Kidney Failure Attributed to Focal Segmental Glomerulosclerosis: A USRDS Retrospective Cohort Study of Epidemiology, Treatment Modalities, and Economic Burden.

Rationale & Objective: This study describes the epidemiology, characteristics, and clinical outcomes of patients with focal segmental glomerulosclerosis (FSGS)-attributed kidney failure in the US Renal Data System (USRDS) during 2008-2018, and health care resource utilization and costs among those with Medicare-linked data. Study Design: This was a retrospective cohort study. Setting & Population: Patients with FSGS-attributed kidney failure in the USRDS were enrolled in the study. Outcomes: The outcomes were as follows: Prevalence and incidence, clinical and demographic characteristics, time to kidney transplant or death, health care resource utilization, and direct health care costs. Analytical Approach: Patients with FSGS as the primary cause of kidney failure were followed from USRDS registration (index date) until death or data end. Prevalence and incidence were calculated per 1,000,000 US persons. Patient characteristics at index and treatment modalities during follow-up were described. Time to kidney transplant or death was assessed with Kaplan-Meier and competing risk analyses. Health care resource utilization and costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including (Medicare Coverage subgroup) or excluding (1-year Medicare Coverage subgroup) those who died. Results: The FSGS cohort and Medicare Coverage and 1-year Medicare Coverage subgroups included 25,699, 6,340, and 5,575 patients, respectively. Mean annual period prevalence and incidence rates of FSGS-attributed kidney failure were 87.6 and 7.5 per 1,000,000 US persons, respectively. Initial treatment for most patients was in-center hemodialysis (72.1%), whereas 7.3% received kidney transplant. Accounting for competing risk of death, year 1 and 5 kidney transplant rates were 15% and 34%, respectively. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 76.6% and 74.2% required inpatient admission, 69.9% and 67.3% visited the emergency room, and mean monthly health care costs were $6,752 and $5,575 in the year postindex, respectively. Limitations: Drug costs may be underestimated because Medicare Part D coverage was not required; kidney acquisition costs were not available. Conclusions: FSGS-attributed kidney failure is associated with substantial clinical and economic burden, prompting the need for novel therapies for FSGS to delay kidney failure.

This study of patients in the US Renal Data System observed increasing prevalence and fluctuating incidence of focal segmental glomerulosclerosis (FSGS)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, including more than 3 years of treatment with dialysis, one-third receiving a kidney transplant, and one-third dying during follow-up. In the first year after US Renal Data System registration, three-quarters of patients with Medicare coverage required hospitalization, and more than two-thirds visited the emergency room. The total annual health care costs were >$68,000 per patient with FSGS-attributed kidney failure, underscoring the high economic burden of this disorder and the treatments required to sustain life. Novel therapies for FSGS are needed to delay or ideally prevent the need dialysis and transplantation after kidney failure.

Kidney Failure Attributed to Immunoglobulin A Nephropathy: A USRDS Retrospective Cohort Study of Epidemiology, Treatment Modalities, and Economic Burden.

Rationale & Objective: This study describes the epidemiology, characteristics, and outcomes of patients with immunoglobulin A nephropathy (IgAN)-attributed kidney failure in the US Renal Data System (USRDS) from 2008 to 2018, including health care resource utilization and costs among patients with Medicare-linked data. Study Design: Retrospective cohort study. Setting & Population: Patients with IgAN-attributed kidney failure in the USRDS. Outcomes: Prevalence/incidence, clinical/demographic characteristics, time to kidney transplant, and health care resource utilization and costs. Analytical Approach: Patients with IgAN as primary cause of kidney failure (IgAN cohort) were followed from USRDS registration (index date) until data end/death. Prevalence/incidence were calculated per 1,000,000 US persons. Demographic and clinical characteristics at index and treatment modality during follow-up were summarized. Time from index to kidney transplant was assessed using Kaplan-Meier and competing risk analyses. Health care resource utilization and health care costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including or excluding those who died (Medicare Coverage and 1-year Medicare Coverage subgroups, respectively). Results: The IgAN cohort, Medicare Coverage, and 1-year Medicare Coverage subgroups included 10,101, 1,696, and 1,510 patients, respectively. Mean annual period prevalence and incidence of IgAN-attributed kidney failure were 39.3 and 2.9 per 1,000,000 US persons, respectively. Initial treatment was in-center hemodialysis (63.1%) or kidney transplant (15.1%). Year 1 and 5 kidney transplant rates were 5% and 17%, respectively, accounting for competing risk of death. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 74.4% and 72.3%, respectively, required inpatient admission, 67.3% and 64.4%, respectively, visited the emergency room, and mean total health care costs were $6,293 (SD: $6,934) and $5,284 ($3,455), respectively, per-patient-per-month in the year postindex. Limitations: Drug costs may be underestimated as Medicare Part D coverage was not required; kidney acquisition costs were unavailable. Conclusions: IgAN-attributed kidney failure is associated with substantial clinical and economic burdens. Novel therapies for IgAN that delay kidney failure are needed.

