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Introduction In the US, there are striking inequities in maternal health outcomes between racial and ethnic groups. Community-based organizations (CBOs) provide social support services that are critical in addressing the needs of clients of color during and after pregnancy. Methods We conducted a descriptive, cross-sectional mixed methods study of CBOs in Greater Boston that provide social support services to pregnant and postpartum clients. In May–August 2020, we administered an online survey about organizational characteristics, client population, and services offered. In July–August 2020, we conducted semi-structured interviews focused on services provided, gaps in services, and the impact of structural racism on clients. We used descriptive statistics to characterize CBOs and services and used thematic analysis to extract themes from the qualitative data. Results A total of 21 unique CBOs participated with 17 CBOs completing the survey and 14 participating in interviews. CBOs served between 10 and 35,000 pregnant and postpartum clients per year (median = 200), and about half (n = 8) focused their programming on pregnant and postpartum clients. The most significant gaps in social support services were housing and childcare. Respondents identified racism and lack of coordination among organizations as the two primary barriers to accessing social support. Discussion CBOs face multiple challenges to providing social support to pregnant and postpartum clients of color, and significant gaps exist in the types of services currently provided. Improved coordination among CBOs and advocacy efforts to develop community-informed solutions are needed to reduce barriers to social support.

Community-based organizations are uniquely positioned to address critical gaps in social support that contribute to inequities in maternal health. Using a human-centered design process, we held 3 design workshops with members of 15 organizations in Greater Boston, including community-based organizations, allied hospital systems, and public health departments, to assess proposed solutions for gaps in social support services during pregnancy and the first year after childbirth. The workshops focused on solutions to problems that emerged from a mixed-methods research study with community-based organizations that provide social support services; workshop attendees explored facilitators and barriers to implementing solutions. Key considerations included colocation of solutions, shared ownership of program and client data, decision making about triage and referrals, and strengthening coordination of existing programs. Collaborative design workshops surfaced potential solutions to improve coordination of services, which require addressing structural and interpersonal racism in Greater Boston.

Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (

ImportanceLittle is known about changes in obstetric outcomes during the COVID-19 pandemic.ObjectiveTo assess whether obstetric outcomes and pregnancy-related complications changed during the COVID-19 pandemic.Design, Setting, and ParticipantsThis retrospective cohort study included pregnant patients receiving care at 463 US hospitals whose information appeared in the PINC AI Healthcare Database. The relative differences in birth outcomes, pregnancy-related complications, and length of stay (LOS) during the pandemic period (March 1, 2020, to April 30, 2021) were compared with the prepandemic period (January 1, 2019, to February 28, 2020) using logistic and Poisson models, adjusting for patients’ characteristics, and comorbidities and with month and hospital fixed effects.ExposuresCOVID-19 pandemic period.Main Outcomes and MeasuresThe 3 primary outcomes were the relative change in preterm vs term births, mortality outcomes, and mode of delivery. Secondary outcomes included the relative change in pregnancy-related complications and LOS.ResultsThere were 849 544 and 805 324 pregnant patients in the prepandemic and COVID-19 pandemic periods, respectively, and there were no significant differences in patient characteristics between periods, including age (≥35 years: 153 606 [18.1%] vs 148 274 [18.4%]), race and ethnicity (eg, Hispanic patients: 145 475 [17.1%] vs 143 905 [17.9%]; White patients: 456 014 [53.7%] vs 433 668 [53.9%]), insurance type (Medicaid: 366 233 [43.1%] vs 346 331 [43.0%]), and comorbidities (all standardized mean differences Conclusions and RelevanceDuring the COVID-19 pandemic, there were increased odds of maternal death during delivery hospitalization, cardiovascular disorders, and obstetric hemorrhage. Further efforts are needed to ensure risks potentially associated with the COVID-19 pandemic do not persist beyond the current state of the pandemic.

