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The cost of treating cutaneous T-cell lymphoma (CTCL) in Spain is unknown. With the advent of new treatments, it is more important than ever to gain an accurate picture of the true ...costs involved. The MICADOS study had 2 primary objectives: 1)to evaluate the impact of CTCL on patient quality of life, and 2)to evaluate the costs associated with the disease. This article reports the results of the cost analysis.
We estimated the cost of treating CTCL over a period of 1year from the perspective of the Spanish National Health System. Twenty-three dermatologists and hematologists from 15 public hospitals analyzed data for adult patients with mycosis fungoides (MF) or Sézary syndrome (SS).
A total of 141 patients (57.4% male) with a mean age of 63.6 years (95%CI: 61.4-65.7 years) were included. The mean direct annual cost of treating CTCL was €34,214 per patient. The corresponding costs by stage were €11,952.47 for stageI disease, €23,506.21 for stageII disease, €38,771.81 for stageIII disease, and €72,748.84 for stageIV disease. The total direct annual cost of treating MF/SS in public hospitals in Spain was estimated at €78,301,171; stageI disease accounted for 81% of all costs, stageII for 7%, and stagesIII andIV for 6% each.
The MICADOS study offers an accurate picture of the direct cost of treating CTCL in patients with MF/SS in Spain and shows that costs vary significantly according to disease stage. Patient-borne and indirect costs should be analyzed in future studies.
No se dispone de datos españoles sobre el coste asociado al linfoma cutáneo de célulasT (LCCT). Además, la incorporación de nuevos tratamientos hace necesario analizar el coste real de la enfermedad. El estudio MICADOS analizó dos objetivos principales: Por un lado, evaluó el impacto en la calidad de vida en los pacientes con LCCT, y por otro lado, estudió los costes de la enfermedad. En esta publicación se recoge el segundo de los objetivos del estudio.
El coste de la enfermedad se estudió bajo la perspectiva del Sistema Nacional de Salud (SNS) con un horizonte temporal de un año. Participaron 23 dermatólogos y hematólogos de 15 hospitales públicos españoles. Se incluyeron pacientes adultos con LCCT del tipo micosis fungoide (MF) y síndrome de Sézary (SS).
Se incluyeron 141 pacientes, el 57,4% masculinos, con una edad media de 63,6 años (IC95%: 61,4-65,7). Los costes directos anuales medios por pacientes del estudio fueron de 34.214€, siendo de 11.952,47€ en estadioI, 23.506,21€ en estadioII, 38.771,81€ en estadioIII y 72.748,84€ en estadioIV. El coste anual directo total estimado de todos los pacientes en España con MF/SS resultó en 78.301.171€, donde el 81% de los costes fueron atribuibles a pacientes en estadioI, el 7% al estadioII, el 6% al estadioIII y el 6% al estadioIV.
Este estudio ofrece una evaluación precisa del coste directo del LCCT en pacientes con MF/SS en España, mostrando costes que varían sustancialmente en función del estadio. Los costes soportados por el paciente y los costes indirectos deberán considerarse en futuras investigaciones.
Exercise training (ET) is a critical component of cardiac rehabilitation (CR), but it remains underused. The aim of this study was to compare clinical outcomes between patients who completed ET ...(A-T), those who accepted ET but did not complete it (A-NT), and those who did not accept to undergo it (R-NT), and to analyze reasons for rejecting or not completing ET.
A unicenter ambispective observational registry study of 497 patients with acute coronary syndrome (ACS) was carried out in Barcelona, Spain, from 2016 to 2019. The primary endpoint was a composite of all-cause mortality, hospitalization for ACS, or need for revascularization during follow-up. Multivariable analysis was carried out to identify variables independently associated with the primary outcome. Initially, 70% of patients accepted participating in the ET, but only 50.5% completed it. The A-T group were younger and had fewer comorbidities. Baseline characteristics in A-NT and R-NT groups were very similar. The main reason for not undergoing or completing ET was rejection (reason unknown) or work/schedule incompatibility. The median follow-up period was 31 months. Both the composite primary endpoint and mortality were significantly lower in the A-T group compared to the A-NT and R-NT (primary endpoint: 3.6% vs. 23.2% vs. 20.4%,
< 0.001, respectively; mortality: 0.8% vs. 9.1% vs. 8.2%,
< 0.001; respectively). During multivariable analysis, the only variables that remained statistically significant with the composite endpoint were ET completion, previous ACS, and anemia.
Completion of ET after ACS was associated with improved prognosis. Only half of the patients completed the ET program, with the leading reasons for not completing it being refusal (reason unknown) and work/schedule incompatibility. These results highlight the need to focus on the needs of patients in order to guarantee that structural barriers to ET no longer exist.
