Abstract
Objective:
Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous ...leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence.
Research design and methods:
This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring.
Results:
Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1-2 tests, and 27.1% had 3-4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3-4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1-2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence.
Limitations:
These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence.
Conclusions:
Frequent molecular monitoring (3-4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.
To assess healthcare costs and hospitalization rates associated with rifaximin therapy versus lactulose alone among patients at risk for hepatic encephalopathy (HE).
IBM Marketscan Commercial and ...Optum's de-identified Clinformatics Data Mart databases were used separately to identify commercially insured HE patients treated with rifaximin or lactulose alone, using an algorithm developed with clinical experts. HE-related hospitalizations were defined based on an algorithm using diagnosis codes and diagnosis-related group codes. HE-related/all-cause hospital admissions/days and healthcare costs were compared between rifaximin and lactulose episodes using incidence rate ratios and adjusted cost differences.
In Marketscan, there were 13,515 Optum: 5,217 rifaximin episodes and 9,946 4,897 lactulose alone episodes included. Yearly rates of HE-related hospital admissions decreased by 33% 34% when treated with rifaximin versus lactulose alone, and rates of HE-related hospital days similarly decreased by 43% 57%. Yearly rates of all-cause hospital admissions decreased by 27% 27%; rates of all-cause hospital days decreased by 33% 37% during rifaximin episodes versus lactulose alone. This translated to $2,417 $2,301 and $173 $397 lower total mean medical costs and HE-related hospital costs per-patient-per-month, respectively (p < .05). Despite increased pharmacy costs associated with rifaximin, there was no change in total healthcare costs. Patients adherent to rifaximin incurred $2,891 $2,340 lower total healthcare costs than non-adherent patients. In a simulated plan of 1 million lives, if 50% of HE patients treated with lactulose alone had rifaximin added on and were adherent to rifaximin therapy, the total cost savings would be $7.5 $6.1 million per year ($0.62 $0.50 per-member-per-month).
Patients incurred significantly lower rates of HE-related and all-cause hospitalizations during rifaximin versus lactulose episodes, resulting in lower facility and professional costs. Cost savings may be possible if rifaximin adherence is improved in HE patients.
The study is subject to limitations common to claims-based analyses.
Metal contamination of urban soils and homegrown vegetables has caused major concern. Some studies showed that cadmium (Cd) was among the most significant hazards in kitchen garden soils and ...prolonged exposure to this metal could cause deleterious health effects in humans. In general, most risk assessment procedures are based on total concentrations of metals in vegetables. The present study assesses human bioaccessibility of Cd in vegetables cultivated in smelter-impacted kitchen garden soils. Seven vegetables (radish, lettuce, French bean, carrot, leek, tomato, and potato) were considered. Using the UBM protocol (unified BARGE bioaccessibility method), the bioaccessibility of Cd was measured in raw/cooked vegetables. A considerable amount of Cd was mobilized from raw vegetables during the digestion process (on average 85 % in the gastric phase and 69 % in the gastrointestinal phase), which could be attributed to a high uptake of Cd during the growth of the vegetables. Most Cd is accumulated in the vacuoles of plant cells, except what is absorbed by the cell wall, allowing Cd to be released from plant tissues under moderate conditions. Cooking by the steaming process generally increased the bioaccessibility of Cd in French bean, carrot, and leek. For potato, few or no significant differences of Cd bioaccessibility were observed after the steaming process, while the frying process strongly decreased bioaccessibility in both phases. The estimation of metal bioaccessibility in vegetables is helpful for human health risk assessment.
Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia due to chronic kidney disease (CKD). In addition to drug acquisition costs, the administration of ESAs can include direct ...and indirect costs due to the needle-based route of administration (eg, time spent by health care staff administering therapy, and patients' and caregivers' time spent receiving or assisting with therapy). However, a comprehensive assessment of the costs associated with the administration of ESAs is lacking.
To estimate the excess costs associated with the needle-based administration of ESAs for the treatment of anemia due to non-dialysis-dependent (NDD) CKD in the United States in 2019 from a societal perspective.