This study of patients in the United States Renal Data System (USRDS) observed fluctuating incidence and increasing prevalence of immunoglobulin A nephropathy (IgAN)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, with 63% receiving in-center dialysis and over 15% receiving transplantation as initial therapy. In the first year after USRDS registration, nearly three-quarters of patients with Medicare coverage required hospitalization, and around two-thirds visited the emergency room. The total annual health care costs were >$63,000 per patient with IgAN-attributed kidney failure, underscoring the high economic burden of this disorder and currently available treatments. Novel therapies for IgAN are needed to delay or prevent the need for costly dialysis and transplantation after kidney failure.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Study Design: Retrospective cohort study. Setting & Study Population: Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. Predictor: High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Outcomes: Standardized prevalence, health care resource utilization, costs. Analytical Approach: Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. Results: The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Limitations: Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Conclusions: Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Plain-Language Summary: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

Economic Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis and Low Surgical Risk: Results from the PARTNER 3 Trial.

BACKGROUND: In patients with severe symptomatic aortic stenosis at low surgical risk, transfemoral transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve has been shown to reduce the composite of death, stroke, or rehospitalization at 2-year follow-up compared with surgical aortic valve replacement (SAVR). Whether TAVR is cost-effective compared with SAVR for low-risk patients remains uncertain. METHODS: Between 2016 and 2017, 1000 low-risk patients with aortic stenosis were randomly assigned to TAVR with the SAPIEN 3 valve or SAVR in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). Of these patients, 929 underwent valve replacement, were enrolled in the United States, and were included in the economic substudy. Procedural costs were estimated using measured resource use. Other costs were determined by linkage with Medicare claims or by regression models when linkage was not feasible. Health utilities were estimated using the EuroQOL 5-item questionnaire. With the use of a Markov model informed by in-trial data, lifetime cost-effectiveness from the perspective of the US health care system was estimated in terms of cost per quality-adjusted life-year gained. RESULTS: Although procedural costs were nearly $19 000 higher with TAVR, total index hospitalization costs were only $591 more with TAVR compared with SAVR. Follow-up costs were lower with TAVR such that TAVR led to 2-year cost savings of $2030/patient compared with SAVR (95% CI, -$6222 to $1816) and a gain of 0.05 quality-adjusted life-years (95% CI, -0.003 to 0.102). In our base-case analysis, TAVR was projected to be an economically dominant strategy with a 95% probability that the incremental cost-effectiveness ratio for TAVR would be <$50 000/quality-adjusted life-year gained (consistent with high economic value from a US health care perspective). These findings were sensitive to differences in long-term survival, however, such that a modest long-term survival advantage with SAVR would render SAVR cost-effective (although not cost saving) compared with TAVR. CONCLUSIONS: For patients with severe aortic stenosis and low surgical risk similar to those enrolled in the PARTNER 3 trial, transfemoral TAVR with the SAPIEN 3 valve is cost saving compared with SAVR at 2 years and is projected to be economically attractive in the long run as long as there are no substantial differences in late death between the 2 strategies. Long-term follow-up will be critical to ultimately determine the preferred treatment strategy for low-risk patients from both a clinical and economic perspective.

Flexible stretchable low-energy X-ray (30-80 keV) radiation shielding material: Low-melting-point Ga1In1Sn7Bi1 alloy/thermoplastic polyurethane composite.

