ABSTRACT
BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.
ABSTRACT
Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.
Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Purpura, Thrombotic Thrombocytopenic , Thrombosis , Humans , Aged , Purpura, Thrombotic Thrombocytopenic/diagnosis , Purpura, Thrombotic Thrombocytopenic/epidemiology , Purpura, Thrombotic Thrombocytopenic/therapy , Purpura, Thrombocytopenic, Idiopathic/therapy , Rituximab/therapeutic use , Thrombosis/therapy , Plasma Exchange , Registries , ADAMTS13 ProteinABSTRACT
Deficits in social cognition and metacognition impact the course of psychosis. Sex differences in social cognition and metacognition could explain heterogeneity in psychosis. 174 (58 females) patients with first-episode psychosis completed a clinical, neuropsychological, social cognitive, and metacognitive assessment. Subsequent latent profile analysis split by sex yielded two clusters common to both sexes (a Homogeneous group, 53% and 79.3%, and an Indecisive group, 18.3% and 8.6% of males and females, respectively), a specific male profile characterized by presenting jumping to conclusions (28.7%) and a specific female profile characterized by cognitive biases (12.1%). Males and females in the homogeneous profile seem to have a more benign course of illness. Males with jumping to conclusions had more clinical symptoms and more neuropsychological deficits. Females with cognitive biases were younger and had lower self-esteem. These results suggest that males and females may benefit from specific targeted treatment and highlights the need to consider sex when planning interventions.
Subject(s)
Cognition Disorders , Metacognition , Psychotic Disorders , Cognition , Cognition Disorders/psychology , Female , Humans , Male , Psychotic Disorders/therapy , Social CognitionABSTRACT
Fundamento: La pandemia por el coronavirus SARS-CoV-2, genera afectaciones en las esferas social, económica y sanitariade un país, y de manera particular, consecuencias psicológicas negativas en el personal sanitario de hospitales públicos,considerados como la primera línea de atención a pacientes con esta enfermedad.Objetivo: Describir factores asociados a la presencia de malestar psicológico en el personal sanitario de un hospital generalpúblico en Ecuador, durante la pandemia de COVID-19.Metodología: Estudio no experimental, de corte transversal, con alcance descriptivo-correlacional. Los datos correspondierona 276 funcionarios de la salud que respondieron un instrumento online, con un módulo de datos sociodemográficos y una escalade tamizaje de malestar psicológico, estos se aplicaron después de una intervención en salud dirigida al personal de saludrealizada al inicio de la pandemia, en mayo del año 2020. Se realizaron análisis descriptivos y de asociación, mediante elsoftware SPSS 25.0.Resultados: La muestra estuvo compuesta por 76.1 porciento de mujeres, 23.9 porciento de hombres, con una media de edad de 36 años,en mayor cantidad con profesionales de Enfermería (33.7 porciento), seguido de Medicina (24.3 porciento). El 70.7 porciento del personal de saludpresentó malestar psicológico, de estos, el 26.1 porciento con indicativo de trastorno mental. Se encontraron tres variables asociadasa la presencia de malestar psicológico: clima laboral, teletrabajo y convivir con grupos de riesgo.Conclusiones: El personal de Salud ha presentado afectación en su salud mental asociado a las condiciones sociolaboralesdurante la pandemia. [AU]
Subject(s)
Humans , Burnout, Professional , Burnout, Professional , Mental Health , Mental Disorders , Coronavirus Infections , Pandemics , Alert Fatigue, Health PersonnelABSTRACT
Subjects with first-episode psychosis experience substantial deficits in social cognition and metacognition. Although previous studies have investigated the role of profiles of individuals in social cognition and metacognition in chronic schizophrenia, profiling subjects with first-episode psychosis in both domains remains to be investigated. We used latent profile analysis to derive profiles of the abilities in 174 persons with first-episode psychosis using the Beck's Cognitive Insight Scale, the Faces Test, the Hinting Task, the Internal, Personal and Situational Attributions Questionnaire, and the Beads Task. Participants received a clinical assessment and a neuropsychological assessment. The best-fitting model was selected according to the Bayesian information criterion (BIC). We assessed the importance of the variables via a classification tree (CART). We derived three clusters with distinct profiles. The first profile (33.3%) comprised individuals with low social cognition. The second profile (60.9%) comprised individuals that had more proneness to present jumping to conclusions. The third profile (5.7%) presented a heterogeneous profile of metacognitive deficits. Persons with lower social cognition presented worse clinical and neuropsychological features than cluster 2 and cluster 3. Cluster 3 presented significantly worst functioning. Our results suggest that individuals with FEP present distinct profiles that concur with specific clinical, neuropsychological, and functional challenges. Each subgroup may benefit from different interventions.
