is too much to pay for the prevention of communicable diseases in children. Further complicating this issue is the fact that conventional ICER thresholds-expressed in terms of cost per quality-adjusted life-year (QALY) gained-accord value only to length and quality of life and may not reflect our preferences as individuals or a society. For example, risk, an important attribute of many healthcare decisions, is ignored by the QALY model, as is the distribution of health benefits across different members of society. Are we indeed indifferent about risk and do we really believe that the value of disease prevention in children should be measured by the same "yardstick" as that for older adults? Accordingly, do we really believe that "a QALY is a QALY"? These issues, which are reviewed and discussed in this article, are more than just of theoretical interest; the answers impact how public health policy is determined, which impacts the lives and well-being of entire populations as well as the budgets of payers.

Risk and Economic Burden of Peristomal Skin Complications Following Ostomy Surgery.

PURPOSE: The purpose of this study was to examine the incidence and economic burden of peristomal skin complications (PSCs) following ostomy surgery. DESIGN: Retrospective cohort study based on electronic health records and administrative data stores at a large US integrated healthcare system. SUBJECTS AND SETTINGS: The sample comprised 168 patients who underwent colostomy (ICD-9-CM 46.1X) (n = 108), ileostomy (46.2X) (n = 40), cutaneous ureteroileostomy (56.5X), or other external urinary diversion (56.6X) (n = 20) between January 1, 2012, and December 31, 2014. The study setting was an integrated health services organization that serves more than 2 million persons in the northeastern United States. METHODS: We scanned electronic health records of all study subjects to identify those with evidence of PSCs within 90 days of ostomy surgery and then examined healthcare utilization and costs over 120 days, beginning with date of surgery, among patients with and without evidence of PSCs. Testing for differences in continuous measures between the 3 ostomy groups was based on one-way analysis of variance; testing for differences in such measures between the PSC and non-PSC groups was based on a t statistic, and the χ statistic was used to test for differences in categorical measures. RESULTS: Sixty-one subjects (36.3%) had evidence of PSCs within 90 days of ostomy surgery (ileostomy, 47.5%; colostomy, 36.1%; urinary diversion, 15.0%; P < .05 for differences between groups). Among patients with evidence of PSCs, the mean (SD) time from surgery to first notation of this complication was 26.4 (19.0) days; it was 24.1 (13.2) days for ileostomy, 27.2 (21.1) days for colostomy, and 31.7 (25.7) days for urinary diversion (P = .752). Patients with PSCs were more likely to be readmitted to hospital by day 120 (55.7% vs 35.5% for those without PSCs; P = .011). The mean length of stay for patients readmitted to hospital was 11.0 days for those with PSCs and 6.8 days for those without PSCs (P = .111). The mean total healthcare cost over 120 days was $58,329 for patients with evidence of PSCs and $50,298 for those without evidence of PSCs (P = .251). CONCLUSIONS: Approximately one-third of ostomy patients developed PSCs within 90 days of their surgery. Peristomal skin complications are associated with a greater likelihood of hospital readmission. Our findings corroborate results of earlier studies.

Relationship of American Spinal Injury Association Impairment Scale Grade to Post-injury Hospitalization and Costs in Thoracic Spinal Cord Injury.

BACKGROUND: The lifetime economic burden of thoracic spinal cord injury (SCI) is known to be high, but evidence of variability of costs in relation to the American Spinal Injury Association Impairment Scale (AIS) grade is limited. OBJECTIVE: To estimate lifetime economic costs of hospitalization by AIS grade in thoracic SCI. METHODS: Using SCI Model Systems data from January 2000 to March 2016 from the National Spinal Cord Injury Statistical Center, we estimated mean total annual days of all-cause hospitalization by AIS grade among persons with thoracic SCI, based on assessments 1, 5, and 10 yr post-injury. We combined this information with secondary cost data and projections of life expectancy to estimate lifetime economic costs of hospitalization by AIS grade in persons aged 35 yr at time of thoracic SCI. Future costs were discounted to present value at 3% annually. RESULTS: One year post-injury, mean total annual days of hospitalization ranged from 2.1 for persons with AIS-D injuries to 5.9 for those who were AIS-A. Similar differences were noted 5 and 10 yr post-SCI. The estimated net present value of expected lifetime costs of hospitalization following thoracic SCI at age 35 yr was $321 534, $249 514, $188 989, and $68 120 (2015 US$) for AIS-A, AIS-B, AIS-C, and AIS-D injuries, respectively. CONCLUSION: Persons with less severe thoracic SCI, as reflected in AIS grade, spend fewer days in hospital over their lifetimes, leading to lower costs of inpatient care. Therapies improving AIS grade following thoracic SCI may provide cost savings in addition to addressing substantial unmet need.