A highly flexible stretchable thermoplastic polyurethane (TPU) composite loaded with a low-melting-point Ga1In1Sn7Bi1 multiprincipal element alloy (LMPEA) was prepared, and its radiation shielding performance was evaluated. The fluid characteristic of LMPEA and the flexibility of TPU enable good interface compatibility. Ga1In1Sn7Bi1 LMPEA consists of two eutectic structures, and the liquid gallium-rich phases are distributed at the boundary of the InBi intermetallic compound and Sn solid solution. In the low-photon energy range of 30-80 keV, LMPEA has a theoretical specific lead equivalent of 0.803 mmPb/mm and a theoretical weight reduction of 17.27% compared with lead. To evaluate the photon attenuation capability for the LMPEA/TPU composites, the Phy-X procedure and Monte Carlo simulations were used to determine the shielding parameters, such as the mass attenuation coefficient, linear attenuation coefficient, half-value layer, tenth-value layer, mean free path, effective atomic number, and fast neutron removal cross section. The attenuation performance test of X-ray protective materials measured the actual lead equivalent. At the same thickness, the LMPEA/TPU composite (66.667, 50.000 wt% LMPEA loading) has a higher measured lead equivalent than the in-service medical shielding materials, which meets the lead equivalent requirements of X-ray protective clothing. LMPEA/TPU composites are nontoxic, lightweight, and have excellent low-energy X-ray shielding ability, offering great potential for application in medical wearable materials.

Co-digestion of cow manure and food waste for biogas enhancement and nutrients revival in bio-circular economy.

Anaerobic co-digestion (AcoD) with suitable substrate ratios may have the potential to improve biogas process and could play a better role in nutrient management for biocircular economy. The goal of this study was to enhance biogas yield from AcoD of cow manure (CM) and canteen food waste (CFW), and pertinent co-digestion of suitable substrate ratios for nutrient management i. e NPK from linear to biocircular economy, using ruminant intestinal fluid as a source of inoculum. A mesophilic (37 ± 1 °C) laboratory-scale AcoD with varying CFW/CM ratios of (0:1, 1:4, 2:3, 1:1, 3:2, 4:1, and 1:0) based on wet weight was performed. The AcoD systems of different CFW/CM ratios were evaluated with a loading rate of 400 g/L in the presence of 100 g cow intestinal fluid (CIF) inoculation. All experimental AcoD systems yielded greater biogas (147-300 cm3/g VS) than the mono-digestion in which only CM (135 cm3/g VS) and CFW (146 cm3/g VS) were digested anaerobically. The AcoD system of CFW/CM with 4:1 showed the highest biogas yield (300 cm3/g VS), and VS and COD reduction rate (39.51% and 65.15%, respectively), and nutrient contents (6.53%). Moreover, the experiment results were verified by modified Gompertz model. This work provided a window of opportunity to examine the anaerobic co-digestion technology beyond biogas production and to put the current low-cost technology to use for nutrient management and as a better component of the biocircular economy for agriculture in Pakistan in order to achieve sustainable development goals.

Corneal in vivo Confocal Microscopy for Assessment of Non-Neurological Autoimmune Diseases: A Meta-Analysis.

Purpose: This study aimed to evaluate the features of corneal nerve with in vivo confocal microscopy (IVCM) among patients with non-neurological autoimmune (NNAI) diseases. Methods: We systematically searched PubMed, Web of Science, and Cochrane Central Register of Controlled Trials for studies published until May 2021. The weighted mean differences (WMDs) of corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), tortuosity, reflectivity, and beadings per 100 µm with a 95% CI between NNAI and control group were analyzed using a random-effects model. Results: The results showed 37 studies involving collective totals of 1,423 patients and 1,059 healthy controls were ultimately included in this meta-analysis. The pooled results manifested significantly decreased CNFL (WMD: -3.94, 95% CI: -4.77--3.12), CNFD (WMD: -6.62, 95% CI: -8.4--4.85), and CNBD (WMD: -9.89, 95% CI: -14--5.79) in NNAI patients. In addition, the NNAI group showed more tortuous corneal nerve (WMD: 1.19, 95% CI:0.57-1.81). The comparison between NNAI patients and healthy controls in beadings per 100 µm corneal nerve length was inconsistent. No significant difference was found in the corneal nerve fiber reflectivity between NNAI and the control group (WMD: -0.21, 95% CI: -0.65-0.24, P = 0.361). Conclusions: The parameters and morphology of corneal nerves observed by IVCM proved to be different in NNAI patients from healthy controls, suggesting that IVCM may be a non-invasive technique for identification and surveillance of NNAI diseases.

