An observational analysis of disease burden in patients with cold agglutinin disease: Results from a large US electronic health record database.

BACKGROUND: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia (AIHA). Information regarding the impact of CAD from the patient and health care system perspective is limited. OBJECTIVE: To understand longitudinal trends in outcomes in patients with CAD, including anemia severity, hemolytic status, administration of CAD-related therapies, and health care resource utilization (HCRU). METHODS: This retrospective, observational cohort study used data from the US Optum Electronic Health Record database. Included patients were aged 18 years and older at the index date (first CAD mention in physician"s notes), had 1 or more medical encounters with an AIHA-related diagnosis code during the study period, and had 3 or more CAD mentions during the patient identification period (January 2008 to March 2019). The baseline period was the 12 months preceding the index date. Anemia severity (severe, hemoglobin < 8.0 g/dL; moderate, 8.0-10.0 g/dL; mild, 10.1-11.9 g/dL; no anemia, ≥ 12.0 g/dL) and hemolytic status (elevated lactate dehydrogenase [LDH; > 250 µ/L] and/or elevated bilirubin [> 1.2 mg/dL]) were assessed at baseline and 6-monthly followup intervals. Use of CAD-related therapies, blood transfusions, and all-cause HCRU were analyzed every 6 months; results were stratified by anemia severity. RESULTS: The analysis included 610 adults with CAD (median [interquartile range; IQR] age 72.0 [61.0-78.0] years; 65.4% female). Median (IQR) duration of follow-up was 42.8 (22.8-68.4) months. The proportion of patients with moderate/severe anemia was 51.0% at baseline, 57.7% over 12 months' follow-up, and 66.6% over full follow-up. During the full follow-up period, approximately 50% of patients had elevated bilirubin and LDH levels. Corticosteroids were the most frequently used medication (65.6% of patients) over full follow-up. Mean (SD) number of blood transfusions per patient was 3.26 (9.21) over 12 months and 5.47 (17.11) over the full follow-up. At full follow-up, 68.7% of patients with severe anemia received a transfusion vs 12.6% and 0.0% with moderate or mild anemia, respectively. At 12 months, 34.1%, 97.7%, and 29.3% of patients had 1 or more hospitalizations, outpatient services, or emergency department visits (full follow-up: 52.5%, 99.0%, and 53.9%), respectively. Across all time periods, HCRU was greater in patients with severe anemia vs mild or moderate anemia. CONCLUSIONS: CAD imposed a substantial long-term burden on patients and health care systems, and despite the use of several therapies, hemolysis and anemia still occurred. The use of CAD-related therapies and HCRU was generally greater with greater anemia severity. These results suggest a lack of effective treatment options available for patients with CAD at the time of this analysis. DISCLOSURES: This study was sponsored by Sanofi. Dr Wilson, Dr Joly, Mr Carita, and Ms Miles are employees and stockholders of Sanofi. Dr Adeyemi was an employee and may have held stocks at Sanofi at the time of the study. Ms Miles and Ms Kuang were employees of Aetion Inc at the time of this study; Aetion Inc is a software company that received funding from Sanofi for the current study. Dr Pham is a consultant for Sanofi and Argenx.

Epidemiology, treatment patterns, clinical outcomes, and disease burden among patients with immune-mediated thrombotic thrombocytopenic purpura in the United States.

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy. Due to its rarity, epidemiology and real-world outcomes data are scarce. Objectives: The aim was to assess epidemiology, treatment patterns, clinical outcomes, and disease burden in patients with iTTP in the United States. Methods: This longitudinal, retrospective observational study of the Optum-Humedica database included patients with an iTTP diagnosis (≥1 documented ADAMTS13 activity less than 10% or one or more iTTP episodes) from January 2007 to December 2019. Results: Of 666 patients with an iTTP diagnosis between October 2015 and December 2019, 302 (45%) had one or more iTTP episodes. The pooled annual incidence of documented iTTP during this period was 3.43/million, and the annual incidence of one or more iTTP episodes was 1.81/million. Patients with one or more iTTP episodes received a median of six therapeutic plasma exchange (TPE) sessions per episode; 86% received corticosteroids, and 59% received rituximab. Exacerbations occurred in 17% (52/302) and relapse in 11% (34/302); 34% (103/302) had one or more thromboembolic events. Mortality rates during the study period were 25% (167/666) among all patients with iTTP diagnosis, and 14% (41/302) among patients with one or more iTTP episodes. In the assessment of disease burden (January 2007 to September 2019), patients in the iTTP cohort (n = 514) presented with a mean of 14 comorbidities, compared with 3 in a matched non-iTTP cohort (n = 2570). In a cluster analysis, duration of iTTP episode and mortality rate were greater in older versus younger patients. Conclusions: Despite treatment with TPE and immunosuppressants, patients with iTTP have high risk of morbidity and mortality, demonstrating the need for more effective therapies.

