Validating the indicator "maternal death review coverage" to improve maternal mortality data: A retrospective analysis of district, facility, and individual medical record data.

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.

Calcium supplementation for people with overweight or obesity.

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.

Validating the implementation of an indicator reporting policies and laws on free public maternal health-related services in the era of universal health coverage: A multi-country cross-sectional study.

BACKGROUND: The concept of universal health coverage (UHC) encompasses both access to essential health services and freedom from financial harm. The World Health Organization's Maternal Newborn Child and Adolescent Health (MNCAH) Policy Survey collects data on policies that have the potential to reduce maternal morbidity and mortality. The indicator, "Are the following health services provided free of charge at point-of-use in the public sector for women of reproductive age?", captures the free provision of 13 key categories of maternal health-related services, to measure the success of UHC implementation with respect to maternal health. However, it is unknown whether it provides a valid measure of the provision of free care. Therefore, this study compared free maternal healthcare laws and policies against actual practice in three countries. METHODS AND FINDINGS: We conducted a cross-sectional study in four districts/provinces in Argentina, Ghana, and India. We performed desk reviews to identify free care laws and policies at the country level and compared those with reports at the global level. We conducted exit interviews with women aged 15-49 years who used a component service or their accompanying persons, as well as with facility chief financial officers or billing administrators, to determine if women had out-of-pocket expenditures associated with accessing services. For designated free services, prevalence of expenditures at the service level for women and reports by financial officers of women ever having expenditures associated with services designated as free were computed. These three sources of data (desk review, surveys of women and administrators) were triangulated, and chi-square analysis was conducted to determine if charges were levied differentially by standard equity stratifiers. Designation of services as free matched what was reported in the MNCAH Policy Survey for Argentina and Ghana. In India, insecticide-treated bed nets and testing and treatment for syphilis were only designated as free for selected populations, differing from the WHO MNCAH Policy Survey. Among 1046, 923, and 1102 women and accompanying persons who were interviewed in Argentina, Ghana, and India, respectively, the highest prevalence of associated expenditures among women who received a component service in each setting was for cesarean section in Argentina (26%, 24/92); family planning in Ghana (78.4%, 69/88); and postnatal maternal care in India (94.4%, 85/90). The highest prevalence of women ever having out of pocket expenditures associated with accessing any free service reported by financial officers was 9.1% (2/22) in Argentina, 64.1% (93/145) in Ghana, and 29.7% (47/158) in India. Across the three countries, self-reports of out of pocket expenditures were significantly associated with district/province and educational status of women. Additionally, wealth quintile in Argentina and age in India were significantly associated with women reporting out of pocket expenditures. CONCLUSIONS: Free care laws were largely accurately reported in the global MNCAH policy database. Notably, we found that women absorbed both direct and indirect costs and made both formal and informal payments for services designated as free. Therefore, the policy indicator does not provide a valid reflection of UHC in the three settings.

Reduced mitochondrial pyruvate carrier expression in hearts with heart failure and reduced ejection fraction patients: ischemic vs. non-ischemic origin.

Introduction and objectives: Mitochondrial pyruvate carrier (MPC) mediates the entry of pyruvate into mitochondria, determining whether pyruvate is incorporated into the Krebs cycle or metabolized in the cytosol. In heart failure (HF), a large amount of pyruvate is metabolized to lactate in the cytosol rather than being oxidized inside the mitochondria. Thus, MPC activity or expression might play a key role in the fate of pyruvate during HF. The purpose of this work was to study the levels of the two subunits of this carrier, named MPC1 and MPC2, in human hearts with HF of different etiologies. Methods: Protein and mRNA expression analyses were conducted in cardiac tissues from three donor groups: patients with HF with reduced ejection fraction (HFrEF) with ischemic cardiomyopathy (ICM) or idiopathic dilated cardiomyopathy (IDC), and donors without cardiac pathology (Control). MPC2 plasma levels were determined by ELISA. Results: Significant reductions in the levels of MPC1, MPC2, and Sirtuin 3 (SIRT3) were observed in ICM patients compared with the levels in the Control group. However, no statistically significant differences were revealed in the analysis of MPC1 and MPC2 gene expression among the groups. Interestingly, Pyruvate dehydrogenase complex (PDH) subunits expression were increased in the ICM patients. In the case of IDC patients, a significant decrease in MPC1 was observed only when compared with the Control group. Notably, plasma MPC2 levels were found to be elevated in both disease groups compared with that in the Control group. Conclusion: Decreases in MPC1 and/or MPC2 levels were detected in the cardiac tissues of HFrEF patients, with ischemic or idiopatic origen, indicating a potential reduction in mitochondrial pyruvate uptake in the heart, which could be linked to unfavorable clinical features.

