To analyse the characteristics and predictors of death in hospitalized patients with coronavirus disease 2019 (COVID-19) in Spain.
A retrospective observational study was performed of the first ...consecutive patients hospitalized with COVID-19 confirmed by real-time PCR assay in 127 Spanish centres until 17 March 2020. The follow-up censoring date was 17 April 2020. We collected demographic, clinical, laboratory, treatment and complications data. The primary endpoint was all-cause mortality. Univariable and multivariable Cox regression analyses were performed to identify factors associated with death.
Of the 4035 patients, male subjects accounted for 2433 (61.0%) of 3987, the median age was 70 years and 2539 (73.8%) of 3439 had one or more comorbidity. The most common symptoms were a history of fever, cough, malaise and dyspnoea. During hospitalization, 1255 (31.5%) of 3979 patients developed acute respiratory distress syndrome, 736 (18.5%) of 3988 were admitted to intensive care units and 619 (15.5%) of 3992 underwent mechanical ventilation. Virus- or host-targeted medications included lopinavir/ritonavir (2820/4005, 70.4%), hydroxychloroquine (2618/3995, 65.5%), interferon beta (1153/3950, 29.2%), corticosteroids (1109/3965, 28.0%) and tocilizumab (373/3951, 9.4%). Overall, 1131 (28%) of 4035 patients died. Mortality increased with age (85.6% occurring in older than 65 years). Seventeen factors were independently associated with an increased hazard of death, the strongest among them including advanced age, liver cirrhosis, low age-adjusted oxygen saturation, higher concentrations of C-reactive protein and lower estimated glomerular filtration rate.
Our findings provide comprehensive information about characteristics and complications of severe COVID-19, and may help clinicians identify patients at a higher risk of death.
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This book offers an innovative rethinking of policy approaches to ‘gender equality’ and of the process of social change. It brings several new chapters together with a series of previously published ...articles to reflect on these topics. A particular focus is gender mainstreaming, a relatively recent development in equality policy in many industrialised and some industrialising countries, as well as in large international organisations such as the World Bank, the International Monetary Fund and the International Labour Organization. The book draws upon poststructuralist organisation and policy theory to argue that it is impossible to ‘script’ reform initiatives such as gender mainstreaming. As an alternative it recommends thinking about such policy developments as fields of contestation, shaped by on-the-ground political deliberations and practices, including the discursive practices that produce specific ways of understanding the ‘problem’ of ‘gender inequality’. In addition to the new chapters Bacchi and Eveline produce brief introductions for each chapter, tracing the development of their ideas over four years. Through these commentaries the book provides exciting insights into the complex processes of collaboration and theory generation. Mainstreaming Politics is a rich resource for both practitioners in the field and for theorists. In particular it will appeal to those interested in public policy, public administration, organisation studies, sociology, comparative politics and international studies.
Prior studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, ...inflammatory dermatosis that characterizes atopic dermatitis (AD). We review here increasing evidence that the inflammation in AD results primarily from inherited abnormalities in epidermal structural and enzymatic proteins that impact permeability barrier function. We also will show that the barrier defect can be attributed to a paracellular abnormality due to a variety of abnormalities in lipid composition, transport and extracellular organization. Accordingly, we also review the therapeutic implications of this emerging pathogenic paradigm, including several current and potentially novel, lipid-based approaches to corrective therapy. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
•Atopic dermatitis (AD) results from inherited abnormalities that impact epidermal barrier function.•The paracellular barrier defect in AD is due to abnormal lipid composition, transport and organization.•Barrier abnormality in AD also allows for pathogen and antigen access into epidermis.•Increased serine protease activity accounts for decreased lipids and further decline in ceramides in AD.•This emerging paradigm may lead to lipid-based approaches for corrective therapy in AD.
Aim
Gamma‐aminobutyric acid (GABA) is a major modulator in brain maturation and its role in many different neurodevelopmental disorders has been widely reported. Although the involvement of GABA in ...different disorders has been related to its regulatory function as an inhibitory neurotransmitter in the mature brain, co‐transmitter, and signalling molecule, little is known about its role as a clinical biomarker in neuropaediatric disorders. The aim of this study is to report the cerebrospinal fluid (CSF) free‐GABA concentrations in a large cohort of patients (n=85) with different neurological disorders.