Clinical and Economic Burden of Peristomal Skin Complications in Patients With Recent Ostomies.

PURPOSE: The purpose of this study was to estimate the risk and economic burden of peristomal skin complications (PSCs) in a large integrated healthcare system in the Midwestern United States. DESIGN: Retrospective cohort study. SUBJECTS AND SETTING: The sample comprised 128 patients; 40% (n = 51) underwent colostomy, 50% (n = 64) underwent ileostomy, and 10% (n = 13) underwent urostomy. Their average age was 60.6 ± 15.6 years at the time of ostomy surgery. METHODS: Using administrative data, we retrospectively identified all patients who underwent colostomy, ileostomy, or urostomy between January 1, 2008, and November 30, 2012. Trained medical abstractors then reviewed the clinical records of these persons to identify those with evidence of PSC within 90 days of ostomy surgery. We then examined levels of healthcare utilization and costs over a 120-day period, beginning with date of surgery, for patients with and without PSC, respectively. Our analyses were principally descriptive in nature. RESULTS: The study cohort comprised 128 patients who underwent ostomy surgery (colostomy, n = 51 [40%]; ileostomy, n = 64 [50%]; urostomy, n = 13 [10%]). Approximately one-third (36.7%) had evidence of a PSC in the 90-day period following surgery (urinary diversion, 7.7%; colostomy, 35.3%; ileostomy, 43.8%). The average time from surgery to PSC was 23.7 ± 20.5 days (mean ± SD). Patients with PSC had index admissions that averaged 21.5 days versus 13.9 days for those without these complications. Corresponding rates of hospital readmission within the 120-day period following surgery were 47% versus 33%, respectively. Total healthcare costs over 120 days were almost $80,000 higher for patients with PSCs. CONCLUSIONS: Approximately one-third of ostomy patients over a 5-year study period had evidence of PSCs within 90 days of surgery. Costs of care were substantially higher for patients with these complications.

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

OBJECTIVE: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. METHODS: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites. CONCLUSION: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02451137.

Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications.

Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate ("5-ASA"), mesalamine suppository, or mesalamine enema ("UP Rx"). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations.

Prevention of group B streptococcal disease in the first 3 months of life: would routine maternal immunization during pregnancy be cost-effective?

BACKGROUND: A vaccine against group B streptococcus (GBS) that is intended for routine maternal immunization during pregnancy is in clinical development. Addition of vaccination to screening and intrapartum antibiotic prophylaxis (IAP) may further reduce the burden of GBS disease in infancy; its potential cost-effectiveness is unknown, however. METHODS: We evaluated the cost-effectiveness of routine immunization at week 28 of pregnancy with the trivalent GBS (serotypes Ia, Ib and III) vaccine that is in clinical development. The vaccine was assumed to be used in addition to screening and IAP, and reduce the risk of invasive infection in infancy due to covered serotypes. We estimated the effectiveness of immunization in terms of additional cases of GBS disease prevented, deaths averted, life-years saved, and quality-adjusted life-years (QALYs) gained; potential reductions in prematurity and stillbirths were not considered. Costs considered included those of acute care for infants with GBS disease, and chronic care for those with long-term disability. The cost of immunization was assumed to be $100 per person. RESULTS: Assuming 85% coverage, routine maternal immunization against GBS added to screening and IAP would prevent an additional 899 cases of GBS disease and an additional 35 deaths among infants in the US. The total annual cost of immunization would be $362.7 million; estimated cost savings from prevention of GBS disease in infancy would be $43.5 million. The cost-effectiveness of immunization was estimated to be $91,321 per QALY gained. Findings were sensitive to assumptions regarding vaccine efficacy and cost. CONCLUSIONS: Addition of a trivalent GBS maternal vaccine to screening and IAP might further reduce the burden of GBS disease among infants in the US, and may be comparable in cost-effectiveness to other vaccines recently approved for use in children and adolescents.

