Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

Manual de simulación clínica en especialidades médicas

Manual sobre técnicas y modos de simulación clínica en diversas especialidades médicas.La enseñanza y formación en medicina necesita el uso de la simulación. Existen evidencias de su uso desde hace cientos de años, pero, en los últimos años se ha incrementado y diseminado. La simulación clínica está validada científicamente en múltiples contextos médicos y de otras áreas profesionales de la salud. Y es considerada de gran importancia como proceso de entrenamiento y de mejora de las competencias y adquisición de habilidades médicas en campos que incluye desde la historia clínica, comunicación con el paciente, exploración, diagnóstico terapéutica médica-farmacológica y quirúrgica y seguridad al tratar al paciente. Hoy en día, para muchas técnicas y situaciones clínicas es inaceptable llegar junto a los pacientes sin un dominio adquirido en simulación. La simulación puede ocurrir sin el uso de recursos adicionales, solo las personas, o utilizando pocos o muchos recursos de baja hasta alta tecnología y se puede adaptar a los recursos disponibles, abarcando todas las áreas de conocimiento, y dentro de ellas competencias técnicas o actitudes, solas o en conjunto. El uso racional y basado en evidencia de la simulación es de la mayor importancia por la necesidad de una mayor efectividad y eficiencia en la transformación de los profesionales de la salud para que puedan mejorar su capacidad de atender a los pacientes. La simulación es también una buena herramienta de evaluación de competencias y habilidades en Medicina y otras disciplinas de las Ciencias de la Salud Este manual incluye técnicas y modos de simulación clínica en diversas especialidades médicas, útiles, para quien busque un manual práctico y actualizado.Cátedra de Mecenazgo de la Universidad de Málaga. Cátedra de Terapias Avanzadas en Patología Cardiovascular Cátedra de Mecenazgo de la Universidad de Málaga. Cátedra de Investigación Biomédica Quirón Salu

Estudio del nervio óptico mediante tomografía de coherencia óptica como biomarcador precoz de deterioro cognitivo.

La enfermedad de Alzheimer (EA) es la causa más prevalente de deterioro cognitivo en el mundo. El diagnóstico precoz de la enfermedad es fundamental para la detección temprana de la misma, que permitiría implementar estrategias preventivas y terapéuticas y por tanto mejorar la calidad de vida de los pacientes. En los últimos años, se han desarrollado nuevos biomarcadores, dentro de los cuales resultan interesantes los marcadores oftalmológicos como el uso de Tomografía de Coherencia Óptica (TCO), por su accesibilidad, bajo coste y carácter no invasivo. Material y métodos Se realizó un estudio observacional, analítico y transversal con muestreo consecutivo, cuyo objetivo fue estudiar la relación entre el grosor de la Capa de Fibras nerviosas de la Retina (CFNR) con el grado de deterioro cognitivo y la presencia de atrofia cerebral y lesiones de sustancia blanca. Se incluyeron 32 pacientes con EA o deterioro cognitivo ligero y un grupo de participantes cognitivamente sanos. El número total de ojos estudiados fue 64. Se realizó un examen neuropsicológico y oftalmológico exhaustivo en todos los participantes. Se cuantificaron también las lesiones de sustancia blanca y la atrofia del hipocampo por medio del análisis de imágenes de RM cerebral. Resultados Observamos una tendencia significativa que mostró un adelgazamiento de la CFNR en paralelo con el empeoramiento del deterioro cognitivo en el cuadrante superior y temporal de la retina. Se encontró también una correlación significativa entre el grosor de la CFNR del cuadrante temporal del ojo izquierdo y la presencia de lesiones de sustancia blanca en el lóbulo occipital (r = −0.579, p = 0.038). Conclusiones La TCO podría ser una herramienta diagnóstica rápida, no invasiva y accesible, y podría constituir un biomarcador válido y robusto para el diagnóstico precoz del deterioro cognitivo y la EA

3. Inicio de anticoagulación oral temprano o demorado en fase aguda del ictus isquémico por fibrilación auricular: estudio TIMING