Method
GABA was measured in the CSF of neuropaediatric patients using capillary electrophoresis with laser‐induced fluorescence detection. Other neurotransmitters (amino acids and monoamines) were also analysed.
Results
GABA concentrations in CSF were abnormal, with a greater frequency (44%) than monoamines (20%) in neuropaediatric patients compared with our reference values. Although we included a few patients with inborn errors of metabolism, GABA levels in CSF were more frequently abnormal in metabolic disorders than in other nosological groups.
Interpretation
Our work suggests further research into brain GABAergic status in neuropaediatric disorders, which could also lead to new therapeutic strategies.
What this paper adds
Homeostasis of GABA seems more vulnerable than that of monoamines in the developing brain.
The highest GABA levels are found in the primary GABA neurotransmitter disorder SSADH deficiency.
GABA alterations are not specific for any clinical or neuroimaging presentation.
Resumen
Niveles de acido gama‐aminobutírico en líquido cefalorraquídeo en trastornos neuropediátricos
Objetivo
El ácido gama‐aminobutírico (GABA) es un modulador mayor en la maduración cerebral y su función en diversos trastornos del neurodesarrollo ha sido ampliamente descripta. La función del GABA en diferentes trastornos se ha relacionado con su función reguladora como neurotransmisor inhibidor en la madurez cerebral, así como co‐transmisor y como molécula indicadora, sin embargo, poco se conoce como bio‐marcador clínico en trastornos neuropediátricos. El objetivo de este estudio es reportar las concentraciones de GABA‐libre en líquido cefalorraquídeo (LCR) en una gran cohorte de pacientes (n=85) con diferentes trastornos neurológicos.
Método
El GABA fue medido en LCR de pacientes neuropediátricos utilizando electroforesis capilar con detección de fluorescencia inducida por láser. También se analizaron otros neurotransmisores (aminoácidos y mono aminos).
Resultados
Las concentraciones de GABA fueron anormales, con una mayor frecuencia (44%) que los mono aminos (20%) en pacientes neuropediátricos en comparación con nuestros valores de referencia. Aunque incluimos algunos pocos pacientes con errores congénitos del metabolismo, los niveles de GABA en LCR fueron más frecuentemente anormales en trastornos metabólicos que en otros grupos nosológicos.
Interpretación
Nuestro trabajo sugiere que es necesario más investigación sobre el estado GABAérgico del cerebro en trastornos neuropediátricos, lo cual además podría llevar a nuevas estrategias terapéuticas.
Resumo
Níveis de ácido gama‐aminobutírico no fluido cerebroespinhal em desordens neuropediátricas
Objetivo
O ácido gama‐aminobutírico (GABA) é um importante modulador da maturação cerebral, e seu papel em diferentes desordens neurodesenvolvimentais tem sido amplamente reportado. Embora o envolvimento do GABA em diferentes desordens tenha sido relacionado com sua função regulatória como neurotransmissor inibitório no cérebro maduro, co‐transmissor e molécula sinalizadora, pouco se sabe sobre o seu papel como biomarcador clínico em desordens neuropediátricas. O objetivo deste estudo é relatar as concentrações de fluido cerebroespinhal (FCE) livre de GABA em uma grande coorte de pacientes (n=85) com diferentes desordens neurológicas.
Método
GABA foi medido no FCE de pacientes neuropediátricos usando eletroforese capilar com detecção de fluorescência induzida por laser. Outros neurotransmissores (aminoácidos e monoaminas) também foram analisados.
Resultados
As concentrações de GABA no FCE foram anormais, com maior frequência (44%) do que monoaminas (20%) em pacientes neuropediátricos em comparação com nossos valores de referência. Embora tenhamos incluído alguns pacientes com erros inatos do metabilismo, os níveis de GABA no FCE foram mais frequentemente anormais nas desordens metabólicas do que em outros grupos nosológicos.
Interpretação
Nosso trabalho sugere que mais pesquisas sobre o estado GABAérgico em desordens neuropediátricas, o que também pode levar a novas estratégias terapêuticas.
What this paper adds
Homeostasis of GABA seems more vulnerable than that of monoamines in the developing brain.