ABSTRACT
Electrophilic borylation of indoles with BX3 (X = Cl or Br) using directing groups installed at N1 can proceed at the C2 or the C7 position. The six membered heterocycle directing groups utilised herein, pyridines and pyrimidine, result in indole C2 borylation being the dominant outcome (in the absence of a C2-substituent). In contrast, C7 borylation was achieved using five membered heterocycle directing groups, such as thiazole and benzoxazole. Calculations on the borylation of indole substituted with a five (thiazole) and a six (pyrimidine) membered heterocycle directing group indicated that borylation proceeds via borenium cations with arenium cation formation having the highest barrier in both cases. The C7 borylated isomer was calculated to be the thermodynamically favoured product with both five and six membered heterocycle directing groups, but for pyrimidine directed indole borylation the C2 product was calculated to be the kinetic product. This is in contrast to thiazole directed indole borylation with BCl3 where the C7 borylated isomer is the kinetic product too. Thus, heterocycle ring size is a useful way to control C2 vs. C7 selectivity in N-heterocycle directed indole C-H borylation.
ABSTRACT
The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into 5 parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them.
Subject(s)
COVID-19/complications , Cardiopulmonary Resuscitation/standards , SARS-CoV-2 , Adult , Advanced Cardiac Life Support/methods , Advanced Cardiac Life Support/standards , Age Factors , Airway Management/methods , Airway Management/standards , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , Cardiopulmonary Resuscitation/methods , Child , Disease Progression , Electric Countershock , Heart Arrest/therapy , Humans , Pandemics , Patient Positioning/methods , Personal Protective Equipment , Protective Clothing , Societies, Medical , SpainABSTRACT
AIMS: There is a need of more quantitative standardised data to compare local Mental Health Systems (MHSs) across international jurisdictions. Problems related to terminological variability and commensurability in the evaluation of services hamper like-with-like comparisons and hinder the development of work in this area. This study was aimed to provide standard assessment and comparison of MHS in selected local areas in Europe, contributing to a better understanding of MHS and related allocation of resources at local level and to lessen the scarcity in standard service comparison in Europe. This study is part of the Seventh Framework programme REFINEMENT (Research on Financing Systems' Effect on the Quality of Mental Health Care in Europe) project. METHODS: A total of eight study areas from European countries with different systems of care (Austria, England, Finland, France, Italy, Norway, Romania, Spain) were analysed using a standard open-access classification system (Description and Evaluation of Services for Long Term Care in Europe, DESDE-LTC). All publicly funded services universally accessible to adults (≥18 years) with a psychiatric disorder were coded. Care availability, diversity and capacity were compared across these eight local MHS. RESULTS: The comparison of MHS revealed more community-oriented delivery systems in the areas of England (Hampshire) and Southern European countries (Verona - Italy and Girona - Spain). Community-oriented systems with a higher proportion of hospital care were identified in Austria (Industrieviertel) and Scandinavian countries (Sør-Trøndelag in Norway and Helsinki-Uusimaa in Finland), while Loiret (France) was considered as a predominantly hospital-based system. The MHS in Suceava (Romania) was still in transition to community care. CONCLUSIONS: There is a significant variation in care availability and capacity across MHS of local areas in Europe. This information is relevant for understanding the process of implementation of community-oriented mental health care in local areas. Standard comparison of care provision in local areas is important for context analysis and policy planning.
Subject(s)
Ambulatory Care Facilities/standards , Mental Disorders/psychology , Mental Health Services/standards , Residential Facilities/standards , Adult , Efficiency, Organizational , Europe , Humans , Mental Disorders/therapy , Mental HealthABSTRACT
A series of Bn-PAHs have been prepared by functionalisation of a B1-PAH, leading to the first only boron doped B3-PAH to the best of our knowledge. These Bn-PAHs represent the first three members of a series of {B-Mes} fused oligo-naphthalenes and trends in key properties of this series have been elucidated.
ABSTRACT
BACKGROUND AND OBJECTIVES: Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood component transfusion therapy, caused by donor T lymphocytes. γ-Irradiation or pathogen inactivation methods, capable of inactivating proliferating T cells in blood components, should be selected to prevent TA-GVHD. This review summarizes the published evidence to support the use of pathogen-reduced platelets with amotosalen (150 µm) and ultraviolet A light (UVA, 320-400 nm, 3 J/cm2 ) for preventing TA-GVHD. MATERIALS AND METHODS: Available literature on the use of pathogen-reduced platelets to prevent TA-GVHD was reviewed. RESULTS: Observational studies, animal models, in vitro studies and mechanistic studies of pathogen-reduced platelets with amotosalen and UVA light showed that inactivation of T cells are equal or even superior to γ-irradiation. CONCLUSION: Pathogen-reduced platelets with amotosalen and UVA light can be used as a measure to prevent TA-GVHD.
