[Relationship between frailty and functional status in lung transplant candidates]. / Relación entre la fragilidad y la capacidad funcional en los pacientes candidatos a trasplante de pulmón.

INTRODUCTION: Lung transplant (LT) is one of the therapeutic options for patients with terminal respiratory diseases. It is highly important to incorporate the functional status and frailty assessment into the selection process of candidates for LT. OBJECTIVES: Identify the prevalence of frailty in the LT waiting list. Study the relationship between frailty, functional status, Lung Allocation Score (LAS) and muscular dysfunction. METHODOLOGY: Descriptive transversal study of patients on the waiting list for LT. POPULATION: 74 patients with chronic respiratory diseases assessed by the lung transplant committee and accepted to be transplanted in a university hospital in Barcelona. The outcome variables were frailty status was evaluate for SPPB test, functional capacity was evaluate for the six-minute walking test (6MWT) and muscular dysfunction. The results were analyzed with the statistical package STATA 12. RESULTS: Sample of 48 men and 26 women, with a median age of 56.55 years (SD 10.87. The prevalence of frailty assessed with the SPPB was 33.8% (8.1% are in frailty and 25.7% are in a state of pre-frailty). There is a relationship between the SPPB, 6MWT and maximal inspiratory pressure, but not with others force values. There is a relationship between the risk of frailty (scores below 9 in SPPB) and the meters walked in 6 but not with the LAS. CONCLUSIONS: The risk of frailty in patients with terminal chronic respiratory diseases is high. Frailty is related with functional capacity, but not with LAS.

[Assessment model for evaluating the preparedness plan for COVID-19 in a tertiary care hospital]. / Modelo de evaluación del plan de respuesta frente a la pandemia de COVID-19 en un hospital de tercer nivel.

BACKGROUND AND PURPOSE: During the first wave of the epidemic caused by SARS-CoV-2, hospitals have come under significant pressure. This scenario of uncertainty, low scientific evidence, and insufficient resources, has generated significant variability in practice between different health organisations. In this context, it is proposed to develop a standards-based model for the evaluation of the preparedness and response system against COVID-19 in a tertiary hospital. MATERIALS AND METHODS: The study, carried out at the University Hospital of Vall d'Hebron in Barcelona (Spain), was designed in two phases: 1) development of the standards-based model, by means of a narrative review of the literature, analysis of plans and protocols implemented in the hospital, a review process by expert professionals from the centre, and plan of action, and 2) validation of usability and usefulness of the model through self-assessment and hospital audit. RESULTS: The model contains 208 standards distributed into nine criteria: leadership and strategy; prevention and infection control; management of professionals and skills; public areas; healthcare areas; areas of support for diagnosis and treatment; logistics, technology and works; communication and patient care; and information and research systems. The evaluation achieved 85.2% compliance, with 42 areas for improvement and 96 good practices identified. CONCLUSIONS: Implementing a standards-based model is a useful tool to identify areas for improvement and good practices in COVID-19 preparedness and response plans in a hospital. In the current context, it is recommended to repeat this methodology in other non-hospital and public health settings.

Modelo de evaluación del plan de respuesta frente a la pandemia de COVID-19 en un hospital de tercer nivel / Assessment model for evaluating the preparedness plan for COVID-19 in a tertiary care hospital

ANTECEDENTES Y OBJETIVO: Durante la primera onda epidémica del SARS-CoV-2, los hospitales han soportado una importante presión asistencial. Este escenario de incertidumbre, baja evidencia científica y medios insuficientes ha generado una importante variabilidad de la práctica entre diferentes centros sanitarios. En este contexto, planteamos desarrollar un modelo basado en estándares para la evaluación del sistema de preparación y respuesta frente a la COVID-19 en un hospital terciario. MATERIALES Y MÉTODOS: El estudio se llevó a cabo en el Hospital Universitario Vall d'Hebron de Barcelona en dos fases: 1) desarrollo de modelo de estándares mediante revisión narrativa de la literatura, análisis de planes y protocolos del hospital, método Delphi por profesionales expertos y plan de actualización y 2) validación de aplicabilidad y utilidad del modelo mediante autoevaluación y auditoría. RESULTADOS: El modelo consta de 208 estándares distribuidos en nueve criterios: liderazgo y estrategia; prevención y control de la infección; gestión de profesionales y competencias; áreas públicas comunes; áreas asistenciales; áreas de apoyo asistencial; logística, tecnología y obras; comunicación y atención al paciente; sistemas de información e investigación. La evaluación alcanza un 85,2% de cumplimiento, y se identifican 42 áreas de mejora y 96 buenas prácticas. CONCLUSIONES: La implementación de un modelo basado en estándares es útil para identificar áreas de mejora y buenas prácticas en los planes de preparación y respuesta frente a la COVID-19 en un hospital. En el actual contexto, proponemos la conveniencia de adaptar esta metodología a otros ámbitos de atención sanitaria no hospitalaria o de salud pública

