Disease severity predicts higher healthcare costs among hospitalized nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients in Spain.

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) presents many public health challenges, including a substantial impact on healthcare resource utilization and costs. There are important regional differences in the burden of NAFLD/NASH, and Spain-specific data are lacking. This retrospective, observational study examined the impact of liver disease severity, comorbidities, and demographics on healthcare resource utilization and costs in Spain.NAFLD/NASH patients in the Spanish National Health System's Hospital Discharge Records Database (1/1/2006 to 4/30/2017) were categorized into disease severity cohorts as NAFLD/NASH overall, NAFLD/NASH non-progressors, compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplant (LT), or hepatocellular carcinoma (HCC). Patients were followed from index date until the earliest of 6 months, disease progression, end of coverage, death, or end of study. Within each cohort, pre- and post-index healthcare resource utilization and costs per patient per month (PPPM) were calculated.A total of 8,205 patients (mean age 58.4; 54% male) were identified; 5,984 (72.9%) were non-progressors, 139 (1.7%) progressed to CC, 2,028 (24.7%) to DCC, 115 (1.4%) to LT, and 61 (0.7%) to HCC. Pre-index comorbidity burden was high across disease cohorts, and the frequency of comorbidities increased with disease severity. From pre- to post-index, average length of stay (LOS) increased significantly (23%-41%) as did all-cause PPPM costs (44%-46%), with significantly longer LOS and costs in patients with increasing disease severity.Progression of NAFLD/NASH was associated with significantly higher costs and longer LOS. A coordinated approach is needed to manage resources and costs in Spain.

Hospitalization costs and risk of mortality in adults with nonalcoholic steatohepatitis: Analysis of a French national hospital database.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has reached high prevalence, paralleling the obesity pandemic. The aggressive form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by fatty infiltration and inflammation of the liver, can progress to compensated cirrhosis (CC) and end-stage liver disease (ESLD: decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), and may ultimately require liver transplantation (LT). Real-world data on the burden of NAFLD/NASH are limited. This study aimed to evaluate the clinical and economic burden of NAFLD/NASH to the French hospital system. METHODS: This retrospective cohort study used data from the French PMSI-MCO database. Adults with NAFLD/NASH diagnosis identified between 2009 and 2015 were categorized into disease severity cohorts (NAFLD/NASH, CC, DCC, HCC, and LT). Demographic and clinical data were assessed at the index (diagnosis) date. Hospitalization resource utilization and costs were assessed in the pre- and post-index periods. Rates of liver disease progression and death were evaluated for each cohort. FINDINGS: During the median follow-up of 34.8 months, of the 131,656 patients included, 1491 patients developed CC (1.1%), 7846 developed DCC (5.9%), 1144 developed HCC (0.9%), and 52 required LT (0.04%). The diagnosis of NAFLD/NASH was associated with increasing annual costs: €7736 vs €5076 before the diagnosis. Rates of comorbidities, hospitalization resource utilization, and costs increased with disease progression. The rate of death at seven-year follow-up was 7.9% in NAFLD/NASH, CC: 18.0%, DCC: 34.9%, and HCC: 48.8%. INTERPRETATION: NAFLD/NASH is associated with high economic burden and imparts substantial risk of negative clinical outcomes and mortality at all stages of disease.

Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy.

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) may progress to advanced liver disease (AdvLD). This study characterized comorbidities, healthcare resource utilization (HCRU) and associated costs among hospitalized patients with AdvLD due to NASH in Italy. METHODS AND RESULTS: Adult nonalcoholic fatty liver disease (NAFLD)/NASH patients from 2011 to 2017 were identified from administrative databases of Italian local health units using ICD-9-CM codes. Development of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), or liver transplant (LT) was identified using first diagnosis date for each severity cohort (index-date). Patients progressing to multiple disease stages were included in >1 cohort. Patients were followed from index-date until the earliest of disease progression, end of coverage, death, or end of study. Within each cohort, per member per month values were annualized to calculate all-cause HCRU or costs(€) in 2017. Of the 9,729 hospitalized NAFLD/NASH patients identified, 97% were without AdvLD, 1.3% had CC, 3.1% DCC, 0.8% HCC, 0.1% LT. Comorbidity burden was high across all cohorts. Mean annual number of inpatient services was greater in patients with AdvLD than without AdvLD. Similar trends were observed in outpatient visits and pharmacy fills. Mean total annual costs increased with disease severity, driven primarily by inpatient services costs. CONCLUSION: NAFLD/NASH patients in Italy have high comorbidity burden. AdvLD patients had significantly higher costs. The higher prevalence of DCC compared to CC in this population may suggest challenges of effectively screening and identifying NAFLD/NASH patients. Early identification and effective management are needed to reduce risk of disease progression and subsequent HCRU and costs.

Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data.

BACKGROUND: Risk factors and timing associated with disease progression and mortality in nonalcoholic fatty liver disease (NAFLD) are poorly understood. AIMS: To evaluate the impact of disease severity, demographics and comorbidities on risk of mortality and time to progression in a large, real-world cohort of diagnosed NAFLD patients. METHODS: Claims data from a 20% Medicare representative sample between 2007 and 2015 were analysed retrospectively. Adults were categorised into disease severity groups: NAFLD/nonalcoholic steatohepatitis (NASH) alone, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma. Cumulative incidence of mortality and disease progression were calculated for each group and multivariate analyses performed adjusting for demographics, comorbidities and disease severity. RESULTS: A total of 10 826 456, patients were assessed and the prevalence of NAFLD was 5.7% (N = 621 253). Among patients with NAFLD, 71.1% had NAFLD/NASH alone and 28.9% had NAFLD cirrhosis. Overall, 85.5% of patients had hypertension, 84.1% dyslipidemia, 68.7% had cardiovascular disease and 55.5% diabetes. The cumulative risk of progression of NAFLD to cirrhosis, and compensated cirrhosis to decompensated cirrhosis was 39% and 45%, respectively, over 8 years of follow-up. The independent predictors of progression included cardiovascular disease, renal impairment, dyslipidemia and diabetes. The cumulative risk of mortality for NAFLD, NAFLD cirrhosis, decompensated cirrhosis and hepatocellular carcinoma was 12.6%, 31.1%, 51.4% and 76.2%, respectively. CONCLUSIONS: The present report (a) demonstrates that NAFLD is grossly underdiagnosed in real-world clinical settings and (b) provides new evidence on the progression rates of NAFLD and risk factors of mortality across the spectrum of severity of NAFLD and cirrhosis.

Idelalisib addition has neutral to beneficial effects on quality of life in bendamustine/rituximab-treated patients: results of a phase 3, randomized, controlled trial.

BACKGROUND: In a phase 3 randomized, double-blind, placebo-controlled trial, treatment with idelalisib, a phosphoinositol-3 kinase δ inhibitor, + bendamustine/rituximab improved progression-free survival (PFS) and overall survival (OS) in adult patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Here we report the results of health-related quality of life (HRQL) analyses from this study. METHODS: From June 15, 2012 to August 21, 2014, 416 patients with R/R CLL were enrolled; 207 patients were randomized to the idelalisib arm and 209 to the placebo arm. In the 416 patients randomized to receive bendamustine/rituximab and either oral idelalisib 150 mg twice-daily or placebo, HRQL was assessed at baseline and throughout the blinded part of the study using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL Five-Dimension (EQ-5D) visual analogue scale (VAS) questionnaires. The assessments were performed at scheduled patient visits; every 4 weeks for the first 6 months from the initiation of treatment, then every 8 weeks for the next 6 months, and every 12 weeks thereafter until end of study. Least-squares mean changes from baseline were estimated using a mixed-effects model by including treatment, time, and treatment-by-time interaction, and stratification factors as fixed effects. Time to first symptom improvement was assessed by Kaplan-Meier analysis. RESULTS: In mixed-effects model analysis, idelalisib + bendamustine/rituximab treatment led to clinically meaningful improvements from baseline in leukemia-associated symptoms. Moreover, per Kaplan-Meier analysis, the proportion of patients with symptom improvement was higher and time to improvement was shorter among patients in the idelalisib-containing arm compared with those who did not receive idelalisib. The physical and social/family FACT-Leu subscale scores, along with the self-rated health assessed by EQ-VAS, showed improvement with idelalisib over placebo, but the difference did not reach statistical significance. The functional and emotional FACT-Leu subscale scores remained similar to placebo. CONCLUSIONS: Addition of idelalisib to bendamustine/rituximab, apart from improving PFS and OS, had a neutral to beneficial impact on HRQL in patients with R/R CLL, particularly by reducing leukemia-specific disease symptoms. TRIAL REGISTRATION: Clinicaltrials.gov NCT01569295. Registered April 3, 2012.

Red blood cell (RBC) transfusion rates among US chronic dialysis patients during changes to Medicare end-stage renal disease (ESRD) reimbursement systems and erythropoiesis stimulating agent (ESA) labels.