Several risk scores have been used to predict risk after an acute coronary syndrome (ACS), but none of these risk scores include functional class. The aim was to assess the predictive value of risk ...stratification (RS), including functional class, and how cardiac rehabilitation (CR) changed RS. Two hundred and thirty-eight patients with ACS from an ambispective observational registry were stratified as low (L) and no-low (NL) risk and classified according to exercise compliance; low risk and exercise (L-E), low risk and control (no exercise) (L-C), no-low risk and exercise (NL-E), and no-low risk and control (NL-C). The primary endpoint was cardiac rehospitalization. Multivariable analysis was performed to identify variables independently associated with the primary endpoint. The L group included 56.7% of patients. The primary endpoint was higher in the NL group (18.4% vs. 4.4%, p < 0.001). After adjustment for age, sex, diabetes, and exercise in multivariable analysis, HR (95% CI) was 3.83 (1.51−9.68) for cardiac rehospitalization. For RS and exercise, the prognosis varied: the L-E group had a cardiac rehospitalization rate of 2.5% compared to 26.1% in the NL-C group (p < 0.001). Completing exercise training was associated with reclassification to low-risk, associated with a better outcome. This easy-to-calculate risk score offers robust prognostic information. No-exercise groups were independently associated with the worst outcomes. Exercise-based CR program changed RS, improving classification and prognosis.
Metal exposure is associated with increased oxidative stress (OS), which is considered an underlying mechanism of metal-induced toxicity. Malondialdehyde (MDA) is a final product of lipid ...peroxidation, and it has been extensively used to evaluate metal-induced OS. Pro-oxidant effects produced by metals can be mitigated by paraoxonase 1 (PON1), an antioxidant enzyme known to prevent cardiovascular disease and atherosclerosis. Among other factors, the Q192R polymorphism and the exposure to heavy metals have been known to alter PON1 activity. Here, we evaluated the association of blood lead (Pb), cadmium (Cd) and mercury (Hg) levels with PON1 activity, and with MDA concentrations in a randomly selected sample of Brazilian adults aged 40 years or older, living in an urban area in Southern Brazil. A total of 889 subjects were evaluated for blood Pb and Cd levels, and 832 were tested for Hg. Geometric mean of blood Pb, Cd and Hg was 1.93μg/dL, 0.06μg/L and 1.40μg/L, respectively. PON1 activity was significantly different among various genotypes: QQ (PON1=121.4U/mL), QR (PON1=87.5U/mL), and RR (PON1=55.2U/mL), p<0.001. PON1 genotypes were associated only with Cd blood levels. Those with QR genotype had Cd concentrations higher (0.07μg/L) than those with the RR genotype (0.04μg/L) with p=0.034. However, PON1 activity was not significantly associated with metal concentrations. Cluster analysis showed that men who reported to be current smokers and drinkers with higher blood Pb and Cd levels, had significantly lower PON1 activity than non-smokers or -drinkers, and women with lower Pb and Cd levels. RR genotype carriers had lower PON1 activity than those with the QR genotype, and had higher levels of Pb and Cd compared with other genotype carriers. For blood Hg, no association with PON1 activity or genotype was noted. We found low levels of Pb, Cd and Hg in environmentally exposed Brazilian adults. Cd concentrations were increased in subjects with QR genotype. Those with RR genotype had lower PON1 activity and higher levels of Pb and Cd than other genotype carriers. The results of cluster analysis suggested that smoking status exerts a significant influence on PON1 activity. Other studies with environmentally exposed populations are required to further clarify whether low blood levels of metals influence OS biomarkers.
•Low levels of lead, cadmium and mercury were found in a sample of Brazilian adults.•PON1 activity and MDA was not significantly associated with metals concentrations.•Blood cadmium was significantly different according with PON1 genotypes, and RR genotype carriers had lower PON1 activity and higher Pb and Cd levels.•Men, smokers, drinkers, with higher blood Pb and Cd levels had lower PON1 activity.•There was not a trend of an association with PON1 activity or genotype with blood mercury.
Aim
Of the few instruments available to measure the important, positive aspects of caring, the Caregiver Reaction Assessment is regarded as the most suitable, but there is no validated Spanish ...version. The aim of this study was to translate the Caregiver Reaction Assessment into Spanish and assess its psychometric properties.
Methods
The Caregiver Reaction Assessment was translated into Spanish and then back translated. Validation included construct validity, criterion validity and reliability: 287 interviews were conducted with informal caregivers of patients with dementia between November 2010 and April 2012.