The highest GABA levels are found in the primary GABA neurotransmitter disorder SSADH deficiency.
GABA alterations are not specific for any clinical or neuroimaging presentation.
This article is commented on by Pearl page 734 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
Aim
To study neurotransmitter status in children with early epileptic and developmental and epileptic encephalopathy (DEE) and to explore the clinical response to dopaminergic and serotoninergic ...therapies in a group of patients.
Method
Two hundred and five patients (111 males 54.1.% and 94 females 45.9%, mean age 10 months at the onset of epilepsy SD 1 year 1 month, range 0–3 year) with epileptic encephalopathy/DEE were recruited, including those with West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, myoclonic encephalopathy in non‐progressive disorders, infantile spasms, Doose syndrome, Lennox–Gastaut syndrome, Landau–Kleffner syndrome, and those unclassified. Cerebrospinal fluid (CSF) neurotransmitter studies and patients' medical records were reviewed. Additionally, we present clinical data of 10 patients with low CSF neurotransmitter levels who received dopaminergic/serotoninergic treatments.
Results
Abnormal neurotransmitter values were identified in 68 (33%) patients. 5‐Hydroxyindoleacetic acid (5‐HIAA) deficit was the most prevalent alteration (91%). Low CSF 5‐HIAA levels were significantly higher in 1‐ to 3‐year‐old children. A negative significant correlation was found between 5‐HIAA levels and epilepsy duration before CSF study (Spearman's ρ=−0.191, p=0.007). Abnormalities in deep grey matter were associated with low levels of CSF homovanillic acid and 5‐HIAA. Ten patients with low CSF neurotransmitter levels received dopamine and/or serotonin therapies. Six of them showed initial decrease of seizure frequency and severity and maintained improvement in some neurodevelopmental skills.
Interpretation
A considerable number of patients showed neurotransmitter abnormalities. Age at seizure onset and duration of epilepsy before CSF study were the principal factors related to neurotransmitter depletion. Early monoamine supplementation would seem advisable as a neuroprotective strategy.
What this paper adds
5‐Hydroxyindoleacetic acid homeostasis is especially vulnerable in patients with epileptic encephalopathy/developmental and epileptic encephalopathy.
Age of seizure onset and duration of epilepsy are determinants of neurotransmitter depletion.
This study aimed to provide an update and compare perioperative outcomes and complications of intracorporeal and extracorporeal urinary diversion following robot-assisted radical cystectomy using ...data from the multi-institutional, prospectively maintained International Robotic Cystectomy Consortium database.
We retrospectively reviewed the records of 2,125 patients from a total of 26 institutions. Intracorporeal urinary diversion was compared with extracorporeal urinary diversion. Multivariate logistic regression models using stepwise variable selection were fit to evaluate preoperative, operative and postoperative predictors of intracorporeal urinary diversion, operative time, high grade complications and 90-day hospital readmissions after robot-assisted radical cystectomy.
In our cohort 1,094 patients (51%) underwent intracorporeal urinary diversion. These patients demonstrated shorter operative time (357 vs 400 minutes), less blood loss (300 vs 350 ml) and fewer blood transfusions (4% vs 19%, all p <0.001). They experienced more high grade complications (13% vs 10%, p = 0.02). Intracorporeal urinary diversion use increased from 9% of all urinary diversions in 2005 to 97% in 2015. Complications after this procedure decreased significantly with time (p <0.001). On multivariable analysis higher annual cystectomy volume (OR 1.02, 95% CI 1.01–1.03, p <0.002), year of robot-assisted radical cystectomy (2013–2016 OR 68, 95% CI 44–105, p <0.001) and American Society of Anesthesiologists® score less than 3 (OR 1.75, 95% CI 1.38–2.22, p <0.001) were associated with undergoing intracorporeal urinary diversion. The procedure was associated with a shorter operative time of 27 minutes (p = 0.001).
The use of intracorporeal urinary diversion has increased in the last decade. A higher annual institutional volume of robot-assisted radical cystectomy was associated with intracorporeal urinary diversion as well as with shorter operative time. Although intracorporeal urinary diversion was associated with higher grade complications than extracorporeal urinary diversion, they decreased with time.
Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine ...effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and ≥60 years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains.
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