RESUMO
BACKGROUND: Understanding causes and contributors to maternal mortality is critical from a quality improvement perspective to inform decision making and monitor progress toward ending preventable maternal mortality. The indicator "maternal death review coverage" is defined as the percentage of maternal deaths occurring in a facility that are audited. Both the numerator and denominator of this indicator are subject to misclassification errors, underreporting, and bias. This study assessed the validity of the indicator by examining both its numerator-the number and quality of death reviews-and denominator-the number of facility-based maternal deaths and comparing estimates of the indicator obtained from facility- versus district-level data. METHODS AND FINDINGS: We collected data on the number of maternal deaths and content of death reviews from all health facilities serving as birthing sites in 12 districts in three countries: Argentina, Ghana, and India. Additional data were extracted from health management information systems on the number and dates of maternal deaths and maternal death reviews reported from health facilities to the district-level. We tabulated the percentage of facility deaths with evidence of a review, the percentage of reviews that met the World Health Organization defined standard for maternal and perinatal death surveillance and response. Results were stratified by sociodemographic characteristics of women and facility location and type. We compared these estimates to that obtained using district-level data. and looked at evidence of the review at the district/provincial level. Study teams reviewed facility records at 34 facilities in Argentina, 51 facilities in Ghana, and 282 facilities in India. In total, we found 17 deaths in Argentina, 14 deaths in Ghana, and 58 deaths in India evidenced at facilities. Overall, >80% of deaths had evidence of a review at facilities. In India, a much lower percentage of deaths occurring at secondary-level facilities (61.1%) had evidence of a review compared to deaths in tertiary-level facilities (92.1%). In all three countries, only about half of deaths in each country had complete reviews: 58.8% (n = 10) in Argentina, 57.2% (n = 8) in Ghana, and 41.1% (n = 24) in India. Dramatic reductions in indicator value were seen in several subnational geographic areas, including Gonda and Meerut in India and Sunyani in Ghana. For example, in Gonda only three of the 18 reviews conducted at facilities met the definitional standard (16.7%), which caused the value of the indicator to decrease from 81.8% to 13.6%. Stratification by women's sociodemographic factors suggested systematic differences in completeness of reviews by women's age, place of residence, and timing of death. CONCLUSIONS: Our study assessed the validity of an important indicator for ending preventable deaths: the coverage of reviews of maternal deaths occurring in facilities in three study settings. We found discrepancies in deaths recorded at facilities and those reported to districts from facilities. Further, few maternal death reviews met global quality standards for completeness. The value of the calculated indicator masked inaccuracies in counts of both deaths and reviews and gave no indication of completeness, thus undermining the ultimate utility of the measure in achieving an accurate measure of coverage.
Assuntos
Morte Materna , Mortalidade Materna , Humanos , Feminino , Mortalidade Materna/tendências , Estudos Retrospectivos , Morte Materna/estatística & dados numéricos , Gana/epidemiologia , Gravidez , Índia/epidemiologia , Argentina/epidemiologia , Instalações de Saúde/estatística & dados numéricos , Prontuários Médicos/estatística & dados numéricos , AdultoRESUMO
BACKGROUND: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends. OBJECTIVES: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity. MAIN RESULTS: We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m2,95% CI -0.22 to -0.13; P < 0.001, I2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I2 = 97%; 12 studies, 812 participants). AUTHORS' CONCLUSIONS: Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition.
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Cálcio da Dieta , Suplementos Nutricionais , Obesidade , Sobrepeso , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de Peso , Humanos , Cálcio da Dieta/administração & dosagem , Masculino , Feminino , Adulto , Qualidade de Vida , Viés , Alimentos Fortificados , Pessoa de Meia-Idade , Cálcio/administração & dosagem , Cálcio/uso terapêutico , Cálcio/efeitos adversosRESUMO
Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography-tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.