Results
Principal component analysis confirmed the original instrument's five subscales. Criterion validity showed a moderate negative correlation between the impact on health and the EQ‐5D (r = −.43), that is, a greater impact on health correlated with lower health‐related quality of life. The Caregiver Reaction Assessment showed good internal consistency, with a Cronbach alpha of .804, and good temporal stability for the distinct subscales, with intraclass correlation coefficients varying from .683 to .729 (p < .001).
Conclusion
The Caregiver Reaction Assessment is a reliable, valid instrument for the measurement of the reactions of informal caregivers of patients with dementia, with good psychometric properties.
SUMMARY STATEMENT
What is already known about this topic?
The Caregiver Reaction Assessment is one of the few instruments that measures positive reactions in caregivers.
A validated Spanish version of the instrument is required for Spain and other Spanish‐speaking countries.
What this paper adds?
The Caregiver Reaction Assessment was shown to be a reliable, valid instrument for the measurement of the reactions of informal caregivers of people with dementia in Spain and has good psychometric properties.
The implications of this paper:
Once validation is complete, the Caregiver Reaction Assessment may be used in all Spanish‐speaking informal caregivers and is suitable for home care and long‐term care institutions.
The Caregiver Reaction Assessment subscales allow healthcare professionals to identify and focus on the areas that could bring about the greatest improvements in the care of people with dementia.
The Caregiver Reaction Assessment permits the caregiver's state to be viewed at any stage of dementia and offers healthcare professionals the opportunity to act to avoid physical and emotional overload in caregivers.
Alterations in the epigenetic machinery in both tumor and immune cells contribute to bladder cancer (BC) development, constituting a promising target as an alternative therapeutic option. Here, we ...have explored the effects of a novel histone deacetylase (HDAC) inhibitor CM-1758, alone or in combination with immune checkpoint inhibitors (ICI) in BC. We determined the antitumor effects of CM-1758 in various BC cell lines together with the induction of broad transcriptional changes, with focus on the epigenetic regulation of PD-L1. Using an immunocompetent syngeneic mouse model of metastatic BC, we studied the effects of CM-1758 alone or in combination with anti-PD-L1 not only on tumor cells, but also in the tumor microenvironment. In vitro, we found that CM-1758 has cytotoxic and cytostatic effects either by inducing apoptosis or cell cycle arrest in BC cells at low micromolar levels. PD-L1 is epigenetically regulated by histone acetylation marks and is induced after treatment with CM-1758. We also observed that treatment with CM-1758 led to an important delay in tumor growth and a higher CD8 + T cell tumor infiltration. Moreover, anti-PD-L1 alone or in combination with CM-1758 reprogramed macrophage differentiation towards a M1-like polarization state and increased of pro-inflammatory cytokines systemically, yielding potential further antitumor effects. Our results suggest the possibility of combining HDAC inhibitors with immunotherapies for the management of advanced metastatic BC.
Despite attempts to improve the definitions of ambiguous lineage leukemia (ALAL) during the last 2 decades, general therapy recommendations are missing. Herein, we report a large cohort of children ...with ALAL and propose a treatment strategy. A retrospective multinational study (International Berlin-Frankfurt-Münster Study of Leukemias of Ambiguous Lineage iBFM-AMBI2012) of 233 cases of pediatric ALAL patients is presented. Survival statistics were used to compare the prognosis of subsets and types of treatment. Five-year event-free survival (EFS) of patients with acute lymphoblastic leukemia (ALL)–type primary therapy (80% ± 4%) was superior to that of children who received acute myeloid leukemia (AML)–type or combined-type treatment (36% ± 7.2% and 50% ± 12%, respectively). When ALL- or AML-specific gene fusions were excluded, 5-year EFS of CD19+ leukemia was 83% ± 5.3% on ALL-type primary treatment compared with 0% ± 0% and 28% ± 14% on AML-type and combined-type primary treatment, respectively. Superiority of ALL-type treatment was documented in single-population mixed phenotype ALAL (using World Health Organization and/or European Group for Immunophenotyping of Leukemia definitions) and bilineal ALAL. Treatment with ALL-type protocols is recommended for the majority of pediatric patients with ALAL, including cases with CD19+ ALAL. AML-type treatment is preferred in a minority of ALAL cases with CD19− and no other lymphoid features. No overall benefit of transplantation was documented, and it could be introduced in some patients with a poor response to treatment. As no clear indicator was found for a change in treatment type, this is to be considered only in cases with ≥5% blasts after remission induction. The results provide a basis for a prospective trial.
•The largest cohort of ambiguous leukemias to date reveals a better prognosis of children who started on lymphoid-directed treatment.•Myeloid-type primary treatment correlated with dismal outcomes in CD19+ leukemias.
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