A Comparative Study of Treatment-Emergent Adverse Events Following Use of Common Bowel Preparations Among a Colonoscopy Screening Population: Results from a Post-Marketing Observational Study.

BACKGROUND: Colonoscopy may be one of the most frequent elective procedures in older adults and is associated with a low occurrence of complications. However, reduction of risks attributable to the bowel preparation may be achieved with the use of effective and safer products. AIM: The aim of this study was to examine the incidence of treatment-emergent adverse events (TEAEs) associated with SUPREP(®) [oral sulfate solution (OSS)] and other common prescription bowel preparations (non-OSS). METHODS: This real-world, observational study used de-identified health insurance claims and laboratory results to identify TEAEs in the 3 months following screening colonoscopy in adults with a prescription for a bowel preparation in the prior 60 days. The unadjusted and adjusted (controlling for patient risk factors) cumulative incidences of TEAEs were estimated using Kaplan-Meier and Poisson regression, respectively. RESULTS: Among patients ≥45 years, the overall cumulative incidence was significantly lower (p < 0.001) in the OSS cohort than in the non-OSS cohort (unadjusted: 2.31 vs. 2.89 %; adjusted: 1.61 vs. 1.95 %), with significantly lower acute cardiac conditions (1.56 vs. 1.90 %; p < 0.001), renal failure/other serious renal diseases (OSS: 0.21 %, non-OSS: 0.32 %; p < 0.001), and serum electrolyte abnormalities (OSS: 0.39 %, non-OSS: 0.49 %; p = 0.017). There were no significant differences between cohorts in death, seizure disorders, aggravation of gout, and ischemic colitis. Results were similar in the adjusted cumulative incidences. CONCLUSIONS: In actual use, the overall cumulative incidence of TEAEs was significantly lower in the OSS cohort, demonstrating that OSS is as safe as, or possibly safer than, non-OSS prescription bowel preparations.

Disulfide reduction abolishes tissue factor cofactor function.

BACKGROUND: Tissue factor (TF), an in vivo initiator of blood coagulation, is a transmembrane protein and has two disulfides in the extracellular domain. The integrity of one cysteine pair, Cys186-Cys209, has been hypothesized to be essential for an allosteric "decryption" phenomenon, presumably regulating TF procoagulant function, which has been the subject of a lengthy debate. The conclusions of published studies on this subject are based on indirect evidences obtained by the use of reagents with potentially oxidizing/reducing properties. METHODS: The status of disulfides in recombinant TF1-263 and natural placental TF in their non-reduced native and reduced forms was determined by mass-spectrometry. Functional assays were performed to assess TF cofactor function. RESULTS: In native proteins, all four cysteines of the extracellular domain of TF are oxidized. Reduced TF retains factor VIIa binding capacity but completely loses the cofactor function. CONCLUSION: The reduction of TF disulfides (with or without alkylation) eliminates TF regulation of factor VIIa catalytic function in both membrane dependent FX activation and membrane independent synthetic substrate hydrolysis. GENERAL SIGNIFICANCE: Results of this study advance our knowledge on TF structure/function relationships.

Lensectomy as treatment for refractory or progressive retinopathy of prematurity narrow-angle glaucoma.

We present the case of a patient with a history of laser-treated retinopathy of prematurity (ROP) who developed narrow angles and intermittent angle closure. Despite laser peripheral iridotomy/iridoplasty, 1 year later, the patient had recurrent narrowing that resolved following clear lens extraction with intraocular lens placement. This case highlights the importance of continued monitoring for narrow angles in patients with ROP history.

Societal and individual burden of illness among fibromyalgia patients in France: association between disease severity and OMERACT core domains.

BACKGROUND: Patients with fibromyalgia (FM) report widespread pain, fatigue, and other functional limitations. This study aimed to provide an assessment of the burden of illness associated with FM in France and its association with disease severity and core domains as defined by Outcome Measures in Rheumatology Clinical Trials (OMERACT) for FM. METHODS: This cross-sectional, observational study recruited patients with a prior diagnosis of FM from 18 community-based physician offices in France. Patients completed questions about FM impact (Fibromyalgia-Impact Questionnaire [FIQ]), core symptoms (defined by OMERACT), health-related quality of life (EQ-5D), current overall health status (rated on a scale from 0 to 100), productivity, treatment satisfaction, and out-of-pocket expenses related to FM. Site staff recorded patients' treatment and health resource use based on medical record review. Costs were extrapolated from 4-week patient-reported data and 3-month clinical case report form data and calculated in 2008 Euros using a societal perspective. Tests of significance used the Kruskal-Wallis test or Fisher's Exact test where P < 0.05 was considered significant. RESULTS: Eighty-eight patients (mean 55.2 y; female:male 74:14) were recruited. The majority of patients (84.1%) were prescribed medications for FM. Patients mainly described medications as a little/not at all effective (40.0%) or somewhat effective (52.9%). Current Overall Health rating was 52.9 (± 17.8) and FIQ total score was 54.8 (± 17.3). FIQ total score was used to define FM severity, and 17 patients scored 0- < 39 (mild FM), 33 patients 39- < 59 (moderate FM), and 38 scored 59-100 (severe FM). As FM severity level worsened, patients had poorer overall health status and perceived their prescription medications to be less effective. Average cost/FM patient was higher for severe (€10,087) vs. moderate (€6,633) or mild FM (€5,473); however, the difference was not significant. CONCLUSIONS: In a sample of 88 patients with FM from France, we found that FM poses a substantial economic and human burden on patients and society. FM severity level was significantly associated with patients' health status and core symptom domains.

