45 research outputs found

    Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

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    Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

    Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

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    Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. FINDINGS: In 2016, there were 27·08 million (95% uncertainty interval [UI] 24·30-30·30 million) new cases of TBI and 0·93 million (0·78-1·16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55·50 million (53·40-57·62 million) and of SCI was 27·04 million (24·98-30·15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8·4% (95% UI 7·7 to 9·2), whereas that of SCI did not change significantly (-0·2% [-2·1 to 2·7]). Age-standardised incidence rates increased by 3·6% (1·8 to 5·5) for TBI, but did not change significantly for SCI (-3·6% [-7·4 to 4·0]). TBI caused 8·1 million (95% UI 6·0-10·4 million) YLDs and SCI caused 9·5 million (6·7-12·4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. INTERPRETATION: TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments

    Global, regional, and national burden of meningitis, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

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    Zunt JR, Kassebaum NJ, Blake N, et al. Global, regional, and national burden of meningitis, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurology. 2018;17(12):1061-1082.Background Acute meningitis has a high case-fatality rate and survivors can have severe lifelong disability. We aimed to provide a comprehensive assessment of the levels and trends of global meningitis burden that could help to guide introduction, continuation, and ongoing development of vaccines and treatment programmes. Methods The Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study estimated meningitis burden due to one of four types of cause: pneumococcal, meningococcal, Haemophilus influenzae type b, and a residual category of other causes. Cause-specific mortality estimates were generated via cause of death ensemble modelling of vital registration and verbal autopsy data that were subject to standardised data processing algorithms. Deaths were multiplied by the GBD standard life expectancy at age of death to estimate years of life lost, the mortality component of disability-adjusted life-years (DALYs). A systematic analysis of relevant publications and hospital and daims data was used to estimate meningitis incidence via a Bayesian meta-regression tool. Meningitis deaths and cases were split between causes with meta-regressions of aetiological proportions of mortality and incidence, respectively. Probabilities of long-term impairment by cause of meningitis were applied to survivors and used to estimate years of life lived with disability (YLDs). We assessed the relationship between burden metrics and Socio-demographic Index (SDI), a composite measure of development based on fertility, income, and education. Findings Global meningitis deaths decreased by 21.0% from 1990 to 2016, from 403 012 (95% uncertainty interval [UI] 319426-458 514) to 318 400 (265 218-408 705). Incident cases globally increased from 2.50 million (95% UI 2.19-2.91) in 1990 to 2.82 million (2.46-3.31) in 2016. Meningitis mortality and incidence were dosely related to SDI. The highest mortality rates and incidence rates were found in the peri-Sahelian countries that comprise the African meningitis belt, with six of the ten countries with the largest number of cases and deaths being located within this region. Haemophilus influenzae type b was the most common cause of incident meningitis in 1990, at 780 070 cases (95% UI 613 585-978 219) globally, but decreased the most (-494%) to become the least common cause in 2016, with 397 297 cases (291076-533 662). Meningococcus was the leading cause of meningitis mortality in 1990 (192833 deaths [95% UI 153 358-221 503] globally), whereas other meningitis was the leading cause for both deaths (136 423 [112 682-178 022]) and incident cases (1.25 million [1.06-1.49]) in 2016. Pneumococcus caused the largest number of YLDs (634458 [444 787-839 749]) in 2016, owing to its more severe long-term effects on survivors. Globally in 2016, 1.48 million (1.04-1.96) YLDs were due to meningitis compared with 21.87 million (18.20-28.28) DALYs, indicating that the contribution of mortality to meningitis burden is far greater than the contribution of disabling outcomes. Interpretation Meningitis burden remains high and progress lags substantially behind that of other vaccine-preventable diseases. Particular attention should be given to developing vaccines with broader coverage against the causes of meningitis, making these vaccines affordable in the most affected countries, improving vaccine uptake, improving access to low-cost diagnostics and therapeutics, and improving support for disabled survivors. Substantial uncertainty remains around pathogenic causes and risk factors for meningitis. Ongoing, active cause-specific surveillance of meningitis is crucial to continue and to improve monitoring of meningitis burdens and trends throughout the world. Copyright (C) The Author(s). Published by Elsevier Ltd

    European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

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    The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

    Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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    BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

    PROPAGACIÓN in vitro y desdiferenciación tisular en Lippia dulcis In vitro propagation and tisular diferentiation in Lippia dulcis