In Mexico, over the last decade, more non-physician medical professionals have been participating in birth care according to recent federal regulations. So far, very few sites have been able to implement birth care models where midwives and obstetric nurses participate. We describe the experience of a group of intern obstetric nurses participating in a model that provides respectful birth care to rural populations, managed by an international NGO in partnership with the Ministry of Health of Chiapas, Mexico. We conducted a case study including individual interviews and focus group discussions with obstetric nurse interns participating in the Compañeros En Salud programme over four years from 2016 to 2019. We applied targeted content analysis to the qualitative data. There were 28 participants from 4 groups of interns. Informants expressed their opinions in four areas: (a) training as a LEO, (b) training experience at CES, (c) LEO role in health care delivery; and (d) LEOs' perspectives about respectful maternity care. Interns identified gaps in their training including a higher load of theoretical content vs practical experience, as well as little supervision of clinical care in public hospitals. Their adaptation to the health services model has increased over time, and recent classes acknowledge the difficulties that earlier ones had to confront, including the challenging interactions with hospital staff. Interns have incorporated the value of respectful birth care and their role to protect this right in rural populations. Findings could be useful to call for the expansion of the model in public birth centres.

Medical librarians collaborate with physicians and other healthcare professionals to improve the quality and accessibility of medical information, which includes assembling the best evidence to advance health equality through teaching and research. This column brings together brief cases highlighting the experiences and perspectives of medical librarians, educators, and healthcare professionals using their organizational, pedagogical, and information-analysis skills to advance health equality indexing.

Background Despite the growing number of patients with limited English proficiency in the United States, not all medical schools offer medical language courses to train future physicians in practicing language-concordant care. Little is known about the long-term use of non-English languages among physicians who took language courses in medical school. We conducted a cross-sectional study to characterize the professional language use of Harvard Medical School (HMS) alumni who took a medical language course at HMS and identify opportunities to improve the HMS Medical Language Program. Methods Between October and November 2019, we sent an electronic survey to 803 HMS alumni who took a medical language course at HMS between 1991 and 2019 and collected responses. The survey had questions about the language courses and language use in the professional setting. We analyzed the data using descriptive statistics and McNemar’s test for comparing proportions with paired data. The study was determined not to constitute human subjects research. Results The response rate was 26% (206/803). More than half of respondents (n = 118, 57%) cited their desire to use the language in their future careers as the motivation for taking the language courses. Twenty-eight (14%) respondents indicated a change from not proficient before taking the course to proficient at the time of survey whereas only one (0.5%) respondent changed from proficient to not proficient (McNemar’s p-value n = 113, 56%) reported that clinical electives abroad influenced their cultural understanding of the local in-country population and their language proficiency. Only 13% (n = 27) of respondents have worked in a setting that required formal assessments of non-English language proficiency. Conclusions HMS alumni of the Medical Language Program reported improved language proficiency after the medical language courses’ conclusion, suggesting that the courses may catalyze long-term language learning. We found that a majority of respondents reported that the medical language courses influenced their desire to work with individuals who spoke the language of the courses they took. Medical language courses may equip physicians to practice language-concordant care in their careers.

IntroductionThe WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia.Methods and analysisENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at Ethics and disseminationENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders.Registration numberISRCTN15116516.

IntroductionReproductive injustices such as forced sterilization, preventable maternal morbidity and mortality, restricted access to family planning services, and policy-driven environmental violence undermine reproductive autonomy and health outcomes, with disproportionate impact on historically marginalized communities. However, curricula focused on reproductive justice (RJ) are lacking in medical education.MethodsWe designed a novel, interactive, case-based RJ curriculum for postclerkship medical students. This curriculum was created using published guidelines on best practices for incorporating RJ in medical education. The session included a prerecorded video on the history of RJ, an article, and four interactive cases. Students engaged in a 2-hour small-group session, discussing key learning points of each case. We evaluated the curriculum's impact with a pre- and postsurvey and focus group.ResultsSixty-eight students participated in this RJ curriculum in October 2020 and March 2021. Forty-one percent of them completed the presurvey, and 46% completed the postsurvey. Twenty-two percent completed both surveys. Ninety percent of respondents agreed that RJ was relevant to their future practice, and 87% agreed that participating in this session would impact their clinical practice. Most respondents (81%) agreed that more RJ content is needed. Focus group participants appreciated the case-based, interactive format and the intersectionality within the cases.DiscussionThis interactive curriculum is an innovative and effective way to teach medical students about RJ and its relevance to clinical practice. Walking alongside patients as they accessed reproductive health care in a case-based curriculum improved students' comfort and self-reported knowledge on several RJ topics.