Subject(s)
Blood Platelets/radiation effects , Blood Safety/methods , Furocoumarins/pharmacology , Graft vs Host Disease/prevention & control , Photosensitizing Agents/pharmacology , Ultraviolet Rays , Animals , Blood Platelets/drug effects , Graft vs Host Disease/etiology , Humans , Platelet Transfusion/adverse effectsABSTRACT
We introduce a new framework to study the non-Newtonian behaviour of fluids at the microscale based on the analysis of front advancement. We apply this methodology to study the non-linear rheology of blood in microchannels. We carry out experiments in which the non-linear viscosity of blood samples is quantified at different haematocrits and ages. Under these conditions, blood exhibits a power-law dependence on the shear rate. In order to analyse our experimental data, we put forward a scaling theory which allows us to define an adhesion scaling number. This theory yields a scaling behaviour of the viscosity expressed as a function of the adhesion capillary number. By applying this scaling theory to samples of different ages, we are able to quantify how the characteristic adhesion energy varies as time progresses. This connection between microscopic and mesoscopic properties allows us to estimate quantitatively the change in the cell-cell adhesion energies as the sample ages.
ABSTRACT
OBJETIVO: Estudiar la organización del transporte interhospitalario pediátrico y neonatal en la península ibérica y Latinoamérica. DISEÑO: Estudio observacional prospectivo mediante una encuesta enviada por correo electrónico con preguntas sobre el sistema de transporte nacional, regional y local, el tipo y vehículo de traslado, el material y el personal y su formación. Ámbito: Responsables pediátricos de hospitales de España, Portugal y Latinoamérica. RESULTADOS: Se analizaron 117 encuestas provenientes de 15 países. De ellas, 55 (47%) procedían de 15 comunidades autónomas de España y el resto de Portugal y de 13 países latinoamericanos. Muy pocas regiones y ciudades tienen un sistema de transporte pediátrico y neonatal específico. El transporte solo está unificado en las comunidades españolas de Baleares y Cataluña y en Portugal. En Chile el sistema de transporte es mixto, pediátrico y del adulto. Solo un 51,4% de los hospitales tiene un sistema de formación del personal de transporte, y solo en el 36,4% la formación es específica en transporte pediátrico. En España y Portugal los sistemas de transporte son fundamentalmente públicos, mientras que en Latinoamérica coexisten sistemas públicos y privados. Los equipos de transporte de la península ibérica tienen más material pediátrico y neonatal y reciben más formación en transporte pediátrico que los de Latinoamérica. CONCLUSIONES: Existe una gran variabilidad en la organización del transporte pediátrico en cada país y región. En la mayoría de los países y ciudades no existe un sistema unificado y específico de transporte pediátrico con un personal cualificado y un material de traslado específico
OBJECTIVE: To study the organization of inter-hospital transport of pediatric and neonatal patients in Spain, Portugal and Latin America. DESIGN: An observational study was performed. An on-line survey was sent by email including questions about characteristics of national, regional and local health transport systems, vehicles, material, and composition of the transport team and their training. SETTING: Hospital pediatric healthcare professionals treating children in Spain, Portugal and Latin America RESULTS: A total of 117 surveys from 15 countries were analyzed. Of them, 55 (47%) come from 15 regions of Spain and the rest from Portugal and 13 Latin American countries. The inter-hospital transport of pediatric patients is unified only in the Spanish regions of Baleares and Cataluña and in Portugal. Chile has a mixed unified transport system for pediatric and adult patients. Only 51.4% of responders have an educational program for the transport personnel, and only in 36.4% of them the educational program is specific for pediatric patients. In Spain and Portugal the transport is executed mostly by public entities, while in Latin America public and private systems coexist. Specific pediatric equipment is more frequent in the transport teams in the Iberian Peninsula than in Latin American teams. The specific pediatric transport training is less frequent for teams in Latin America than on Spain and Portugal. CONCLUSIONS: There is a great variation in the organization of children transport in each country and region. Most of countries and cities do not have unified and specific teams of pediatric transport, with pediatric qualified personnel and specific material
Subject(s)
Humans , Child , Patient Transfer , Ambulances/organization & administration , Prehospital Care/methods , Intensive Care Units, Pediatric/organization & administration , Intensive Care Units, Neonatal/organization & administration , Health Personnel/statistics & numerical dataABSTRACT