Clinical and economic consequences of post-operative infections following major elective surgery in U.S. hospitals.

BACKGROUND: The incidence and consequences of post-operative infections in patients undergoing major elective surgery is not well understood. METHODS: Using a large U.S. healthcare claims database, we identified all patients who underwent major elective surgery between January 1, 2007, and December 31, 2009. For each such patient, date of the first-noted surgery during this period was designated as the index date. Patients who developed infections within 30 d of their index date were matched to those who did not using propensity score matching. We compared hospital readmissions, mortality, and total healthcare cost during the 30-d period following index date between patients who developed post-operative infections versus those who did not. RESULTS: A total of 327,618 patients met all selection criteria. At 30 d following major elective surgery, 10.9% of patients had evidence of post-operative infections, 39% of which occurred during the index admission. In propensity-matched analyses, patients with post-operative infections were about five times as likely to be readmitted to hospital (11.3% vs. 2.1%) and more than twice as likely to die (0.8% vs. 0.3%) in the 30-d period following surgery; their average total healthcare cost was $8,417 higher ($29,229 vs. $20,812) (all comparisons, p<0.01). CONCLUSION: Approximately one in 10 patients undergoing major elective surgery develop post-operative infections by day 30. Post-operative infections are associated with significantly worse clinical outcomes and higher total healthcare cost.

Can dialysis patients be accurately identified using healthcare claims data?

BACKGROUND: While health insurance claims data are often used to estimate the costs of renal replacement therapy in patients with end-stage renal disease (ESRD), the accuracy of methods used to identify patients receiving dialysis - especially peritoneal dialysis (PD) and hemodialysis (HD) - in these data is unknown. METHODS: The study population consisted of all persons aged 18 - 63 years in a large US integrated health plan with ESRD and dialysis-related billing codes (i.e., diagnosis, procedures) on healthcare encounters between January 1, 2005, and December 31, 2008. Using billing codes for all healthcare encounters within 30 days of each patient's first dialysis-related claim ("index encounter"), we attempted to designate each study subject as either a "PD patient" or "HD patient." Using alternative windows of ± 30 days, ± 90 days, and ± 180 days around the index encounter, we reviewed patients' medical records to determine the dialysis modality actually received. We calculated the positive predictive value (PPV) for each dialysis-related billing code, using information in patients' medical records as the "gold standard." RESULTS: We identified a total of 233 patients with evidence of ESRD and receipt of dialysis in healthcare claims data. Based on examination of billing codes, 43 and 173 study subjects were designated PD patients and HD patients, respectively (14 patients had evidence of PD and HD, and modality could not be ascertained for 31 patients). The PPV of codes used to identify PD patients was low based on a ± 30-day medical record review window (34.9%), and increased with use of ± 90-day and ± 180-day windows (both 67.4%). The PPV for codes used to identify HD patients was uniformly high - 86.7% based on ± 30-day review, 90.8% based on ± 90-day review, and 93.1% based on ± 180-day review. CONCLUSIONS: While HD patients could be accurately identified using billing codes in healthcare claims data, case identification was much more problematic for patients receiving PD.

Economic burden of adverse events in patients with metastatic renal cell carcinoma.