Dysphagia occurs commonly in the intensive care unit (ICU). Despite the clinical relevance, there is little worldwide research on prevention, assessment, evaluation, and/or treatment of dysphagia for ICU patients. We aimed to gain insight into this international knowledge gap. We conducted a multi-center, international online cross-sectional survey of adult ICUs. Local survey distribution champions were recruited through professional and personal networks. The survey was administered from November 2017 to June 2019 with three emails and a final telephone reminder. Responses were received from 746 ICUs (26 countries). In patients intubated > 48 h, 17% expected a > 50% chance that dysphagia would develop. This proportion increased to 43% in patients intubated > 7 days, and to 52% in tracheotomized patients. Speech-language pathologist (SLP) consultation was available in 66% of ICUs, only 4% reported a dedicated SLP. Although 66% considered a routine post-extubation dysphagia protocol important, most (67%) did not have a protocol. Few ICUs routinely assessed for dysphagia after 48 h of intubation (30%) or tracheostomy (41%). A large proportion (46%) used water swallow screening tests to determine aspiration, few (8%) used instrumental assessments (i.e., flexible endoscopic evaluation of swallowing). Swallowing exercises were used for dysphagia management by 30% of ICUs. There seems to be limited awareness among ICU practitioners that patients are at risk of dysphagia, particularly as ventilation persists, protocols, routine assessment, and instrumental assessments are generally not used. We recommend the development of a research agenda to increase the quality of evidence and ameliorate the implementation of evidence-based dysphagia protocols by dedicated SLPs.

To assess trends in childbirth at a hospital-birth center among women living in Compañeros En Salud (CES)-affiliated communities in Chiapas, Mexico and explore barriers to childbirth care. Our hypothesis was that despite interventions to support and incentivize childbirth at the hospital-birth center, the proportion of births at the hospital-birth center among women from Compañeros En Salud-affiliated communities has not significantly changed after two years. We suspected that this may be due to structural factors impacting access to care and/or perceptions of care impacting desire to deliver at the birth center.This explanatory mixed-methods study included a retrospective Compañeros En Salud maternal health census review followed by quantitative surveys and semi-structured qualitative interviews.Participants were women living in municipalities in the mountainous Sierra Madre region of Chiapas, Mexico who received prenatal care in one of 10 community clinics served by Compañeros En Salud. Participants were recruited if they gave birth anywhere other than the primary-level rural hospital and adjacent birth center supported by Compañeros En Salud, either at home or at other facilities.We compared rates of birth at the hospital-birth center, other health facilities, and at home from 2017-2018. We conducted surveys and interviews with women who gave birth between January 2017-July 2018 at home or at facilities other than the hospital-birth center to understand perceptions of care and decision-making surrounding childbirth location.We found no significant difference in rates of overall number of women birthing at the hospital-birth center from Compañeros En Salud-affiliated communities between 2017 and 2018 (p=0.36). Analysis of 158 surveys revealed distance (30.4%), time (27.8%), and costs (25.9%) as reasons for not birthing at the hospital-birth center. From 27 interviews, negative perceptions and experiences of the hospital included low-quality and disrespectful care, low threshold for medical interventions, and harm and suffering. Partners or family members influenced most decisions about childbirth location.Interventions to minimize logistical barriers may not be sufficient to overcome distance and perceptions of low-quality, disrespectful care.Better understanding of complex decision-making around childbirth will guide Compañeros En Salud in developing interventions to further meet the needs and preferences of birthing women in rural Chiapas.