<p>La fibrilación auricular es la causa más frecuente de ictus cardioembólico. Su tratamiento una vez que se detecta y para prevenir la recurrencia del ictus, es la anticoagulación. Sin embargo, el momento idóneo de inicio del tratamiento anticoagulante sigue constituyendo un punto controvertido. El presente trabajo muestra que el inicio temprano de la anticoagulación es seguro y no inferior al inicio tardío, aunque quedan puntos por esclarecer y se necesitan más estudios al respecto centrados en la extensión del ictus, características clínicas y de neuroimagen para mejorar la evidencia disponible y dilucidar si el inicio temprano de la anticoagulación es superior al inicio tardío.  </p><p><i>Atrial fibrillation is the most frequent cause of cardioembolic stroke. Treatment, once atrial fibrillation is detected, is aimed at preventing stroke recurrence, and lies upon oral anticoagulation. Nevertheless, the optimal moment for anticoagulation starting is still controversial. The present study shows early starting of anticoagulation is safe and non-inferior to delayed starting, but there are still questions and clinical controversies to solve, and further studies are needed, focused in stroke extension, clinical and neuroimaging characteristics, in order to improve the available evidence and to firmly establish if early starting is superior to delayed starting.</i></p&gt

Spermal selection in ejaculated and epididimary samples of domestic dogs and the effect of prostatic fluid addition