BACKGROUND: Although targeted therapies (ie, tyrosine kinase inhibitors and antiangiogenesis agents) are effective as first-line treatment of metastatic renal cell carcinoma (mRCC), moderate-to-severe adverse events have been reported in clinical trials of these agents. Information concerning the economic burden of these events is limited. OBJECTIVE: The purpose of this study was estimate the costs associated with adverse events in patients with mRCC receiving selected targeted agents indicated for first-line treatment of this disease. METHODS: Retrospective study based on health care claims data for patients with mRCC, aged ≥18 years, receiving first-line treatment with targeted therapies. Adverse events of interest included abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue and/or asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea and/or vomiting, neutropenia, proteinuria, and thrombocytopenia. Patients receiving care for these events were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis and procedure codes on health care claims. Costs were examined during a 30-day period, beginning with date of first mention of each event; nonevented patients similarly were assigned a shadow index date. We estimated total costs during 30 days after the index date for patients with and without adverse events, excluding the costs of targeted therapy. RESULTS: Sixty-four percent of patients receiving targeted therapies for mRCC had health care encounters for ≥1 adverse events. Events that occurred with a frequency >20% included severe abdominal pain, back pain, fatigue and/or asthenia, and nausea and/or vomiting, respectively; 10% to 20% of patients had encounters for diarrhea, dyspnea, and extremity pain, respectively. Mean (SD) total costs of care during the 30-day, postevent period were substantially higher among patients with versus without adverse events-$12,177 ($19,621) versus $4070 ($8142). Adjusting for differences in baseline characteristics, the estimated cost difference was $11,373 (95% CI, $5286-$21,419). CONCLUSIONS: Costs of adverse events are substantial in patients receiving targeted therapies, specifically, sunitinib, sorafenib, or bevacizumab, for mRCC. Efforts to prevent and/or better manage these events may reduce health care costs.

Cost of venous thromboembolism in hospitalized medically ill patients.

PURPOSE: The results of a study to estimate the economic costs of venous thromboembolism (VTE) in hospitalized nonsurgical patients during initial admissions and subsequent to hospital discharge are presented. METHODS: Using a database linking admission records from more than 150 U.S. hospitals to health insurance claims, 49,948 patients 40 years of age or older who were hospitalized at least once during a 6-year period for diagnoses other than VTE or traumatic injury and who met other inclusion criteria were identified. Costs were tallied from the index admission to postdischarge day 180 for patients with and patients without evidence of VTE. Ordinary least-squares regression was used to estimate the independent relationship between VTE and total health care costs, controlling for differences in patient characteristics. RESULTS: Two hundred forty-two patients (0.5%) had VTE during the index admission, 317 (0.6%) had VTE after the index admission discharge; in total, 559 (1.1%) had VTE through postdischarge day 180. Among the 242 patients with VTE during their index admission, the adjusted mean total health care costs over 180 days were $17,848 higher than among those without VTE ($47,416 versus $29,568, p < 0.001); for the 317 patients with postdischarge VTE, the adjusted mean total 180-day costs were $51,863 higher than for those without postdischarge VTE ($74,136 versus $22,273, p < 0.001). CONCLUSION: Among medically ill patients admitted to the hospital, health care costs were significantly higher among those who developed VTE during hospitalization or after discharge compared with those who did not develop VTE.

Economic burden of selected adverse events in patients aged ≥65 years with metastatic renal cell carcinoma.