Cost-effectiveness analysis of Coblation versus mechanical shaver debridement in patients following knee chondroplasty.

BACKGROUND: To compare costs and outcomes following knee chondroplasty with Coblation versus mechanical shaver debridement (MSD) in patients with grade III articular cartilage lesions of the knee. METHODS: A decision-analytic model was developed to compare costs and outcomes of the two methods from a US payer perspective. We used published clinical data from a single-center randomized clinical trial (RCT) designed to compare outcomes between Coblation and MSD in patients with grade III articular cartilage lesions of the medial femoral condyle. Following primary knee chondroplasty, patients experienced either treatment success (no additional surgery required) or required a revision over the 4 year follow-up period. Costs associated with the initial chondroplasty, physical therapy sessions through the 6 week postoperative period, and revision rates at 4 years post-surgery were estimated using 2018 US Medicare Physician Fee Schedule. Sensitivity analyses including a 10 year time horizon and threshold analyses were performed to test the robustness of the model. RESULTS: The estimated total cost per patient was $4614 and $7886 for Coblation and MSD, respectively, resulting in cost-savings of $3272 in favor of Coblation, making it a dominant strategy because of lower costs and improved clinical outcomes. Threshold analysis showed that Coblation remained dominant even when revision rates were assumed to increase from the base case rate of 14-66%. Sensitivity analyses showed that cost-saving results were insensitive to variations in revision rates, number of physical therapy sessions and the time horizon used. CONCLUSION: Coblation chondroplasty is a cost-saving procedure compared with MSD in the treatment of patients with grade III articular cartilage lesions of the knee.

Incidence and Economic Burden of Intertrochanteric Fracture: A Medicare Claims Database Analysis.

BACKGROUND: There is limited information on current cost estimates associated with intertrochanteric hip fractures in the United States. The purpose of the present study was to estimate the incidence and economic burden of both intertrochanteric and all hip fracture types in the Medicare patient population to the U.S. health-care system. METHODS: This retrospective database analysis of the 2014 Medicare database involved Standard Analytic File (SAF) 5% sample claims and total enrollment files. Patients ≥65 years of age with a new principal diagnosis of hip fracture (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 820.xy) who were continuously enrolled for 18 months were included; those with intertrochanteric hip fracture were further identified with use of ICD-9-CM code 820.21. The total direct medical costs associated with hip fracture in the 90-day and 12-month post-fracture periods were estimated. The relevant costs were estimated on the basis of a propensity-score-matched analysis. The health-care services responsible for major expenses within the 90-day episode-of-care period were also identified. RESULTS: The total annual direct medical costs associated with all hip fractures was $50,508 per patient, resulting in a yearly estimate of $5.96 billion to the U.S. health-care system. Intertrochanteric hip fractures accounted for an annual estimate of $52,512 per patient, corresponding to an overall annual economic burden of $2.63 billion to the U.S. health-care system and representing 44% of all hip fracture costs. Inpatient hospitalization and skilled nursing facility services jointly accounted for 76.3% of the $44,135 estimated cost per patient and 75.6% of the $42,388 estimated cost per patient within the 90-day post-acute care period for intertrochanteric and all hip fractures, respectively. CONCLUSIONS: Hip fracture represents a substantial economic burden to the U.S. health-care system, accounting for $5.96 billion per year, with intertrochanteric hip fracture accounting for 44% of total costs. LEVEL OF EVIDENCE: Economic and decision analysis, Level IV. See Instructions for Authors for a complete description of levels of evidence. CLINICAL RELEVANCE: The present study provides a comprehensive and updated annual estimate of the economic burden of all hip fracture types and estimates the economic burden of intertrochanteric hip fractures in the Medicare population; to our knowledge, prior availability of this information in the literature is limited.