Background Low birthweight (LBW) ( Methods A comparative pre-post study was performed in selected rural health facilities located in West Gojjam and South Gondar zones. At baseline, a retrospective review of delivery records from February to May 2018 was performed in 14 health centers to collect birthweight data. A birthweight QI initiative was introduced in August 2019, which included provision of high-quality digital infant weight scales (precision 5 g), routine calibration, training in birth weighing and data recording, and routine field supervision. After the QI implementation, birthweight data were prospectively collected from late August to early September 2019, and December 2019 to June 2020. Data quality, as measured by heaping (weights at exact multiples of 500 g) and rounding to the nearest 100 g, and the prevalence of LBW were calculated before and after QI implementation. Results We retrospectively reviewed 1383 delivery records before the QI implementation and prospectively measured 1371 newborn weights after QI implementation. Heaping was most frequently observed at 3000 g and declined from 26% pre-initiative to 6.7% post-initiative. Heaping at 2500 g decreased from 5.4% pre-QI to 2.2% post-QI. The percentage of rounding to the nearest 100 g was reduced from 100% pre-initiative to 36.5% post-initiative. Before the QI initiative, the prevalence of recognized LBW was 2.2% (95% confidence interval [CI]: 1.5–3.1) and after the QI initiative increased to 11.7% (95% CI: 10.1–13.5). Conclusions A QI intervention can improve the quality of birthweight measurements, and data measurement quality may substantially affect estimates of LBW prevalence.

International audience; Human induced environmental change may require rapid adaptation of plant populations and crops, but the genomic basis of environmental adaptation remain poorly understood. We analysed polymorphic loci from the perennial crop Medicago sativa (alfalfa or lucerne) and the annual legume model species M. truncatula to search for a common set of candidate genes that might contribute to adaptation to abiotic stress in both annual and perennial Medicago species. We identified a set of candidate genes of adaptation associated with environmental gradients along the distribution of the two Medicago species. Candidate genes for each species were detected in homologous genomic linkage blocks using genome-environment (GEA) and genome-phenotype association analyses. Hundreds of GEA candidate genes were species-specific, of these, 13.4% (M. sativa) and 24% (M. truncatula) were also significantly associated with phenotypic traits. A set of 168 GEA candidates were shared by both species, which was 25.4% more than expected by chance. When combined, they explained a high proportion of variance for certain phenotypic traits associated with adaptation. Genes with highly conserved functions dominated among the shared candidates and were enriched in gene ontology terms that have shown to play a central role in drought avoidance and tolerance mechanisms by means of cellular shape modifications and other functions associated with cell homeostasis. Our results point to the existence of a molecular basis of adaptation to abiotic stress in Medicago determined by highly conserved genes and gene functions. We discuss these results in light of the recently proposed omnigenic model of complex traits.

OBJECTIVE. The purpose of this study was to evaluate the technologist productivity and accuracy in assigning protocols for abdominal CT and MRI examinations compared with a standard work flow whereby protocols are assigned by physicians. MATERIALS AND METHODS. In this quality improvement project at a large academic medical center, two CT technologists and two MRI technologists assigned protocols for examinations during a 15-week study period. The primary outcome measure was mean number of protocols assigned by technologists per hour. Secondary outcome measures were proportion of examinations with protocols assigned by technologists and rate of filing of quality assurance reports for protocols completed by technologists. A two-tailed t test was used to compare mean number of protocols; a chi-square test was used to compare proportions between CT and MRI. RESULTS. The mean number of protocols assigned by technologists per hour was not different between CT and MRI (CT, 22/h; MRI, 19/h; p = 0.28). CT and MRI technologist protocols accounted for 1650 of 4867 (33.9%) CT examinations (range, 23-275 per week) and 569 of 2388 (23.8%) MRI examinations (range, 0-95 per week) (p < 0.001). Radiologist quality assurance reports on inaccurate protocols were rare: three for CT (3/1650 [0.18%]), five for MRI (5/569 [0.88%]) (p = 0.017). A retrospective review of randomly selected CT and MRI protocols revealed no errors (80/80 correct). No patients were called back for repeat imaging due to protocol error. CONCLUSION. Technologists can efficiently and accurately assign protocols for abdominal CT and MRI examinations at an academic medical center, leading to increased radiologist time spent on other value-added activities.

