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BACKGROUND: Patients with homozygous familial hypercholesterolemia (HoFH) remain at very high cardiovascular risk despite the best standard of care lipid-lowering treatment. The addition of evinacumab, an angiopoietin-like protein 3 monoclonal antibody, more than halves low-density lipoprotein cholesterol in short-term studies. This study evaluated whether the evinacumab response was durable in the long term and improved cardiovascular outcome. METHODS: The OLE ELIPSE HoFH (Open-Label Extension to Evinacumab Lipid Studies in Patients With HoFH) study included newly diagnosed patients and those completing the ELIPSE HoFH trial, on stable lipid-lowering therapy including lipoprotein apheresis but not lomitapide. All patients received evinacumab (15 mg/kg intravenously) every 4 weeks, with no change in concomitant lipid-lowering treatment during the first 6 months. The primary efficacy end points were the mean absolute and percentage changes in low-density lipoprotein cholesterol from baseline to 6 months. A key secondary end point was cardiovascular event-free survival, which was compared with a control HoFH cohort not treated with evinacumab or lomitapide and matched for age, sex, and lipoprotein apheresis, derived from French Registry of Familial hypercholesterolemia. RESULTS: Twelve patients, 5 women and 7 men (12-57 years), were enrolled in 3 centers in France. At 6 months, the mean low-density lipoprotein cholesterol reduction with evinacumab was 3.7 mmol/L or 56% (from 6.5 mmol/L at baseline to 2.8 mmol/L; P<0.0001) and was sustained over the median 3.5-year follow-up. No patients on evinacumab experienced cardiovascular events versus 13 events for 5/21 (24%) over 4 years in the control cohort (likelihood P=0.0267). CONCLUSIONS: Real-life, long-term evinacumab adjunctive to lipid-lowering therapy including lipoprotein apheresis led to sustained low-density lipoprotein cholesterol lowering and improved cardiovascular event-free survival of patients with HoFH.
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Proteína 3 Similar a la Angiopoyetina , Anticolesterolemiantes , LDL-Colesterol , Homocigoto , Hiperlipoproteinemia Tipo II , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/mortalidad , Masculino , Femenino , LDL-Colesterol/sangre , Adulto , Persona de Mediana Edad , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/efectos adversos , Eliminación de Componentes Sanguíneos , Biomarcadores/sangre , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Factores de Tiempo , Supervivencia sin Progresión , Adulto Joven , Resultado del Tratamiento , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , AdolescenteRESUMEN
Nitrogen oxides represent one of the main threats for the environment. Despite decades of intensive research efforts, a sustainable solution for NOx removal under environmental conditions is still undefined. Using theoretical modelling, material design, state-of-the-art investigation methods and mimicking enzymes, it is found that selected porous hybrid iron(II/III) based MOF material are able to decompose NOx, at room temperature, in the presence of water and oxygen, into N2 and O2 and without reducing agents. This paves the way to the development of new highly sustainable heterogeneous catalysts to improve air quality.
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BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. OBJECTIVE: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. METHODS: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. RESULTS: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. CONCLUSION: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.
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Anticolesterolemiantes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Adolescente , Niño , Femenino , Humanos , Masculino , Anticolesterolemiantes/uso terapéutico , LDL-Colesterol/uso terapéutico , Estudios de Cohortes , Ezetimiba/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/epidemiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Herein, a robust microporous aluminum tetracarboxylate framework, MIL-120(Al)-AP, (MIL, AP: Institute Lavoisier and Ambient Pressure synthesis, respectively) is reported, which exhibits high CO2 uptake (1.9 mmol g-1 at 0.1 bar, 298 K). In situ Synchrotron X-ray diffraction measurements together with Monte Carlo simulations reveal that this structure offers a favorable CO2 capture configuration with the pores being decorated with a high density of µ2-OH groups and accessible aromatic rings. Meanwhile, based on calculations and experimental evidence, moderate host-guest interactions Qst (CO2) value of MIL-120(Al)-AP (-40 kJ mol-1) is deduced, suggesting a relatively low energy penalty for full regeneration. Moreover, an environmentally friendly ambient pressure green route, relying on inexpensive raw materials, is developed to prepare MIL-120(Al)-AP at the kilogram scale with a high yield while the Metal- Organic Framework (MOF) is further shaped with inorganic binders as millimeter-sized mechanically stable beads. First evidences of its efficient CO2/N2 separation ability are validated by breakthrough experiments while operando IR experiments indicate a kinetically favorable CO2 adsorption over water. Finally, a techno-economic analysis gives an estimated production cost of ≈ 13 $ kg-1, significantly lower than for other benchmark MOFs. These advancements make MIL-120(Al)-AP an excellent candidate as an adsorbent for industrial-scale CO2 capture processes.