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Neoplasias da Mama , Mifepristona , Humanos , Camundongos , Animais , Feminino , Mifepristona/uso terapêutico , Mifepristona/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptores de Progesterona , Antagonistas de Hormônios/uso terapêutico , Antagonistas de Hormônios/farmacologia , PrognósticoRESUMO
BACKGROUND: The 2020 Law on Access to the Voluntary Interruption of Pregnancy is a landmark piece of legislation regarding access to abortion in Argentina. Under the new law, abortion is legal up to 14 weeks and 6 days gestation, with exceptions made to the gestational age limit to save a woman´s life, to preserve a woman´s health, and in case of rape. However, widespread refusal to provide care by authorized health providers (due to conscientious objection or lack of awareness of the new law) could hinder access to legal abortion. This study aimed to assess knowledge of the current legal framework and willingness to perform abortions by authorized professionals in Argentina, to compare perceptions about any requirements necessary to perform abortions on legal grounds between willing and unwilling providers and to explore factors associated with refusal to provide care. METHODS: We conducted a cross-sectional study based on a self-administered, anonymous survey to authorized abortion providers in public health facilities in four provinces of Argentina. FINDINGS: Most authorized providers knew the grounds upon which it is currently legal to perform abortions; however, almost half reported being unwilling to perform abortions, mainly due to conscientious objection. Both willing and unwilling providers believed there were additional requirements not actually stipulated by law. Using logistic regression, we found that province where providers serve, working in a tertiary level facility, and older age were factors associated with unwillingness to provide care. CONCLUSIONS: The results of our study indicate that, even in a favorable legal context, barriers at the provider level may hinder access to abortion in Argentina. They help to demonstrate the need for specific actions that can improve access such as training, further research and public policies that guarantee facilities have sufficient professionals willing to provide abortion care.
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Aborto Induzido , Gravidez , Feminino , Humanos , Estudos Transversais , Argentina , Aborto Legal , Idade GestacionalRESUMO
Availability of emergency obstetric and newborn care (EmONC) is a strong supply side measure of essential health system capacity that is closely and causally linked to maternal mortality reduction and fundamentally to achieving universal health coverage. The World Health Organization's indicator "Availability of EmONC facilities" was prioritized as a core indicator to prevent maternal death. The indicator focuses on whether there are sufficient emergency care facilities to meet the population need, but not all facilities designated as providing EmONC function as such. This study seeks to validate "Availability of EmONC" by comparing the value of the indicator after accounting for key aspects of facility functionality and an alternative measure of geographic distribution. This study takes place in four subnational geographic areas in Argentina, Ghana, and India using a census of all birthing facilities. Performance of EmONC in the 90 days prior to data collection was assessed by examining facility records. Data were collected on facility operating hours, staffing, and availability of essential medications. Population estimates were generated using ArcGIS software using WorldPop to estimate the total population, and the number of women of reproductive age (WRA), pregnancies and births in the study areas. In addition, we estimated the population within two-hours travel time of an EmONC facility by incorporating data on terrain from Open Street Map. Using these data sources, we calculated and compared the value of the indicator after incorporating data on facility performance and functionality while varying the reference population used. Further, we compared its value to the proportion of the population within two-hours travel time of an EmONC facility. Included in our study were 34 birthing facilities in Argentina, 51 in Ghana, and 282 in India. Facility performance of basic EmONC (BEmONC) and comprehensive EmONC (CEmONC) signal functions varied considerably. One facility (4.8%) in Ghana and no facility in India designated as BEmONC had performed all seven BEmONC signal functions. In Argentina, three (8.8%) CEmONC-designated facilities performed all nine CEmONC signal functions, all located in Buenos Aires Region V. Four CEmONC-designated facilities in Ghana (57.1%) and the three CEmONC-designated facilities in India (23.1%) evidenced full CEmONC performance. No sub-national study area in Argentina or India reached the target of 5 BEmONC-level facilities per 20,000 births after incorporating facility functionality yet 100% did in Argentina and 50% did in India when considering only facility designation. Demographic differences also accounted for important variation in the indicator's value. In Ghana, the total population in Tolon within 2 hours travel time of a designated EmONC facility was estimated at 99.6%; however, only 91.1% of women of reproductive age were within 2 hours travel time. Comparing the value of the indicator when calculated using different definitions reveals important inconsistencies, resulting in conflicting information about whether the threshold for sufficient coverage is met. This raises important questions related to the indicator's validity. To provide a valid measure of effective coverage of EmONC, the construct for measurement should extend beyond the most narrow definition of availability and account for functionality and geographic accessibility.