Steroid profile in patients with breast cancer and in mice treated with mifepristone.

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.

Validation of a measure to assess decision-making autonomy in family planning services in three low- and middle-income countries: The Family Planning Autonomous Decision-Making scale (FP-ADM).

BACKGROUND: Integrating measures of respectful care is an important priority in family planning programs, aligned with maternal health efforts. Ensuring women can make autonomous reproductive health decisions is an important indicator of respectful care. While scales have been developed and validated in family planning for dimensions of person-centered care, none focus specifically on decision-making autonomy. The Mothers Autonomy in Decision-Making (MADM) scale measures autonomy in decision-making during maternity care. We adapted the MADM scale to measure autonomy surrounding a woman's decision to use a contraceptive method within the context of contraceptive counselling. This study presents a psychometric validation of the Family Planning Autonomous Decision-Making (FP-ADM) scale using data from Argentina, Ghana, and India. METHODS AND FINDINGS: We used cross-sectional data from women in four subnational areas in Argentina (n = 890), Ghana (n = 1,114), and India (n = 1,130). In each area, 20 primary sampling units (PSUs) were randomly selected based on probability proportional to size. Households were randomly selected in Ghana and India. In Argentina, all facilities providing reproductive and maternal health services within selected PSUs were included and women were randomly selected upon exiting the facility. Interviews were conducted with a sample of 360 women per district. In total, 890 women completed the FP-ADM in Argentina, 1,114 in Ghana and 1,130 in India. To measure autonomous decision-making within FP service delivery, we adapted the items of the MADM scale to focus on family planning. To assess the scale's psychometric properties, we first examined the eigenvalues and conducted a parallel analysis to determine the number of factors. We then conducted exploratory factor analysis to determine which items to retain. The resulting factors were then identified based on the corresponding items. Internal consistency reliability was assessed with Cronbach's alpha. We assessed both convergent and divergent construct validity by examining associations with expected outcomes related to the underlying construct. The Eigenvalues and parallel analysis suggested a two-factor solution. The two underlying dimensions of the construct were identified as "Bidirectional Exchange of Information" (Factor 1) and "Empowered Choice" (Factor 2). Cronbach's alpha was calculated for the full scale and each subscale. Results suggested good internal consistency of the scale. There was a strong, significant positive association between whether a woman expressed satisfaction with quality of care received from the healthcare provider and her FP-ADM score in all three countries and a significant negative association between a woman's FP-ADM score and her stated desire to switch contraceptive methods in the future. CONCLUSIONS: Our results suggest the FP-ADM is a valid instrument to assess decision-making autonomy in contraceptive counseling and service delivery in diverse low- and middle-income countries. The scale evidenced strong construct, convergent, and divergent validity and high internal consistency reliability. Use of the FP-ADM scale could contribute to improved measurement of person-centered family planning services.

"Factors associated with provider unwillingness to perform induced abortion in Argentina: A cross-sectional study in four provinces following the legalization of abortion on request".

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.

Empathic Resonance: A Case of Dissociative Identity Disorder (DID)

Dissociative identity disorder (DID) also referred as multiple personality disorder can be accompanied by related alterations in affect, behavior and sensory-motor functioning. This article describes the case of a 33-year-old woman with a diagnostic of DID and who required intensive treatment, who suffered bullying at the age of 15 with a demon personality. Despite psychopharmacological treatment there was no improvement until the emphatic resonance therapy was carried out. Our case report shows the complexity of providing treatment for patient with DID (AU)

Validating indicators for monitoring availability and geographic distribution of emergency obstetric and newborn care (EmoNC) facilities: A study triangulating health system, facility, and geospatial data.

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.