OBJECTIVE: To estimate the costs of adverse events (AEs) in patients aged ≥65 years with metastatic renal cell carcinoma (mRCC). METHODS: Retrospective study using the linked Surveillance, Epidemiology and End Results (SEER) Medicare database. Study subjects consisted of persons in SEER-Medicare, aged ≥65 years, with evidence of newly diagnosed mRCC between January 1, 2007 and December 31, 2007. Adverse events of interest consisted of Grade 3 or 4 toxicities that have been reported with frequency ≥5% in randomized controlled trials of sunitinib, sorafenib, bevacizumab, and pazopanib (i.e., targeted therapies for mRCC), and included abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, proteinuria, and thrombocytopenia. Patients in SEER-Medicare with these events were identified based on ICD-9-CM diagnosis codes on Medicare claims. For each AE of interest, costs were tallied among evented patients over 30 days, beginning with the date of each patient's first mention of the AE, and were compared with those of non-evented patients over a similar 30-day period beginning with an identical 'shadow' index date. Total costs were compared on an unadjusted basis and with adjustment for differences in baseline characteristics using a generalized linear model. RESULTS: A total of 881 patients with mRCC met study entry criteria; 60% of these patients had Medicare claims with mention of one or more AEs of interest. Events occurring with frequency >20% included abdominal pain, dyspnea, and fatigue/asthenia; 10-20% of study subjects had encounters for back pain, extremity pain, and nausea/vomiting. Mean (standard deviation) total cost of care over 30 days was substantially higher among patients with AEs ($13,944 [$14,529]) compared with those without mention of these events ($1878 [$5264]). Adjusting for differences in baseline characteristics, the mean (95% confidence interval) difference in costs between evented and non-evented patients was $12,410 ($9217-$16,522). Study limitations include problems in event ascertainment due to inaccuracies in ICD-9-CM coding on Medicare claims data, and restriction of the study population to patients with metastatic involvement at initial diagnosis of RCC. CONCLUSIONS: Costs of care are substantially higher in patients aged ≥65 years with mRCC who experience AEs commonly associated with sunitinib, sorafenib, bevacizumab, and pazopanib. Efforts to prevent and/or better manage these events potentially can reduce healthcare costs.

Initial treatment failure in non-ICU community-acquired pneumonia: risk factors and association with length of stay, total hospital charges, and mortality.

OBJECTIVES: To identify risk factors for initial treatment failure in patients with community-acquired pneumonia (CAP) in non-intensive care unit (non-ICU) settings, and to characterize the association between initial treatment failure and length of stay, total hospital charges, and mortality. METHODS: Retrospective cohort study. Using data from >100 US hospitals, this study identified all adults (age ≥18 years) hospitalized for pneumonia between January 1, 2000 and June 30, 2009 who began antibiotic therapy within 24 h of admission and were treated for at least 48 h if alive; patients admitted to intensive care within the first 24 h in hospital were excluded. Initial therapy was defined as all parenteral antibiotics administered within the first 24 h in hospital. Treatment failure was assessed based on subsequent receipt of new antibiotic(s), excluding agents of similar/narrower spectrum and those begun at discharge. Multivariate logistic regression was used to identify risk factors for treatment failure, and multivariate linear and logistic regression to compare length of stay, total hospital charges, and in-hospital mortality between patients experiencing initial treatment failure and those who did not. RESULTS: Among 32,324 patients with non-ICU CAP, 4695 (14.6%) experienced initial treatment failure, most often within 72 h of hospital admission. Significant predictors of initial treatment failure included malnourishment (OR = 1.87; 95% CI = 1.60-2.18), receipt of vasoactive medications within 24 h of admission (1.51 [1.17-1.94]), and renal failure (1.45 [1.32-1.59]). Treatment failure was associated with higher case fatality (8.5% vs 3.3%), longer hospital stays (mean [SD] = 10.1 [8.1] days vs 4.9 [3.3] days), and higher total hospital charges ($37,602 [$71,876] vs $14,371 [$21,633]) (all comparisons, p < 0.01). Study limitations include possible inclusion of patients with healthcare-associated pneumonia (HCAP) in the study sample, our focus on the 40 most commonly used antibiotic regimens, and indirect measurement of treatment failure. CONCLUSIONS: Approximately one in seven non-ICU CAP patients experience failure of initial antibiotic therapy. Risk of failure is higher for patients with significant comorbidities and/or severe infections. Non-ICU patients who experience initial treatment failure have significantly longer hospital stays, higher total hospital charges, and higher rates of mortality.

Changes in healthcare utilization and costs associated with sildenafil therapy for pulmonary arterial hypertension: a retrospective cohort study.