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Serviços Médicos de Emergência , Recém-Nascido , Gravidez , Feminino , Humanos , Tratamento de Emergência , Argentina , Censos , Assistência Integral à SaúdeRESUMO
BACKGROUND: Midwives' authorization to deliver the seven basic emergency obstetric and newborn care (BEmONC) functions is a core policy indicator in global monitoring frameworks, yet little evidence supports whether such data are captured accurately, or whether authorization demonstrates convergence with midwives' skills and actual provision of services. In this study, we aimed to validate the data reported in global monitoring frameworks (criterion validity) and to determine whether a measure of authorization is a valid indicator for BEmONC availability (construct validity). METHODS: We conducted a validation study in Argentina, Ghana, and India. To assess accuracy of the reported data on midwives' authorization to provide BEmONC services, we reviewed national regulatory documents and compared with reported country-specific data in Countdown to 2030 and the World Health Organization Maternal, Newborn, Child and Adolescent Health Policy Survey. To assess whether authorization demonstrates convergent validity with midwives' skills, training, and performance of BEmONC signal functions, we surveyed 1257 midwives/midwifery professionals and assessed variance. RESULTS: We detected discrepancies between data reported in the global monitoring frameworks and the national regulatory framework in all three countries. We found wide variations between midwives' authorization to perform signal functions and their self-reported skills and actual performance within the past 90 days. The percentage of midwives who reported performing all signal functions for which they were authorized per country-specific regulations was 17% in Argentina, 23% in Ghana, and 31% in India. Additionally, midwives in all three countries reported performing some signal functions that the national regulations did not authorize. CONCLUSION: Our findings suggest limitations in criterion and construct validity for this indicator in Argentina, Ghana, and India. Some signal functions such as assisted vaginal delivery may be obsolete based on current practice patterns. Findings suggest the need to re-examine the emergency interventions that should be included as BEmONC signal functions.
Assuntos
Parto Obstétrico , Serviços Médicos de Emergência , Saúde Global , Saúde do Lactente , Serviços de Saúde Materno-Infantil , Tocologia , Adolescente , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Argentina , Parto Obstétrico/métodos , Gana , Índia , Tocologia/métodosRESUMO
BACKGROUND: Global mechanisms have been established to monitor and facilitate state accountability regarding the legal status of abortion. However, there is little evidence describing whether these mechanisms capture accurate data. Moreover, it is uncertain whether the "legal status of abortion" is a valid proxy measure for access to safe abortion, pursuant to the global goals of reducing preventable maternal mortality and advancing reproductive rights. Therefore, this study sought to assess the accuracy of reported monitoring data, and to determine whether evidence supports the consistent application of domestic law by health care professionals such that legality of abortion functions as a valid indicator of access. METHODS AND FINDINGS: We conducted a validation study using three countries as illustrative case examples: Argentina, Ghana, and India. We compared data reported by two global monitoring mechanisms (Countdown to 2030 and the Global Abortion Policies Database) against domestic source documents collected through in-depth policy review. We then surveyed health care professionals authorized to perform abortions about their knowledge of abortion law in their countries and their personal attitudes and practices regarding provision of legal abortion. We compared professionals' responses to the domestic legal frameworks described in the source documents to establish whether professionals consistently applied the law as written. This analysis revealed weaknesses in the criterion validity and construct validity of the "legal status of abortion" indicator. We detected discrepancies between data reported by the global monitoring and accountability mechanisms and the domestic policy reviews, even though all referenced the same source documents. Further, provider surveys unearthed important context-specific barriers to legal abortion not captured by the indicator, including conscientious objection and imposition of restrictions at the provider's discretion. CONCLUSIONS: Taken together, these findings denote weaknesses in the indicator "legal status of abortion" as a proxy for access to safe abortion, as well as inaccuracies in data reported to global monitoring mechanisms. This information provides important groundwork for strengthening indicators for monitoring access to abortion and for renewed advocacy to assure abortion rights worldwide.
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Aborto Induzido , Aborto Legal , Gravidez , Feminino , Humanos , Fonte de Informação , Pessoal de Saúde , Política de SaúdeRESUMO
INTRODUCTION: Most efforts to assess maternal health indicator validity focus on measures of service coverage. Fewer measures focus on the upstream enabling environment, and such measures are typically not research validated. Thus, methods for validating system and policy-level indicators are not well described. This protocol describes original multicountry research to be conducted in Argentina, Ghana and India, to validate 10 indicators from the monitoring framework for the 'Strategies toward Ending Preventable Maternal Mortality' (EPMM). The overall aim is to improve capacity to drive and track progress towards achieving the priority recommendations in the EPMM strategies. This work is expected to contribute new knowledge on validation methodology and reveal important information about the indicators under study and the phenomena they target for monitoring. Validating the indicators in three diverse settings will explore the external validity of results. METHODS AND ANALYSIS: This observational study explores the validity of 10 indicators from the EPMM monitoring framework via seven discrete validation exercises that will use mixed methods: (1) cross-sectional review of policy data, (2) retrospective review of facility-level patient and administrative data and (3) collection of primary quantitative and qualitative cross-sectional data from health service providers and clients. There is a specific methodological approach and analytic plan for each indicator, directed by unique, relevant validation research questions. ETHICS AND DISSEMINATION: The protocol was approved by the Office of Human Research Administration at Harvard University in November 2019. Individual study sites received approval via local institutional review boards by January 2020 except La Pampa, Argentina, approved June 2020. Our dissemination plan enables unrestricted access and reuse of all published research, including data sets. We expect to publish at least one peer-reviewed publication per validation exercise. We will disseminate results at conferences and engage local stakeholders in dissemination activities in each study country.