Economic burden of surgical site infections within the episode of care following joint replacement.

BACKGROUND: Recent policy initiatives, including Bundled Payments for Care Improvement (BPCI) Initiative by the Centers for Medicare and Medicaid Health Services (CMS), encourage healthcare providers to manage the total episode of care, rather than just the surgical episode. Surgical site infections (SSI) following total joint replacement result in preventable morbidity and suffering for patients and excess healthcare utilization for healthcare providers. This study sought to estimate the additional resources associated with SSIs within the 90-day episode of care following hip and knee joint replacement. METHODS: Using the 2013 Nationwide Readmissions Database (NRD), healthcare resource utilization was compared between propensity score matched patient groups with and without SSI-related readmissions within the 90-day episode of care following total joint replacement. RESULTS: Surgical site infections were associated with significantly longer hospital length of stay and increased costs following hip and knee joint replacement procedures. Generalized estimating equation regression results confirmed that additional costs associated with SSIs following both cohorts were significant, with additional hospital length of stay and costs following total hip and knee replacement procedures ranging from 4.9 to 5.2 days and $12,689 to $12,890, respectively. CONCLUSION: Surgical site infections following total joint replacement account for significant additional healthcare resource use within the 90-day episode of care.

Cost-minimization Analysis of Negative Pressure Wound Therapy in Long-term Care Facilities.

OBJECTIVE: This study aims to conduct a cost-minimization analysis comparing wound treatment costs between single-use negative pressure wound therapy (sNPWT) and traditional negative pressure wound therapy (tNPWT). MATERIALS AND METHODS: Assuming comparable outcomes, cost data obtained from the ECRI Institute were compared between the 2 NPWT options using data extracted from an electronic wound management program between August 2010 and March 2016. RESULTS: Use of sNPWT versus tNPWT resulted in daily and total treatment duration cost savings of $55 and $1586, respectively. CONCLUSIONS: Long-term care facilities can potentially accrue significant cost savings by using sNPWT instead of tNPWT on a majority of eligible wounds.

Impact of a telephonic outreach program on medication adherence in Medicare Advantage Prescription Drug (MAPD) plan beneficiaries.

OBJECTIVES: To determine the impact of a telephone call reminder program provided by a campus-based medication therapy management call center on medication adherence in Medicare Advantage Part D (MAPD) beneficiaries with hypertension. METHODS: The reminder call services were offered to eligible MAPD beneficiaries, and they included a live interactive conversation with patients to assess the use of their medications. This study used a quasi-experimental design for comparing the change in medication adherence between the intervention and matched control groups. Adherence, defined by proportion of days covered (PDC), was measured using incurred medication claims 6 months before and after the adherence program was implemented. A difference-in-differences approach with propensity score matching was used. RESULTS: After propensity score matching, paired samples included 563 patients in each of the intervention and control groups. The mean PDC (standard deviation) increased significantly during postintervention period by 17.3% (33.6; P <0.001) and 13.8% (32.3; P <0.001) for the intervention and the control groups, respectively; the greater difference-in-differences increase of 3.5% (36.3) in the intervention group over the control group was statistically significant (P = 0.022). A generalized estimating equation model adjusting for covariates further confirmed that the reminder call group had a significant increase in pre-post PDC (P = 0.021), as compared with the control group. CONCLUSIONS: Antihypertensive medication adherence increased in both reminder call and control groups, but the increase was significantly higher in the intervention group. A telephonic outreach program was effective in improving antihypertensive medication adherence in MAPD beneficiaries.