Este trabalho foi realizado com o objetivo de avaliar a eficiência da seleção espermática em amostras de ejaculados e epididimárias de cães domésticos, assim como verificar o efeito da adição de fluido prostático em amostras epididimárias, previamente ao resfriamento. Para tal, foram realizados três experimentos. No experimento 1, objetivou-se testar a eficiência da técnica de seleção espermática swim- up modificado com adição de um coloide comercial (Androcoll-C TM ) (SU-AC), quando realizada em diferentes formatos e grau de inclinação do tubo de migração, na tentativa de aumentar as taxas de recuperação e a qualidade espermática em sêmen canino fresco. Quinze amostras seminais obtidas de três cães foram submetidas aos tratamentos a seguir: T0-Controle: sêmen diluído em diluente comercial; T1: SU-AC em tubo Falcon, em posição vertical; T2: SU-AC em tubo de base arredondada, em posição vertical e T3: SU-AC em tubo de base arredondada, posicionado a 45°; após 3 minutos o T2 e T3 foram avaliados e outra alíquota de meio diluente foi reposta e avaliada 30 minutos depois, constituindo os tratamentos T2a e T3a, respectivamente. Não houve diferenças nas taxas de recuperação espermática, defeitos espermáticos totais, integridade de membrana plasmática e integridade de membrana acrossomal entre os tratamentos (P>0,05); houve uma diminuição dos parâmetros cinéticos, independente do formato do tubo de migração e sua inclinação em relação ao T0 (P0,05); houve diminuição das patologias espermáticas quando usado o tubo de base arredondada inclinado, verificado na avaliação de 30 min após a renovação do meio. Conclui-se que não há melhora dos parâmetros cinéticos avaliados após a técnica de SU-AC; as taxas de recuperação espermática e a integridade celular, não são influenciadas pelo uso de tubos de migração de diferentes formatos e inclinação durante a realização da técnica de SU-AC; o SU-AC permite a obtenção de um número menor de patologias espermáticas, quando realizado em tubo de migração de base arredondada e inclinado com renovação do meio no tubo de migração, com recuperação e avaliação aos 30’. No experimento 2, objetivou-se verificar o efeito da adição de 10 % de fluido prostático (FP) canino, em amostras espermáticas epididimárias (AEEs) prévio ao resfriamento por 24 horas entre 4 - 6 °C, obtidas por meio da técnica de fluxo retrógrado (FR) com uso de meio de manutenção comercial (MM) e soro fisiológico (SF). Foram obtidas AEEs a partir de oito pares de conjuntos testículo-epidídimo, pela técnica de FR com perfusão de MM ou SF com adição de ar. As AEEs foram padronizadas para 50 x 10 6 de espermatozoides / mL em MM (T1); as amostras coletadas com SF, foram subdivididas em três alíquotas, sendo uma ajustada para 50 x 10 6 de espermatozoides / mL em SF (T2); outra alíquota foi ajustada para 50 x 10 6 de espermatozoides / mL com MM acrescido de 10 % de SF (T3); a terceira alíquota foi ajustada para 50 x 10 6 de espermatozoides / mL com MM acrescido de 10 % de FP (T4). Durante 24 horas os tratamentos foram resfriados entre 4 – 6 °C e posteriormente avaliados quanto a motilidade espermática (MOT), vigor espermático (VIG), morfologia espermática, integridade funcional da membrana plasmática e teste de termorresistência (TTR). Não houve efeito (P>0,05) do MM ou do SF, na quantidade e qualidade dos espermatozoides recém coletados, porém, a preservação das amostras em presença de MM durante o resfriamento, influenciou favoravelmente na MOT, VIG e longevidade das amostras (P0,05) após resfriamento. Ao avaliar isoladamente a influência da adição 10 % de FP ao MM, não foram observadas diferenças nos parâmetros avaliados (P>0,05). Conclui-se que a técnica de fluxo retrógrado para recuperação de espermatozoides caninos pode ser realizada mediante perfusão de SF ou MM com adição de ar, sem alterar a qualidade imediata da amostra; para obtenção de características espermáticas desejáveis e duradouras, as amostras armazenadas em MM oferecem melhores resultados após 24 horas de resfriamento; o MM com acréscimo de 10 % de fluido prostático adicionado em AEEs submetidas à refrigeração por 24 horas entre 4 - 6 °C não melhora significativamente os parâmetros qualitativos cinéticos, de integridade de membrana plasmática e do percentual de células normais. Já no experimento 3, objetivou-se avaliar a qualidade de AEEs coletadas por FR, submetidas ao processo de seleção em camada única de coloide (SLC) e à adição de 10 % de FP canino, prévio ao resfriamento por até 72 horas entre 4 – 6 °C. Oito pares de conjuntos testículo- epidídimo foram refrigerados durante 24 horas entre 4 – 6 °C (resfriamento in situ). As AEEs de ambos os epidídimos foram obtidas por FR usando para a perfusão MM e ar, sendo as AEEs associadas posteriormente em uma única amostra. Após avaliações espermáticas, as AEEs de cada animal foram subdivididas e submetidas a dois grupos de centrifugação: G1 – AEEs submetidas à SLC, com o coloide Androcoll-C TM (AC), e G2 – AEEs centrifugada com SF; as amostras obtidas em cada grupo foram ressuspendidas com ou sem FP, para preparação dos tratamentos: T1, AEE centrifugada com AC ressuspendida em MM acrescido de 10 % de FP; T2, AEE centrifugada com AC ressuspendida em MM acrescido de 10 % de SF; T3, AEE centrifugada com SF ressuspendida em MM acrescido de 10 % de FP e T4, AEE centrifugada com SF ressuspendida em MM acrescido de 10 % de SF. Após novas avaliações espermáticas os tratamentos foram refrigerados por até 72 horas entre 4 - 6 °C (resfriamento ex situ). Após 24 horas de resfriamento ex situ e após 48 horas adicionais (ou seja, 72 horas