Cost effectiveness of treatments of psoriasis with a PASI 75 and one period of 12 weeks

Fundamentos: Los nuevos tratamientos biológicos, si bien mejoran la calidad de vida del paciente, incrementan los costes exponencialmente en relación al resto de tratamientos. El objetivo fue calcular el tratamiento más coste efectivo de los existentes para la psoriasis. Métodos: Se desarrolló un modelo de evaluación económica en psoriasis recogiendo todos los costes directos e indirectos de cada tratamiento. El indicador de efectividad que se utilizó fue Psoriasis Area Severity Index (PASI 75), que es el aceptable de manera general en estudios de psoriasis. Posteriormente se realizó un análisis de incremento coste efectividad (ICER) para el periodo de 12 semanas y PASI 75, ordenando los tratamientos por nivel de efectividad en detrimento de los costes de los tratamientos. Resultados: El tratamiento más coste efectivo fue el metotrexato (ICER -7,5) seguido de acitretina (ICER 29,5). El menos coste efectivo resultó ser PUVA (ICER 4.651) seguido de UVB de banda estrecha (2.886,1). Conclusiones: Aunque el tratamiento más económico teniendo en cuenta solo los costes directos sería el UVBbe, al incluir los costes indirectos y ajustarlos por la efectividad el tratamiento más coste efectivo es el metotexatoBackground: The objective was to evaluate the efficiency (relation between the cost and the results in health) of the treatments in psoriasis, seeking a higher quality of economic evaluations, consistency and transparency in these studies. Methods: We developed a model of economic evaluation in psoriasis collecting all the many direct and indirect costs of each treatment. The effectiveness indicator used was Psoriasis Area Severity Index [PASI 75] which is generally acceptable in studies of psoriasis. The effectiveness indicator was a PASI 75. Subsequently we calculated the Incremental Cost-Effectiveness Ratio (ICER) for the period of 12 weeks and PASI 75, ordering treatments by level of effectiveness at the expense of treatment costs. Results: The most cost effective treatment was methotrexate (ICER -7.5) followed by acitretin (ICER 29.5). The least cost has proved effective PUVA (ICER 4,651), followed by UVB narrow band (2,886.1). Conclusions: When taking into account both direct and indirect costs together with efficiency, methotrexate is the most cost effective treatmen

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival. (C) 2021 The Authors. Published by Elsevier Ltd

Repeated pancreatic resection for pancreatic metastases from renal cell Carcinoma: A Spanish multicenter study (PANMEKID)

Background and objectives: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease -free survival. Methods: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected. Results: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895). Conclusion: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection

Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse. This article reports that the expression of CD1a is mainly restricted to developing cortical thymocytes, and neither CD34+ progenitors nor T cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. We thus developed and preclinically validated a CD1a-specific CAR with robust and specific cytotoxicity in vitro and antileukemic activity in vivo in xenograft models of coT-ALL, using both cell lines and coT-ALL patient–derived primary blasts. CD1a-CARTs are fratricide resistant, persist long term in vivo (retaining antileukemic activity in re-challenge experiments), and respond to viral antigens. Our data support the therapeutic and safe use of fratricide-resistant CD1a-CARTs for relapsed/refractory coT-ALL.This research was supported by the European Research Council (H2020) (CoG-2014-646903), the Agencia Estatal de Investigacion/European Re- ´ gional Development Fund (SAF2016-80481-R and SAF2016-75442-R), and the Catalunya Government (SGR330 and PERIS 2017) (P.M.), as well as the Asociacion Española Contra el C ´ ancer, Beca FERO, and the ´ ISCIII/FEDER (PI17/01028) (C.B.). P.M. also acknowledges institutional support from the Obra Social La Caixa-Fundacio Josep Carreras. J.G.P. ` holds a Miguel Servet contract (CP15/00014), and O.B.-L. is supported by an AGAUR-FI fellowship from the Catalan Government. P.M. is an investigator of the Spanish Cell Therapy cooperative network (TERCEL).Peer reviewe

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Modifying the learning rate of FLNG dealing with imbalanced datasets

IEEE World Congress on Computational Intelligence, WCCI 2010 - 2010 International Joint Conference on Neural Networks, IJCNN 2010 ( 6. 2010. Barcelona

Coste efectividad de diferentes tratamientos para la psoriasis

ABSTRACT Background: The objective was to evaluate the efficiency (relation between the cost and the results in health) of the treatments in psoriasis, seeking a higher quality of economic evaluations, consistency and transparency in these studies. Methods: We developed a model of economic evaluation in psoriasis collecting all the many direct and indirect costs of each treatment. The effectiveness indicator used was Psoriasis Area Severity Index [PASI 75] which is generally acceptable in studies of psoriasis. The effectiveness indicator was a PASI 75. Subsequently we calculated the Incremental Cost-Effectiveness Ratio (ICER) for the period of 12 weeks and PASI 75, ordering treatments by level of effectiveness at the expense of treatment costs. Results: The most cost effective treatment was methotrexate (ICER -7.5) followed by acitretin (ICER 29.5). The least cost has proved effective PUVA (ICER 4,651), followed by UVB narrow band (2,886.1). Conclusions: When taking into account both direct and indirect costs together with efficiency, methotrexate is the most cost effective treatment.RESUMEN Fundamentos: Los nuevos tratamientos biológicos, si bien mejoran la calidad de vida del paciente, incrementan los costes exponencialmente en relación al resto de tratamientos. El objetivo fue calcular el tratamiento más coste efectivo de los existentes para la psoriasis. Métodos: Se desarrolló un modelo de evaluación económica en psoriasis recogiendo todos los costes directos e indirectos de cada tratamiento. El indicador de efectividad que se utilizó fue Psoriasis Area Severity Index (PASI 75), que es el aceptable de manera general en estudios de psoriasis. Posteriormente se realizó un análisis de incremento coste efectividad (ICER) para el periodo de 12 semanas y PASI 75, ordenando los tratamientos por nivel de efectividad en detrimento de los costes de los tratamientos. Resultados: El tratamiento más coste efectivo fue el metotrexato (ICER -7,5) seguido de acitretina (ICER 29,5). El menos coste efectivo resultó ser PUVA (ICER 4.651) seguido de UVB de banda estrecha (2.886,1). Conclusiones: Aunque el tratamiento más económico teniendo en cuenta solo los costes directos sería el UVBbe, al incluir los costes indirectos y ajustarlos por la efectividad el tratamiento más coste efectivo es el metotexato

Bioavailability of once-daily tacrolimus formulations used in clinical practice in the management of De Novo kidney transplant recipients: the better study.

Multicenter, prospective, observational study to compare the relative bioavailability of once-daily tacrolimus formulations in de novo kidney transplant recipients. De novo kidney transplant recipients who started a tacrolimus-based regimen were included 14 days post-transplant and followed up for 6 months. Data from 218 participants were evaluated: 129 in the LCPT group (Envarsus) and 89 in the PR-Tac (Advagraf) group. Patients in the LCPT group exhibited higher relative bioavailability (Cmin /total daily dose [TDD]) vs. PR-Tac (61% increase; P