Extrahepatic Manifestations of Hepatitis C: A Meta-analysis of Prevalence, Quality of Life, and Economic Burden.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has hepatic and extrahepatic manifestations with various costs and impairments to health-related quality of life (HRQL). We performed a meta-analysis to determine the prevalence of extrahepatic manifestations in patients with HCV infection, how these impair HRQL, and their costs. METHODS: We performed systematic reviews of the literature using MEDLINE, CINAHL, and the Cochrane Systematic Review Database, from 1996 through December 2014, to identify studies of the following extrahepatic manifestations of HCV infection: mixed cryoglobulinemia, chronic kidney or end-stage renal disease, type 2 diabetes, B-cell lymphoma, lichen planus, Sjögren's syndrome, porphyria cutanea tarda, rheumatoid-like arthritis, or depression. We performed a separate meta-analysis for each condition to determine prevalence rates of extrahepatic manifestations of HCV infection and their effects on HRQL. We determined the annual costs (inpatient, outpatient, and pharmacy) associated with extrahepatic manifestations of HCV infection. RESULTS: In an analysis of data from 102 studies, we found the most common extrahepatic manifestations to be diabetes (in 15% of patients) and depression (in 25% of patients). HRQL data showed that HCV infection had negative effects on overall physical and mental health. Total direct medical costs of extrahepatic manifestations of HCV infection, in 2014 US dollars, were estimated to be $1506 million (range, $922 million-$2208 million in sensitivity analysis). CONCLUSIONS: In a systematic review and meta-analysis we determined the prevalence, risks, and costs associated with extrahepatic manifestations of HCV infection. These estimates should be added to the liver-related burden of disease to obtain a more accurate assessment of the total burden of chronic HCV infection. Prospective, real-world studies are needed to increase our understanding of the total clinical and economic effects of HCV infection and treatment on patients and society.

Direct Medical Costs and Utilization of Health Care Services to Treat Pneumonia in the United States: An Analysis of the 2007-2011 Medical Expenditure Panel Survey.

PURPOSE: This study aimed to assess how pneumonia incidence, health care resource utilization, costs, and hospital length of stay differ by age category in the United States. METHODS: A retrospective cross-sectional analysis of the Medical Expenditure Panel Survey database was conducted from 2007 to 2011 for patients with pneumonia. Study outcomes were pneumonia incidence, annual health care utilization, and expenditures across 5 age groups. Early trends of outcomes in the period after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) (2011) were compared with the pre-PCV13 period (2007-2009). FINDINGS: Pneumonia incidence rates for the 1790 patients ranged from 9.2 to 33.0 per 1000 patients. Patients <5 years old had the highest incidence rate at 33.0 per 1000 patients, followed by patients ≥65 years old (27.2 per 1000 patients) and patients ≥45 to <65 years old (14.4 per 1000 patients). The percentages of patients with pneumonia-related hospitalization were 26%, 7%, 15%, 24%, and 46%, respectively (P < 0.0001). Mean (SD) days in hospital stay were 1.73 (0.08), 0.31 (0.50), 0.58 (0.10), 1.86 (0.29), and 3.05 (0.33), respectively (P < 0.05), for patients <5, ≥5 to <18, ≥18 to <45, ≥45 to <65, and ≥65 years old. Mean total pneumonia-related medical costs in patients aged <5 years ($3376; P = 0.009), ≥45 to ≤65 years ($4726; P < 0.0001), and >65 years ($7206; P < 0.0001) were significantly higher compared with patients ≥5 to <18 years old ($1175) after controlling for covariates. Compared with the pre-PCV13 period (2007-2009; n = 1075), a 16% decrease in incidence, a 27% decrease length of stay in hospital, and a 22% decrease in medical costs were observed in the post-PCV13 period (2011; n = 382), although these differences were not statistically significant (P > 0.05). IMPLICATIONS: Pneumonia remains a disease with significant burden in the United States, and clinical and economic outcomes varied widely by age. Hospitalization for pneumonia has a considerable effect on economic burden, particularly for the very young (<5 years old), middle-aged (≥45 to <65 years old), and elderly (≥65 years old) populations. A trend toward reductions in pneumonia incidence and associated medical costs was observed after the PCV13 was introduced, although these findings were not statistically significant.

Adherence to oral diabetes medications among users and nonusers of antipsychotic medication.