Cost-effectiveness of transcatheter edge-to-edge repair in secondary mitral regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TMVr) improves symptoms and survival for patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and severe secondary mitral regurgitation despite guideline-recommended medical therapy (GRMT). Whether TMVr is cost-effective from a UK National Health Service (NHS) perspective is unknown. METHODS: We used patient-level data from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial to perform a cost-effectiveness analysis of TMVr +GRMT versus GRMT alone from an NHS perspective. Costs for the TMVr procedure were based on standard English tariffs and device costs. Subsequent costs were estimated based on data acquired during the trial. Health utilities were estimated using the Short-Form 6-Dimension Health Survey. RESULTS: Costs for the index procedural hospitalisation were £18 781, of which £16 218 were for the TMVr device. Over 2-year follow-up, TMVr reduced subsequent costs compared with GRMT (£10 944 vs £14 932, p=0.006), driven mainly by reductions in heart failure hospitalisations; nonetheless, total 2-year costs remained higher with TMVr (£29 165 vs £14 932, p<0.001). When survival, health utilities and costs were projected over a lifetime, TMVr was projected to increase life expectancy by 1.57 years and quality-adjusted life expectancy by 1.12 quality-adjusted life-years (QALYs) at an incremental cost of £21 980, resulting in an incremental cost-effectiveness ratio (ICER) of £23 270 per QALY gained (after discounting). If the benefits of TMVr observed in the first 2 years were maintained without attenuation, the ICER improved to £12 494 per QALY. CONCLUSIONS: For patients with HFrEF and severe secondary mitral regurgitation similar to those enrolled in COAPT, TMVr increases life expectancy and quality-adjusted life expectancy compared with GRMT at an ICER that represents good value from an NHS perspective.

Predicting the EQ-5D utilities from the Kansas City Cardiomyopathy Questionnaire in patients with heart failure.

INTRODUCTION: Evaluation of health status benefits, cost-effectiveness, and value of new heart failure therapies is critical for supporting their use. The Kansas City Cardiomyopathy Questionnaire (KCCQ) measures patients' heart failure-specific health status but does not provide utilities needed for cost-effectiveness analyses. We mapped the KCCQ scores to EQ-5D scores so that estimates of societal-based utilities can be generated to support economic analyses. METHODS: Using data from two US cohort studies, we developed models for predicting EQ-5D utilities (3L and 5L versions) from the KCCQ (23- and 12-item versions). In addition to predicting scores directly, we considered predicting the five EQ-5D health state items and deriving utilities from the predicted responses, allowing different countries' health state valuations to be used. Model validation was performed internally via bootstrap and externally using data from two clinical trials. Model performance was assessed using R2, mean prediction error, mean absolute prediction error, and calibration of observed vs. predicted values. RESULTS: The EQ-5D-3L models were developed from 1000 health status assessments in 547 patients with heart failure and reduced ejection fraction (HFrEF), while the EQ-5D-5L model was developed from 3925 patients with HFrEF. For both versions, models predicting individual EQ-5D items performed as well as those predicting utilities directly. The selected models for the 3L had internally validated R2 of 48.4-50.5% and 33.7-45.6% on external validation. The 5L version had validated R2 of 57.7%. CONCLUSION: Mappings from the KCCQ to the EQ-5D can yield the estimates of societal-based utilities to support cost-effectiveness analyses when EQ-5D data are not available.

Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial.

BACKGROUND: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown. METHODS: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey. RESULTS: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P=0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P<0.001). When in-trial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life expectancy by 1.13 years and quality-adjusted life-years by 0.82 years at a cost of $45 648, yielding a lifetime incremental cost-effectiveness ratio of $40 361 per life-year gained and $55 600 per quality-adjusted life-year gained. CONCLUSIONS: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Intermediate Risk.

