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Purpose:Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA/PRB isoform ratio (MIPRA; NCT02651844).Patients and Methods:Twenty patients with luminal breast carcinomas with PRA/PRB > 1.5 (determined by Western blots), and PR ≥ 50%, naïve from previous treatment, were included for mifepristone treatment (200 mg/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment.Results:A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (P = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions:Our results support the use of mifepristone in patients with luminal breast cancer with high PRA/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients.See related commentary by Ronchi and Brisken, p. 833

RNA-Seq and Proteomics analysis. A and B, Dot plot of relevant enriched pathways from GSEA results (Reactome and Hallmark databases) separating responsive (A) and unresponsive tumors (B). C, Immune cell deconvolution (xcell) in the different tumors analyzed by RNA-Seq. Plots with significant p values analyzed by Wilcoxon test and the T cell CD8+ plot are shown. D, Kegg diagram of the Cell cycle pathway, that may explain mifepristone therapeutics effects. A colored code was used: the first half of the box is colored according to the RNA-Seq data (8 tumors) and the last half of the box is colored according to the proteomic data (n=10 tumors; nuclear fraction).

RNA-Seq Variant calling

Purpose:Preclinical data suggest that antiprogestins inhibit the growth of luminal breast carcinomas that express higher levels of progesterone receptor isoform A (PRA) than isoform B (PRB). Thus, we designed a presurgical window of opportunity trial to determine the therapeutic effects of mifepristone in patients with breast cancer, based on their high PRA/PRB isoform ratio (MIPRA; NCT02651844).Patients and Methods:Twenty patients with luminal breast carcinomas with PRA/PRB > 1.5 (determined by Western blots), and PR ≥ 50%, naïve from previous treatment, were included for mifepristone treatment (200 mg/day orally; 14 days). Core needle biopsies and surgical samples were formalin fixed for IHC studies, while others were snap-frozen to perform RNA sequencing (RNA-seq), proteomics, and/or Western blot studies. Plasma mifepristone levels were determined using mass spectrometry. The primary endpoint was the comparison of Ki67 expression pretreatment and posttreatment.Results:A 49.62% decrease in Ki67 staining was observed in all surgical specimens compared with baseline (P = 0.0003). Using the prespecified response parameter (30% relative reduction), we identified 14 of 20 responders. Mifepristone induced an increase in tumor-infiltrating lymphocytes; a decrease in hormone receptor and pSer118ER expression; and an increase in calregulin, p21, p15, and activated caspase 3 expression. RNA-seq and proteomic studies identified downregulated pathways related to cell proliferation and upregulated pathways related to immune bioprocesses and extracellular matrix remodeling.Conclusions:Our results support the use of mifepristone in patients with luminal breast cancer with high PRA/PRB ratios. The combined effects of mifepristone and estrogen receptor modulators warrant clinical evaluation to improve endocrine treatment responsiveness in these patients.See related commentary by Ronchi and Brisken, p. 833

Morphological evaluation of CNBs and matched surgical samples; RNA-Seq analysis; Proteomics

Calcium intake remains inadequate in many low- and middle-income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food-based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium-deficiency rickets). Specifically, some animal-source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple-food fortification with calcium can also be a cost-effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high-calcium varieties or through the application of calcium-rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population.

This article challenges the “tyranny of P-value” and promote more valuable and applicable interpretations of the results of research on health care delivery. We provide here solid arguments to retire statistical significance as the unique way to interpret results, after presenting the current state of the debate inside the scientific community. Instead, we promote reporting the much more informative confidence intervals and eventually adding exact P-values. We also provide some clues to integrate statistical and clinical significance by referring to minimal important differences and integrating the effect size of an intervention and the certainty of evidence ideally using the GRADE approach. We have argued against interpreting or reporting results as statistically significant or statistically non-significant. We recommend showing important clinical benefits with their confidence intervals in cases of point estimates compatible with results benefits and even important harms. It seems fair to report the point estimate and the more likely values along with a very clear statement of the implications of extremes of the intervals. We recommend drawing conclusions, considering the multiple factors besides P-values such as certainty of the evidence for each outcome, net benefit, economic considerations and values and preferences. We use several examples and figures to illustrate different scenarios and further suggest a wording to standardize the reporting. Several statistical measures have a role in the scientific communication of studies, but it is time to understand that there is life beyond the statistical significance. There is a great opportunity for improvement towards a more complete interpretation and to a more standardized reporting.