Excess costs associated with ESA administration were estimated as the sum of annual costs that could be avoided with the introduction of an oral treatment with comparable safety and efficacy to ESAs. Cost components included direct health care costs, transportation costs, and work productivity loss costs from the perspective of both patients and caregivers (as applicable). Costs were estimated based on scientific publications, governmental agencies, and the results of a recent survey of US patients and caregivers of patients with anemia and CKD. The setting of the administration (ie, at home vs in clinic), frequency of administration, and insurance type were considered.
At the societal level, annual excess costs associated with ESA administration were estimated at $2.5 billion in the United States in 2019, based on an estimated 462,005 patients with anemia and NDD-CKD treated with ESAs. Overall, 94.4% ($2.4 billion) of these costs were incurred from in-clinic ESA administration. When stratifying costs by insurance type, Medicare-insured patients accounted for 79.4% ($2.0 billion) of total annual excess costs. The largest contributor to total annual excess costs was direct health care costs ($1.4 billion, 54.9%), followed by patient work productivity loss costs ($846 million, 33.9%), caregiver work productivity loss costs ($197 million, 7.9%), and transportation costs ($81 million, 3.3%). Total annual excess costs of in-clinic administration ranged from $2,572 per patient receiving monthly administration to $20,948 per patient receiving thrice-weekly administration, while the total annual excess costs of at-home administration ranged from $1,123 per patient receiving monthly administration to $2,109 per patient receiving thrice-weekly administration. At the ESA administration level (ie, for each ESA administration), total excess costs were estimated at $128 per in-clinic ESA administration and $7 per at-home ESA administration, excluding monitoring costs.
The needle-based administration of ESAs in patients with NDD-CKD is associated with a substantial economic burden. The introduction of an oral treatment has the potential to result in important cost savings from a societal perspective.
: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc., and Akebia Therapeutics, Inc. The study sponsors participated in the study design, data collection, analysis, interpretation of the data, writing of the report, and in the decision to submit the manuscript for publication. Gauthier-Loiselle, Cloutier, Serra, Bungay, and Guérin are employees of Analysis Group, Inc., a consulting firm that received funding from Otsuka Pharmaceutical Development & Commercialization, Inc., for the conduct of this study. Michalopoulos was an employee of Otsuka Pharmaceutical Development & Commercialization, Inc., at the time the study was conducted. Szabo is an employee of Akebia Therapeutics, Inc.
To build upon previous outdated studies by comprehensively assessing the direct healthcare burden of autosomal dominant polycystic kidney disease (ADPKD).
Patients with ≥2 diagnoses for ADPKD (ADPKD ...cohort) were identified in the US fee-for-use IBM Truven Health Analytics MarketScan Commercial Claims and Encounters and IBM Truven Health Analytics MarketScan Medicare Supplemental databases (01 January 2015-31 December 2017) and matched (1:3) to controls without ADPKD (non-ADPKD cohort). The index date was the last calendar date followed by 12 months continuous enrollment (study period). Patients with ADPKD were stratified into one of seven mutually exclusive groups based on chronic kidney disease (CKD) stages (I-V), end-stage renal disease requiring renal replacement therapy (ESRD-RRT), and unknown stage.
During the 12-month study period, patients with ADPKD incurred significantly higher total healthcare costs than those without ADPKD (mean cost difference = $22,879 per patient per year PPPY; p < .001). Besides CKD stages I and II, total healthcare cost differences increased as patients progressed beyond CKD stage III, with the greatest difference observed among patients with ESRD-RRT. Total healthcare cost differences between cohorts were more pronounced in subgroups of patients with hypertension ($29,347) and with high risk of rapid progression ($39,976). Similar results were observed in the Medicare Supplemental population, with a total mean cost difference of $42,694 PPPY (p < .001); cost difference was also higher in the hypertension ($46,461 PPPY) and high risk of rapid progression ($45,708 PPPY) subgroups.
Results may not be representative of the overall ADPKD US population; CKD stage was based on diagnosis and procedure codes; criteria used to identify ADPKD at risk of rapid progression did not rely on laboratory values; there may be billing inaccuracies and omissions in health insurance claims data.