BACKGROUND: Several major ESRD-related regulatory and reimbursement changes were introduced in the United States in 2011. In several large, national datasets, these changes have been associated with decreases in erythropoiesis stimulating agent (ESA) utilization and hemoglobin concentrations in the ESRD population, as well as an increase in the use of red blood cell (RBC) transfusions in this population. Our objective was to examine the use of RBC transfusion before and after the regulatory and reimbursement changes implemented in 2011 in a prevalent population of chronic dialysis patients in a large national claims database. METHODS: Patients in the Truven Health MarketScan Commercial and Medicare Databases with evidence of chronic dialysis were selected for the study. The proportion of chronic dialysis patients who received any RBC transfusion and RBC transfusion event rates per 100 patient-months were calculated in each month from January 1, 2007 to March 31, 2012. The results were analyzed overall and stratified by primary health insurance payer (commercial payer or Medicare). RESULTS: Overall, the percent of chronic dialysis patients with RBC transfusion and RBC transfusion event rates per 100 patient-months increased between January 2007 and March 2012. When stratified by primary health insurance payer, it appears that the increase was driven by the primary Medicare insurance population. While the percent of patients with RBC transfusion and RBC transfusion event rates did not increase in the commercially insured population between 2007 and 2012 they did increase in the primary Medicare insurance population; the majority of the increase occurred in 2011 during the same time frame as the ESRD-related regulatory and reimbursement changes. CONCLUSIONS: The regulatory and reimbursement changes implemented in 2011 may have contributed to an increase in the use of RBC transfusions in chronic dialysis patients in the MarketScan dataset who were covered by Medicare plus Medicare supplemental insurance.

Synchronization of administrations of chemotherapy and erythropoiesis-stimulating agents and frequency of associated healthcare visits.

PURPOSE: The erythropoiesis-stimulating agents (ESAs), darbepoetin alfa (DA), and epoetin alfa (EA) differ with respect to dosing schedule in chemotherapy-induced anemia. DA can be administered less frequently than EA, which may increase synchronicity between chemotherapy and ESA schedules. This study compared DA and EA with respect to frequency of synchronization and frequencies of total and ESA healthcare visits in current clinical practice. METHODS: A retrospective analysis of ESA utilization during ESA episodes of care was conducted on all cancer patients identified in the SDI health oncology electronic medical records database who underwent chemotherapy and received ESA therapy from July 1, 2007 to March 31, 2010 (n = 6522 DA, n = 3,439 EA). RESULTS: The frequency of synchronization (chemotherapy and ESA therapy on the same day) was higher with DA (67 %) than EA (58 %) (p < 0.001). The odds that an ESA administration was synchronized with chemotherapy were higher with DA compared with EA (odds ratio = 1.46, 95 % CI: 1.37, 1.54). Compared with EA, DA patients had 2.3 fewer visits with an ESA administration (p < 0.001) and 3.0 fewer total visits (p < 0.001). CONCLUSIONS: Compared with patients receiving EA, DA patients were more likely to have an ESA administration on the same healthcare visit as chemotherapy and had fewer visits for any cause or for ESA administration. These results suggest that through greater synchronization of ESA and chemotherapy administrations, DA may reduce patient and practice burden and healthcare utilization.

Staff time and motion assessment for administration of erythropoiesis-stimulating agents: a two-phase pilot study in clinical oncology practices.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are used for the management of anaemia in patients with non-myeloid malignancies where anaemia is due to the effect of concomitant myelosuppressive chemotherapy. Assessing the impact of different ESA dosing regimens on office staff time and projected labour costs is an important component of understanding the potential for optimization of oncology practice efficiencies. OBJECTIVES: A two-phase study was conducted to evaluate staff time and labour costs directly associated with ESA administration in real-world oncology practice settings among cancer patients undergoing chemotherapy. The objective of Phase 1 was to determine the mean staff time required for the process of ESA administration in patients with anaemia due to concomitantly administered chemotherapy. The objective of Phase 2 was to quantify and compare the mean staff time and mean labour costs of ESA administered once weekly (qw) with ESA once every 3 weeks (q3w) over an entire course of chemotherapy. METHODS: Phase 1 was a prospective, cross-sectional time and motion study conducted in six private oncology practices in the US based on nine steps associated with ESA administration. Using findings from Phase 1, Phase 2 was conducted as a retrospective chart review to collect data on the number and types of visits in two private oncology practices for patients receiving a complete course of myelosuppressive chemotherapy. RESULTS: In Phase 1, the mean total time that clinic staff spent on ESA administration was 23.2 min for patient visits that included chemotherapy administration (n(chemo) = 37) and 21.5 min when only ESA was administered (n(ESAonly) = 36). In Phase 2, the mean duration of treatment was significantly longer for q3w than qw (53.84 days for qw vs. 113.38 for q3w, p < 0.0001); thus, analyses were adjusted using analysis of covariance (ANCOVA) for episode duration for between-group comparisons. Following adjustment by ANCOVA, qw darbepoetin alfa (DA) patients (n(qw) = 83) required more staff time for ESA + chemotherapy visits and ESA-only visits than q3w patients (n(q3w) = 118) over a course of chemotherapy. Overall, mean total staff time expended per chemotherapy course was greater for patients receiving qw versus q3w DA. Weekly DA dosing was associated with greater projected mean labour costs ($US38.16 vs. $US31.20 [average for 2007-2010]). CONCLUSIONS: The results from this real-world study demonstrate that oncology practices can attain staff time and labour costs savings through the use of q3w ESA. The degree of savings depends on the individual oncology practice's staffing model and ESA administration processes, including those that allow for optimized synchronization of patient visits for ESA and chemotherapy administration. These findings indicate that additional research using standard ESA administration protocols for longer periods of time with a larger number of oncology practices and patients should be conducted to confirm these findings.