INTRODUCTION: Though interest is growing for trials comparing planned delivery mode (vaginal delivery [VD]; cesarean section [CS]) in low-risk nulliparous women, appropriate study design is unclear. Our objective was to assess feasibility of three designs (preference trial [PCT], randomized controlled trial [RCT], partially randomized patient preference trial [PRPPT]) for a trial comparing planned delivery mode in low-risk women. METHODS: A cross-sectional survey of low-risk, nulliparous pregnant women (N=416) and healthcare providers (N=168) providing prenatal care and/or labor/delivery services was conducted in Argentina (2 public, 2 private hospitals). Proportion of pregnant women and providers willing to participate in each design and reasons for not participating were determined. RESULTS: Few women (85%). Believing randomization unacceptable (RCT, PRPPT) and desiring choice of delivery mode (RCT) were women’s reasons for not participating. For providers, commonly cited reasons for not participating included unacceptability of performing CS without medical indication, difficulty obtaining informed consent, discomfort enrolling patients (all designs), and violating women’s right to choose (RCT). CONCLUSIONS FOR PRACTICE: Important limitations were found for each trial design evaluated. The necessity of stronger evidence regarding delivery mode in low-risk women suggests consideration of additional designs, such as a rigorously designed cohort study or an RCT within an obstetric population with equivocal CS indications.

Introduction: Obesity is a major and challenging public health problem. The aim of this substudy is to evaluate the effect of calcium supplementation on body weight in women recruited in the Calcium and Preeclampsia trial. Methods: Women were recruited before pregnancy and randomized to receive a calcium supplement containing 500 mg of elemental calcium or placebo until 20 weeks’ gestation; all women received 1.5 g from 20 weeks until delivery. Results: A total of 630 women conceived during the study, 322 allocated to calcium and 308 to placebo. Among these, 230 allocated to calcium and 227 allocated to placebo had information on body weight at baseline and at 8 weeks' gestation. During the study period, women allocated to calcium had a mean weight increase of 1.1 (SD ±5.5) kg, whereas those allocated to placebo had a mean increase of 1.5 (SD ±6.1) kg, a mean difference of 0.4 kg (95% −0.4 (−1.4 to 0.6); P =.408). Women classified as obese at the start of the trial had a lower body weight gain at 8 weeks’ gestation (1.0 kg; 95% CI: −3.2 to 1.2; P =.330) and at 32 weeks’ gestation (2.1 kg; 95% CI: 5.6-1.3; P =.225) if they received calcium as compared to placebo. However, none of these differences were statistically significant. Conclusion: The smaller increase in body weight found in women supplemented with 500 mg elemental calcium daily is quantitatively consistent with previous studies. However, in this study, the difference was not statistically significant. Fil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Universidad Nacional de La Matanza; Argentina. University of Cape Town; Sudáfrica Fil: Betrán, Ana Pilar. Organizacion Mundial de la Salud; Argentina Fil: Harbron, Janetta. University of Cape Town; Sudáfrica Fil: Seuc, Armando. Instituto Nacional de Higiene; Cuba Fil: White, Cintia. Universidad Nacional de La Matanza; Argentina Fil: Roberts, James M.. University of Pittsburgh; Estados Unidos Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Hofmeyr, G. Justus. University of the Witwatersrand; Sudáfrica

Summary Background & aims Monitoring gestational weight gain (GWG) is relevant for perinatal outcomes, especially in the context of increasing obesity and overweight in the female population. This study analyses the association between GWG in Brazilian women, according to different body mass index (BMI) categories, and different outcomes, including hypertensive disorders of pregnancy (HDP), gestational diabetes (GD) and caesarean section. Methods Data on women from all the major regions of Brazil with a single pregnancy of a gestational age of 28 weeks or more and information available for anthropometric evaluation were included in the Birth in Brazil survey. Adequacy of GWG was assessed according to the percentile distribution of GWG of women with favourable neonatal outcomes, with the median of the distribution referred to as 100% adequacy in the GWG evaluation. Results The study consisted of 18,953 women, 58.3% of whom were normal weight and 35.1% were overweight. The adequacy of GWG was better amongst the normal weight women (91.1%) and worse amongst those with class III obesity (46.0% with excessive GWG), with the latter showing the highest occurrence of adverse outcomes. Results of the multivariate logistic regression analysis revealed that weight gain above 200% of the median in the normal weight, overweight and obese women was positively associated with HDP and caesarean section, but not with GD. Conclusions The proposed ranges of appropriate GWG associated with favourable neonatal outcomes based on the data from the Birth in Brazil survey proved good predictors of HDP and caesarean section amongst the women included in the study.