Real-World Evaluation of Clinical Response and Long-Term Healthcare Resource Utilization Patterns Following Treatment with a Digital Therapeutic for Chronic Insomnia.

Background and Objectives: This analysis evaluated insomnia severity and long-term impact on healthcare resource utilization (HCRU) and costs after treatment with Somryst® (previously called SHUTi), a digital therapeutic delivering cognitive behavioral therapy for insomnia (CBT-I). Methods: Change from baseline in insomnia severity index (ISI) score was assessed using last observed ISI score. A pre/post analysis of claims data was conducted, comparing HCRU in patients with self-identified sleep problems who successfully initiated the therapeutic (index date) between June 1, 2016 and December 31, 2018. Results: A total of 248 patients were analyzed (median age 56.5 years, 57.3% female, mean ISI score 19.13, 52.4% treated with sleep aid medications pre-index). After 9 weeks, mean ISI score declined by 37.2% from baseline (19.1 vs 12.0), 58.8% of patients achieved ISI responder status (ISI score improved by =>7; NNT: 1.7), and 26.6% of patients achieved insomnia remission (ISI score <8; NNT for remission: 3.8). After two-year follow-up, post-index events were reduced (compared to 2 years pre-index) for emergency department visits (-53%; IRR: 0.47; 95% CI 0.27, 0.82; P=0.008), hospiatizations (-21%; IRR: 0.79; 95% CI 0.46, 1.35; P=0.389) and hospital outpatient visits (-13%; IRR: 0.87; 95% CI 0.66, 1.14; P=0.315). Slightly increased rates were observed for ambulatory surgical center visits (2%; IRR: 1.02; 95% CI 0.73, 1.44; P=0.903) and office visits (2%; IRR: 1.02; 95% CI 0.92, 1.14; P=0.672). The number of patients treated with sleep aid medications dropped 18.5% (52.4% pre-index vs 42.7% post-index). Average number of prescriptions decreased from 3.98 pre-index to 3.73 post-index (P= 0.552). Total two-year cost reduction post-index vs pre-index was $510,678, or -$2059 per patient. Conclusion: In a real-world cohort of patients with chronic insomnia, treatment with a digital therapeutic delivering CBT-I was associated with reductions in insomnia severity, emergency department visits, and net costs.

Real-World Characteristics and Treatment Patterns of Patients With Insomnia Prescribed Trazodone in the United States.

PURPOSE: This study sought to describe patient characteristics and treatment patterns among patients with insomnia prescribed trazodone in the United States. METHODS: This real-world, retrospective, descriptive cohort study used US commercial insurance claims from July 1, 2009, through June 30, 2019. The index date was the first prescription for trazodone between January 1, 2010, and December 31, 2018, with 6 months for the preindex period and ≥6 months for the postindex period. FINDINGS: Among 5.8 million patients with insomnia, 17.7% were prescribed trazodone, and 357,380 adults (6.2%) and 7564 children (0.1%) met the study eligibility criteria. The mean (SD) age was 48.8 (15.8) years for adults and 14.8 (2.7) years for pediatrics. Most patients were female (229,280 adults [64.2%] and 4481 children [59.2%]). Insomnia due to mental disorder was the most common specific diagnosis. The most common (>25%) comorbid conditions were anxiety, depression, and hypertensive disease, and 1 of 10 had a history of substance abuse. Zolpidem was previously prescribed (73,342 adults [20.5%] and 233 children [3.1%]) and continued to be prescribed. Concomitant antidepressants were most common (216,893 adults [60.7%] and 5414 children [71.6%]), but benzodiazepines (132,740 adults [37.1%] and 1188 children [15.7%]), antiepileptics (115,064 adults [32.2%] and 2103 children [27.8%]), nonbenzodiazepines (90,946 adults [25.4%] and 542 children [7.2%]), and antipsychotics (40,490 adults [11.3%] and 2063 children [27.3%]) were also prescribed. IMPLICATIONS: This study provides current evidence that trazodone use is widespread among patients with insomnia and is often associated with other specific comorbidities, such as psychiatric conditions. A deeper knowledge of the real-world management of patients with insomnia may facilitate steps toward improving sleep quality, daytime functioning, and clinical outcomes for patients.

Clinical and economic outcomes in Medicare beneficiaries with stage 3 or stage 4 chronic kidney disease and anemia: the role of intravenous iron therapy.