The burden of blood transfusion: a utilization and economic analysis--a pilot study in patients with chemotherapy-induced anemia (CIA).

OBJECTIVE: The objective is to measure the burden of blood transfusion of Packed Red Blood Cells (PRBCs) in patients with chemotherapy-induced anemia (CIA) on the institutional outpatient transfusion center. METHODS: This is a retrospective chart review (starting July 1, 2010, working backwards until 120 evaluable patients are accrued) at a single institutional transfusion center in the US. The mean and standard deviation (SD) were calculated for patient's age, pre-transfusion Hgb level, and other transfusion-related activities. RESULTS: One hundred and twenty records were reviewed. The majority included patients who were female (71%), African American (61%), and had either Medicare (48%) or private insurance (39%). The mean patient age was 59 years and the average pre-transfusion Hgb was 7.9 g/dL. The average patient visit to facility ranged from 213 min for one PRBC unit to 411 minutes for three PRBC units. The mean staff time for patient evaluation was 66 minutes. Actual time for transfusion was ∼100 min for each PRBC unit; 90% of patients received two PRBC units. Staff was engaged in direct patient care for an average of 322 min for two PRBC units. The labor cost of transfusion (in 2011 $US) ranged from $46.13-$49.33 per PRBC unit. The estimated fully loaded bundled cost was $596.49 for transfusion of one unit of PRBC. Limitations of the study include: the site included in this study may not be applicable to all sites in practice and the evaluated patient population was varied, with the exception that all patients were treated for some type of malignancy; and the review of blood bank records for 120 patients was not 120 independent events and, as such, may not have adequately captured actual variability. CONCLUSIONS: This analysis quantifies expense in terms of time for administration of the transfusion, as well as costs associated with outpatient blood transfusions.

A retrospective study to evaluate the time burden associated with outpatient red blood transfusions indicated for anemia due to concomitantly administered chemotherapy in cancer patients.

PURPOSE: Anemia in cancer patients can be treated with red blood cell (RBC) transfusions. The patient burden associated with a treatment in terms of total time spent is an important factor to consider when measuring the benefits and challenges of a therapy. This study estimates the time-related patient burden associated with outpatient RBC transfusion. METHODS: A retrospective chart review of outpatient cancer patients receiving a RBC transfusion was conducted at 10 US centers. RBC transfusion time was measured as time elapsed from pre- to post-transfusion vital sign assessment and from transfusion start to stop time. Elapsed time from hemoglobin level testing and blood draw for cross-match to transfusion, estimated travel time and distance, and clinical and demographic data were also collected. RESULTS: Data from 110 patients (48.2 % male; mean age 64 ± 12 years) showed that the mean elapsed time between pre- and post-vital sign assessment was 4.2 h (95 % confidence interval (CI), 3.64-4.81) including 3.6 h (95 % CI, 3.0-4.1) on average to receive the actual RBC transfusion treatment. Hemoglobin level testing (mean Hg level, 8.33 g/dL ± 0.67) and blood drawn for cross-match were completed in an average of 31.2 h (95 % CI, 17.0-45.5) and 18.2 h (95 % CI, 12.1-24.2) prior to transfusion, respectively. Patient one-way travel time averaged 30.0 min (95 % CI, 25.9-34.3). CONCLUSIONS: In the US, CIA patients experience an important time burden when being treated with RBC transfusion in addition to the burden already added by chemotherapy.

Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.

OBJECTIVES: To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. METHODS: This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. RESULTS: ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. CONCLUSION: Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W dosing may also reduce inpatient ESA utilization by reducing the number of ESA doses required for previously maintained outpatients.