Variation in the COVID-19 infection-fatality ratio by age, time, and geography during the pre-vaccine era: a systematic analysis

Background The infection-fatality ratio (IFR) is a metric that quantifies the likelihood of an individual dying once infected with a pathogen. Understanding the determinants of IFR variation for COVID-19, the disease caused by the SARS-CoV-2 virus, has direct implications for mitigation efforts with respect to clinical practice, non-pharmaceutical interventions, and the prioritisation of risk groups for targeted vaccine delivery. The IFR is also a crucial parameter in COVID-19 dynamic transmission models, providing a way to convert a population's mortality rate into an estimate of infections.Methods We estimated age-specific and all-age IFR by matching seroprevalence surveys to total COVID-19 mortality rates in a population. The term total COVID-19 mortality refers to an estimate of the total number of deaths directly attributable to COVID-19. After applying exclusion criteria to 5131 seroprevalence surveys, the IFR analyses were informed by 2073 all-age surveys and 718 age-specific surveys (3012 age-specific observations). When seroprevalence was reported by age group, we split total COVID-19 mortality into corresponding age groups using a Bayesian hierarchical model to characterise the non-linear age pattern of reported deaths for a given location. To remove the impact of vaccines on the estimated IFR age pattern, we excluded age-specific observations of seroprevalence and deaths that occurred after vaccines were introduced in a location. We estimated age-specific IFR with a non-linear meta-regression and used the resulting age pattern to standardise all-age IFR observations to the global age distribution. All IFR observations were adjusted for baseline and waning antibody-test sensitivity. We then modelled age-standardised IFR as a function of time, geography, and an ensemble of 100 of the top-performing covariate sets. The covariates included seven clinical predictors (eg, age-standardised obesity prevalence) and two measures of health system performance. Final estimates for 190 countries and territories, as well as subnational locations in 11 countries and territories, were obtained by predicting age-standardised IFR conditional on covariates and reversing the age standardisation.Findings We report IFR estimates for April 15, 2020, to January 1, 2021, the period before the introduction of vaccines and widespread evolution of variants. We found substantial heterogeneity in the IFR by age, location, and time. Age-specific IFR estimates form a J shape, with the lowest IFR occurring at age 7 years (0-0023%, 95% uncertainty interval [UI] 0-0015-0-0039) and increasing exponentially through ages 30 years (0-0573%, 0-0418-0-0870), 60 years (1-0035%, 0-7002-1-5727), and 90 years (20-3292%, 14-6888-28-9754). The countries with the highest IFR on July 15, 2020, were Portugal (2-085%, 0-946-4-395), Monaco (1-778%, 1-265-2-915), Japan (1-750%, 1-302-2-690), Spain (1-710%, 0-991-2-718), and Greece (1-637%, 1-155-2-678). All-age IFR varied by a factor of more than 30 among 190 countries and territories.After age standardisation, the countries with the highest IFR on July 15, 2020, were Peru (0-911%, 0-636-1-538), Portugal (0-850%, 0-386-1-793), Oman (0-762%, 0-381-1-399), Spain (0-751%, 0-435-1-193), and Mexico (0-717%, 0-426-1-404). Subnational locations with high IFRs also included hotspots in the UK and southern and eastern states of the USA. Sub-Saharan African countries and Asian countries generally had the lowest all-age and age-standardised IFRs. Population age structure accounted for 74% of logit-scale variation in IFRs estimated for 39 in-sample countries on July 15, 2020. A post-hoc analysis showed that high rates of transmission in the care home population might account for higher IFRs in some locations. Among all countries and territories, we found that the median IFR decreased from 0-466% (interquartile range 0-223-0-840) to 0-314% (0-143-0-551) between April 15, 2020, and Jan 1, 2021.Interpretation Estimating the IFR for global populations helps to identify relative vulnerabilities to COVID-19. Information about how IFR varies by age, time, and location informs clinical practice and non-pharmaceutical interventions like physical distancing measures, and underpins vaccine risk stratification. IFR and mortality risk form a J shape with respect to age, which previous research, such as that by Glynn and Moss in 2020, has identified to be a common pattern among infectious diseases. Understanding the experience of a population with COVID-19 mortality requires consideration for local factors; IFRs varied by a factor of more than 30 among 190 countries and territories in this analysis. In particular, the presence of elevated age-standardised IFRs in countries with well resourced health-care systems indicates that factors beyond health-care capacity are important. Potential extenuating circumstances include outbreaks among care home residents, variable burdens of severe cases, and the population prevalence of comorbid conditions that increase the severity of COVID-19 disease. During the pre-vaccine period, the estimated 33% decrease in median IFR over 8 months suggests that treatment for COVID-19 has improved over time. Estimating IFR for the pre-vaccine era provides an important baseline for describing the progression of COVID-19 mortality patterns.Funding Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

A randomized, controlled, crossover trial of oral midazolam and hydroxyzine for pediatric dental sedation Sedação com midazolam e hidroxizina por via oral em Odontopediatria: ensaio clínico randomizado, controlado e cruzado