This study demonstrated the substantial healthcare costs associated with ADPKD, which increased as patients progressed through more severe CKD stages.
Objectives
The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the ...treatment of adult patients with newly diagnosed
FLT3
-mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective.
Methods
A lifetime partitioned survival model with four health states (active disease, complete remission CR, relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness.
Results
In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY.
Conclusions
This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed
FLT3
-mutated AML, from a US third-party payer perspective.
Background: Tyrosine kinase inhibitors (TKIs) are the standard-of-care treatment for chronic myeloid leukemia in chronic phase (CML-CP). Despite advances in therapy, there remains a proportion of ...patients with CML-CP that are refractory/intolerant to TKIs, and these patients cycle through multiple lines of therapy. Moreover, even with TKIs, some patients progress to accelerated phase/blast crisis (AP/BC), which is associated with particularly poor clinical outcomes.
Objectives: To describe real-world treatment patterns, healthcare resource utilization (HRU), and costs of patients with CML-CP reaching later lines of therapy or progressing to AP/BC in the United States.
Methods: Adult CML patients from administrative claims data (January 1, 2000–June 30, 2019) were classified by health state: on third-line (CML-CP On Treatment), on fourth or later lines (CML-CP Post-Discontinuation), or progressed to AP/BC (CML-AP/BC). Outcomes were assessed by health state.
Results: There were 296 (4620 patient-months), 83 (1644 patient-months), and 949 (25 593 patient-months) patients classified in the CML-CP On Treatment, CML-CP Post-Discontinuation, and CML-AP/BC cohorts, respectively. Second-generation TKIs (nilotinib, dasatinib, and bosutinib) were most commonly used in the CML-CP On Treatment (69.1% of patient-months) and CML-CP Post-Discontinuation cohorts (59.1% of patient-months). Three-month outpatient incidence rates (IRs) were 7.6, 8.3, and 7.0 visits in the CML-CP On Treatment, CML-CP Post-Discontinuation, and CML-AP/BC cohort, respectively, with mean costs of $597 per service. Three-month inpatient IRs were 0.6, 0.7, and 1.4 days in the CML-CP On Treatment, CML-CP Post-Discontinuation, and CML-AP/BC cohort, respectively, with mean costs of $5892 per day. Mean hematopoietic stem cell transplantation cost was $352 333; mean 3-month terminal care cost was $107 013.
Discussion: Cost of CML care is substantial among patients with CML reaching third-line, fourth or later lines, or progressing to AP/BC, suggesting that the disease is associated with a significant economic and clinical burden. From third-line to fourth or later lines, HRU was observed to increase, and the incidence of inpatient days was particularly high for those who progressed to AP/BC.
Conclusion: In this study, patients with CML cycling through TKIs in later lines of therapy or progressing to AP/BC experienced substantial HRU and costs, suggesting unmet treatment needs.
Preference valuations of health status are essential in health technology and economic appraisal. This study estimated utilities for treatment-related health states of acute myeloid leukemia (AML) ...and disutilities of severe adverse events (SAEs) using a representative sample of adults from the general population in the United States (US).
Treatment-related AML health states, defined based on literature and interviews with clinicians, included complete remission (CR), no CR, relapse, stem cell transplant (SCT), and post SCT short-term recovery. Six attributes with varying levels, including fever, lack of energy, problems with daily function, anxiety/depression, blood transfusions, and hospitalization, were used to define health states. An online survey using discrete choice experiment methodology was designed to capture preferences for health status scenarios including the identified attributes and key grade 3/4 chemotherapy-related SAEs. Health state utilities and SAE disutilities were generated from a conditional logistic regression with generalized estimating equations.
Of the 300 survey participants, the demographic distributions were within a 3% margin of those in the 2010 US Census. CR had the highest utility value (0.875), followed by post-SCT short-term recovery (0.398), relapse (0.355), no CR (0.262), and SCT (0.158). Of the SAEs, serious infection had the highest decline in utility (0.218), followed by severe diarrhea (0.176), abnormally low blood cell counts (0.100), and severe redness/skin peeling (0.060).