The rising trend in pregnancy-related deaths during the past 2 decades in the United States stands out among other high-income countries where pregnancy-related deaths are declining. Cardiomyopathy and other cardiovascular conditions, hemorrhage, and other chronic medical conditions are all important causes of death. Unintentional death from violence, overdose, and self-harm are emerging causes that require medical and public health attention. Significant racial/ethnic inequities exist in pregnancy care with non-Hispanic black women incurring 3 to 4 times higher rates of pregnancy-related death than non-Hispanic white women. Varied terminology and lack of standardized methods for identifying maternal deaths in the United States have resulted in nuanced data collection and interpretation challenges. State maternal mortality review committees are important mechanisms for capturing and interpreting data on cause, timing, and preventability of maternal deaths. Importantly, a thorough standardized review of each maternal death leads to recommendations to prevent future pregnancy-associated deaths. Key interventions to improve maternal health outcomes include 1) integrating multidisciplinary care for women with high-risk comorbidities during preconception care, pregnancy, postpartum, and beyond; 2) addressing structural racism and the social determinants of health; 3) implementing hospital-wide safety bundles with team training and simulation; 4) providing patient education on early warning signs for medical complications of pregnancy; and 5) regionalizing maternal levels of care so that women with risk factors are supported when delivering at facilities with specialized care teams.

Objective To evaluate changes in quality of care after implementing an adapted safe childbirth checklist (SCC) in Chiapas, Mexico. Methods A convergent mixed-methods study was conducted among 447 women in labor who attended a rural community hospital between September 1, 2016, and June 30, 2017. Logistic regression analysis was used to evaluate adherence to evidence-based practices over time, adjusting for provider. Participants were surveyed about their perceptions of care after hospital discharge. A purposefully sampled subgroup also completed in-depth interviews. Thematic analysis was performed to evaluate perceptions of care. Results 384 (85.9%) women were attended by staff that used the adapted SCC during delivery. Of these, 221 and 28 completed the hospital discharge survey and in-depth interview, respectively. Adherence with offering a birth companion (odds ratio [OR] 3.06, 95% CI 1.40-6.68), free choice of birth position (2.75, 1.21-6.26), and immediate skin-to-skin contact (4.53, 1.97-10.39) improved 6-8 months after implementation. Participants' perceived quality of care improved over time. Provider communication generated positive perceptions. Reprimanding women for arriving in early labor or complaining of pain generated negative perceptions. Conclusion Use of the adapted SCC improved quality of care through increased adherence with essential and respectful delivery practices.

* Abbreviations: RCT: : randomized controlled trial ToC: : theory of change WHO: : World Health Organization Complex interventions—those that contain several interacting components—to improve clinical outcomes and population health are growing because of the increasing recognition that multilevel approaches are needed to solve complex problems in health systems and care delivery. (1) In maternal and neonatal health, complex interventions are needed to improve quality of care. Yet few studies of these complex interventions are powered to detect true differences in mortality because of the numbers needed for a relatively rare outcome, such as maternal mortality. Although perinatal mortality is more common, large sample sizes are still required. Studies are often powered to examine outcomes or process measures proximal to mortality, such as morbidity or complications that could lead to mortality. The BetterBirth Trial was one of the largest cluster randomized controlled trials (RCTs) to target maternal and perinatal mortality as primary outcomes. Given its scale, this trial has led to important lessons learned that could be applied to other large-scale studies with complex interventions in maternal and newborn health. Many epidemiology and biostatistics textbooks have described how to theoretically design RCTs to maximize scientific rigor. (2) However, there are few, if any, resources on how to actually implement complex interventions on a large scale, evaluate their impact, and disseminate the results. (3) Balancing an unbiased and robust study design with the reality of implementing a complex intervention in the real world can pose ongoing challenges for research teams. Some generally accepted best practices to minimize common challenges of trial implementation do exist, such as for institutional review board navigation, site selection, and stakeholder engagement. This perspective reflects on the experience of the BetterBirth Trial and provides insights around best practices of important components of trial design and implementation that may be initially overlooked. The BetterBirth Trial was a matched-pair cluster RCT designed to establish whether the …