Characteristics of Pediatric Emergency Department Presentations of Anaphylaxis in Spain.

OBJECTIVE: This study aimed to identify the triggers of pediatric anaphylaxis in Spain and to analyze the circumstances of the episode. METHODS: Planned secondary analysis of a prospective observational multicenter study endorsed by the Spanish Society of Pediatric Emergencies including children aged younger than 18 years diagnosed with anaphylaxis in 7 Spanish pediatric emergency departments (EDs) between 2016 and 2018. We analyzed factors related to the anaphylaxis episode and its management. RESULTS: Four hundred fifty-three cases were registered, happening mainly at home (295 [65.1%]), school (65 [14.3%]), and street (61 [13.5%]). The median age was 5 years, 143 (31.6%) had previous episodes, and 165 (36.4%) had previously been prescribed an epinephrine autoinjector, used in 40 (24.2% of those prescribed). Two thirds were well-appearing when arriving to the pediatric ED. Food was the trigger in 396 (87.4%). In 349 with a single food involved, the most frequent were milk (108 [30.4%]), nuts (103 [29.0%]), hen's egg (40 [11.3%]), and fish (31 [8.7%]), with variations related to the age of the child. CONCLUSIONS: Food, especially milk and nuts, are responsible for most anaphylaxis diagnosed in Spanish pediatric EDs. Consideration should be given to improving health education due to the low use of epinephrine autoinjectors.

Validating midwifery professionals' scope of practice and competency: A multi-country study comparing national data to international standards.

BACKGROUND: There is a global shortage of midwives, whose services are essential to meet the healthcare needs of pregnant women and newborns. Evidence suggests that if enough midwives, trained and regulated to global standards, were deployed worldwide, maternal, and perinatal mortality would decline significantly. Health workforce planning estimates the number of midwives needed to achieve population coverage of midwifery interventions. However, to provide a valid measure of midwifery care coverage, an indicator must consider not only the raw number of midwives, but also their scope and competency. The tasks midwives are authorized to deliver and their competency to perform essential skills and behaviors provide crucial information for understanding the availability of safe, high-quality midwifery services. Without reliable estimates for an adequate midwifery workforce, progress toward ending preventable maternal and perinatal mortality will continue to be uneven. The International Labor Organization (ILO) and the International Confederation of Midwives (ICM) suggest standards for midwifery scope of practice and competencies. This paper compares national midwifery regulations, scope, and competencies in three countries to the ILO and ICM standards to validate measures of midwife density. We also assess midwives' self-reported skills/behaviors from the ICM competencies and their acquisition. METHODS AND FINDINGS: We compared midwives' scope of practice in Argentina, Ghana, and India to the ILO Tasks and ICM Essential Competencies for Midwifery Practice. We compared midwives self-reported skills/behaviors with the ICM Competencies. Univariate and bivariate analysis was conducted to describe the association between midwives' skills and selected characteristics. National scopes of practice matched two ILO tasks in Argentina, four in India, and all in Ghana. National standards partially reflected ICM skills in Categories 2, 3, and 4 (pre-pregnancy and antenatal care; care during labor and birth; and ongoing care of women and newborns, respectively) in Argentina (range 11% to 67%), mostly in India (range 74% to 100%) and completely in Ghana (100% match). 1,266 midwives surveyed reported considerable variation in competency for skills and behaviors across ICM Category 2, 3, and 4. Most midwives reported matching skills and behaviors around labor and childbirth (Category 2). Higher proportions of midwives reported gaining basic skills through in-service training and on-job-experience than in pre-service training. CONCLUSION: Estimating the density of midwives needed for an adequate midwifery workforce capable of providing effective population coverage is predicated on a valid numerator. A reliable and valid count of midwives to meet population needs assumes that each midwife counted has the authority to exercise the same behaviors and reflects the ability to perform them with comparable competency. Our results demonstrate variation in midwifery scopes of practice and self-reported competencies in comparison to global standards that pose a threat to the reliability and validity of the numerator in measures of midwife density, and suggest the potential for expanded authorization and improved education and training to meet global reference standards for midwifery practice has not been fully realized. Although the universally recognized standard, this study demonstrates that the complex, composite descriptions of skills and behaviors in the ICM competencies make them difficult to use as benchmark measures with any precision, as they are not defined or structured to serve as valid measures for assessing workforce competency. A simplified, content-validated measurement system is needed to facilitate evaluation of the competency of the midwifery workforce.