BACKGROUND: Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure. OBJECTIVES: To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi‐random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta‐analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) ‐1.37 mmHg, 95% confidence interval (CI) ‐2.08, ‐0.66; 3140 participants; 18 studies; I(2) = 0%, high‐certainty evidence; and MD ‐1.45, 95% CI ‐2.23, ‐0.67; 3039 participants; 17 studies; I(2) = 45%, high‐certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD ‐1.86, 95% CI ‐3.45, ‐0.27; 452 participants; eight studies; I(2) = 19%, moderate‐certainty evidence; MD ‐2.50, 95% CI ‐4.22, ‐0.79; 351 participants; seven studies ; I(2) = 54%, moderate‐certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD ‐0.97, 95% CI ‐1.83, ‐0.10; 2688 participants; 10 studies; I(2) = 0%, high‐certainty evidence; MD ‐0.59, 95% CI ‐1.13, ‐0.06; 2688 participants; 10 studies; I(2) = 0%, high‐certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD ‐1.25, 95% CI ‐2.53, 0.03; 1915 participants; eight studies; I(2) = 0%, high‐certainty evidence; MD ‐1.04, 95% CI ‐1.86, ‐0.22; 1915 participants; eight studies; I(2) = 4%, high‐certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD ‐2.14, 95% CI ‐3.71, ‐0.59; 507 participants; five studies; I(2) = 8%, moderate‐certainty evidence; MD ‐1.99, 95% CI ‐3.25, ‐0.74; 507 participants; five studies; I(2) = 41%, moderate‐certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD ‐0.02, 95% CI ‐2.23, 2.20; 302 participants; 3 studies; I(2) = 0%, moderate‐certainty evidence with doses less than 1000 mg; MD ‐1.05, 95% CI ‐1.91, ‐0.19; 2488 participants; 9 studies; I(2) = 0%, high‐certainty evidence with doses 1000 to 1500 mg; and MD ‐2.79, 95% CI ‐4.71, 0.86; 350 participants; 7 studies = 8; I(2) = 0%, moderate‐certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD ‐0.41, 95% CI ‐2.07, 1.25; 201 participants; 2 studies; I(2) = 0, moderate‐certainty evidence; MD ‐2.03, 95% CI ‐3.44, ‐0.62 ; 1017 participants; 8 studies; and MD ‐1.35, 95% CI ‐2.75, ‐0.05; 1821 participants; 8 studies; I(2) = 51%, high‐certainty evidence, respectively. None of the studies reported adverse events. AUTHORS' CONCLUSIONS: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately‐powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake.

Low calcium intake and its impact on maternal and child health are a major concern in low- and middle-income countries. Given the low calcium in diet, as well as the low adherence and acceptability of calcium pills in those settings, the discussion about policies to increase calcium intake has moved toward staple food fortification strategies. Nevertheless, there is scarce information on the economic feasibility of implementing these strategies. We aimed to design and propose a novel costing tool to estimate the cost of the flour fortification with calcium by carrying out a literature review about costing studies for staple food fortification programs and costing tools previously developed. A deliberative meeting with stakeholders was held to discuss and face-validate the conceptual framework proposed. We showed the costing tool application for the case of Costa Rica (a country with a population with low calcium intake), including the absolute cost of the staple food fortification production process, the incremental cost of fortification according to the public/private sector, and the incremental cost by target population. This open-source and publicly available costing tool can be useful to inform policymaking in countries considering the implementation of staple food fortification programs.

