Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Guía oficial de la Sociedad Española de Neurología de práctica clínica en epilepsia

Resumen: Las anteriores Guías oficiales de práctica clínica en epilepsia elaboradas por el Grupo de Estudio de Epilepsia de la Sociedad Española de Neurología (GE-SEN) estaban basadas en la opinión de expertos.La actual Guía de práctica clínica (GPC) en epilepsia se basa en el método científico que extrae recomendaciones a partir de evidencias científicas constatadas. Su principal función es disminuir la variabilidad de la práctica clínica a través de la homogeneización de la práctica médica. Alcance y objetivos: Esta GPC se centra en la atención integral de personas afectadas por una epilepsia, como síntoma principal y predominante, independiente de la edad de inicio y ámbito asistencial. Metodología: 1) Constitución del grupo de trabajo integrado por neurólogos del GE-SEN, con la colaboración de neuropediatras, neurofisiólogos y neurorradiólogos; 2) determinación de los aspectos clínicos a cubrir: diagnóstico, pronóstico y tratamiento; 3) búsqueda y selección de la evidencia científica relevante; 4) formulación de recomendaciones basadas en la clasificación de las evidencias científicas disponibles. Resultados: Contienen 192 recomendaciones. El 57% son de consenso entre autores y editores, como consecuencia del desconocimiento en muchos campos de esta patología. Conclusiones: Esta GPC, en epilepsia, con una metodología formal y rigurosa en la búsqueda de evidencias explícitas donde ha sido posible, formula recomendaciones extraídas de las mismas.En este artículo incluimos el capítulo de la GPC dedicado a situaciones de urgencia en crisis epilépticas y epilepsia, que pueden presentarse como una primera crisis epiléptica, una evolución desfavorable en un paciente con una epilepsia conocida o en su forma más grave como un estado epiléptico. Abstract: Previous Official Clinical Practice Guidelines (CPGs) in Epilepsy were based on expert opinions and developed by the Epilepsy Study Group of the Spanish Neurological Society (GE-SEN).The current CPG in epilepsy is based on the scientific method, which extracts recommendations from published scientific evidence. A reduction in the variability in clinical practice through standardization of medical practice has become its main function. Scope and objectives: This CPG is focused on comprehensive care for individuals affected by epilepsy as a primary and predominant symptom, regardless of the age of onset and medical policy. Methodology: 1. Creation of GE-SEN neurologists working group, in collaboration with Neuropediatricians, Neurophysiologists and Neuroradiologists. 2. Identification of clinical areas to be covered: diagnosis, prognosis and treatment. 3. Search and selection of the relevant scientific evidence. 4. Formulation of recommendations based on the classification of the available scientific evidence. Results: It contains 161 recommendations of which 57% are consensus between authors and publishers, due to an important lack of awareness in many fields of this pathology. Conclusions: This Epilepsy CPG formulates recommendations based on explicit scientific evidence as a result of a formal and rigorous methodology, according to the current knowledge in the pre-selected areas.This paper includes the CPG chapter dedicated to emergency situations in seizures and epilepsy, which may present as a first seizure, an unfavorable outcome in a patient with known epilepsy, or status epilepticus as the most severe manifestation. Palabras clave: Guía de práctica clínica en epilepsia, Urgencias en crisis epilépticas, Primera crisis epiléptica, Evolución desfavorable de una epilepsia, Estados epilépticos, Keywords: Clinical practice guidelines in epilepsy, Emergencies in seizures, First seizure, Unfavorable outcome in epilepsy, Status epilepticu

The Spanish Society of Neurology's official clinical practice guidelines for epilepsy

