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: Introduction: Global guidelines emphasize the ethical obligation of investigators to help participants in HIV‐endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre‐exposure prophylaxis (PrEP) has increasingly become part of state‐of‐the‐art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods: ECHO was an open‐label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part‐way through the course of the trial, oral PrEP was provided to study participants either off‐site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi‐squared tests or t‐tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. Results: PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow‐up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p < 0.05). PrEP initiation did not differ across study randomized groups (p = 0.7). Two‐thirds of PrEP users were continuing PrEP at study exit. Conclusions: There is a need for improved HIV prevention services in clinical trials with HIV endpoints, especially trials among African women. PrEP as a component of a comprehensive HIV prevention package provided to women in a large clinical trial is practical and feasible. Provision of PrEP within clinical trials with HIV outcomes should be standard of prevention., Introduction Within the context of clinical trials in which incident HIV infection is a primary study outcome, global guidelines emphasize an ethical imperative to assist participants reduce HIV risk by [...]

Background: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most.Objectives: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing.Search Strategy: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239).Selection Criteria: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses.Data Collection and Analysis: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates.Main Results: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake.Conclusions: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate.Tweetable Abstract: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low. [ABSTRACT FROM AUTHOR]

Objective To review maternal deaths and the dose-related effects of misoprostol on blood loss and pyrexia in randomized trials of misoprostol use for the prevention or treatment of postpartum haemorrhage. Methods We searched the Cochrane Controlled Trials Register and Pubmed, without language restrictions, for "(misoprostol AND postpartum) OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage)", and we evaluated reports identified through the Cochrane Pregnancy and Childbirth Group search strategy. Randomized trials comparing misoprostol with either placebo or another uterotonic to prevent or treat postpartum haemorrhage were checked for eligibility. Data were extracted, tabulated and analysed with Reviewer Manager (RevMan) 4.3 software. Findings We included 46 trials with more than 40 000 participants in the final analysis. Of 11 deaths reported in 5 trials, 8 occurred in women receiving [greater than or equal to] 600 [micro]g of misoprostol (Peto odds ratio, OR: 2.49; 95% confidence interval, CI: 0.76-8.13). Severe morbidity, defined as the need for major surgery, admission to intensive care, organ failure or body temperature [greater than or equal to] 40 [degrees]C, was relatively infrequent. In prevention trials, severe morbidity was experienced by 16 of 10 281 women on misoprostol and by 16 of 10 292 women on conventional uterotonics; in treatment trials, it was experienced by 1 of 32 women on misoprostol and by 1 of 32 women on conventional uterotonics. Misoprostol recipients experienced more adverse events than placebo recipients: 8 of 2070 versus 5 of 2032, respectively, in prevention trials, and 5 of 196 versus 2 of 202, respectively, in treatment trials. Meta-analysis of direct and adjusted indirect comparisons of the results of randomized trials showed no evidence that 600 [micro]g are more effective than 400 [micro]g for preventing blood loss [greater than or equal to] 1000 ml (relative risk, RR: 1.02; 95% CI: 0.71-1.48). Pyrexia was more than twice as common among women who received [greater than or equal to] 600 [micro]g rather than 400 [micro]g of misoprostol (RR: 2.53; 95% CI: 1.78-3.60). Conclusion Further research is needed to more accurately assess the potential beneficial and harmful effects of misoprostol and to determine the smallest dose that is effective and safe. In this review, 400 [micro]g of misoprostol were found to be safer than [greater than or equal to] 600 [micro]pg and just as effective. Objectif Etudier la mortalite maternelle et les effets dose-dependants du misoprostol sur la perte de sang et la pyrexie dans le cadre d&apos;essais randomises portant sur l&apos;utilisation de ce medicament pour prevenir et traiter les hemorragies postpartum. Methodes Nous avons fait des recherches dans le registre Cochrane des essais controles et dans Pubmed sans emettre de restriction concernant la langue et en utilisant l&apos;expression <> OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage), puis nous avons evalue les rapports identifies avec la strategie de recherche du Groupe Cochrane Pregnancy and Childbirth. Nous avons verifie la conformite avec les criteres d&apos;admissibilite dans l&apos;etude des essais randomises comparant le misoprostol a un placebo ou a un autre uterotonique dans la prevention ou le traitement des hemorragies postpartum. Nous avons extrait