BACKGROUND: In patients with severe aortic stenosis (AS) at intermediate surgical risk, treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) results in similar rates of death or stroke at 2 years. Whether TAVR is cost-effective compared with SAVR for intermediate-risk patients remains uncertain. METHODS: Between 2011 and 2014, 3110 intermediate-risk AS patients were treated with TAVR or SAVR in the PARTNER 2 trial (Placement of Aortic Transcatheter Valves 2). A total of 2032 patients were randomized to receive TAVR using the SAPIEN XT valve (XT-TAVR) or SAVR in the PARTNER 2A trial, whereas the PARTNER S3i registry included an additional 1078 patients treated with TAVR using the SAPIEN 3 valve (S3-TAVR), which offers a lower delivery profile and sealing skirt designed to reduce paravalvular regurgitation compared with XT-TAVR. Procedural costs were estimated using measured resource utilization. Other in-trial costs were assessed by linkage of trial data with Medicare claims (n=2333) or by linear regression models for unlinked patients (n=682). Health utilities were estimated using the EQ-5D at baseline and 1, 12, and 24 months. Using a Markov model informed by in-trial costs, utilities, and survival data, lifetime cost-effectiveness from the perspective of the US healthcare system was estimated in terms of cost per quality-adjusted life-year gained. RESULTS: Although procedural costs were ≈$20 000 higher with TAVR than SAVR, total cost differences for the index hospitalization were only $2888 higher with XT-TAVR ( P=0.014) and were $4155 lower with S3-TAVR ( P<0.001) owing to reductions in length of stay with TAVR. Follow-up costs were significantly lower with XT-TAVR (Δ=-$9304; P<0.001) and S3-TAVR (Δ=-$11 377; P<0.001) than with SAVR. Over a lifetime horizon, TAVR was projected to lower total costs by $8000 to $10 000 and to increase quality-adjusted survival by 0.15 to 0.27 years. XT-TAVR and S3-TAVR were found to be economically dominant compared with SAVR in 84% and 97% of bootstrap replicates, respectively. CONCLUSIONS: Among intermediate-risk AS patients, TAVR is projected to be economically dominant from the perspective of the US healthcare system by providing both greater quality-adjusted life expectancy and lower long-term costs than SAVR. If long-term data demonstrate comparable late mortality with TAVR and SAVR, these findings suggest that TAVR might be the preferred treatment strategy for intermediate-risk AS patients based on both clinical and economic considerations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01314313.

Cost-Effectiveness of Long-Term Ticagrelor in Patients With Prior Myocardial Infarction: Results From the PEGASUS-TIMI 54 Trial.

BACKGROUND: In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. OBJECTIVES: The authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. METHODS: The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA. Medical resource use data were collected over a median 33-month follow-up. Costs were assessed from the U.S. health care system perspective. In-trial data relating to survival, utility, and costs were combined with lifetime projections to evaluate lifetime cost-effectiveness of the Food and Drug Administration-approved lower-dose ticagrelor regimen (60 mg twice daily). RESULTS: Hospitalization costs were similar for ticagrelor 60 mg and placebo ($2,262 vs. $2,333; 95% confidence interval for difference -$303 to $163; p = 0.54); after inclusion of a daily ticagrelor 60 mg cost of $10.52, total costs were higher for ticagrelor ($10,016 vs. $2,333; 95% CI: $7,441 to $7,930; p < 0.001). In-trial quality-adjusted life-years (QALYs) were similar (2.28 vs. 2.27; p = 0.34). Over a lifetime horizon, ticagrelor was associated with QALY gains of 0.078 and incremental costs of $7,435, yielding an incremental cost-effectiveness ratio (ICER) of $94,917/QALY gained. Several high-risk groups had more favorable ICERs, including patients with >1 prior MI, multivessel disease, diabetes, renal dysfunction (all with ICERs $50,000 to $70,000/QALY gained), patients age <75 years (ICER = $44,779/QALY gained), and patients with peripheral artery disease (ICER = $13,427/QALY gained). CONCLUSIONS: For patients with a history of MI >1 year previously, long-term treatment with ticagrelor 60 mg + low-dose ASA yields a cost-effectiveness ratio suggesting intermediate value based on current guidelines. Ticagrelor appears to provide higher value for patients in several recognized high-risk subgroups. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Cost-Effectiveness of Edoxaban vs. Warfarin in Patients with Atrial Fibrillation Based on Results of the ENGAGE AF - TIMI 48 Trial: Taiwanese Perspective.