OBJECTIVE: This study compared adherence to oral diabetes medications among users and nonusers of oral antipsychotic medications. Adherence to oral antidiabetics and antipsychotics among antipsychotic users was also compared. METHODS: Texas Medicaid prescription claims data from July 1, 2008, to December 31, 2011, were used to examine adherence to oral antidiabetics among users and nonusers of antipsychotics for 12 months after the first prescription for oral diabetes medication. Users and nonusers of antipsychotics were matched on the basis of their chronic disease score (CDS). Medication adherence was measured by proportion of days covered (PDC), and patients with a PDC value ≥.80 were considered to be adherent. Bivariate and multivariate analyses were used to compare adherence between cohorts. RESULTS: A total of 1,821 patients from each group were matched. The mean PDC for oral antidiabetics was significantly higher among antipsychotic users (.63) than nonusers (.55) (p<.001). About 37% (N=678) of antipsychotic users and 24% (N=473) of nonusers were adherent to oral antidiabetics. After adjustment for age, gender, CDS, and number of prescriptions, antipsychotic users were 2.10 times more likely than nonusers to be adherent to oral antidiabetics (p<.001). Antipsychotic users had higher mean PDC values for antipsychotic medications than for oral antidiabetics (.78±.25 versus .63±.29, p<.001). CONCLUSIONS: Adherence to oral antidiabetics in the Texas Medicaid population was better among antipsychotic medication users than nonusers, but overall adherence was poor for both groups. Low adherence rates highlight the need for interventions to help improve medication management.

Adherence to oral antidiabetic medications in the pediatric population with type 2 diabetes: a retrospective database analysis.

BACKGROUND: Little has been done in assessing adherence to oral antidiabetic (OAD) medications in the pediatric population presenting with type 2 diabetes. This study provided information on adherence rates in the Texas Medicaid pediatric population with type 2 diabetes, which is rare in the literature. The knowledge of adherence rates in the pediatric population with type 2 diabetes might help improve the care given to pediatric patients with type 2 diabetes. OBJECTIVE: To describe OAD medication use, and assess trends in medication adherence and persistence among Texas pediatric Medicaid patients. METHODS: Texas Medicaid prescription claims data of patients between 10 and 18 years of age, with at least 2 prescriptions of the same OAD medication from January 1, 2006 to December 31, 2009, were analyzed. Adherence was assessed using the medication possession ratio (MPR) as a proxy. RESULTS: A total of 3109 patients met the study's inclusion criteria. The mean (SD) age of the 3109 eligible patients was 14.2 (2.3) years; 60% were Hispanics, 14% were blacks, 13% were whites, and another 13% were other minority races; 67% of the population were females; and 91% were on metformin of the 6 OAD medications included in the study The overall mean (SD) MPR for patients was 44.69% (27.06%). Adherence differed by gender (P < 0.0001), race (P < 0.0001), and age category (P < 0.0001). Males had higher mean (SD) MPR (47.47% [27.42%]) compared with females (43.29% [26.78%]). Mean MPR for whites (50.04% [29.65%]) was significantly higher compared with blacks (44.24% [26.16%]) and Hispanics (42.50% [26.10%]). Patients ≤12 years of age had significantly higher mean MPR (48.82% [27.37%]) compared with those in older age categories. Logistic regression analysis suggested that age was significantly related (odds ratio [OR] = 0.91; 95% CI, 0.87-0.95) to being adherent (MPR ≥80%). Males were 25% (OR = 1.25; 95% CI, 1.02-1.53; P = 0.034) more likely to be adherent (MPR ≥80%) compared with females, and whites were twice as likely to be adherent (MPR ≥80%) compared with Hispanics (OR = 2.02; 95% CI, 1.54-2.66; P = 0.0012). Overall, mean (SD) days to nonpersistence was 108 (86) days. Persistence was significantly and negatively associated with age (P < 0.0001). White race was significantly related to longer persistence. CONCLUSION: Adherence and persistence to OAD medications in the selected Texas Medicaid pediatric population between 10 and 18 years was generally suboptimal, especially in adolescents.

Influence of starch steeping period on dimensionless disintegration values of a paracetamol tablet formulation.

In this study, tapioca starches obtained after different steeping periods, i.e. TS 24, TS 48 and TS 72, were used as disintegrants with corn starch BP as the standard disintegrant in a paracetamol tablet formulation. Two dimensionless disintegration quantities, T(N) and T(C) were used in the determination of the influence that steeping period of starch disintegrant would have on the crushing strength friability-disintegration time ratio (CSFR/DT). These quantities were used to assess the influence of steeping period, relative density and disintegrant concentration on CSFR/DT as well as to compare disintegrant efficiency. The results suggest that the CSFR/DT is more dependent on the disintegrant concentration than on steeping period and relative density. The study further showed that TS 72 is a more reliable disintegrant because its activity would not be influenced by changes in relative density of tablets. This work concludes that the T(N) would be more useful for quantitative assessment while T(C) is more relevant for qualitative assessment.