AML and treatments can result in reduced quality of life and impaired ability to perform daily activities. Findings of this study underline the value that society places on treatment-related AML health states and SAEs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Redox processes, which are widespread in soils, need to be quantified for an improved comprehension of the dynamics of Fe- and Mn-oxides and their associated trace elements. The classical methodology ...used to study these redox processes generally relies on the quantification of all mineral species in the various pedological features that can be related to different redox stages. However, this approach usually encounters the difficulty of precisely quantifying the different forms of poorly crystallised Fe- and Mn-oxides.
In this study, we use the signature of rare earth elements (REEs) to visualise and, eventually, quantify the importance of redox processes in soils. Our approach relies on that developed by Laveuf et al. (2008) and the idea that the relative contribution to the mobilisation of REEs that is made by the primary minerals reactive to redox conditions depends on the following factors: (i) their initial proportion in the different pedological features that can be related to various redox processes, (ii) their relative mobilisation during the redox process in question, and (iii) their initial REE signatures.
The catena studied is characterised by two stages of redox conditions: the first is related to the formation and subsequent dissolution of Fe–Mn concretions, and the second is related to the bleaching of the soil matrix due to morphological degradation. In this soil, the main minerals reactive to redox conditions are Mn-oxides, ferrihydrite, goethite and (fluor)apatite. The results indicate that the primary redox conditions can be characterised by a positive Ce anomaly on the REE pattern, which has been attributed to a preferential immobilisation of this element, due to its association with Mn-oxides. The results also indicate that the secondary redox conditions can be characterised by depletion in medium REEs (MREEs) in the REE pattern, which has been attributed to a preferential release of these elements during the dissolution of (fluor)apatite and, to a lesser extent, of ferrihydrite.
These results emphasise the potential of REE signatures of the visualisation of the various redox processes that have been active in a soil. Additionally, REE signatures are a proxy of the frequency and intensity of the redox conditions.
► Identification of redoximorphic features. ► Speciation of rare earth elements in redoximorphic features. ► Impact of redox conditions on rare earth mobilization. ► Interpretation of changes in speciation and of fractionations. ► Use of rare earth elements as tracers of redox processes.
Background:
Irritable bowel syndrome (IBS) reduces quality of life and burdens healthcare systems. This study identified factors associated with frequent use of IBS diagnostic tests and procedures.
...Methods:
Using a United States claims database (2001–2012), tests and procedures in IBS patients occurring in the 2-year study period (12 months before/following the first IBS diagnosis) were analyzed: endoscopy, GI transit testing, anorectal procedures, and radiologic imaging. Patients were classified based on test/procedure frequency (3+, 1–2, or 0). Multivariate logistic regression identified factors associated with more frequent tests/procedures.
Results:
Among 201,322 IBS patients, 41.7% had 3+ tests/procedures, 35.1% had 1–2, and 23.3% had 0. Patients with more tests/procedures were older mean age 50.6 (3+ group), more likely to be female and had more comorbidities, including anxiety, depressive disorders, and somatization. Dyspepsia odds ratio (95% confidence interval): 1.80 (1.72–1.87), interstitial cystitis 1.60 (1.45–1.77), gastroesophageal reflux disease 1.59 (1.55–1.63), constipation 1.50 (1.45–1.54), and dyspareunia 1.38 (1.25–1.52) were significantly associated with more tests/procedures (3+ versus 1–2), while anxiety, depressive disorders, and somatization were not. Patients with more frequent specialist visits emergency department (ED; 1.10 (1.09–1.11)) and gastroenterologists (1.26 (1.26–1.27)) or at least one GI-related ED visit or inpatient admission 1.95 (1.86–2.04) and 3.67 (3.48–3.87), respectively were more likely to have more tests/procedures (all p < 0.05).
Conclusions:
Test frequency in patients with IBS is strongly associated with demographic and clinical characteristics, especially comorbid conditions related to IBS. Presence of common overlapping comorbid conditions should increase clinicians’ confidence in making the diagnosis of IBS, thus curtailing redundant testing and reducing healthcare costs.
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