The effectiveness of oral midazolam in pediatric dentistry is controversial. This randomized, controlled, crossover, double blind clinical trial was conducted in order to study the effect of midazolam, used either alone or in association with hydroxyzine, during child dental treatment. Thirty seven dental sedation sessions were carried out on 11 ASA I uncooperative children less than five years-old. In each appointment children were randomly assigned to groups: P - placebo, M - midazolam (1.0 mg/kg), or MH - midazolam (0.75 mg/kg) plus hydroxyzine (2.0 mg/kg). Vital signs (blood pressure, breathing rate, pulse and oxygen saturation) and behavior parameters (consciousness, crying, movement, overall behavior) were evaluated every 15 minutes. Friedman and Wilcoxon statistical tests were used to compare groups and different moments in the same group. Normal values of vital signs were usually registered. Heart rate increased in groups P and M as the session went on. Group M presented less crying and movement at the first 15 minutes of treatment. Group MH caused more drowsiness at the beginning of the session. Overall behavior was better in group M than in groups P or MH. Group M produced effective sedation in 77% of the cases, and group MH did so in 30.8%. It was concluded that midazolam was effective and safe, and its association with hydroxyzine did not lead to additional advantages in pediatric dental sedation.<br>Há controvérsias quanto aos benefícios do midazolam na sedação de crianças durante a atenção odontológica. Conduziu-se um ensaio clínico controlado, cruzado e duplo-cego para comparar o efeito sedativo em Odontopediatria da administração oral do midazolam, associado ou não à hidroxizina. Trinta e sete sessões foram realizadas em 11 crianças menores de cinco anos, ASA I. Em cada atendimento, os pacientes receberam aleatoriamente o medicamento conforme os grupos: P - placebo, M - midazolam (1,0 mg/kg); MH - midazolam (0,75 mg/kg) associado à hidroxizina (2,0 mg/kg). Os sinais vitais (pressão arterial, freqüência respiratória, pulso e saturação de oxigênio) e os parâmetros comportamentais (consciência, choro, movimento, comportamento geral) foram avaliados a cada 15 minutos. As comparações entre grupos e entre momentos de atendimento num mesmo grupo foram estabelecidas estatisticamente através dos testes Friedman e Wilcoxon. Os grupos P, M e MH não diferiram quanto aos sinais vitais, os quais se mantiveram dentro de valores aceitáveis. A freqüência cardíaca aumentou nos grupos P e M com o transcorrer da sessão. O grupo M esteve associado a menos choro e movimento nos primeiros 15 minutos de tratamento. O grupo MH apresentou mais sonolência no início da sessão. O comportamento geral foi melhor em M do que em P e MH. M produziu sedação efetiva em 77% dos casos, e MH em 30,8%. Concluiu-se que o midazolam foi efetivo e seguro, e que sua associação à hidroxizina não repercutiu em vantagens adicionais na sedação odontopediátrica

Gender in STEM Education: an Exploratory Study of Student Perceptions of Math and Science Instructors in the United Arab Emirates

© 2015, Ministry of Science and Technology, Taiwan. The current study addresses student perceptions of math and science professors in the Middle East. Gender disparity in science, technology, engineering, and math (STEM) education continues to exist in higher education, with male professors holding a normative position. This disparity can also be seen in the United Arab Emirates. As female participation in STEM education lags behind men, it is possible that gender stereotypes may influence students’ first impressions of male and female instructors. The United Arab Emirates provides a unique context to study this phenomenon as it is a traditional patriarchal society that is highly dependent on the engineering discipline, especially within the oil and gas sectors. A total of 176 undergraduate students from 2 universities in the United Arab Emirates completed a survey about teaching effectiveness based on their perceptions of photographs of hypothetical male and female instructors. A factor analysis of survey items revealed 2 main subcategories of teacher effectiveness: namely teacher warmth and professionalism. A 2-way between-groups analysis of variance was conducted to explore the impact of teacher gender and student gender on perceptions of overall teaching effectiveness, as well as their perceptions of teacher warmth and professionalism. Findings revealed that there was a significant cross-gender effect on student perceptions of math and science instructors in the United Arab Emirates

Sanitation, Stress, and Life Stage: A Systematic Data Collection Study among Women in Odisha, India

Emerging evidence demonstrates how inadequate access to water and sanitation is linked to psychosocial stress, especially among women, forcing them to navigate social and physical barriers during their daily sanitation routines. We examine sanitation-related psychosocial stress (SRPS) across women's reproductive lives in three distinct geographic sites (urban slums, rural villages, and rural tribal villages) in Odisha, India. We explored daily sanitation practices of adolescent, newly married, pregnant, and established adult women (n = 60) and identified stressors encountered during sanitation. Responding to structured data collection methods, women ranked seven sanitation activities (defecation, urination, menstruation, bathing, post-defecation cleaning, carrying water, and changing clothes) based on stress (high to low) and level of freedom (associated with greatest freedom to having the most restrictions). Women then identified common stressors they encountered when practicing sanitation and sorted stressors in constrained piles based on frequency and severity of each issue. The constellation of factors influencing SRPS varies by life stage and location. Overall, sanitation behaviors that were most restricted (i.e., menstruation) were the most stressful. Women in different sites encountered different stressors, and the level of perceived severity varied based on site and life stage. Understanding the influence of place and life stage on SRPS provides a nuanced understanding of sanitation, and may help identify areas for intervention