BACKGROUND: Anemia in patients with chronic kidney disease (CKD) is associated with increased morbidity and mortality, decreased quality of life, and substantial health care costs. Iron therapy is recommended, usually in combination with an erythropoiesis-stimulating agent (ESA), in many CKD patients with anemia and low iron levels to raise hemoglobin levels to a range of 10 to 12 grams per deciliter; iron deficiency is defined by a ferritin score less than 100 micrograms (mcg) per liter and transferrin saturation (TSAT) less than 20%. OBJECTIVE: To examine the use of intravenous (IV) iron and its associated economic and clinical outcomes in Medicare beneficiaries with stage 3 or stage 4 CKD and anemia. METHODS: This was a retrospective cohort analysis using 2006 and 2007 Medicare 5% Standard Analytic Files (SAF). Use of therapy with IV iron and/or ESAs was identified among patients diagnosed with CKD and anemia. The study index quarter was the first quarter in 2006 during which the patient had primary or secondary diagnoses of both CKD and anemia. Based on the receipt of IV iron or ESA treatment in the index quarter, patients were classified into 1 of 4 treatment groups: IV iron and ESA; IV iron without ESA; ESA without IV iron; neither IV iron nor ESA. Therapy with oral iron was not measurable with this database. Clinical and economic outcomes, including the progression to advanced CKD stages, development of anemia, mortality, hospitalization, and net Medicare reimbursement (i.e., not including patient or supplemental plan contribution) for all-cause health care services, were examined for 1 year following the index quarter. Between-group differences were tested using Pearson chi-square for categorical variables and the Kruskal-Wallis nonparametric test for reimbursement. Multivariate logistic regression models were estimated to assess the associations of mortality, inpatient hospitalization, skilled nursing facility (SNF) admission, and hospice care with treatment regimen, controlling for patient demographic and clinical characteristics. RESULTS: Of the 4,310 study patients with both CKD and anemia, 2,913 (67.6%) received neither IV iron nor ESA; 984 (22.8%) received ESA without IV iron; 277 (6.4%) received IV iron and ESA; and 136 (3.2%) received IV iron without ESA in the index quarter. Logistic regression analyses showed that patients receiving neither IV iron nor ESA (reference group) were at increased risk of death compared with patients receiving both IV iron and ESA (OR = 0.62, 95% CI = 0.42-0.90). Additionally, patients receiving neither IV iron nor ESA were more likely to be hospitalized compared with patients receiving both IV iron and ESA (OR = 0.66, 95% CI = 0.50-0.87), IV iron without ESA (OR = 0.55, 95% CI = 0.38-0.79), and ESA without IV iron (OR = 0.73, 95% CI = 0.62-0.87). Further, patients not receiving IV iron or ESA were more likely to be admitted to an SNF than patients receiving both IV iron and ESA (OR = 0.44, 95% CI = 0.32-0.61), IV iron without ESA (OR = 0.57, 95% CI = 0.36-0.88), and ESA without IV iron (OR = 0.56, 95% CI = 0.47-0.67). Patients receiving neither IV iron nor ESA in the index quarter had the highest mean [SD] total Medicare reimbursement per patient in the subsequent year ($42,353 [$52,887]) compared with patients receiving IV iron without ESA ($28,654 [$32,068]), IV iron and ESA ($34,152 [$30,506]), or ESA without IV iron ($38,172 [$35,591], P = 0.001). CONCLUSIONS: Use rates of IV iron and ESA in a sample of Medicare enrollees with CKD and anemia in 2006 suggest that anemia management therapies may be underutilized; however, oral iron therapy use was not measurable with the study database, and therapies initiated after the index quarter were not measured. Patients not treated with IV iron or ESA had significantly higher rates of hospitalization and SNF admission than patients treated with either IV iron or ESA. Further, mortality was significantly higher in patients receiving neither IV iron nor ESA than in patients who received IV iron and ESA. Additionally, total all-cause health care costs were higher among patients receiving neither IV iron nor ESA treatment compared with patients treated with IV iron and/or ESA.

Economic Burden of Checkpoint Inhibitor Immunotherapy for the Treatment of Non-Small Cell Lung Cancer in US Clinical Practice.