et tabule des donnees, puis nous les avons analysees avec le Iogiciel Reviewer Manager (RevMan) 4.3. Resultats Dans l&apos;analyse finale, nous avons pris en compre 46 essais portant sur plus de 40 000 participantes. Sur 11 deces rapportes dans 5 essais, 8 sont survenus chez des femmes ayant recu [greater than or equal to] 600 [micro]g de misoprostol (Odds ratio de Peto, OR : 2,49; intervalle de confiance a 95%, IC: 0,76-8,13). La morbidite grave, definie comme la necessite d&apos;une intervention chirurgicale importante, l&apos;admission en soins intensifs, la defaillance d&apos;un organe ou une temperature corporelle [greater than or equal to] 40 [degrees]C, etait relativement rare. Dans les essais de prevention, nous avons releve une morbidite grave chez 16 des 10281 femmes sous misoprostol et chez 16 des 10292 parturientes recevant un uterotonique classique et, dans les essais therapeutiques, chez une des 32 femmes sous misoprostol et chez une des 32 femmes sous uterotonique classique. Les retomes recevant du misoprostol ont manifeste plus d&apos;effets indesirables que celles recevant un placebo : 8 sur 2070 contre 5 sur 2032 respectivement dans les essais de prevention et 5 sur 196 contre 2 sur 202 dans les essais therapeutiques. La meta-analyse des comparaisons directes et indirectes ajustees des resultats d&apos;essais randomises n&apos;a fait apparaitre aucune preuve d&apos;une efficacite superieure de la dose de 600 [micro]g de misoprostol par rapport a la dose de 400 [micro]g, dans la prevention d&apos;une perte de sang [greater than or equal to]1000 mi (risque relatif, RR : 1,02; IC a 95% : 0,71-1,48). La pyrexie etait plus de deux fois plus frequente chez les femmes ayant recu [greater than or equal to] 600 [micro]g de misoprostol que chez celles ayant recu une dose de 400 pg (RR : 2,53; IC a 95% : 1,78-3,60). Conclusion Des recherches supplementaires sont necessaires pour evaluer plus precisement les effets benefiques et nocifs potentiels du misoprostol et pour identifier la plus faible dose de ce medicament a la fois efficace et sans risque. La presente etude a trouve qu&apos;une dose de 400 [micro]g de misoprostol etait plus sure qu&apos;une dose [greater than or equal to] 600 [micro]g et tout aussi efficace. Objetivo Analizar la mortalidad materna y los efectos dosisdependientes del misoprostol sobre la perdida de sangre y en forma de fiebre en los ensayos aleatorizados realizados sobre su uso con tines de prevencion o tratamiento de la hemorragia posparto. Metodos Utilizamos el Registro de Ensayos Controlados de Cochrane y Pubmed para realizar una busqueda en todos los idiomas planteada en los siguientes terminos: << (misoprostol AND postpartum) OR (misoprostol AND haemorrhage) OR (misoprostol AND hemorrhage) >>. Se procedio a evaluar los trabajos identificados mediante la estrategia de busqueda del Grupo Cochrane de Embarazo y Parto, y se determino la elegibilidad de los ensayos aleatorizados en que se comparo el misoprostol ya fuera con un placebo o con otro uterotonico como forma de prevencion o tratamiento de la hemorragia posparto. Los datos extraidos fueron tabulados y analizados con el software Reviewer Manager (RevMan) 4.3. Resultados Incluimos en el analisis final 46 ensayos que abarcaron a mas de 40 000 participantes. De las 11 defunciones notificadas en 5 ensayos, 8 correspondian a mujeres que habian recibido [greater than or equal to] 600 [micro]g de misoprostol (oportunidad relativa [OR] de Peto: 2,49; intervalo de confianza [IC] del 95%: 0,76-8,13). La morbilidad grave, definida como la necesidad de cirugia mayor, el ingreso en cuidados intensivos, la aparicion de insuficiencia organica o una temperatura corporal [greater than or equal to]40 [degrees]C, fue relativamente poco frecuente. En los ensayos de prevencion, sufrieron morbilidad grave 16 de las 10 281 mujeres a las que se administro misoprostol, y 16 de las 10 292 mujeres sometidas a uterotonicos convencionales; en los ensayos de tratamiento, sufrieron cuadros graves 1 de 32 mujeres sometidas a misoprostol y 1 de 32 mujeres tratadas con uterotonicos convencionales. Quienes recibieron misoprostol sufrieron mas eventos adversos que quienes recibieron placebo: 8 de 2070 frente a 5 de 2032, respectivamente, en los ensayos de prevencion, y 5 de 196 frente a 2 de 202, respectivamente, en los ensayos de tratamiento. El metanalisis de las comparaciones directas e indirectas ajustadas de los resultados de los ensayos aleatorizados no aporto ningun indicio de que la dosis de 600 pg sea mas eficaz que la de 400 [micro]g para prevenir las hemorragias [greater than or equal to]1000 ml (riesgo relativo, RR: 1,02; IC95%: 0,71-1,48). La frecuencia de fiebre entre las mujeres que recibieron [greater than or equal to]600 [micro]g de misoprostol fue mas del doble que en las tratadas con 400 [micro]g (RR: 2,53; IC95%: 1,78-3,60). Conclusion Es necesario realizar nuevas investigaciones para evaluar con mas precision los posibles erectos beneficiosos y nocivos del misoprostol y para determinar la dosis mas baja eficaz y segura. Segun los resultados de este analisis, las dosis de 400 [micro]g de misoprostol son mas seguras que las dosis [greater than or equal to]600 [micro]g y tienen la misma eficacia., Introduction In low-income countries, postpartum haemorrhage is a major cause of maternal death (1) and arguably the most preventable. Attempts to reduce deaths from postpartum haemorrhage have been complicated by [...]