BACKGROUND: Aims were to assess the efficacy of metacognitive training (MCT) in people with a recent onset of psychosis in terms of symptoms as a primary outcome and metacognitive variables as a secondary outcome. METHOD: A multicenter, randomized, controlled clinical trial was performed. A total of 126 patients were randomized to an MCT or a psycho-educational intervention with cognitive-behavioral elements. The sample was composed of people with a recent onset of psychosis, recruited from nine public centers in Spain. The treatment consisted of eight weekly sessions for both groups. Patients were assessed at three time-points: baseline, post-treatment, and at 6 months follow-up. The evaluator was blinded to the condition of the patient. Symptoms were assessed with the PANSS and metacognition was assessed with a battery of questionnaires of cognitive biases and social cognition. RESULTS: Both MCT and psycho-educational groups had improved symptoms post-treatment and at follow-up, with greater improvements in the MCT group. The MCT group was superior to the psycho-educational group on the Beck Cognitive Insight Scale (BCIS) total (p = 0.026) and self-certainty (p = 0.035) and dependence self-subscale of irrational beliefs, comparing baseline and post-treatment. Moreover, comparing baseline and follow-up, the MCT group was better than the psycho-educational group in self-reflectiveness on the BCIS (p = 0.047), total BCIS (p = 0.045), and intolerance to frustration (p = 0.014). Jumping to Conclusions (JTC) improved more in the MCT group than the psycho-educational group (p = 0.021). Regarding the comparison within each group, Theory of Mind (ToM), Personalizing Bias, and other subscales of irrational beliefs improved in the MCT group but not the psycho-educational group (p < 0.001-0.032). CONCLUSIONS: MCT could be an effective psychological intervention for people with recent onset of psychosis in order to improve cognitive insight, JTC, and tolerance to frustration. It seems that MCT could be useful to improve symptoms, ToM, and personalizing bias.
Subject(s)
Cognitive Behavioral Therapy/methods , Cognitive Remediation/methods , Metacognition/physiology , Outcome Assessment, Health Care , Psychotic Disorders/physiopathology , Psychotic Disorders/therapy , Theory of Mind/physiology , Thinking/physiology , Adult , Female , Follow-Up Studies , Humans , Male , Single-Blind Method , Young AdultABSTRACT
OBJECTIVE: To study the organization of inter-hospital transport of pediatric and neonatal patients in Spain, Portugal and Latin America. DESIGN: An observational study was performed. An on-line survey was sent by email including questions about characteristics of national, regional and local health transport systems, vehicles, material, and composition of the transport team and their training. SETTING: Hospital pediatric healthcare professionals treating children in Spain, Portugal and Latin America RESULTS: A total of 117 surveys from 15 countries were analyzed. Of them, 55 (47%) come from 15 regions of Spain and the rest from Portugal and 13 Latin American countries. The inter-hospital transport of pediatric patients is unified only in the Spanish regions of Baleares and Cataluña and in Portugal. Chile has a mixed unified transport system for pediatric and adult patients. Only 51.4% of responders have an educational program for the transport personnel, and only in 36.4% of them the educational program is specific for pediatric patients. In Spain and Portugal the transport is executed mostly by public entities, while in Latin America public and private systems coexist. Specific pediatric equipment is more frequent in the transport teams in the Iberian Peninsula than in Latin American teams. The specific pediatric transport training is less frequent for teams in Latin America than on Spain and Portugal. CONCLUSIONS: There is a great variation in the organization of children transport in each country and region. Most of countries and cities do not have unified and specific teams of pediatric transport, with pediatric qualified personnel and specific material.
Subject(s)
Transportation of Patients/organization & administration , Adolescent , Child , Child, Preschool , Health Care Surveys , Humans , Infant , Infant, Newborn , Latin America , Portugal , Prospective Studies , SpainABSTRACT
Heteroatom doping into polyaromatic hydrocarbons (PAHs) is a powerful approach for modifying key physical properties, however, there are extremely few modular routes that enable facile formation of B-, B2- and B,N-(specifically not containing direct B-N bonds) doped PAHs despite the growing importance of these materials. Sequential, one pot borylative cyclisation/intramolecular electrophilic C-H borylation of naphthyl-alkynes provides a simple new route to access novel B-, B,N- and B2-doped (PAHs). The initial products, dihydronaphthalene/dihydroquinoline B-mesityl PAHs, were reacted with [Ph3C][BF4]/pyridyl base to form the oxidised B-, and B,N-doped PAHs. However, for B-triisopropylphenyl (Trip) PAH congeners oxidation has to be performed prior to Trip installation due to preferential oxidation of an isopropylaryl moiety to the styrene. This alternative sequence enables access to Trip-B-PAHs and to structurally constrained B and B2-PAHs. Analysis of the solid state structures and optoelectronic properties of these PAHs confirm that frontier orbital energies, extended packing structures, Stokes shift and quantum yields all can be rationally modified using this methodology. The simplicity of this synthetic approach makes it a powerful tool for rapidly generating novel bench stable boron doped PAHs, which is important for facilitating further structure-property relationship studies and the wider utilisation of these materials in optoelectronic applications.