PURPOSE: The efficacy of checkpoint inhibitor (CPI) immunotherapy in patients with non-small cell lung cancer (NSCLC) is limited by a lack of strongly predictive response markers, subjecting patients to potential underutilization of alternative effective treatments, increased risk for futile care, and unnecessary costs. Here, we characterize the extent to which basic molecular tumor-marker testing has been performed for NSCLC therapy selection in the United States, and compare medical resource utilization and costs in CPI-treated patients versus CPI-eligible patients treated with other therapies. METHODS: We identified a cohort of CPI-treated patients with NSCLC and a propensity score-matched cohort of CPI-eligible patients with NSCLC treated with non-CPI therapies (3095 patients in each group), using US administrative claims data covering the pre- and postinitial FDA-approval period for nivolumab, pembrolizumab, and atezolizumab (October 2012 to September 2017). We describe the utilization of recommended baseline molecular testing for CPI selection (pre-index date for CPI or other anticancer therapy), including programmed death ligand 1 (PD-L1) immunohistochemistry, ALK rearrangement and EGFR mutation testing, and pre- and postindex treatment patterns. All-cause medical resource utilization and semiannual total reimbursement (costs) were compared between CPI-treated and non-CPI-treated patients. FINDINGS: At baseline, in the propensity score-matched CPI- and non-CPI-treated patient cohorts, mean PD-L1 immunohistochemistry test utilization for CPI selection was moderate (0.6 vs 0.7 per patient, respectively). However, we observed much lower mean utilization of testing for EGFR mutations (0.1 vs 0.1 per patient) and ALK rearrangements (0.1 vs 0.2 per patient). Postindex, the use of both chemotherapy and ALK- and EGFR-targeted therapies were decreased in both cohorts. The CPI-treated group had significantly higher mean medical resource utilization in nearly all categories in the postindex period, and total per-patient semiannual costs, than did the CPI-eligible patients who received other therapies (141,537 vs 75,429 US dollars [USD]; P < 0.0001), driven by CPI drug reimbursement. Median (interquartile range) time on CPI was longest with pembrolizumab (113 [106-127] days), followed by nivolumab (105 [97-106] days) and atezolizumab (64 [50-85] days). Despite being associated with the lowest drug cost and the shortest treatment duration, atezolizumab was associated with the highest mean total per-patient semiannual costs (160,540 USD) compared with pembrolizumab (153,003 USD) and nivolumab (138,542 USD). IMPLICATIONS: The advent of CPI treatment for NSCLC has added substantial care-related costs for patients and payers, concurrent with underutilization of minimum recommended molecular testing for therapy selection. Broad uptake of panel-based comprehensive targeted-therapy and immunotherapy profiling can promote optimal treatment selection and sequencing, reduce the likelihood of futile treatment, and further improve patient outcomes.

Projected Medicare Savings Associated With Lowering the Risk of Total Hip Arthroplasty Revision: An Administrative Claims Data Analysis.

In the United States, demand for total hip arthroplasty (THA) and THA revision procedures are increasing due to an aging population, a longer life expectancy, and an increasing prevalence of osteoarthritis. This retrospective cohort study identified patients 65 years and older in the Medicare 5% Standard Analytic Files who underwent THA for osteoarthritis between January 1, 2009, and September 30, 2010. The authors estimated the 5-year cumulative revision risk (CRR) using the Kaplan-Meier method, revision-related complications, and Medicare expenditures. Using a 6.22% compound annual growth rate from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, the authors estimated the number of THAs that will be performed from 2018 to 2027 and calculated the 10-year projected savings to Medicare for a 1% reduction in CRR. Among 7820 patients, the mean age was 74.4 years, and 62.4% were female. Cumulative revision risk was 4.2% at 5 years (through September 30, 2015), with 30.8% of revisions occurring within 90 days of the THA. At least 24.4% of revision patients had a complication. Median revision inpatient stay and episode of care (through 90 days) expenditures were $23,847 and $36,157, respectively. With a 1% absolute reduction in CRR, Medicare could save $697 million over a 10-year period, or $985 million when including Medicare Advantage, which represented 29.2% of 2016 Medicare payments. Strategies to reduce the risk of THA revision, such as the use of implant constructs with lower CRR and value-based payment models, are needed to achieve Medicare payment reductions while maintaining or improving quality of care for Medicare beneficiaries. [Orthopedics. 2019; 42(1):e86-e92.].

Health care utilization and costs following amplified versus non-amplified molecular probe testing for symptomatic patients with suspected vulvovaginitis: a US commercial payer population.

BACKGROUND: Vulvovaginitis (VV) is a common reason women seek medical attention in the USA. Both the non-specific clinical presentation and risk of preterm labor or delivery necessitate accurate identification of the causative agents to guide appropriate therapy. The diagnostic accuracy of amplified molecular probe testing (AMP) has been shown to exceed that of non-amplified molecular probe (NAMP) by 20%-25%. OBJECTIVE: To evaluate the impact of diagnosis with AMP testing on health care utilization, direct costs, and health outcomes, compared with NAMP, for symptomatic patients with suspected VV from a commercial payer perspective. METHODS: Symptomatic women (aged 18-64 years) who underwent VV testing with AMP or NAMP from January 1, 2012-December 31, 2016 were identified using the Truven Health Analytics MarketScan Database; those with continuous medical and pharmacy benefit enrollment 6 months pre/post AMP or NAMP testing were included. Patients were propensity score (PS) matched and 6-month all-cause health care resource utilization, all-cause direct costs (2017 USD), risk of all-cause hospitalization, and risk of preterm labor or delivery were compared between cohorts. RESULTS: After PS match (N=46,810 per group, mean age 34.2 years), AMP had significantly (all P<0.0001) fewer mean hospital outpatient visits (AMP 0.9 vs NAMP 1.0), primary care physician office visits (AMP 1.1 vs NAMP 1.2), and prescription medications (AMP 7.3 vs NAMP 8.0), and a 21% reduction in risk of hospitalization (risk ratio [RR]=0.79, 95% CI= 0.75-0.83, P<0.0001). Total medical expenditures per patient were lower for AMP than NAMP (mean AMP $3,287 vs NAMP $3,555, P<0.0001). Among pregnant women (N=2,175 per group), AMP had a 12% reduction in risk of preterm labor or delivery (RR =0.88, 95% CI=0.77-0.99, P=0.041). CONCLUSION: This real-world study offers evidence on the clinical utility for symptomatic patients with suspected VV diagnosed with AMP compared to NAMP - demonstrating an opportunity to improve the patient journey while delivering value-based care.