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We report the development of a new method of investigation of the mass transport properties of acidic zeolite-based materials aiming to overcome the limitations of classical approaches. It consists in hyphenating gravimetric analysis and infrared spectroscopy. The former allows assessing the diffusion from the gas phase to all the porosity, while IR allows for selective assessment of diffusion to the zeolite active sites located in the micropores. Furthermore, the data are processed by an original methodology allowing the recovery of the distribution of diffusion domains by inversion of the integral equations describing the uptake curves or the evolution of the infrared spectra. The combination of gravimetric analysis and IR spectroscopy makes it possible to monitor and distinguish diffusion within the various components of the material. The methodology has been applied to the isooctane uptake in the mechanical mixture of FAU and MFI zeolites. Analysis of both gravimetric uptake curves and evolving infrared spectra allows distinguishing and assigning diffusion domains to the H-FAU and H-MFI components of the mixture, with high and low effective diffusion rate constants, respectively. The advantages and limits of the methodology are discussed.
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OBJECTIVE: Prognostic models in patients living with diabetes allow physicians to estimate individual risk based on medical records and biological results. Clinical risk factors are not always all available to evaluate these models so that they may be complemented with models from claims databases. The objective of this study was to develop, validate and compare models predicting the annual risk of severe complications and mortality in patients living with type 2 diabetes (T2D) from a national claims data. RESEARCH DESIGN AND METHODS: Adult patients with T2D were identified in a national medical claims database through their history of treatments or hospitalizations. Prognostic models were developed using logistic regression (LR), random forest (RF) and neural network (NN) to predict annual risk of outcome: severe cardiovascular (CV) complications, other severe T2D-related complications, and all-cause mortality. Risk factors included demographics, comorbidities, the adjusted Diabetes Severity and Comorbidity Index (aDSCI) and diabetes medications. Model performance was assessed using discrimination (C-statistics), balanced accuracy, sensibility and specificity. RESULTS: A total of 22,708 patients with T2D were identified, with mean age of 68 years and average duration of T2D of 9.7 years. Age, aDSCI, disease duration, diabetes medications and chronic cardiovascular disease were the most important predictors for all outcomes. Discrimination with C-statistic ranged from 0.715 to 0.786 for severe CV complications, from 0.670 to 0.847 for other severe complications and from 0.814 to 0.860 for all-cause mortality, with RF having consistently the highest discrimination. CONCLUSION: The proposed models reliably predict severe complications and mortality in patients with T2D, without requiring medical records or biological measures. These predictions could be used by payers to alert primary care providers and high-risk patients living with T2D.
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Advanced IR vibrational spectroscopic techniques, e.g., using a coupled gravimetric-IR surface analyzer (AGIR) and a high-throughput in situ IR cell (Carroucell), have been used for the quantitative studies of the adsorption and coadsorption of ethanol and water on MFI zeolites with different Si/Al ratios. The AGIR coupling is a powerful tool for the accurate determination of the molar adsorption coefficients during coadsorption experiments since their evaluation is based on the measurement of the exact amount of adsorbed species. The use of the Carroucell set up allows characterizing all the samples simultaneously, strictly in the same gaseous and temperature environment. The molar absorption coefficients of pure adsorbed ethanol and water are determined: their values are constant whatever the Si/Al ratio of the MFI zeolites. Moreover, these coefficients are found to be identical in the case of the water-ethanol coadsorption experiments. Their use allows obtaining the exact quantity of each adsorbate specie in the binary system. At low partial pressures, the unary water adsorption experiments suggest that the amount of adsorbed water results mainly from the preferential adsorption on Brønsted acid sites in tetrameric clusters. In contrast, the adsorption of EtOH occurs on both silanol groups and Brønsted acid sites (BASs). The effect of the Si/Al ratio is only observed at relatively low partial pressures. The effect of the Si/Al ratio on the ethanol adsorption capacity is also investigated. This study directs the choice of an appropriate zeolite once it is used in membranes for drying ethanol.