Previous official clinical practice guidelines (CPGs) for epilepsy were based on expert opinions and developed by the Epilepsy Study Group of the Spanish Society of Neurology (GE-SEN).The current CPG in epilepsy is based on the scientific method, which extracts recommendations from published scientific evidence. Reducing variability in clinical practice through standardisation of medical practice is its main function. Scope and objectives: This CPG focuses on comprehensive care for individuals affected by epilepsy as a primary and predominant symptom, regardless of the age of onset and medical policy. Methodology: (1) Creation of a working group of GE-SEN neurologists, in collaboration with neuropediatricians, neurophysiologists and neuroradiologists. (2) Identification of clinical areas to be covered: diagnosis, prognosis and treatment. (3) Search and selection of the relevant scientific evidence. (4) Formulation of recommendations based on the classification of the available scientific evidence. Results: The CPG contains 161 recommendations of which 57% were established by consensus between authors and publishers, due to significant lack of awareness of this disorder in many fields. Conclusions: This epilepsy CPG formulates recommendations based on explicit scientific evidence as a result of a formal and rigorous methodology, according to the current knowledge in the pre-selected areas.This paper includes the CPG chapter dedicated to emergency situations in seizures and epilepsy. These may present as a first seizure, an unfavourable outcome in a patient with known epilepsy, or status epilepticus (SE) as the most severe manifestation. Resumen: Las anteriores Guías oficiales de práctica clínica en epilepsia elaboradas por el Grupo de Estudio de Epilepsia de la Sociedad Española de Neurología (GE-SEN) estaban basadas en la opinión de expertos.La actual Guía de práctica clínica (GPC) en epilepsia se basa en el método científico que extrae recomendaciones a partir de evidencias científicas constatadas. Su principal función es disminuir la variabilidad de la práctica clínica a través de la homogeneización de la práctica médica. Alcance y objetivos: Esta GPC se centra en la atención integral de personas afectadas por una epilepsia, como síntoma principal y predominante, independiente de la edad de inicio y ámbito asistencial. Metodología: 1) Constitución del grupo de trabajo integrado por neurólogos del GE-SEN, con la colaboración de neuropediatras, neurofisiólogos y neurorradiólogos; 2) determinación de los aspectos clínicos a cubrir: diagnóstico, pronóstico y tratamiento; 3) búsqueda y selección de la evidencia científica relevante; 4) formulación de recomendaciones basadas en la clasificación de las evidencias científicas disponibles. Resultados: Contienen 192 recomendaciones. El 57% son de consenso entre autores y editores, como consecuencia del desconocimiento en muchos campos de esta patología. Conclusiones: Esta GPC, en epilepsia, con una metodología formal y rigurosa en la búsqueda de evidencias explícitas donde ha sido posible, formula recomendaciones extraídas de las mismas.En este artículo incluimos el capítulo de la GPC dedicado a situaciones de urgencia en crisis epilépticas y epilepsia, que pueden presentarse como una primera crisis epiléptica, una evolución desfavorable en un paciente con una epilepsia conocida o en su forma más grave como un estado epiléptico. Keywords: Clinical practice guidelines in epilepsy, Seizure emergencies, First seizure, Unfavourable outcome in epilepsy, Status epilepticus, Palabras clave: Guía de práctica clínica en epilepsia, Urgencias en crisis epilépticas, Primera crisis epiléptica, Evolución desfavorable de una epilepsia, Estados epiléptico

Effectiveness and persistence of golimumab as a second biological drug in patients with spondyloarthritis : A retrospective study

Altres ajuts: Merck Sharp & Dohme Spain.This observational, longitudinal retrospective, noncomparative study was designed to assess the persistence and effectiveness of golimumab as a second anti-tumor necrosis factor (TNF) drug in patients with spondyloarthritis requiring discontinuation from a first anti-TNF drug.Data were collected retrospectively for all patients with axial spondyloarthritis or psoriatic arthritis from 20 rheumatology clinics in Spain who started golimumab as a second anti-TNF drug between January 2013 and December 2015. Golimumab persistence was assessed with Kaplan-Meier survival analysis, and associated factors were assessed with Cox regression analysis.210 patients started golimumab as a second anti-TNF drug: 131 with axial spondyloarthritis and 79 with psoriatic arthritis. In axial spondyloarthritis patients, the mean (standard deviation) Bath Ankylosing Spondylitis Disease Activity Index score at baseline was 5.5 (2.1), decreasing to 3.9 (2.0) at month 3 and 3.5 (2.0) at year 1, and remaining stable thereafter. In psoriatic arthritis patients, mean (standard deviation) baseline Disease Activity Score was 4.0 (1.3), reducing to 2.5 (1.2) at month 3 and to 2.2 (1.3) at year 1. Corresponding improvements were recorded from baseline in C-reactive protein levels and erythrocyte sedimentation rates. The probability of persistence of treatment with golimumab was 80% at year 1, 70% at year 2 and 65% at years 3 and year 4, and was similar in those who had stopped the first anti-TNF due to loss of efficacy or other reasons. Cox regression analysis showed that the probability of survival with golimumab was higher in patients with higher erythrocyte sedimentation rate, in patients with axial spondyloarthritis than with psoriatic arthritis, and in those who had discontinued adalimumab as first anti-TNF. Seventy-two patients (34.3%) discontinued golimumab during follow-up, 50 of them due to lack of efficacy.In patients with spondyloarthritis requiring discontinuation from a first anti-TNF drug, treatment with golimumab was effective and showed a high probability of persistence up to 4years of treatment

Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma

The benefit of intrathecal therapy and systemic rituximab on the outcome of diffuse large B-cell lymphoma at risk of central nervous system disease is controversial. Furthermore, the effect of intrathecal treatment and rituximab in diffuse large B-cell and Burkitt lymphoma with occult leptomeningeal disease detected by flow cytometry at diagnosis is unknown. Untreated diffuse large B-cell (n=246) and

Validation of the NCCN‐IPI for diffuse large B‐cell lymphoma (DLBCL): the addition of β2‐microglobulin yields a more accurate GELTAMO‐IPI

The study included 1848 diffuse large B‐cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI) and explore the effect of adding high Beta‐2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN‐IPI variables in order to develop an improved index. Comparing survival curves, NCCN‐IPI discriminated better than IPI, separating four risk groups with 5‐year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high‐risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III‐IV, and β2M as independently significant, whereas the NCCN‐IPI‐selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)‐IPI developed here, with 7 points, significantly separated four risk groups (0, 1-3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5‐year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN‐IPI. In conclusion, GELTAMO‐IPI is more accurate than the NCCN‐IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high‐risk group and is not influenced by primary extranodal presentation or treatments of different intensity