Authorization of midwives to perform basic emergency obstetric and newborn care signal functions in Argentina, Ghana, and India: A multi-country validation study of a key global maternal and newborn health indicator.

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.

Improving measures of access to legal abortion: A validation study triangulating multiple data sources to assess a global indicator.

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.

Detection of bipolar disorder in the prodromal phase: A systematic review of assessment instruments.

BACKGROUND: Early detection of prodromal symptoms may contribute to improving the prognosis of patients with bipolar disorder (BD). The main objective of this systematic review is to present the different procedures for the identification of initial and relapse prodromes in these patients. METHODS: PsycINFO, Web of Science and PubMed databases were searched using a predetermined strategy, until January 4, 2022. Then, by means of a regulated process, studies that used a BD prodrome detection procedure, in English-language and all ages participants were selected. Quantitative and qualitative studies were assessed using a modified version of the Newcastle-Ottawa Scale and by Critical Appraisals Skills Programme checklist, respectively. RESULTS: Forty-five studies were selected. Of these, 26 used procedures for identifying initial prodromes (n = 8014) and 19 used procedures for detecting relapse prodromes (n = 1136). The interview was the most used method in the detection of both types of prodromes (k = 30 papers, n = 4068). It was variable in its degree of structure. Mobile applications and digital technologies are gaining importance in the detection of the relapse prodromes. LIMITATIONS: A retrospective design in most papers, small samples sizes, existence of persistent subsyndromal symptoms and difficulty to identify the end of the prodrome and the onset of the disorder. CONCLUSIONS: There is a wide variety of assessment instruments to detect prodromes in BD, among which the clinical interview is most frequently used. Future research should consider development of a brief tool to be applied in different formats to patients and family members.

Impacto del tratamiento previo con estatinas sobre la supervivencia de los pacientes hospitalizados con COVID-19 / Survival impact of previous statin therapy in patients hospitalized with COVID-19

Introducción: El tratamiento con estatinas podría presentar un efecto pronóstico beneficioso en pacientes con COVID-19, dadas sus propiedades inmunomoduladoras, antiinflamatorias y estabilizadoras de la placa de ateroma. Nuestro propósito fue analizar esta hipótesis tomando como base el registro de COVID-19 de un hospital universitario español.MétodosRealizamos un estudio observacional y retrospectivo en el que se incluyeron los pacientes hospitalizados con COVID-19 diagnosticado mediante PCR entre marzo de 2020 y octubre de 2020 en un centro. Mediante regresión logística, diseñamos una puntuación de propensión para estimar la probabilidad de que un paciente recibiese tratamiento con estatinas antes del ingreso. Comparamos la supervivencia de los pacientes con y sin tratamiento con estatinas mediante la regresión de Cox ponderada por la inversa de la probabilidad de recibir el tratamiento (IPT). La mediana de seguimiento fue de 406días.ResultadosEstudiamos 1.122 pacientes hospitalizados con COVID-19, cuya mediana de edad era de 71años y de los cuales 488 (43,5%) eran mujeres. 451 (40,2%) pacientes recibían estatinas antes del ingreso. En el análisis de supervivencia ponderado por la IPT, el tratamiento previo con estatinas se asoció a una reducción significativa de la mortalidad (HR: 0,76; IC95%: 0,59-0,97). El mayor beneficio del tratamiento previo con estatinas se observó en los subgrupos de pacientes con enfermedad arterial coronaria (HR: 0,32; IC95%: 0,18-0,56) y enfermedad arterial extracardiaca (HR: 0,45; IC95%: 0,28-0,73).ConclusionesNuestro estudio mostró una asociación significativa entre el tratamiento previo con estatinas y una menor mortalidad en pacientes hospitalizados con COVID-19. El beneficio pronóstico observado fue mayor en los pacientes con enfermedad aterosclerótica coronaria o extracardiaca previa. (AU)

Introduction: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital.MethodsWe conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days.ResultsWe studied 1122 hospitalized patients with COVID-19, whose median age was 71years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95%CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95%CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95%CI: 0.28-0.73).ConclusionsOur study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease. (AU)

Survival impact of previous statin therapy in patients hospitalized with COVID-19.