BACKGROUND: Novel anticoagulants, such as factor Xa inhibitors, have entered clinical practice as alternatives to warfarin for the prevention of stroke and systemic embolic event (SEE) in patients with atrial fibrillation (AF). It is not known whether edoxaban, the fourth-to-market factor Xa inhibitor approved for this indication, will be cost-effective in Taiwan, where the cost of warfarin monitoring is prohibitive. METHODS: A Markov model projecting lifetime results of edoxaban 60 mg/30 mg dose-reduced versus warfarin in patients with nonvalvular AF, based on the ENGAGE AF - TIMI 48 trial, found edoxaban to be of high value relative to warfarin, from the perspective of the US health care system. We applied Taiwan-specific cost inputs to this model structure to assess the relative cost-effectiveness of edoxaban versus warfarin from the perspective of the Taiwanese health care system. Event rates and hazard ratios from the ENGAGE AF - TIMI 48 East Asian subpopulation were explored in sensitivity analyses. RESULTS: Edoxaban was found to be highly cost-effective compared with warfarin, based on guidelines proposed by the World Health Organization (WHO), with a base case incremental cost-effectiveness ratio of $12,902 per quality-adjusted life year gained. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of-life impact of stroke and bleeding events, and assuming East Asian-specific (as opposed to full-trial-population) rates for combinations of ischemic stroke, SEE, and major bleeding. CONCLUSIONS: Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SEE in patients with AF in Taiwan.

Health Status Benefits of Transcatheter vs Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Intermediate Surgical Risk: Results From the PARTNER 2 Randomized Clinical Trial.

Importance: In patients with severe aortic stenosis (AS) at intermediate surgical risk, treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) results in similar 2-year survival. The effect of TAVR vs SAVR on health status in patients at intermediate surgical risk is unknown. Objective: To compare health-related quality of life among intermediate-risk patients with severe AS treated with either TAVR or SAVR. Design, Setting, and Participants: Between December 2011 and November 2013, 2032 intermediate-risk patients with severe AS were randomized to TAVR with the Sapien XT valve or SAVR in the Placement of Aortic Transcatheter Valve 2 Trial and were followed up for 2 years. Data analysis was conducted between March 1, 2016, to April 30, 2017. Main Outcomes and Measures: Health status was assessed at baseline, 1 month, 1 year, and 2 years using the Kansas City Cardiomyopathy Questionnaire (KCCQ) (23 items covering physical function, social function, symptoms, self-efficacy and knowledge, and quality of life on a 0- to 100-point scale; higher scores indicate better quality of life), Medical Outcomes Study Short Form-36 (36 items covering 8 dimensions of health status as well as physical and mental summary scores; higher scores represent better health status), and EuroQOL-5D (assesses 5 dimensions of general health on a 3-level scale, with utility scores ranging from 0 [death] to 1 [ideal health]). Analysis of covariance was used to examine changes in health status over time, adjusting for baseline status. Results: Of the 2032 randomized patients, baseline health status was available for 1833 individuals (950 TAVR, 883 SAVR) who formed the primary analytic cohort. A total of 1006 (54.9%) of the population were men; mean (SD) age was 81.4 (6.8) years. Over 2 years, both TAVR and SAVR were associated with significant improvements in both disease specific (16-22 points on the KCCQ-OS scale) and generic health status (3.9-5.1 points on the SF-36 physical summary scale). At 1 month, TAVR was associated with better health status than SAVR, but this difference was restricted to patients treated via transfemoral access (mean difference in the KCCQ overall summary [KCCQ-OS] score, 14.1 points; 95% CI, 11.7 to 16.4; P < .01) and was not seen in patients treated via transthoracic access (mean difference in KCCQ-OS, 3.5 points; 95% CI, -1.4 to 8.4; P < .01 for interaction). There were no significant differences between TAVR and SAVR in any health status measures at 1 or 2 years. Conclusions and Relevance: Among intermediate-risk patients with severe AS, health status improved significantly with both TAVR and SAVR through 2 years of follow up. Early health status improvement was greater with TAVR, but only among patients treated via transfemoral access. Longer term follow-up is needed to assess the durability of quality-of-life improvement with TAVR vs SAVR in this population. Trial Registration: clinicaltrials.gov Identifier: NCT01314313.