Economic burden of bilateral neovascular age-related macular degeneration: multi-country observational study.

BACKGROUND: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. OBJECTIVE: To document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective. STUDY DESIGN, SETTING AND PARTICIPANTS: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians' records and subjects' standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMD-related socioeconomic costs were calculated in euro, year 2005 values. MAIN OUTCOME MEASURES: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures. RESULTS: The demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12-22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21-59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54-81%) were living with a spouse or family member and 19-41% reported receiving assistance for activities of daily living. The average annual societal cost per bilateral NV-AMD patient treated was estimated to be euro 7879 in Canada, euro 7349 in France, euro 12 445 in Germany, euro 5732 in Spain and euro 5300 in the UK, and direct vision-related medical costs accounted for 23-63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with an average length of 5 months; there were no statistically significant differences in total annual costs per patient between these patients and those who were diagnosed with bilateral disease for > or =1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from euro 268 to euro 1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from euro 671 to euro 3278 million. CONCLUSIONS: Bilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab.

BACKGROUND: Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. METHODS: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. RESULTS: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%-75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). CONCLUSION: Patients treated with RCI had less PPPM non-medication MRU and costs than those treated with IVIg and/or rituximab, particularly in the hospital setting where significant costs are incurred.

Burden of Iron Deficiency Anemia in a Bariatric Surgery Population in the United States.

BACKGROUND: Obesity is a serious condition affecting more than 35% of adults in the United States. In obese individuals for whom other weight control methods have been ineffective, bariatric surgery is a safe and effective method of weight control. An estimated 150,000 to 160,000 bariatric surgeries are performed in the United States yearly. Iron deficiency anemia is common in patients after bariatric surgery, with incidence rates up to 49%, and may be due to malabsorption of nutrients.  OBJECTIVES: To (a) compare the medical resource utilization (MRU)- both medical care and treatment resources-and associated costs in a sample of commercially insured adult bariatric surgery patients with and without iron deficiency anemia (IDA), and (b) describe anti-anemia treatment patterns in those bariatric surgery patients diagnosed with IDA. METHODS: Using Truven Health MarketScan claims data, bariatric surgery patients were identified by the ICD-9-CM and CPT procedure codes for bariatric surgery and classified by surgery and IDA diagnosis within 2 years of initial surgery. Intravenous (IV) iron treatment was determined by HCPCS codes, prescription oral iron by NDC numbers, and blood transfusions by CPT and ICD-9-CM codes. Clinical, MRU, and economic outcomes for all-cause health services were compared between IDA and non-IDA patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, controlling for demographic and clinical characteristics on outcomes of complications and hospitalization. RESULTS: Of the 24,344 bariatric surgery patients analyzed, 11.6% received an IDA diagnosis 2 years after surgery (average days to diagnosis = 279). Most IDA patients (78.5%) received a test for iron in the post-index period; only 9.1% received IV iron treatment, with iron dextran (3.8%) and iron sucrose (3.4%) being the most common (average days to IV iron treatment = 403 days). Prescription oral iron was found in 4.9% of all IDA patients (average days to oral iron treatment = 476.7). Approximately 9% of IDA patients received a blood transfusion (average days to transfusion = 304.8). For the total sample, the average age was 46 years with a higher percentage of females (83.9% IDA; 78.7% non-IDA). Most clinical characteristics were similar among patients with and without IDA, except heart disease (1.3% IDA vs. 0.8% non-IDA; P = 0.005) and gallbladder disease (0.0% IDA vs. 0.2% non-IDA; P = 0.037). More IDA patients had complications after surgery (40.4% vs. 27.7%; P less than 0.001), such as nonabsorption (22.4% vs. 16.5%; P less than 0.001); digestive (15.6% vs. 10.2%; P less than 0.001); and gastrojejunal ulcer (7.6% vs. 2.0%; P less than 0.001). Multivariate results showed that IDA patients were more likely to have a bariatric surgery complication over non-IDA patients (OR = 1.367, 95% CI = 1.257-1.487; P less than 0.05). Adjusted results showed IDA patients more than twice as likely to be hospitalized (OR = 2.567, 95% CI = 2.363-2.790; P less than 0.05). Total costs were twice as much in the IDA group compared with the non-IDA group ($37,882 vs. $19,253; P less than 0.001).  CONCLUSIONS: Bariatric surgery patients who develop IDA may be subject to higher complication rates, MRU, and direct medical costs. Although most bariatric surgery patients who develop IDA are tested for iron, most are not treated with IV iron or oral iron and do not receive blood transfusions. Further research is needed to determine if IDA is a result of bariatric surgery complications or a predictor of increased MRU and costs.