Introduction: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. Methods: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. Results: We studied 1122 hospitalized patients with COVID-19, whose median age was 71 years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95% CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95% CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95% CI: 0.28-0.73). Conclusions: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease.

Introducción: El tratamiento con estatinas podría presentar un efecto pronóstico beneficioso en pacientes con COVID-19, dadas sus propiedades inmunomoduladoras, antiinflamatorias y estabilizadoras de la placa de ateroma. Nuestro propósito fue analizar esta hipótesis tomando como base el registro de COVID-19 de un hospital universitario español. Métodos: Realizamos un estudio observacional y retrospectivo en el que se incluyeron los pacientes hospitalizados con COVID-19 diagnosticado mediante PCR entre marzo de 2020 y octubre de 2020 en un centro. Mediante regresión logística, diseñamos una puntuación de propensión para estimar la probabilidad de que un paciente recibiese tratamiento con estatinas antes del ingreso. Comparamos la supervivencia de los pacientes con y sin tratamiento con estatinas mediante la regresión de Cox ponderada por la inversa de la probabilidad de recibir el tratamiento (IPT). La mediana de seguimiento fue de 406 días. Resultados: Estudiamos 1.122 pacientes hospitalizados con COVID-19, cuya mediana de edad era de 71 años y de los cuales 488 (43,5%) eran mujeres. 451 (40,2%) pacientes recibían estatinas antes del ingreso. En el análisis de supervivencia ponderado por la IPT, el tratamiento previo con estatinas se asoció a una reducción significativa de la mortalidad (HR: 0,76; IC 95%: 0,59­0,97). El mayor beneficio del tratamiento previo con estatinas se observó en los subgrupos de pacientes con enfermedad arterial coronaria (HR: 0,32; IC 95%: 0,18­0,56) y enfermedad arterial extracardiaca (HR: 0,45; IC 95%: 0,28­0,73). Conclusiones: Nuestro estudio mostró una asociación significativa entre el tratamiento previo con estatinas y una menor mortalidad en pacientes hospitalizados con COVID-19. El beneficio pronóstico observado fue mayor en los pacientes con enfermedad aterosclerótica coronaria o extracardiaca previa.

Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial.

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.

[Survival impact of previous statin therapy in patients hospitalized with COVID-19]. / Impacto del tratamiento previo con estatinas sobre la supervivencia de los pacientes hospitalizados con COVID-19.

INTRODUCTION: Statin therapy might have a beneficial prognostic effect in patients with COVID-19, given its immunomodulative, anti-inflammatory and anti-atherosclerotic properties. Our purpose was to test this hypothesis by using the COVID-19 registry of a Spanish university hospital. METHODS: We conducted a single-center, observational and retrospective study in which hospitalized patients with COVID-19 diagnosed by PCR between March 2020 and October 2020 were included. By means of logistic regression, we designed a propensity score to estimate the likelihood that a patient would receive statin treatment prior to admission. We compared the survival of COVID-19 patients with and without statin treatment by means of Cox regression with inverse probability of treatment weighting (IPTW). The median follow-up was 406 days. RESULTS: We studied 1122 hospitalized patients with COVID-19, whose median age was 71years and of which 488 (43.5%) were women. 451 (40.2%) patients received statins before admission. In the IPTW survival analysis, prior statin treatment was associated with a significant reduction in mortality (HR: 0.76; 95%CI: 0.59-0.97). The greatest benefit of previous statin therapy was seen in subgroups of patients with coronary artery disease (HR: 0.32; 95%CI: 0.18-0.56) and extracardiac arterial disease (HR: 0.45; 95%CI: 0.28-0.73). CONCLUSIONS: Our study showed a significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19. The observed prognostic benefit was greater in patients with previous coronary or extracardiac atherosclerotic disease.

Multisite, mixed methods study to validate 10 maternal health system and policy indicators in Argentina, Ghana and India: a research protocol.

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.

Progesterone receptor isoform ratio dictates antiprogestin/progestin effects on breast cancer growth and metastases: A role for NDRG1.

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.