OBJECTIVE To understand the prevalence of intrapartum oxytocin use, assess associated perinatal and maternal outcomes, and evaluate the impact of a WHO Safe Childbirth Checklist intervention on oxytocin use at primary-level facilities in Uttar Pradesh, India. DESIGN Secondary analysis of a cluster-randomised controlled trial. SETTING Thirty Primary and Community public health facilities in Uttar Pradesh, India from 2014 to 2017. POPULATION Women admitted to a study facility for childbirth at baseline, 2, 6 or 12 months after intervention initiation. METHODS The BetterBirth intervention aimed to increase adherence to the WHO Safe Childbirth Checklist. We used Rao-Scott Chi-square tests to compare (1) timing of oxytocin use between study arms and (2) perinatal mortality and resuscitation of infants whose mothers received intrapartum oxytocin versus who did not. MAIN OUTCOME MEASURES Intrapartum and postpartum oxytocin administration, perinatal mortality, use of neonatal bag and mask. RESULTS We observed 5484 deliveries. At baseline, intrapartum oxytocin was administered to 78.2% of women. Two months after intervention initiation, intrapartum oxytocin (I) was administered to 32.1% of women compared with 70.6% in the control (C) (P

This study sought to better understand specific factors contributing to fatigue in survivors of pediatric cancer and hematopoietic stem cell transplant (HSCT). As part of a larger study evaluating long-term psychosocial functioning of pediatric cancer survivors, N = 87 participants completed measures assessing fatigue and emotional and behavioral functioning. Chart abstraction was used to catalog diagnosis, treatments received, treatment intensity, and late effects. Results suggest clinically significant fatigue in n = 4 (4.6%) of survivors participating in this study. Fatigue was greater for participants with more recent diagnoses and who were more recently off treatment and was positively associated with parent and self-report of internalizing (emotional) and externalizing (behavioral) symptoms. Participants with more severe late effects suffered greater fatigue; however, fatigue was not associated with treatment intensity or therapy type. Fatigue is an important variable to consider in evaluating the social, emotional, behavioral, and physical well-being of cancer and HSCT survivors. Interventions are needed to address fatigue directly, while also addressing both contributing factors to fatigue and potential negative outcomes that result from fatigue in survivorship.

BackgroundP-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function.ResultsWe have identified a “functional core” microbiome of the intestinal gut community, specifically genera within theClostridiaandBacilliclasses, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression.ConclusionOverall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation.

While some medical indications for cesarean delivery are clear, subjective provider and patient factors contribute to the rising cesarean delivery rates and marked disparities between racial/ethnic groups. We aimed to determine the association between language preference and risk of primary cesarean delivery.We conducted a retrospective cohort study of nulliparous, term, singleton, vertex (NTSV) deliveries of patients over 18 years old from 2011-2016 at an academic medical center, supplemented with data from the Massachusetts Department of Public Health. We used modified Poisson regression with robust error variance to calculate risk ratios for cesarean delivery between patients with English language preference and other language preference, with secondary outcomes of Apgar score, maternal readmission, blood transfusion, and NICU admission.Of the 11,298 patients included, 10.3% reported a preferred language other than English, including Mandarin and Cantonese (61.7%), Portuguese (9.7%), and Spanish (7.5%). The adjusted risk ratio for cesarean delivery among patients with a language preference other than English was 0.85 (95% CI 0.72-0.997; p = 0.046) compared to patients with English language preference. No significant differences in risk of secondary outcomes between English and other language preference were found.After adjusting for confounders, this analysis demonstrates a decreased risk of cesarean delivery among women who do not have an English language preference at one institution. This disparity in cesarean delivery rates in an NTSV population warrants future research, raising the question of what clinical and social factors may be contributing to these lower cesarean delivery rates.