desde a coleta das AEEs), foram realizadas avaliações espermáticas nos diferentes tratamentos. As taxas de recuperação espermática foram de 18 e 38 % (para SLC e centrifugação convencional, respectivamente). Não houve diferenças (P>0,05) entre os parâmetros espermáticos antes e após centrifugações. Após 24 horas de resfriamento ex situ foi observada maior MOT no T4 em relação T2, e maior VIG no T3 em relação ao T2 (P0.05); there was a decrease in kinetic parameters, regardless of the shape of the migration tube and its slope in relation to T0 (P0.05); there was a decrease in the spermatic pathologies when the slant rounded base tube was used, verified in the 30 min evaluation after the renewal of the medium. It is concluded that there is no improvement of the kinetic parameters evaluated after the SU-AC technique; sperm recovery rates and cell integrity are not influenced by the use of migration tubes of different shapes and slope during the SU-AC technique; the SU-AC allows to obtain a smaller number of spermatic pathologies, when performed in a rounded and inclined base migration tube, with renewal of the medium in the migration tube with recovery and evaluation at 30 min. In the experiment 2, the objective was to verify the effect of the addition of prostatic fluid (PF) on epididymal sperm samples (ESS), cooled for 24 hours, at 4 - 6 ° C, obtained through a retrograde flow (RF) using a commercial maintenance’s medium (MM) and saline solution (SS). ESS were obtained from eight pairs of testis-epididymis sets by the RF technique with infusion of MM or SS with addition of air. The ESS were standardized to 50 x 10 6 spermatozoa / mL in MM (T1); the samples collected with SS were subdivided into three aliquots, witch one of them was adjusted to 50 x 10 6 spermatozoa / mL in SS (T2); another aliquot was adjusted to 50 x 10 6 spermatozoa / mL with MM plus 10 % SS (T3); and the third aliquot was adjusted to 50 x 10 6 spermatozoa / mL with MM plus 10 % PF (T4). During 24 hours the treatments were cooled at 4 - 6 ° C and later evaluated for sperm motility (MOT), sperm vigor (VIG), sperm morphology, functional integrity of the plasma membrane and thermoresistance test (TRT). There was no effect (P>0.05) of MM or SS, on the quantity and quality of newly collected spermatozoids; however, the preservation of the samples in the presence of MM during the cooling, favorably influenced (P0.05) after cooling. When evaluating the influence of the 10 % PF addition to the MM, no significant differences (P>0,05) were observed in the evaluated parameters. It is concluded that the RF technique for canine sperm retrieval can be performed by infusion of SS or MM with addition of air, without altering the immediate quality of the sample; to obtain desirable and long lasting sperm characteristics, samples stored in MM give better results after 24 hours of cooling; the MM with a PF 10% added in EES subjected to refrigeration for 24 hours between 4 - 6 ° C does not significantly improve the kinetic parameters, plasma membrane integrity and the percentage of normal cells. In the experiment 3, the objective was to evaluate the quality of ESS collected by RF, submitted to the single-layer centrifugation process through colloid (SLC) and sensitization with PF prior to cooling for up to 72 hours at 4 - 6 ° C. Eight pairs of testis-epididymis were refrigerated for 24 hours at 4 - 6 ° C (in situ). The ESS of both epididymis were obtained by RF using MM and air for perfusion and were later associated in a single sample. After sperm evaluation, the ESS of each animal were subdivided and submitted to two groups of centrifugation: G1 - ESS submitted to SLC with Androcoll-C TM (AC), and G2 - ESS centrifuged with SS; the samples obtained in each group were resuspended with or without PF to prepare the treatments: T1, ESS centrifuged with AC resuspended in MM plus 10 % PF; T2, ESS centrifuged with AC resuspended in MM plus 10 % SS; T3, ESS centrifuged with SS resuspended in MM plus 10 % PF and T4, ESS centrifuged with SS resuspended in MM plus 10 % SS. After further sperm evaluations, the treatments were refrigerated for up to 72 hours at 4 - 6 ° C (ex situ). After 24 hours of cooling and after an additional 48 hours (resulting in 72 hours from the collection of ESS), sperm evaluation of each treatment was performed. Sperm recovery rates were 18 and 38% (for SLC and conventional centrifugation, respectively). There were no differences (P>0.05) between the sperm parameters before and after centrifugations. After 24 hours of cooling, it was observed higher MOT in T4 in relation to T2, and higher VIG in T3 with respect to T2 (P <0.05). After TRT, T3 and T4 presented higher performance than those submitted to SLC. After 72 hours of cooling VIG at T3 was higher compared to T1 and T2 (P<0.05). The major, minor and total defects were lower in at least one of the treatments submitted to SLC (P<0.05). Thus, perfusion by RF with addition of air allow to obtain ESS with acceptable sperm characteristics; the recovery rate is higher in ESS centrifuged with SS than that obtained after SLC; however, SLC prevent the increase of sperm pathologies after 72 hours of cooling; yet, the increase of 10 % of PF in the MM has no effect on the ESS in this experimental conditions; the ESS cooled for 24 hours in situ and up to 72 hours ex situ between a 4 - 6 ° C have compatible sperm parameters for use in reproduction programs, with potential use in wild carnivores.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Reproductive parameters of Alpine goats from birth to sexual maturity