Medical resource utilization and costs associated with autosomal dominant polycystic kidney disease in the USA: a retrospective matched cohort analysis of private insurer data.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) results in kidney cyst development and enlargement, resulting in chronic kidney disease (CKD) leading to renal failure. This study sought to determine if ADPKD patients in the early stages of CKD contribute to a sizable economic burden for the US health care system. METHODS: This was a retrospective, matched cohort study, reviewing medical resource utilization (MRU) and costs for adults in a US private-payer claims database with a diagnosis code of ADPKD (ICD-9-CM 753.13). ADPKD patients were matched by age grouping (0-17, 18-34, 35-44, 45-54, 55-64, and 65+ years) and sex to controls to understand the burden of ADPKD. Descriptive statistics on 6-month MRU and costs were assessed by CKD stages, dialysis use, or previous renal transplant. RESULTS: The analysis included ADPKD patients in CKD stages 1-5 (n=316 to n=860), dialysis (n=586), and post-transplant (n=615). Mean ages did not differ across CKD stages (range 43-56 years). Men were the majority in the later stages but the minority in the early stages. The proportion of patients with at least one hospitalization increased with CKD stage, (12% to >40% CKD stage 2 to stage 5, dialysis or post-transplant). The majority had at least one hospital outpatient visit and at least one pharmacy claim. Total 6-month per-patient costs were greater among ADPKD patients than in age-matched and sex-matched healthy non-ADPKD controls (P<0.001 for all comparisons). CONCLUSION: ADPKD patients with normal kidney function are associated with a significant economic burden to the health care system relative to the general population. Any treatments that delay progression to later stages of CKD may provide potential health care cost offsets.

Risk of constipation in patients prescribed fentanyl transdermal system or oxycodone hydrochloride controlled-release in a California Medicaid population.

OBJECTIVE: To compare the risk of developing constipation between patients prescribed fentanyl transdermal system or oxycodone hydrochloride (HCl) controlled-release. DESIGN: California Medicaid (Medi-Cal) claims data. SETTING: Medicaid beneficiaries in California. PARTICIPANTS: Chronic pain patients who received a prescription for transdermal fentanyl or oxycodone controlled-release between October 1, 1997, and February 28, 2000, for at least three consecutive months. MAIN OUTCOME MEASURES: Constipation was defined using the International Classification of Diseases, Ninth Revision, Clinical Modification code (ICD-9-CM 564.0). The association between long-acting opioid use and constipation was determined by multivariate logistic regression after controlling for drug strength, short-acting opioid usage, and comorbidities. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were reported. RESULTS: A total of 2,095 patients were included in the regression analysis (transdermal fentanyl = 877; oxycodone controlled-release = 1,218). Seventy-five patients received a constipation diagnosis (transdermal fentanyl = 28; oxycodone controlled-release = 47). Approximately 40% of patients were at least 65 years of age. Overall, oxycodone controlled-release patients had a significantly greater risk of developing constipation compared with transdermal fentanyl patients (transdermal fentanyl: n = 877; oxycodone controlled-release: n=1,218; OR = 2.55; 95% CI = 1.33-4.89; P = 0.005). Among patients who were 65 years or older, oxycodone controlled-release patients were 7.33 times more likely to be constipated than transdermal fentanyl patients (transdermal fentanyl: n = 518; oxycodone controlled-release: n = 317; OR = 7.33; 95% CI = 1.98-27.13; P = 0.003). CONCLUSION: These findings suggest that patients prescribed transdermal fentanyl may have a significantly lower risk of developing constipation compared with oxycodone controlled-release, particularly in the elderly.

Nonoperative care to manage sacroiliac joint disruption and degenerative sacroiliitis: high costs and medical resource utilization in the United States Medicare population.