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BACKGROUND AND OBJECTIVES: Implementing a ferritin testing policy for whole blood (WB) donors may prevent iron deficiency (ID, ferritin <26 ng/mL) and anaemia, but may induce donation losses. As part of a national prevention plan in France, we aimed to estimate its impact on ID, anaemias and WB donations among donors at high risk of ID. MATERIALS AND METHODS: A micro-simulation model was developed to evaluate different scenarios compared to the current situation without ferritin testing as a reference scenario. The following scenarios were simulated: a minimum scenario with a 6-month deferral for donors with absent iron store (AIS, ferritinemia <15 ng/ml), a main scenario with additional delayed invitations for donors with ferritinemia 15-25 ng/ml and a supplementation scenario with additional iron supplementation for 50% of the donors with AIS. RESULTS: In the main scenario, 52,699 WB donations per year were estimated to be lost after 1 year (-8%), falling to 27,687 (-4.7%) after 5 years. IDs and anaemias were reduced by 13.6% and 29.3%, respectively, after 1 year. The supplementation scenario increased the number of prevented IDs and anaemias to 24.1% and 35.4%, respectively, after 1 year, and halved the number of anaemias at 5 years. The latter scenario also had the least impact on the number of donations (-3.2% after 5 years). CONCLUSION: A ferritin testing policy resulting in delayed donations for ID donors is effective in reducing IDs and anaemias, but significantly impacts the number of donations, thereby posing a self-sufficiency challenge.
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Anemia , Deficiencias de Hierro , Humanos , Hierro/uso terapéutico , Ferritinas , Donantes de Sangre , FranciaRESUMEN
OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.
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Aterosclerosis , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Humanos , Niño , Adolescente , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios de Cohortes , LDL-Colesterol , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/genética , Hipercolesterolemia/complicaciones , Aterosclerosis/etiología , Aterosclerosis/genéticaRESUMEN
CONTEXT: The need for patient navigator is growing, and there is a lack of cost evaluation, especially during survivorship. OBJECTIVE: The objective of this study is to evaluate the cost-effectiveness of an Ambulatory Medical Assistance (AMA) programme in patients with haematological malignancies (HM). DESIGN: A cost-effectiveness analysis of the AMA programme was performed compared to a simulated control arm. SETTING: An interventional, single-arm and prospective study was conducted in a French reference haematology-oncology centre between 2016 and 2020. PARTICIPANTS: Adult patients were enrolled with histologically documented malignant haematology, during their active therapy phase, and treated either by intravenous chemotherapy or oral therapy. METHODS: An extrapolation of the effectiveness was derived from a similar nurse monitoring programme (CAPRI study). Cost effectiveness of the programme was evaluated through adverse events of Grade 3 or 4 avoided in different populations. RESULTS: Included patient (n = 797) from the AMA programme were followed during 125 days (IQR: 0-181), and adverse events (Grade 3/4) were observed in 10.1% of patients versus 13.4% in the simulated control arm. The overall cost of AE avoided was estimated to 81,113, leading to an ICER of 864. CONCLUSION: The AMA programme was shown to be cost-effective compared to a simulated control arm with no intervention.
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Neoplasias Hematológicas , Adulto , Humanos , Análisis Costo-Beneficio , Estudios Prospectivos , Neoplasias Hematológicas/tratamiento farmacológico , Asistencia MédicaRESUMEN
Encapsulating ultrasmall Cu nanoparticles inside Zr-MOFs to form core-shell architecture is very challenging but of interest for CO2 reduction. We report for the first time the incorporation of ultrasmall Cu NCs into a series of benchmark Zr-MOFs, without Cu NCs aggregation, via a scalable room temperature fabrication approach. The Cu NCs@MOFs core-shell composites show much enhanced reactivity in comparison to the Cu NCs confined in the pore of MOFs, regardless of their very similar intrinsic properties at the atomic level. Moreover, introducing polar groups on the MOF structure can further improve both the catalytic reactivity and selectivity. Mechanistic investigation reveals that the CuI sites located at the interface between Cu NCs and support serve as the active sites and efficiently catalyze CO2 photoreduction. This synergetic effect may pave the way for the design of low-cost and efficient catalysts for CO2 photoreduction into high-value chemical feedstock.