Impact of Ezetimibe on the Rate of Cardiovascular-Related Hospitalizations and Associated Costs Among Patients With a Recent Acute Coronary Syndrome: Results From the IMPROVE-IT Trial (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

BACKGROUND: Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown. METHODS AND RESULTS: We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99; P=0.031), mainly attributable to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke. Consequently, cardiovascular-related hospitalization costs over 7 years were $453 per patient lower with ezetimibe (95% confidence interval, -$38 to -$869; P=0.030). Although all prespecified subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus, patients aged ≥75 years, and patients at higher predicted risk for recurrent ischemic events had even greater cost offsets. CONCLUSIONS: Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878.

Effects of thermal treatment on high solid anaerobic digestion of swine manure: Enhancement assessment and kinetic analysis.

Anaerobic digestion (AD), which is a process for generating biogas, can be applied to the treatment of organic wastes. Owing to its smaller footprint, lower energy consumption, and less digestate, high solid anaerobic digestion (HSAD) has attracted increasing attention. However, its biogas production is poor. In order to improve biogas production and decrease energy consumption, an improved thermal treatment process was proposed. Raw swine manure (>20% solid content) without any dilution was thermally treated at 70±1°C for different retention times, and then its effect on HSAD was investigated via batch AD experiments at 8.9% solid content. Results showed that the main organic components of swine manure hydrolyzed significantly during the thermal treatment, and HSAD's methane production rate was improved by up to 39.5%. Analysis using two kinetic models confirmed that the treatment could increase biodegradable organics (especially the readily biodegradable organics) in swine manure rather than upgrading its hydrolysis rate. It is worth noting that the superimposed first-order kinetics model was firstly applied in AD, and was a good tool to reveal the AD kinetics mechanism of substrates with complex components.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. METHODS: In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. RESULTS: Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. CONCLUSIONS: Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

Cost-Effectiveness of Transcatheter Aortic Valve Replacement With a Self-Expanding Prosthesis Versus Surgical Aortic Valve Replacement.

BACKGROUND: Previous studies of the cost-effectiveness of transcatheter aortic valve replacement (TAVR) have been based primarily on a single balloon-expandable system. OBJECTIVES: The goal of this study was to evaluate the cost-effectiveness of TAVR with a self-expanding prosthesis compared with surgical aortic valve replacement (SAVR) for patients with severe aortic stenosis and high surgical risk. METHODS: We performed a formal economic analysis on the basis of individual, patient-level data from the CoreValve U.S. High Risk Pivotal Trial. Empirical data regarding survival and quality of life over 2 years, and medical resource use and hospital costs through 12 months were used to project life expectancy, quality-adjusted life expectancy, and lifetime medical costs in order to estimate the incremental cost-effectiveness of TAVR versus SAVR from a U.S. RESULTS: Relative to SAVR, TAVR reduced initial length of stay an average of 4.4 days, decreased the need for rehabilitation services at discharge, and resulted in superior 1-month quality of life. Index admission and projected lifetime costs were higher with TAVR than with SAVR (differences $11,260 and $17,849 per patient, respectively), whereas TAVR was projected to provide a lifetime gain of 0.32 quality-adjusted life-years ([QALY]; 0.41 LY) with 3% discounting. Lifetime incremental cost-effectiveness ratios were $55,090 per QALY gained and $43,114 per LY gained. Sensitivity analyses indicated that a reduction in the initial cost of TAVR by ∼$1,650 would lead to an incremental cost-effectiveness ratio <$50,000/QALY gained. CONCLUSIONS: In a high-risk clinical trial population, TAVR with a self-expanding prosthesis provided meaningful clinical benefits compared with SAVR, with incremental costs considered acceptable by current U.S. STANDARDS: With expected modest reductions in the cost of index TAVR admissions, the value of TAVR compared with SAVR in this patient population would become high. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement [Medtronic CoreValve U.S. Pivotal Trial]; NCT01240902).

Cost-effectiveness of edoxaban vs warfarin in patients with atrial fibrillation based on results of the ENGAGE AF-TIMI 48 trial.