OBJECT: Low-back pain (LBP) is highly prevalent among older adults, and the cost to treat the US Medicare population is substantial. Recent US health care reform legislation focuses on improving quality of care and reducing costs. The sacroiliac (SI) joint is a recognized generator of LBP, but treatments traditionally have included either nonoperative medical management or open SI joint fusion, which has a high rate of complications. New minimally invasive technologies have been developed to treat SI joint disruption and degenerative sacroiliitis, so it is important to understand the current cost impact of nonoperative care to the Medicare program. The objective of this study was to evaluate the medical resource use and associated Medicare reimbursement for patients managed with nonoperative care for degenerative sacroiliitis/SI joint disruption. METHODS: A retrospective study was conducted using claim-level data from the Medicare 5% Standard Analytical Files (SAFs) for the years 2005-2010. Included were patients with a primary ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis code for degenerative sacroiliitis/SI joint disruption (ICD-9-CM diagnosis codes 720.2, 724.6, 739.4, 846.9, or 847.3) with continuous enrollment for at least 1 year before and 5 years after diagnosis. Claims attributable to degenerative sacroiliitis/SI joint disruption were identified using ICD-9-CM diagnosis codes (claims with a primary or secondary ICD-9-CM diagnosis code of 71x.xx, 72x.xx, 73x.xx, or 84x.xx), and the 5-year medical resource use and Medicare reimbursement (in 2012 US dollars) were tabulated across practice settings. A subgroup analysis was performed among patients who underwent lumbar spinal fusion. RESULTS: Among all Medicare patients with degenerative sacroiliitis or SI joint disruption (n = 14,552), the mean cumulative 5-year direct medical costs attributable to degenerative sacroiliitis/SI joint disruption was $18,527 ± $28,285 (± SD) per patient. The cumulative 5-year cost was $63,913 ± $46,870 per patient among the subgroup of patients who underwent lumbar spinal fusion (n = 538 [3.7%]) and $16,769 ± $25,753 per patient among the subgroup of patients who had not undergone lumbar spinal fusion (n = 14,014 [96.3%]). For the total population, the largest proportion of cumulative 5-year costs was due to inpatient hospitalization (42.1%), outpatient physician office (20.6%), and hospital outpatient costs (14.9%). The estimated cumulative 5-year Medicare reimbursement across practice settings attributable to SI joint disruption or degenerative sacroiliitis is approximately $270 million among these 14,552 Medicare beneficiaries ($18,527 per patient). CONCLUSIONS: In patients who suffer from LBP due to SI joint disruption or degenerative sacroiliitis, this retrospective Medicare claims data analysis demonstrates that nonoperative care is associated with substantial costs and medical resource utilization. The economic burden of SI joint disruption and degenerative sacroiliitis among Medicare beneficiaries in the US is substantial and highlights the need for more cost-effective therapies to treat this condition and reduce health care expenditures.

Management of sacroiliac joint disruption and degenerative sacroiliitis with nonoperative care is medical resource-intensive and costly in a United States commercial payer population.

INTRODUCTION: Low back pain is common and originates in the sacroiliac (SI) joint in 15%-30% of cases. Traditional SI joint disruption/degenerative sacroiliitis treatments include nonoperative care or open SI joint fusion. To evaluate the usefulness of newly developed minimally-invasive technologies, the costs of traditional treatments must be better understood. We assessed the costs of nonoperative care for SI joint disruption to commercial payers in the United States (US). METHODS: A retrospective study of claim-level medical resource use and associated costs used the MarketScan® Commercial Claims and Encounters as well as Medicare Supplemental Databases of Truven Healthcare. Patients with a primary ICD-9-CM diagnosis code for SI joint disruption (720.2, 724.6, 739.4, 846.9, or 847.3), an initial date of diagnosis from January 1, 2005 to December 31, 2007 (index date), and continuous enrollment for ≥1 year before and 3 years after the index date were included. Claims attributable to SI joint disruption with a primary or secondary ICD-9-CM diagnosis code of 71x.xx, 72x.xx, 73x.xx, or 84x.xx were identified; the 3-year medical resource use-associated reimbursement and outpatient pain medication costs (measured in 2011 US dollars) were tabulated across practice settings. A subgroup analysis was performed among patients with lumbar spinal fusion. RESULTS: The mean 3-year direct, attributable medical costs were $16,196 (standard deviation [SD] $28,592) per privately-insured patient (N=78,533). Among patients with lumbar spinal fusion (N=434), attributable 3-year mean costs were $91,720 (SD $75,502) per patient compared to $15,776 (SD $27,542) per patient among patients without lumbar spinal fusion (N=78,099). Overall, inpatient hospitalizations (19.4%), hospital outpatient visits and procedures (14.0%), and outpatient pain medications (9.6%) accounted for the largest proportion of costs. The estimated 3-year insurance payments attributable to SI joint disruption were $1.6 billion per 100,000 commercial payer beneficiaries. CONCLUSION: The economic burden of SI joint disruption among privately-insured patients in the US is substantial, highlighting the need for more cost-effective therapies.

Comparison of the costs of nonoperative care to minimally invasive surgery for sacroiliac joint disruption and degenerative sacroiliitis in a United States commercial payer population: potential economic implications of a new minimally invasive technology.