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BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in men in Europe. The impact of PCa natural history and therapeutic management on the outcomes of castration-resistant prostate cancer patients with metastasis (mCRPC) remains unclear. OBJECTIVE: The objective of this study was to describe retrospectively patterns of clinical progression through diagnosis sequences before the mCRPC stage and to assess how these sequences impacted patients' disease progression and overall survival at mCRPC stage. PATIENTS AND METHODS: Patients with mCRPC were identified from the Prostate Cancer Registry (PCR), an observational study in a real-world setting in 16 countries between 2013 and 2016. Patients were grouped in diagnosis sequences before mCRPC and defined by date of PCa diagnosis, first metastasis, and castration resistance. Distribution of time-to-event variables were estimated using Kaplan-Meier product-limit survival curves for overall survival (OS) and progression-free survival (PFS). Non-adjusted Cox models were conducted for efficacy endpoints (OS, PFS) to estimate hazard ratios between diagnosis sequences. RESULTS: At the end of study, 2859 mCRPC patients were included in this analysis. Among mCRPC four diagnosis sequences were identified: 35% developed metastases (mHSPC) before becoming castration resistant (sequence 1, metachronous mHSPC), 10% developed castration resistance (nmCRPC) before metastases (sequence 2), 27% developed metastases and castration resistance within 4 months (sequence 3) and 28% of patients were de novo mHSPC (sequence 4). Median OS was 17.7 months (interquartile range (IQR): 8.8-29.9) and PFS was 6.4 months (IQR: 3.2-12.0). The univariate analyses showed no correlation between mCRPC patients' OS or PFS and the diagnosis sequence. CONCLUSION: This large European study describe four different patterns of prostate cancer progression to mCRPC stage. Our results indicate that patient survival becomes comparable after progression to mCRPC, regardless of the diagnosis sequence. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02236637; registered September 2014.
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Neoplasias de la Próstata Resistentes a la Castración , Humanos , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background and aims: Heterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL). Methods: We studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system. Results: The database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention. Conclusions: The incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.
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INTRODUCTION: The extended half-life of dalbavancin justifies a once-a-week dosing schedule and is supposed to favour early discharge. These advantages may therefore compensate for the cost of dalbavancin, but no real-life assessment has been conducted to date. We aimed to assess the real-life budget impact of dalbavancin through its impact on the length of stay in French hospitals. METHODS: A multicentre cohort based on the French registry of dalbavancin use in 2019 was compared to the French national discharge summary database. Lengths of stay and budget impact related to the infection type, the time of introduction of dalbavancin, the type of catheter and patient subgroups were assessed. An early switch was defined when dalbavancin was administered as the first or second treatment and within less than 11 days of hospitalization. RESULTS: A total of 179 patients were identified in the registry, and 154 were included in our study. Dalbavancin was mostly used for bone and joint infections (56.0%), infective endocarditis (19.0%) and acute bacterial skin and skin structure infections (6.0%). When compared to the data for similar patients in the national database, the length of stay was almost always shorter for patients treated with dalbavancin (up to a reduction of 13 days). The budget impact for dalbavancin was heterogeneous but frequently generated savings (up to 2257.0 ). Early switching (within less than 11 days) was associated with savings (or lesser costs), with even greater benefits within 7 days of hospitalization. Patients who required a deep venous catheter as well as the most severe patients benefited the most from dalbavancin. CONCLUSION: Our study confirms that dalbavancin is associated with early discharge, which can offset its cost and generate savings. The greatest benefit is achieved with an early switch.
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BACKGROUND: Innovative provider payment methods that avoid adverse selection and reward performance require accurate prediction of healthcare costs based on individual risk adjustment. Our objective was to compare the performances of a simple neural network (NN) and random forest (RF) to a generalized linear model (GLM) for the prediction of medical cost at the individual level. METHODS: A 1/97 representative sample of the French National Health Data Information System was used. Predictors selected were: demographic information; pre-existing conditions, Charlson comorbidity index; healthcare service use and costs. Predictive performances of each model were compared through individual-level (adjusted R-squared (adj-R2), mean absolute error (MAE) and hit ratio (HiR)), and distribution-level metrics on different sets of covariates in the general population and by pre-existing morbid condition, using a quasi-Monte Carlo design. RESULTS: We included 510,182 subjects alive on 31st December, 2015. Mean annual costs were 1894 (standard deviation 9326) (median 393, IQ range 95; 1480), including zero-claim subjects. All models performed similarly after adjustment on demographics. RF model had better performances on other sets of covariates (pre-existing conditions, resource counts and past year costs). On full model, RF reached an adj-R2 of 47.5%, a MAE of 1338 and a HiR of 67%, while GLM and NN had an adj-R2 of 34.7% and 31.6%, a MAE of 1635 and 1660, and a HiR of 58% and 55 M, respectively. RF model outperformed GLM and NN for most conditions and for high-cost subjects. CONCLUSIONS: RF should be preferred when the objective is to best predict medical costs. When the objective is to understand the contribution of predictors, GLM was well suited with demographics, conditions and base year cost.