Objetivou-se com este estudo avaliar os parâmetros quantitativos e qualitativos do sêmen e o desenvolvimento testicular de caprinos de raça Alpina durante os primeiros 13 meses de idade, além de verificar o efeito do clima sob as características reprodutivas avaliadas. Foram utilizados quatro animais contemporâneos desde o primeiro mês de idade, criados em regime intensivo no município de Viçosa MG. Foram realizadas biometrias testiculares semanais desde o primeiro até o décimo terceiro mês de idade. As coletas de sêmen foram realizadas duas vezes por semana a partir dos seis meses de idade, quando os animais tinham aproximadamente 25 kg de peso corporal, para avaliação das características seminais e análise da integridade de membrana plasmática pelo teste hiposmótico (HOST). Os testículos foram avaliados a cada quinze dias por meio de imagens ultrassonográficas para avaliar a ecotextura testicular. O crescimento foi acompanhado semanalmente por meio da mensuração da altura e peso corporal. Para caracterização do micro-clima foi colocado numa das baias um termômetro de máxima e mínima além de bulbo seco e bulbo úmido para determinação do Índice de Temperatura e Umidade (ITU), sendo realizadas as leituras uma vez por semana em quatro horários diferentes. O peso corporal e perímetro escrotal (PE) mostraram um comportamento linear (P<0,05), o último passou de 9,9±1,2 cm no primeiro mês para 25,7±1,3 cm aos treze meses de idade, sendo as variações de maior magnitude entre o primeiro e o quinto mês. O comprimento, largura e volume testicular aumentaram progressivamente até o oitavo mês com variações nos meses seguintes. Comportamento semelhante foi observado na ecotextura testicular, que foi maior no oitavo mês, indicando que a partir dessa faixa etária ocorreram a estruturação e estabilização do parênquima testicular e as alterações nas mensurações testiculares devem-se ao aumento do comprimento dos túbulos seminíferos e às mudanças do fotoperíodo na região. O inicio das avaliações seminais aos seis meses de idade demonstrou que os animais se encontravam em fase de transição, entre a adolescência e a maturidade sexual, atingindo a maturidade sexual aos nove meses de idade. O HOST mostrou ser uma importante ferramenta para avaliação da integridade da membrana plasmática dos espermatozóides caprinos. Quanto aos parâmetros ambientais, por meio do ITU se verificou que os animais não ficaram em condições de estresse térmico, assim como as características reprodutivas não foram influenciadas pelos fatores do clima. A avaliação ultrassonográfica dos testículos por sua vez, mostrou-se um método eficaz capaz de detectar as mudanças no parênquima testicular ao longo do tempo e como ferramenta alternativa para diferenciação de condições normais e patológicas em caprinos.The objective of this study was evaluate the quantitative and qualitative parameters of semen and testicular development of Alpine goats during the first 13 months of age, and verify the effect of climate on reproductive characteristics. Four steers with similar age were used were from the first month, raised in Viçosa-MG and managed intensively. Testicular samples were collected weekly between the first and thirteenth month of age. The semen collection was performed twice a week starting at six months of age, when the animals had approximately 25 kg body weight, to assess the seminal characteristics and analysis of plasma membrane integrity by hypo-osmotic swelling test (HOST) for membrane integrity evaluation. The testes were evaluated every two weeks through ultrasound images to assess testicular echotexture. The growth was monitored weekly by measuring the height and body weight. To characterize micro-climate a maximum and minimum thermometer and a dry bulb and wet bulb, was placed in the stalls to determine the temperature and humidity index (THI). The readings were taken once a week at four different times. Body weight and scrotal circumference (SC) showed a linear course (P<0.05), and the latter varied from 9.9±1.2 cm in the first month to 25.7±1.3 cm at thirteenth months, and the changes of greater magnitude were between the first and fifth months. The length, width and testicular volume increased progressively until the eighth month to become unstable for the next ones. Similar behavior was observed in testicular echotexture, which was largest in the eighth month, indicating that in this age structuring and stabilization of the testicular parenchyma occurred, and the changes in testicular measurements may be due to the increased length of the seminiferous tubules and changes in the photoperiod region. The beginning of the seminal evaluations at six months of age showed that the animals were in transition between teenage and sexual maturity, reaching sexual maturity at nine months of age. The HOST was an important tool to evaluate the integrity of goat sperm plasma membrane. The animals have not heated to thermic stress as seen by the THI index and the reproductive characteristics were not influenced by seasonal variations of the environment parameters. The testicular ultrasonography was an effective exam, capable of detecting changes in testicular parenchyma over time and as a alternative tool to differentiate normal and pathological conditions in goats

Correction: Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

[This corrects the article DOI: 10.1371/journal.pmed.1001967.]

Experimental treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial) : a historically controlled, single-arm proof-of-concept trial in Guinea

BACKGROUND:Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.METHODS AND FINDINGS:Inclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in "cycle threshold" [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated.CONCLUSIONS:In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not conclude on the efficacy of the drug, and our conclusions on tolerance, although encouraging, are not as firm as they could have been if we had used randomization. On the other hand, we learned about how to quickly set up and run an Ebola trial, in close relationship with the community and non-governmental organizations; we integrated research into care so that it improved care; and we generated knowledge on EVD that is useful to further research. Our data illustrate the frequency of renal dysfunction and the powerful prognostic value of low Ct values. They suggest that drug trials in EVD should systematically stratify analyses by baseline Ct value, as a surrogate of viral load. They also suggest that favipiravir monotherapy merits further study in patients with medium to high viremia, but not in those with very high viremia.TRIAL REGISTRATION:ClinicalTrials.gov NCT02329054.Evaluation of the efficacy and of the antiviral activity of T-705 (favipiravir) duringEbola virus infection in non-human primates humansEbola Virus Disease - correlates of protection, determinants of outcome, and clinical managemen