BACKGROUND: Little is known concerning the degree to which initiation of sildenafil for pulmonary arterial hypertension (PAH) impacts patterns of healthcare utilization and costs. METHODS: Using a large US health insurance claims database, we identified all patients with evidence of PAH (ICD-9-CM diagnosis codes 416.0, 416.8) who received sildenafil between 1/1/2005 and 9/30/2008. Date of the first-noted prescription for sildenafil was designated the "index date," and claims data were compiled for all study subjects for 6 months prior to their index date ("pretreatment") and 6 months thereafter ("follow-up"); patients with incomplete data during either of these periods were excluded. Healthcare utilization and costs were then compared between pretreatment and follow-up for all study subjects. RESULTS: A total of 567 PAH patients were identified who began therapy with sildenafil and met all other study entry criteria. Mean (SD) age was 52 (10) years; 73% were women. Healthcare utilization was largely unchanged between pretreatment and follow-up, the only exceptions being decreases in the mean number of emergency department visits (from 0.7 to 0.5 per patient; p<0.01) and the percentage of patients hospitalized (from 35% to 29%; p=0.01). The mean cost of all PAH-related medication was $7139 during pretreatment and $14,095 during follow-up (sildenafil cost during follow-up= $5236); exclusive of PAH-related medications, however, total healthcare costs decreased modestly (from $30,104 to $27,605) (p<0.01 for all comparisons). CONCLUSIONS: The cost of sildenafil therapy may be partially offset by reductions in other healthcare costs.

Change in healthcare utilization and costs following initiation of benzodiazepine therapy for long-term treatment of generalized anxiety disorder: a retrospective cohort study.

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<0.01); costs of accident-related encounters and other care that was possibly related to use of benzodiazepines increased by an average of $1099 ($1757 [$7656] vs $2856 [$14,836]; p=0.03). 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.

Cost-effectiveness of adjunctive therapy with atypical antipsychotics for acute treatment of major depressive disorder.

BACKGROUND: While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. OBJECTIVE: To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. METHODS: Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. RESULTS: With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. CONCLUSIONS: Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

Utilization and cost in clinical practice of darbepoetin alfa and epoetin alfa for anemia concomitant with chemotherapy.

BACKGROUND: In 2005, the mean weekly dose ratio of epoetin alfa (EA) to darbepoetin alfa (DA) in clinical practice was estimated to be ∼400 to 1. In 2006, a 500-µg dose and new dosing schedule was approved for DA in the United States. In 2007, the warnings and dosing/administration sections were modified for both agents. All of these factors may have changed the way that physicians use EA and DA. Previous studies of the use of erythropoiesis-stimulating agents (ESAs) in patients with anemia concomitant with chemotherapy may thus not reflect current clinical practice. OBJECTIVE: The goal of this study was to examine the use and costs of ESAs in clinical practice in patients with anemia concomitant with chemotherapy. METHODS: Using 2 large US health care claims databases, all adults (aged ≥18 years) were identified who received ESAs in 2008 and had evidence of receipt of chemotherapy ≤42 days before initial ESA receipt (ie, the index date). Episodes of care were defined as beginning on the index date and ending on the date of the last ESA claim that was followed by a ≥42-day gap without any receipt of ESAs, to which was added an assumed duration of clinical benefit (in days) based on the ESA and corresponding dose received. DA- and EA-treated patients were matched using propensity scoring. The mean weekly dose and cost of DA and EA during episodes of care was calculated using all information from relevant claims noted during such episodes. Each database was analyzed separately. RESULTS: In the first database, 475 patients with DA episodes of care were matched to an equal number of patients with EA episodes; in the second database, there were 424 matched pairs. In the first database, the mean (95% CI) weekly dose was 37,444 U (35,942 U-39,001 U) during EA episodes and 110 µg (108 µg-113 µg) during DA episodes; the mean weekly EA/DA dose ratio was 340 to 1. In the second database, the mean (95% CI) weekly dose was 37,047 U (35,944 U-38,175 U) during EA episodes and 121 µg (117 µg-125 µg) during DA episodes; the mean weekly EA/DA dose ratio was 306 to 1. CONCLUSIONS: The mean weekly EA/DA dose ratio during episodes of ESA care has declined in patients with anemia concomitant with chemotherapy, due at least in part to the availability and use of a new dose/dosing schedule for DA without similar changes for EA.