Objective To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. Methods A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird--Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). Findings Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). Conclusions Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries. Objectif Faire etat de la mortinatalite et de la mortalite neonatale precoce et quantifier l&apos;importance relative des principales causes obstetricales de mortalite perinatale observees pour 171 deces perinatals lies a 7993 grossesses interrompues apres la 28eme semaine chez des femmes nullipares. Methodes L&apos;examen a porte sur tous les cas de mortinatalite et deces neonatals precoces signales dans l&apos;essai OMS de supplementation calcique pour la prevention de la preeclampsie mene dans sept centres collaborateurs situes en Afrique du Sud, en Argentine, en Egypte, en Inde, au Perou et au Vietnam. On a utilise le systeme de Baird-Pattinson pour attribuer les principales causes obstetricales de deces et classe les causes des deces neonatals precoces sur la base de la Classification internationale des maladies et des problemes de sante connexes, dixieme revision (CIM 10). Resultats Le taux de mortinatalite est de 12,5 pour 1000 naissances et le taux de mortalite neonatale precoce de 9,0 pour 1000 naissances vivantes. L&apos;accouchement premature spontane et l&apos;hypertension gravidique sont les problemes obstetricaux les plus frequemment a l&apos;origine d&apos;un deces perinatal (respectivement 28,7% et 23,6 %). La prematurite est la principale cause de deces neonatal precoce (62 %). Conclusion Des progres dans les soins aux prematures et la prevention du travail premature spontane et de l&apos;hypertension gravidique permettraient d&apos;obtenir une diminution sensible de la mortalite perinatale en milieu hospitalier dans les pays en developpement. Objetivo Informar sobre la mortinatalidad y la mortalidad neonatal precoz y cuantificar la importancia relativa de diferentes causas obstetricas primarias de mortalidad perinatal en 171 defunciones perinatales correspondientes a 7993 embarazos de mas de 28 semanas en mujeres nuliparas. Metodos Se examinaron todos los casos de mortinatalidad y defuncion precoz de recien nacidos notificados en un ensayo OMS de administracion de suplementos de calcio para la prevencion de la preeclampsia, llevado a cabo en siete centros colaboradores de la OMS en la Argentina, Egipto, la India, el Peru, Sudafrica y Viet Nam. Usamos el sistema de Baird-Pattinson para asignar causas obstetricas primarias de muerte y causas clasificadas de mortalidad neonatal precoz mediante la Clasificacion Estadistica Internacional de Enfermedades y Problemas de Salud Conexos, decima revision (CIE-10). Resultados La tasa de mortinatalidad fue del 12,5 por 1000 nacimientos, y la tasa de mortalidad neonatal precoz, de 9,0 por 1000 nacidos vivos. EI parto pretermino espontaneo y los trastornos hipertensivos fueron los casos obstetricos mas comunes asociados a las defunciones perinatales (28,7% y 23,6%, respectivamente). La prematuridad fue la causa principal de las defunciones neonatales precoces (62%). Conclusiones Los progresos de la atencion a los lactantes prematuros y la prevencion del parto pretermino espontaneo y de los trastornos hipertensivos del embarazo podrian propiciar una disminucion sustancial de la mortalidad perinatal en los entornos hospitalarios en los paises en desarrollo., Introduction A two-thirds reduction of mortality in children less than 5 years old by 2015 is one of the UN Millennium Development Goals. (1) Despite a decline in mortality in [...]