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Costos de la Atención en Salud , Aprendizaje Automático , Bases de Datos Factuales , Servicios de Salud , Humanos , Modelos LinealesRESUMEN
BACKGROUND: Between 2015 and 2017, nearly 80,000 hospital stays in orthopaedic surgery were entered into a home discharge support programme (PRADO) offered by the statutory health insurance system. The objective of this study was to assess the impact of the PRADO programme on enrolled stays in orthopaedic surgery over the last three years. HYPOTHESIS: The home discharge support programme used in orthopaedic surgery shortens hospital stays and decreases the rate of readmission within 30days. MATERIAL AND METHODS: The home discharge support programme PRADO was evaluated both quantitatively and qualitatively. The quantitative study used a multicentre retrospective cohort design with matching to controls identified in the national healthcare database. All hospital stays entered into the home discharge support programme between January 2015 and December 2017 were enrolled in the study. Follow-up was 6months after discharge. The main outcome measure was the rate of readmission within 30days after discharge. The secondary outcome measures were emergency department visits, admission to rehabilitation, mean stay duration, visits to recommended healthcare professionals, medication consumption, and total healthcare expenditure at 6months. The statistical analysis used the per protocol approach. The qualitative study involved semi-structured individual and group interviews designed to investigate adhesion of the professionals and their perceptions of programme implementation, funding, and costs. RESULTS: Of 82,202 stays in the programme, 71,761 (87%) were matched and included in the analysis. Characteristics were comparable between the programme stays and the control stays. The programme stays had a significant reduction in the number of all-cause ambulatory and non-ambulatory readmissions (4.5% vs. 4.9%, p<0.0001 and 3.9% vs. 4.2%, p=0.0009, respectively). Emergency department visits and rehabilitation admissions within 30days were significantly less common in the programme group than in the control group (mean values, 2.1% vs. 2.3%, p=0.01 and 3.4% vs. 8.4%, p≤0.0001, respectively). Mean stay length was not significantly different between the two groups. Visits to recommended healthcare professionals occurred significantly more often and earlier in the programme group. The delivery of analgesics and heparin was significantly higher in the programme group, whereas no difference occurred in the delivery of antibiotics. Mean total health expenditures at 6months were lower in the programme group (2248 vs. 2485 ). The success of the PRADO programme was dependent on leadership from the medical staff within the institution and on assistance provided by the hospital throughout its implementation. The criteria for patient eligibility to the programme were not routinely shared by or clear to the healthcare staff. DISCUSSION: The PRADO programme effectively improves the care of orthopaedic surgery patients and raises the issue of whether some admissions to rehabilitation may be unnecessary. LEVEL OF EVIDENCE: III; comparative retrospective study.
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Procedimientos Ortopédicos , Alta del Paciente , Humanos , Estudios Retrospectivos , Tiempo de Internación , HospitalizaciónRESUMEN
OBJECTIVES: This study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH). BACKGROUND: Common cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death. RESULTS: We included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%. CONCLUSIONS: CAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Hiperlipoproteinemia Tipo II , Calcificación Vascular , Adulto , Calcio , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico por imagen , Hiperlipoproteinemia Tipo II/genética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Calcificación Vascular/diagnóstico por imagenRESUMEN
BACKGROUND AND AIMS: Current guidelines recommend colonoscopy every 3-5 years for colorectal cancer (CRC) screening of individuals with a familial history of CRC. The objective of this study was to compare the cost effectiveness of screening alternatives in this population. METHODS: Eight screening strategies were compared with no screening: fecal immunochemical test (FIT), Stool DNA and blood-based screening every 2 years, colonoscopy, computed tomography colonography, colon capsules, and sigmoidoscopy every 5 years, and colonoscopy at 45 years followed, if negative, by FIT every 2 years. Screening test and procedures performance were obtained from the literature. A microsimulation model reproducing the natural history of CRC was used to estimate the cost (2018) and effectiveness [quality-adjusted life-years (QALYs)] of each strategy. A lifetime horizon was used. Costs and effectiveness were discounted at 3.5% annually. RESULTS: Compared with no screening, colonoscopy and sigmoidoscopy at a 30% uptake were the most effective strategy (46.3 and 43.9 