Maternal mortality (MM) reflects one of the most striking global health inequalities. Global figures of MM fell significantly from 1990 to 2017. The reduction was largely due to a 70% fall in haemorrhages, and a limited (18.2%) improvement in hypertensive disorders of pregnancy (HDP). If this trend continues, by 2021 HDP will be the main cause of global MM.MM reductions due to haemorrhage is reassuring, however MM due to HDP show a more complex situation as early detection of HDP requires regular contact of pregnant women with the health system. In order to reduce MM due to HDP, population wide preventive actions such as low dose aspirin and adequate calcium intake are required, especially in areas where women have little contact with the health systems.Calcium supplementation for women with low calcium intake has reduced the risk of pre-eclampsia, with further reductions starting daily supplementation with 500 mg of calcium preconceptionally, however adherence to supplementation is limited.To reduce global inequities in calcium intake and consequently in the HDP, food fortification seem to be an attractive strategy to achieve an increase of calcium intake.

This study explores postpartum depression (PPD) in women who screened negative in mid-pregnancy to assess the impact of the peripartum period on the development of depressive symptoms.A prospective cohort study was carried out in two facilities in Argentina. The Edinburgh postnatal depression scale (EPDS) scale was applied to pregnant women between weeks 20-24 gestation, and those screening negative (10) were included in the cohort. Participants were followed up until the 4th week postpartum, when the EPDS was repeated. If positive, a semi-structured clinical interview was applied (MINI) to define the diagnosis.A total of 112 pregnant women were eligible for the follow-up. At the 4th week postpartum, 14 women (12.5%, CI 95% 7.0; 20.1) screened positive using a cutoff point of 10 or more in the EPDS. Of those screened positive in the EPDS, two participants (1.8%, CI 95% 0.2-6.3) had a Major Depressive Disorder. Newborn admission to the Intensive Care Unit, hospitalization of the newborn after discharge, abuse during childbirth, and lack of company during labor were identified as peripartum risk factors.This study reinforces the relevance of women and newborn mental health care during the hospitalization process surrounding peripartum. The women and newborn hospitalization process should be better explored to understand the contribution to PPD and design and test strategies to alleviate the impact of maternal depression.

Calcium intake is low in many countries, especially in low-income countries. Our objective was to perform a simulation exercise on the impact, effectiveness, and safety of a flour fortification strategy using the Intake Modelling, Assessment, and Planning Program. Modeling of calcium fortification scenarios was performed with available dietary intake databases from Argentina, Bangladesh, Italy, the Lao People's Democratic Republic (Lao PDR), Uganda, Zambia, and the United States. This theoretical exercise showed that simulating a fortification with 156 mg of calcium per 100 g of flour would decrease the prevalence of low calcium intake, and less than 2% of the individuals would exceed the recommended calcium upper limit (UL) in Argentina, Italy, Uganda, and Zambia. Bangladesh and the Lao PDR showed little impact, as flour intake is uncommon. By contrast, in the United States, this strategy would lead to some population groups exceeding the UL. This exercise should be replicated and adapted to each country, taking into account the updated prevalence of calcium inadequacy, flour consumption, and technical compatibility between calcium and the flour-type candidate for fortification. A fortification plan should consider the impact on all age groups to avoid the risk of exceeding the upper levels of calcium intake.

Objective This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth. Data Sources The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov , and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted. Study Eligibility Criteria Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study. Methods Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability. Results A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62–1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80–1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56–1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, −49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45–1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24–2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72–6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96–2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis. Conclusion Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.

Objective:To simulate the impact - effectiveness and safety - of water fortification with different concentrations of Ca using the Intake Modelling, Assessment and Planning Program.Design:This is a secondary analysis of national or sub-national dietary intake databases.Setting and Participants:Uganda, Lao People's Democratic Republic (PDR), Bangladesh, Zambia, Argentina, USA and Italy.Results:We found that for dietary databases assessed from low- and middle-income countries (LMIC), the strategy of fortifying water with 500 mg of Ca/l would decrease the prevalence of low Ca intake in all age groups. We also found that this strategy would be safe as no group would present a percentage of individuals exceeding the upper limit in >2 %, except women aged 19-31 years in Lao PDR, where 6·6 % of women in this group would exceed the upper limit of Ca intake. The same strategy would lead to some groups exceeding the upper limit in USA and Italy.Conclusions:We found that for most LMIC countries, water fortified with Ca could decrease the prevalence of Ca intake inadequacy without exceeding the upper levels of Ca intake. Fil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Universidad Nacional de La Matanza; Argentina Fil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