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    Se describe una metodología para el establecimiento, la multiplicación y la obtención in vitro de callos de Lippia dulcis (Verbenaceae). Adicionalmente, se logró el establecimiento de una suspensión celular. Se utilizaron como explantes iniciales yemas apicales y segmentos nodales de plantas mantenidas en casa malla. El tratamiento más efectivo para el establecimiento y multiplicación de L. dulcis a partir de yemas apicales o segmentos nodales fue el medio MS libre de reguladores de crecimiento. Para lograr la textura y color adecuados, el medio para formación y multiplicación de callos (MS suplementado con 2,4D 0,1 mg/l) requiere ser renovado cada 20 días. El establecimiento de la suspensión celular, con alto porcentaje de viabilidad, fue posible en el medio de cultivo MS y la combinación hormonal 2,4 D (0,5 mg/l) + Kinetina (0,1 mg/l).<br>A methodology for in vitro establishment, multiplication and callus formation of Lippia dulcis (Verbenaceae) is described. Furthermore, an essay for establishment of cellular suspension was realized. Initial explants shoot tips and nodal segments from plants grown under greenhouse were used. The treatment more effective for induction and multiplication of L. dulcis from shoot tips or nodal segments was MS medium free of growth regulators. To achieve the colour and adequate texture, the medium for callus formation and multiplication (MS by adding 2,4D 0,1 mg/l) needs to be renew each 20 days. The cellular suspension establishment, with a high percentage of viability, was possible in MS medium and the hormonal combination 2,4 D (0.5 mg/l) + Kinetina (0.1 mg/l

    Injertos óseos - Nueva alternativa. Fase I. Extracción de proteínas morfogenéticas parcialmente purificadas de hueso bovino

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    El propósito de esta investigación fue extraer a partir de hueso bovino y mediante procedimientos químicos, Proteínas Morfogenéticas Óseas (PMO), parcialmente purificadas que posean características osteoinductivas, de alta calidad, baja antigenicidad y alta biodisponibilidad, para ser utilizadas como material de injerto óseo. El procedimiento se llevó a cabo mediante cinco etapas básicas así: Molienda del material; extracción de lípidos; desmineralización; extracción del colágeno; obtención de la fracción proteica. Para verificar la efectividad de la desmineralización y demás procesos, se procedió como sigue: Método de Soxhlet; espectrometría de Absorción Atómica de Calcio; tinción de picrofucsina de Van Gieson; electroforesis en Gel de Poliacrilamida-Dodecil Sulfato Sódico. Se obtuvo un material con proteínas de peso molecular aparente en el rango de 18 a 120 KDa, principalmente en las bandas correspondientes a 18, 24, 34, 68, 72, 90, 120 KDa, mediante electroforesis en Gel de Poliacrilamida Dodecil Sulfato Sódico (SDS-PAGE) el cual fue liofilizado y almacenado en ampollas de vidrio selladas al vacío para su conservación y uso posterior

    Injertos óseos - Nueva alternativa. Fase III. Obtención, caracterización y evaluación de Hidroxiapatita Sintética y el compuesto de Hidroxiapatita Sintética porosa � Proteínas Morfogenéticas Óseas en un modelo experimental Lapino

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    El propósito de esta investigación fue obtener Hidroxiapatita (HA) sintética de porosidad inducida con características osteoconductivas y mezclarlas con Proteínas Morfogenéticas Óseas (PMO) de características osteoinductivas, para que actuaran sinérgicamente y formaran un material de injerto biocompatible capaz de inducir la diferenciación de células locales a células formadoras de hueso y al mismo tiempo proporcionar un andamio osteoconductivo que dirigiera la formación de nuevo hueso, inmovilizara la molécula inductiva en el sitio de implantación por un tiempo suficiente para influenciar las células de respuesta y actuara como una barrera mecánica inicial para el crecimiento de tejido fibroso o la interposición de músculo en el defecto, para lograr finalmente el crecimiento de nuevo hueso en un tiempo considerablemente reducido y el total reemplazo del injerto por hueso enteramente autólogo. Para evaluar las características de este material, se utilizaron un total de 20 conejos machos raza Blanca de Nueva Zelanda, con un peso promedio de 2.2 kg y 75 días de edad, a los cuales se les creó un defecto óseo de forma rectangular de 8 mm de longitud y de profundidad igual a la corteza, en las diáfisis de las tibias, cara medial. En un miembro se implantaron placas de hidroxiapatita de 8mm de longitud y 2 mm de grosor; en el miembro contrario se implantó el compuesto HA-PMO. Se distribuyeron en 4 grupos de evaluación, a las 3, 6, 9 y 12 semanas de evolución, para valorar las características del implante; se realizó inferencia estadística de los datos tomados en el experimento, con un diseño en parcelas divididas siguiendo como estructura básica de aleatorización un DCA (Diseño Completamente al Azar), aplicando el factor t (tiempo) a las parcelas principales (conejos), y el factor i (tipo de implante) a las subparcelas (miembros posteriores)

    Confirming the presence of Lasiurus frantzii (Peters, 1870) (Chiroptera, Vespertilionidae) in South America: more questions than answers

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    The western or desert red bat, Lasiurus frantzii, is a cryptic insectivore species distributed in the Neotropics from Mexico south through Central America to Panama. L. frantzii was long considered a subspecies of the red bat, Lasiurus blossevillii, but recently it was elevated to full-species status based on genetic information. Here we present evidence of the presence of L. frantzii in the Andean Region of Colombia, confirming the species' presence in South America; the new record, from 3836 m a.s.l., is also the highest elevation known for the species. We suggest that L. frantzii might be widely distributed in trans-Andean areas of Colombia, Ecuador, Venezuela, and perhaps Peru and Bolivia. However, a review and exploration of additional morphological traits to identify the species are necessary because of the uncertainty of the distribution of L. frantzii
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