BACKGROUND: In 21,105 patients with atrial fibrillation (AF), the ENGAGE AF-TIMI 48 trial demonstrated that both higher dose (60mg/30mg dose reduced) and lower dose (30mg/15mg dose reduced) once-daily regimens of edoxaban were non-inferior to warfarin for the prevention of stroke or systemic embolism (SE), with significantly lower rates of bleeding and cardiovascular death. Higher dose edoxaban was associated with a greater reduction in the risk of ischemic stroke than lower dose edoxaban, and the FDA approved higher dose edoxaban in patients with creatinine clearance ≤95mL/min. This study evaluated the economic value of higher dose edoxaban vs warfarin based on data from patients in ENGAGE within the FDA-approved population. METHODS: We assessed the cost-effectiveness of edoxaban vs warfarin over a lifetime horizon from the US healthcare system perspective using a Markov model based on a combination of ENGAGE AF-TIMI 48 trial data, US life tables, and published literature on the costs and long-term outcomes of non-fatal cardiovascular and bleeding events. Data from the ENGAGE AF-TIMI 48 trial were used to calculate age-adjusted event rates for warfarin and hazard ratios (HRs) for the relative impact of edoxaban on embolic and bleeding complications. Based on the wholesale acquisition price, edoxaban and warfarin were assumed to cost $9.24 and $0.36/day, respectively. RESULTS: For edoxaban vs warfarin, lifetime incremental costs and QALYs were $16,384 and 0.444, respectively, yielding an incremental cost-effectiveness ratio (ICER) of $36,862/QALY gained, using data from patients with creatinine clearance ≤95mL/min in ENGAGE AF-TIMI 48. ICERs were more favorable for patients without compared to those with prior warfarin use; ICERs differed minimally by CHADS2 score. CONCLUSIONS: Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SE in patients with atrial fibrillation and creatinine clearance ≤95mL/min. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of-life impact of stroke and bleeding events, and were favorable across both CHADS2 score stroke-risk categories.

Cost-effectiveness of percutaneous coronary intervention versus bypass surgery from a Dutch perspective.

AIMS: Recent cost-effectiveness analyses of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) have been limited by a short time horizon or were restricted to the US healthcare perspective. We, therefore, used individual patient-level data from the SYNTAX trial to evaluate the cost-effectiveness of PCI versus CABG from a European (Dutch) perspective. METHODS AND RESULTS: Between 2005 and 2007, 1800 patients with three-vessel or left main coronary artery disease were randomised to either CABG (n=897) or PCI with drug-eluting stents (DES; n=903). Costs were estimated for all patients based on observed healthcare resource usage over 5 years of follow-up. Health state utilities were evaluated with the EuroQOL questionnaire. A patient-level microsimulation model based on Dutch life-tables was used to extrapolate the 5-year in-trial data to a lifetime horizon. Although initial procedural costs were lower for CABG, total initial hospitalisation costs per patient were higher (€17 506 vs €14 037, p<0.001). PCI was more costly during the next 5 years of follow-up, due to more frequent hospitalisations, repeat revascularisation procedures and higher medication costs. Nevertheless, total 5-year costs remained €2465/patient higher with CABG. When the in-trial results were extrapolated to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with gains in both life expectancy and quality-adjusted life expectancy. The incremental cost-effectiveness ratio (ICER) (€5390/quality-adjusted life year (QALY) gained) was favourable and remained <€80 000/QALY in >90% of the bootstrap replicates. Outcomes were similar when incorporating the prognostic impact of non-fatal myocardial infarction and stroke, as well as across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. However, DES-PCI was economically dominant compared with CABG in patients with a SYNTAX Score ≤22 or in those with left main disease. In patients for whom the SYNTAX Score II favoured PCI based on lower predicted 4-year mortality, PCI was also economically dominant, whereas in those patients for whom the SYNTAX Score II favoured surgery, CABG was highly economically attractive (ICER range, €2967 to €3737/QALY gained). CONCLUSIONS: For the broad population with three-vessel or left main disease who are candidates for either CABG or PCI, we found that CABG is a clinically and economically attractive revascularisation strategy compared with DES-PCI from a Dutch healthcare perspective. The cost-effectiveness of CABG versus PCI differed according to several anatomic factors, however. The newly developed SYNTAX Score II provides enhanced prognostic discrimination in this population, and may be a useful tool to guide resource allocation as well. TRIAL REGISTRATION NUMBER: Clinical trial unique identifier: NCT00114972 (http://www.clinical-trials.gov).