Objective To compare the effectiveness and safety of dexamethasone versus betamethasone for preterm birth (registered in PROSPERO CRD42017078006). Search strategy We searched in MEDLINE, EMBASE, Cochrane Library, LILACS, Clinical Trials.gov, International Clinical Trials Registry Platform, reference lists and contacted field experts. Selection criteria, data collection and analysis Randomized controlled trials comparing any corticosteroids against each other or against placebo. Three researchers independently selected, extracted data and assessed the risk of bias of the included studies by using EROS and COVIDENCE software. We performed a pairwise meta-analysis and Bayesian network meta-analysis. Main results We included 45 trials (11227 women, 11878 infants). There was no important difference between corticosteroids in neonatal death (odds ratio[OR] 1.05; 95% confidence interval 0.62-1.84; moderate-certainty evidence[CE]), neurodevelopmental disability (OR 1.03; 0.80-1.33; moderate-CE), intraventricular haemorrhage (OR 1.04; 0.56-1.78); low-CE) and birthweight (+5.29 gr; -49.79 to 58.97; high-CE). Compared with betamethasone, dexamethasone may reduce chorioamnionitis (OR 0.70; 0.45-1.06; moderate-CE), foetal death (OR 0.81; 0.24-2.41; low-CE) while may increase puerperal sepsis (OR 2.04; 0.72-6.06; low-CE) and respiratory distress syndrome (OR 1.34; 0.96-2.11; moderate-CE), however, the confidence interval indicates both beneficial and detrimental effects. Conclusions We found no important difference on neonatal death, neurodevelopmental disability, intraventricular haemorrhage and birthweight between corticosteroids. Compared with betamethasone, dexamethasone may reduce chorioamnionitis and foetal death, but may increase endometritis/puerperal sepsis and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence. Keywords preterm birth, antenatal corticosteroids, dexamethasone, betamethasone, systematic review, network meta-analysis

Daily calcium intake is well below current recommendations in most low- and middle-income countries (LMICs). Calcium intake is usually related to bone health, however an adequate calcium intake has also been shown to reduce hypertensive disorders of pregnancy, lower blood pressure and cholesterol values, and to prevent recurrent colorectal adenomas. Food fortification of foods has been identified as a cost-effective strategy to overcome micronutrient gaps in public health. This review summarizes regulatory aspects of fortification of commonly consumed foods with micronutrients, with an emphasis on calcium. We selected a convenient sample of 15 countries from differentWHOregions and described the regulatory framework related to calcium fortification of staple foods. We assessed the relevant policies in electronic databases including the WHO Global database on the Implementation of Nutrition Action (GINA) for fortification policies and the Global Fortification Data Exchange Database, a fortification database developed and maintained by Food Fortification Initiative (FFI), Global Alliance for Improved Nutrition (GAIN), Iodine Global Network (IGN), and Micronutrient Forum. Food fortification with micronutrients is widely used in many of the selected countries. Most countries had national legislation for the addition of micronutrients to staple foods, especially wheat flour. These national legislations, that includes regulations and standards, can provide the framework to consider the implementation of adding calcium to the fortification strategies, including the selection of the adequate food vehicle to reach the targeted population at risk safely. The strategy to include calcium in the fortification mix in fortified staple foods seems promising in these countries. However, potential undesired changes on the organoleptic characteristics of fortified foods and products thereof, and operational feasibility at the manufacturing site should be evaluated by the stakeholders during the planning stage. Codex Alimentarius standards should be considered by regulators in order to assure adherence to international standards. While the selected countries already have established national regulations and/or standards for fortification of key staple food vehicles, and there are experiences in the implementation of fortification of some staple foods, national food intake surveys can help plan, design, and modify existing fortification programs as well as monitor food and nutrient consumption to assess risk and benefits. Fil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Universidad Nacional de La Matanza; Argentina Fil: Betrán, Ana Pilar. Organizacion Mundial de la Salud; Argentina Fil: Metz, Fletcher. Carleton College; Estados Unidos Fil: Palacios, Cristina. Florida International University; Estados Unidos Fil: Beltrán Velazquez, Filiberto. Organizacion Mundial de la Salud; Argentina Fil: de las Nieves García-Casal, María. Organizacion Mundial de la Salud; Argentina Fil: Peña Rosas, Juan Pablo. Organizacion Mundial de la Salud; Argentina Fil: Hofmeyr, G. Justus. University Of Fort Hare; Sudáfrica Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

