Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab-cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab-cilgavimab in preventing progression to severe COVID-19 or death. METHODS: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab-cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. FINDINGS: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab-cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab-cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6-71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1-8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab-cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab-cilgavimab group and six in the placebo group. INTERPRETATION: A single intramuscular tixagevimab-cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab-cilgavimab might lead to more favourable outcomes. FUNDING: AstraZeneca.

Importancia del estigma en epilepsia / Importance of Stigma in Epilepsy

Resumen El estigma es un fenómeno caracterizado por una respuesta negativa hacia una persona poseedora de un atributo diferente dentro del grupo social en el que se desarrolla. Se han descrito dos tipos de estigma: el percibido (sentido o interiorizado) y el promovido (social o promulgado). Dentro de las enfermedades con más carga asociada a estigma se encuentra la epilepsia, una de las enfermedades neurológicas más prevalentes a nivel mundial y de curso crónico. En los últimos años, se ha mostrado mayor interés en el estudio de este fenómeno, ya que afecta de manera directa la calidad de vida de las personas con epilepsia, influyendo en su desarrollo personal, escolar, laboral y pronóstico.

Abstract Stigma is a phenomenon characterized by a negative response to a person possessing a different attribute within the social group it develops. Two types of stigmas have been described: perceived (felt) and promoted (enacted). Among the diseases with the greatest burden associated with stigma is epilepsy, one of the most prevalent neurological diseases worldwide and with a chronic course. In recent years, greater interest has been shown in the study of this phenomenon since it directly affects the quality of life of people with epilepsy, influencing their personal, academic and work development and prognosis.

Prevalence of nutritional deficiencies in Mexican adolescent women with early and late prenatal care.

The objective was to evaluate the prevalence of specific nutritional deficiencies in a group of pregnant adolescents according to the gestational age when they started to receive prenatal care. A group of 163 pregnant adolescents that attended the Instituto Nacional de Perinatología (Mexico City) for the first time to receive prenatal care was evaluated. An anthropometrical evaluation was performed and a blood sample taken to determine hemoglobin, ferritin, erythrocyte folate and plasma zinc to all cases. The mean age was 15 years (11 to 17 years). The mean gestational age when starting prenatal care was 27 +/- 7 gestation weeks and most of them tended to have low weight (97 +/- 12% expected weight for height and gestational age). Eight of every ten adolescents had anemia and iron deficiency. Late prenatal care (> or = 25 weeks) was associated with the risk of presenting anemia OR 5.11 (CI 95% 2.4-10.7) iron deficiency (OR 3.5; CI 95% 1.7 to 7.1) and zinc deficiency (OR 2.9; CI 95% 1.1 a 7.6). In relation to folate deficiency, the opposite effect was observed (OR 0.10; CI 95% 0.02 a 0.48). Lack of opportune prenatal care was associated with the presence of iron and zinc depletion. Probably iron deficiency contributes to an erythrocyte folate accumulation.