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Saúde Materna , Políticas , Argentina , Estudos Transversais , Feminino , Gana , Humanos , Estudos Observacionais como AssuntoRESUMO
Progesterone receptors (PRs) ligands are being tested in luminal breast cancer. There are mainly two PR isoforms, PRA and PRB, and their ratio (PRA/PRB) may be predictive of antiprogestin response. Our aim was to investigate: the impact of the PR isoform ratio on metastatic behaviour, the PR isoform ratio in paired primary tumours and lymph node metastases (LNM) and, the effect of antiprogestin/progestins on metastatic growth. Using murine and human metastatic models, we demonstrated that tumours with PRB > PRA (PRB-H) have a higher proliferation index but less metastatic ability than those with PRA > PRB (PRA-H). Antiprogestins and progestins inhibited metastatic burden in PRA-H and PRB-H models, respectively. In breast cancer samples, LNM retained the same PRA/PRB ratio as their matched primary tumours. Moreover, PRA-H LNM expressed higher total PR levels than the primary tumours. The expression of NDRG1, a metastasis suppressor protein, was higher in PRB-H compared to PRA-H tumours and was inversely regulated by antiprogestins/progestins. The binding of the corepressor SMRT at the progesterone responsive elements of the NDRG1 regulatory sequences, together with PRA, impeded its expression in PRA-H cells. Antiprogestins modulate the interplay between SMRT and AIB1 recruitment in PRA-H or PRB-H contexts regulating NDRG1 expression and thus, metastasis. In conclusion, we provide a mechanistic interpretation to explain the differential role of PR isoforms in metastatic growth and highlight the therapeutic benefit of using antiprogestins in PRA-H tumours. The therapeutic effect of progestins in PRB-H tumours is suggested.
Assuntos
Neoplasias da Mama , Proteínas de Ciclo Celular , Peptídeos e Proteínas de Sinalização Intracelular , Receptores de Progesterona , Animais , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Metástase Neoplásica , Progesterona/farmacologia , Progestinas/metabolismo , Isoformas de Proteínas/metabolismo , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE: To identify risk factors associated with severe anaphylaxis in children. STUDY DESIGN: We carried out a multicenter prospective observational study including children less than 18 years old diagnosed with anaphylaxis in 7 Spanish pediatric emergency departments (EDs) between May 2016 and April 2018. Children were considered to have severe anaphylaxis if they met one or more of the following criteria: requirement for 2 or more doses of epinephrine, clinically important biphasic reaction, endotracheal intubation, intensive care unit admission, and/or death. RESULTS: We included 453 episodes of anaphylaxis. Of these, 61 were classified as severe anaphylaxis (13.5%, 95% CI [10.6-16.9]): 53 (11.7%) required more than 1 dose of epinephrine, and there were 14 (3.1%) cases of clinically important biphasic reactions, 2 (0.4%) intubations in the ED, and 6 (1.3%) admissions to the intensive care unit. No patients died. In the multivariable regression, we identified 5 independent risk factors for severe anaphylaxis: history of asthma (P = .002; OR 2.705, 95% CI [1.431-5.113]), onset of the symptoms less than 5 minutes after the allergen exposure (P = .002; OR 2.619, 95% CI [1.410-4.866]), non-well appearance (P = .005; OR 2.973, 95% CI [1.380-6.405]), tachycardia (P = .014; OR 2.339, 95% CI [1.191-4.959]), and hypotension (P = .036; OR 3.725, 95% CI [1.087-12.762]). CONCLUSIONS: Childhood anaphylaxis is usually well controlled in the ED. Children with a history of asthma, rapid onset of the symptoms, who are non-well appearing, or have tachycardia or hypotension upon arrival to the ED are more likely to have severe episodes.