Reproductive Health has an interest in reproductivehealth status globally, but it has particular interest inphenomena affecting disadvantaged populations. This isthe reason why this journal encourages submissionsfrom researchers conducting studies in low- and middleincome countries (LMICs). Fil: Pingray, Verónica. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Ortega, Vanesa. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Yaya, Sanni. University of Oxford; Reino Unido Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina

Objective: To describe the calcium concentration of tap and bottled waters from Argentina and to estimate the contribution of drinking water to calcium recommendations. Results: Calcium concentrations provided by water authorities ranged from 6 to 105 mg/L. The mean calcium level of samples analysed at the Laboratorio de Ingeniería Sanitaria, National University of La Plata was 15.8 (SD ± 13.2) mg/L and at the Bone Biology Laboratory of the National University of Rosario was 13.1 (± 10.0) mg/L. Calcium values of samples from supply systems and private wells was similar. Most bottled waters had calcium levels well below 50 mg/L. The intake of one litre of drinking water from Argentina could represent in average between 1.2 and 8.0% of the calcium daily values for an adult., Centro de Investigaciones del Medioambiente

To assess whether the implementation of a package of activities through the joint action of three international healthcare professional associations (HCPAs) increased the use of essential interventions (EIs) for delivery and neonatal care.A noncontrolled pre-intervention versus post-intervention study was conducted from June 13 to December 13, 2016, among women older than 18 years of age, who had delivered at one of two urban tertiary hospitals in Nepal.The study included 9252 women. Minimal change was found after the implementation of EIs that were used frequently at baseline (e.g. social support during delivery in the emergency room, and promotion and support for early initiation of breastfeeding). By contrast, an increase was recorded for some EIs that had not been used regularly at baseline. For example, the rate of timely administration of prophylactic antibiotics before cesarean delivery increased from 0.0% (0/496) to 94.0% (409/435) at one hospital. Nonetheless, some EIs with low use at baseline did not show improvement after implementation (e.g. kangaroo mother care).The present study strengthened previous findings regarding the uptake of EIs following joint promotion by HCPAs in low-income settings.

Background: Food fortification is an effective strategy that has been recommended for improving population calcium inadequate intakes. Increasing calcium concentration of water has been proposed as a possible strategy to improve calcium intake. The objective of this study was to determine the sensory threshold of different calcium salts added to drinking water using survival analysis. Methods: We performed the triangle test methodology for samples of water with added calcium using three different calcium salts: calcium chloride, calcium gluconate and calcium lactate. For each salt, a panel of 54 consumers tested seven batches of three water samples. Data were adjusted for chance and sensory threshold was estimated using the survival methodology and a discrimination of 50%. Results: The threshold value estimation for calcium gluconate was 587 ± 131 mg/L of water, corresponding to 25% discrimination, for calcium lactate was 676 ± 186 mg/L, corresponding to 50% discrimination, and for calcium chloride was 291 ± 73 mg/L, corresponding to 50% discrimination. Conclusions: These results show that water with calcium added in different salts and up to a concentration of 500 mg of calcium/L of water is feasible. The calcium salt allowing the highest calcium concentration with the lowest perceived changes in taste was calcium gluconate. Future studies need to explore stability and acceptability over longer periods of time.

Objective To assess whether the implementation of a package of activities through the joint action of the three international healthcare professionals associations (HCPAs) increased the use of intrapartum and postnatal essential interventions (EIs) in two hospitals in Uganda. Methods A non-controlled before-and-after study was undertaken to evaluate the effect of a package of activities designed to change practice relating to nine EIs among providers. Coverage of the EIs was measured in a 3-month pre-implementation period and a 3-month post-implementation period in 2014. Data were obtained for women older than 18 years who delivered vaginally or by cesarean. Results: Overall, 4816 women were included. Level of use remained high for EIs used widely at baseline. Some EIs that had low use at baseline did not show improvement after the implementation. Promotion of breastfeeding showed a significant improvement in the Kampala hospital, from 8.5% (8/94) to 25.6% (30/117; P=0.001), whereas promotion of hygiene in cord care improved at the Mbarara hospital, from 0.1% (2/1592) to 46.0% (622/1351; P