INTRODUCTION: Low back pain is common and treatment costly with substantial lost productivity and lost wages in the working-age population. Chronic low back pain originating in the sacroiliac (SI) joint (15%-30% of cases) is commonly treated with nonoperative care, but new minimally invasive surgery (MIS) options are also effective in treating SI joint disruption. We assessed whether the higher initial MIS SI joint fusion procedure costs were offset by decreased nonoperative care costs from a US commercial payer perspective. METHODS: An economic model compared the costs of treating SI joint disruption with either MIS SI joint fusion or continued nonoperative care. Nonoperative care costs (diagnostic testing, treatment, follow-up, and retail pharmacy pain medication) were from a retrospective study of Truven Health MarketScan(®) data. MIS fusion costs were based on the Premier's Perspective™ Comparative Database and professional fees on 2012 Medicare payment for Current Procedural Terminology code 27280. RESULTS: The cumulative 3-year (base-case analysis) and 5-year (sensitivity analysis) differentials in commercial insurance payments (cost of nonoperative care minus cost of MIS) were $14,545 and $6,137 per patient, respectively (2012 US dollars). Cost neutrality was achieved at 6 years; MIS costs accrued largely in year 1 whereas nonoperative care costs accrued over time with 92% of up front MIS procedure costs offset by year 5. For patients with lumbar spinal fusion, cost neutrality was achieved in year 1. CONCLUSION: Cost offsets from new interventions for chronic conditions such as MIS SI joint fusion accrue over time. Higher initial procedure costs for MIS were largely offset by decreased nonoperative care costs over a 5-year time horizon. Optimizing effective resource use in both nonoperative and operative patients will facilitate cost-effective health care delivery. The impact of SI joint disruption on direct and indirect costs to commercial insurers, health plan beneficiaries, and employers warrants further consideration.

Health-resource use and costs associated with fibromyalgia in France, Germany, and the United States.

BACKGROUND: Fibromyalgia (FM) is a chronic disorder characterized by widespread, persistent pain. Prospective and retrospective studies have demonstrated substantial health-care costs associated with FM in a number of countries. This study evaluated and compared health-resource use (HRU) and associated costs related to FM in routine clinical practice across the US, France, and Germany. METHODS: Two separate, cross-sectional, observational studies of subjects with FM were conducted: one in the US and one in France and Germany. HRU related to prescription medication, physician office visits, diagnostic tests, and hospitalizations was abstracted from chart review; patient out-of-pocket costs and lost productivity were collected via subject self-report. Costs were assigned to HRU based on standard algorithms. Direct and indirect costs were evaluated and compared by simple linear regression. RESULTS: A total of 442 subjects (203 US, 70 France, 169 Germany) with FM were analyzed. The mean (standard deviation) age in the US, France, and Germany was 47.9 (10.9), 51.2 (9.5), and 49.2 (9.8), respectively (P = 0.085). Most subjects were female (95% US, 83% France, 80% Germany) (P < 0.001). Adjusted annual direct costs per subject for FM were significantly higher in the US ($7087) than in France ($481, P < 0.001) or Germany ($2417, P < 0.001). Adjusted mean annual indirect costs per subject for FM were lower in the US ($6431) than in France ($8718) or Germany ($10,001), but represented a significant proportion of total costs in all countries. CONCLUSION: The significant HRU and costs associated with FM in the US, France, and Germany documented in this study highlight the substantial global economic burden of FM. Indirect costs represented a significant proportion of the total costs, particularly in Europe. Comparisons between the three countries show differences in HRU, with significantly higher direct costs in the US compared with France and Germany.

Comparison of the costs of nonoperative care to minimally invasive surgery for sacroiliac joint disruption and degenerative sacroiliitis in a United States Medicare population: potential economic implications of a new minimally-invasive technology.

INTRODUCTION: The economic burden associated with the treatment of low back pain (LBP) in the United States is significant. LBP caused by sacroiliac (SI) joint disruption/degenerative sacroiliitis is most commonly treated with nonoperative care and/or open SI joint surgery. New and effective minimally invasive surgery (MIS) options may offer potential cost savings to Medicare. METHODS: An economic model was developed to compare the costs of MIS treatment to nonoperative care for the treatment of SI joint disruption in the hospital inpatient setting in the US Medicare population. Lifetime cost savings (2012 US dollars) were estimated from the published literature and claims data. Costs included treatment, follow-up, diagnostic testing, and retail pharmacy pain medication. Costs of SI joint disruption patients managed with nonoperative care were estimated from the 2005-2010 Medicare 5% Standard Analytic Files using primary International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes 720.2, 724.6, 739.4, 846.9, or 847.3. MIS fusion hospitalization cost was based on Diagnosis Related Group (DRG) payments of $46,700 (with major complications - DRG 459) and $27,800 (without major complications - DRG 460), weighted assuming 3.8% of patients have complications. MIS fusion professional fee was determined from the 2012 Medicare payment for Current Procedural Terminology code 27280, with an 82% fusion success rate and 1.8% revision rate. Outcomes were discounted by 3.0% per annum. RESULTS: The extrapolated lifetime cost of treating Medicare patients with MIS fusion was $48,185/patient compared to $51,543/patient for nonoperative care, resulting in a $660 million savings to Medicare (196,452 beneficiaries at $3,358 in savings/patient). Including those with ICD-9-CM code 721.3 (lumbosacral spondylosis) increased lifetime cost estimates (up to 478,764 beneficiaries at $8,692 in savings/patient). CONCLUSION: Treating Medicare beneficiaries with MIS fusion in the hospital inpatient setting could save Medicare $660 million over patients' lifetimes.