BACKGROUND AND PURPOSE: During the first wave of the epidemic caused by SARS-CoV-2, hospitals have come under significant pressure. This scenario of uncertainty, low scientific evidence, and insufficient resources, has generated significant variability in practice between different health organisations. In this context, it is proposed to develop a standards-based model for the evaluation of the preparedness and response system against COVID-19 in a tertiary hospital. MATERIALS AND METHODS: The study, carried out at the University Hospital of Vall d'Hebron in Barcelona (Spain), was designed in two phases: 1) development of the standards-based model, by means of a narrative review of the literature, analysis of plans and protocols implemented in the hospital, a review process by expert professionals from the centre, and plan of action, and 2) validation of usability and usefulness of the model through self-assessment and hospital audit. RESULTS: The model contains 208 standards distributed into nine criteria: leadership and strategy; prevention and infection control; management of professionals and skills; public areas; healthcare areas; areas of support for diagnosis and treatment; logistics, technology and works; communication and patient care; and information and research systems. The evaluation achieved 85.2% compliance, with 42 areas for improvement and 96 good practices identified. CONCLUSIONS: Implementing a standards-based model is a useful tool to identify areas for improvement and good practices in COVID-19 preparedness and response plans in a hospital. In the current context, it is recommended to repeat this methodology in other non-hospital and public health settings

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by a high genetic heterogeneity with several related genes recently described, including BMPR2,TBX4 and KCNK3. The association between KCNK3 and PAH has been recently identified, but the prognosis and phenotype associated with these mutations have been poorly described. We studied a series of 136 idiopathic and hereditary PAH Spanish patients for BMPR2, TBX4 and KCNK3 mutations. We report the results of KCNK3 in which we were able to describe two new mutations (p.Gly106Arg and p.Leu214Arg) in three patients. The first one was found in a patient belonging to a consanguineous Romani family, who carried a homozygous mutation in KCNK3 and developed a severe and early form of the disease. To the best of our knowledge, this is the first time that a homozygous mutation in KCNK3 is reported in a PAH patient. The second one was found in a patient who presented at the young adult age a severe form of the disease. The present report supports the contribution of KCNK3 mutations to the genetic etiology of PAH and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients.

Management and outcomes in chronic thromboembolic pulmonary hypertension: From expert centers to a nationwide perspective.

BACKGROUND: The Spanish "Registry of Pulmonary Arterial Hypertension" (REHAP), started in 2007, includes chronic thromboembolic hypertension (CTEPH) patients. Based on data provided by this registry and retrospective data from patients diagnosed during 2006 (≤ 12 months since the registry was created), clinical management and long-term outcomes of CTEPH patients are analyzed nationwide for the first time in a scenario of a decentralized organization model of CTEPH management. METHODS AND RESULTS: A total of 391 patients (median [Q1:Q3] age 63.7 [48.0;73.3] years, 58% females) with CTEPH included during the period January 1, 2006-December 31, 2013 in the REHAP registry were analyzed. Rate of pulmonary endarterectomy (PEA) was 31.2%, and highly asymmetric among centers: rate was 47.9% at two centers designated as CTEPH expert centers, while it was 4.6% in other centers. Among patients not undergoing PEA, 82% were treated with therapies licensed for pulmonary arterial hypertension (PAH). Five-year survival rate was 86.3% for PEA patients, and 64.9% for non-PEA patients. Among non-PEA patients, presenting proximal lesions (42% of non-referred patients) was associated with a 3-fold increase in mortality. PEA patients achieved significantly better hemodynamic and clinical outcomes at one-year follow-up compared to non-PEA patients. Patients not being referred for PEA assessment were older and had a worse functional capacity. Older age was the most deterrent factor for non-operability. CONCLUSION: Despite the increase in diagnosis and expertise in PEA-specialized centers, an important percentage of patients do not benefit of PEA in a decentralized organization model of CTEPH management.

Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosage.

BACKGROUND: Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. PATIENTS AND METHODS: Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. RESULTS: Mean BU exposure (AUCss) (+/-DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade > or = II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. CONCLUSIONS: The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD.

Cytogenetic study in peripheral blood lymphocytes from asthmatic patients receiving continued therapy with theophylline.

Possible cytogenetic effects of theophylline have been investigated in asthmatic patients undergoing continuous therapy with this drug. Sister-chromatid exchanges (SCE), chromosome aberrations (CA) and proliferating rate indices (PRI) were evaluated in cultured peripheral blood lymphocytes from patients receiving theophylline alone, theophylline plus inhaled beta 2 adrenergic drugs or theophylline in combination with beta 2 adrenergic agents and corticoids. Two samples from each individual were obtained in order to perform a prospective study: before the theophylline medication (sample A) and at a time after the beginning of treatment (sample B). After treatment (66.3 +/- 37.8 days), an increase in SCE was observed without modifications either in PRI or in CA. Patients receiving beta 2 adrenergics or beta 2 adrenergics plus glucocorticoids before and during theophylline treatment, did not respond differently than those on theophylline alone.