QALY/1000). FIT at a 30 µg/g threshold with 30% uptake was only half as effective (25.7 QALY). Colonoscopy was associated with a cost of 484,000 per 1000 individuals whereas sigmoidoscopy and FIT were associated with much lower costs (123,610 and 66,860). Incremental cost-effectiveness rate for FIT and sigmoidoscopy were 2600/QALY (versus no screening) and 3100/QALY (versus FIT), respectively, whereas it was 150,000/QALY for colonoscopy (versus sigmoidoscopy). With a lower threshold (10 µg/g) and a higher uptake of 45%, FIT was more effective and less costly than colonoscopy at a 30% uptake and was associated with an incremental cost-effectiveness ratio (ICER) of 4240/QALY versus no screening. CONCLUSION: At 30% uptake, current screening is the most effective screening strategy for high-risk individuals but is associated with a high ICER. Sigmoidoscopy and FIT at lower thresholds (10 µg/g) and a higher uptake should be given consideration as cost-effective alternatives. PLAIN LANGUAGE SUMMARY: Cost-effectiveness analysis of colorectal cancer screening strategies in high-risk individuals Fecal occult blood testing with an immunochemical test (FIT) is generally considered as the most cost-effective alternative in colorectal cancer screening programs for average risk individuals without family history.Current screening guidelines for high-risk individuals with familial history recommend colonoscopy every 3-5 years.Colonoscopy every 3-5 years for individuals with familial history is the most effective strategy but is associated with a high incremental cost-effectiveness ratio.Compared with colonoscopy, if screening based on FIT is associated with a higher participation rate, it can achieve a similar effectiveness at a lower cost.
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BACKGROUND: A nationwide colorectal cancer (CRC) screening program was set up in France from 2009 for average-risk, asymptomatic people aged 50-74 years based on an immunochemical fecal occult blood test [faecal immunochemical test (FIT)] every 2 years, followed by colonoscopy if positive. The European standard recommends a participation rate of 45% for the program to be cost-effective, yet the latest published rate in France was 34%. The objective of this study was to compare the cost effectiveness of screening alternatives taking real-world participation rates into account. METHODS: Eight screening strategies were compared, based either on a screening test (Guaiac or FIT testing, blood-based, stool DNA, computed tomography colonography, colon capsules, and sigmoidoscopy) followed by full colonoscopy if positive or direct colonoscopy. A microsimulation model was used to estimate the cost effectiveness associated with each strategy. RESULTS: Compared with no screening, FIT was associated with a 14.0 quality-adjusted life year (QALY) increase of 50,520 per 1000 individuals, giving an incremental cost-effectiveness ratio (ICER) of 3600/QALY. Only stool DNA and blood-based testing were associated with a QALY increase compared with FIT, with stool DNA weakly dominated by blood-based testing, and the latter associated with an ICER of 154,600/QALY compared with FIT. All other strategies were dominated by FIT. CONCLUSION: FIT every 2 years appears to be the most cost-effective CRC screening strategy when taking into account a real-world participation rate of 34%.
RESUMEN
BACKGROUND AND AIMS: Patients with heterozygous familial hypercholesterolemia (HeFH) present elevated cardiovascular (CV) risk. Current CV risk stratification algorithms developed for the general population are not adapted for heFH patients. It is therefore of singular importance to develop and validate CV prediction tools, which are dedicated to the HeFH population. METHODS: Our first objective was to validate the Spanish SAFEHEART-risk equation (RE) in the French HeFH cohort (REFERCHOL), and the second to compare SAFEHEART-RE with the low-density-lipoprotein-cholesterol (LDL-C)-year-score for the prediction of CV events in the HeFH French population. RESULTS: We included HeFH (nâ¯=â¯1473) patients with a genetic or clinical diagnosis (DLCN score ≥8). Among them, 512 patients with a 5-year follow-up were included to validate the 5 year-CV-RE. A total of 152 events (10.3%) occurred in the entire population of 1473 patients during a mean follow-up of 3.9 years. Over the five-year follow-up, non-fatal CV events occurred in 103 patients (20.2%). Almost all the parameters used in the SAFEHEART-RE were confirmed as strong predictors of CV events in the REFERCHOL cohort. The C-statistic revealed a satisfactory performance of both the SAFEHEART-RE and LDL-C-year-scores in predicting CV events for all the patients (primary and secondary prevention) (C-index 0.77 and 0.70, respectively) as well as for those in primary prevention at inclusion (C-index 0.78 and 0.77, respectively). CONCLUSIONS: This analysis represents the first external validation of the SAFEHEART-RE and demonstrated that both SAFEHEART-RE and the LDL-C-year-score are good predictors of CV events in primary prevention HeFH patients.