Health professions educators continuously adapt curricular content in response to new scientific knowledge but can struggle to incorporate content about current social issues that profoundly affect students and learning environments. This article offers recommendations to support innovation and action as students and faculty grapple with ongoing unrest in the United States, including racism, murders of Black people by police, and COVID-19.

BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of

Objective:Acute peripheral arterial events, such as aortic dissection, carotid artery dissection, vertebral artery dissection, and ruptured renoviseral aneurysms, have been reported during pregnancy in case series, but there is a paucity of population-based data. This study sought to establish pregnancy and preeclampsia as risk factors for acute peripheral arterial events.Approach and Results:All women who gave birth between 1998 and 2020 within a multicenter health care system were identified. Births that occurred in women 50 years of age were excluded. Primary outcome was any acute peripheral arterial event that was symptomatic or required intervention. Cox regression model was used to evaluate the association between vascular events and pregnancy as a time-varying covariate. The pregnancy exposure period was from the estimated date of conception to 3 months postpartum. There were 277 697 pregnancies (81.3% deliveries, 17.0% abortions, and 1.7% ectopics) among 176 635 women with 1.68 million patient-years of total follow-up (median, 7.9 years; interquartile range, 2.4–16.2). Preeclampsia complicated 5.3% of pregnancies; 67 790 of 225 763 (30.0%) deliveries were delivered by cesarean. Ninety-six acute arterial events occurred during follow-up, of which 24 occurred during pregnancy, including the postpartum period. Pregnancy (hazard ratio, 1.85 [95% CI, 1.01–3.38];P=0.046) and preeclampsia (hazard ratio, 10.9 [95% CI, 5.24–22.7];PConclusions:While taking into account limitations from estimating conception and outcome dates, pregnancy, especially when complicated by preeclampsia, is associated with an increased risk of acute peripheral arterial events.

Curable sexually transmitted infections in pregnant women may cause poor maternal and newborn outcomes worldwide. Syndromic management is practiced in many settings yet fails to identify most infections. Etiologic screening has promise, but further effectiveness and cost-effectiveness studies are needed. Supplemental digital content is available in the text., Background Sexually transmitted infections (STI), such as chlamydial, gonorrheal, and trichomonal infections, are prevalent in pregnant women in many countries and are widely reported to be associated with increased risk of poor maternal and neonatal outcomes. Syndromic STI management is frequently used in pregnant women in low- and middle-income countries, yet its low specificity and sensitivity lead to both overtreatment and undertreatment. Etiologic screening for chlamydial, gonorrheal, and/or trichomonal infection in all pregnant women combined with targeted treatment might be an effective intervention. However, the evidence base is insufficient to support the development of global recommendations. We aimed to describe key considerations and knowledge gaps regarding chlamydial, gonorrheal, and trichomonal screening during pregnancy to inform future research needed for developing guidelines for low- and middle-income countries. Methods We conducted a narrative review based on PubMed and clinical trials registry searches through January 20, 2020, guidelines review, and expert opinion. We summarized our findings using the frameworks adopted by the World Health Organization for guideline development. Results Adverse maternal-child health outcomes of potential interest are wide-ranging and variably defined. No completed randomized controlled trials on etiologic screening and targeted treatment were identified. Evidence from observational studies was limited, and trials of presumptive STI treatment have shown mixed results. Subgroups that might benefit from specific recommendations were identified. Evidence on harms was limited. Cost-effectiveness was influenced by STI prevalence and availability of testing infrastructure and high-accuracy/low-cost tests. Preliminary data suggested high patient acceptability. Discussion Preliminary data on harms, acceptability, and feasibility and the availability of emerging test technologies suggest that etiologic STI screening deserves further evaluation as a potential tool to improve maternal and neonatal health outcomes worldwide.

Crisis standards of care (CSOC) scores designed to allocate scarce resources during the COVID-19 pandemic could exacerbate racial disparities in health care.To analyze the association of a CSOC scoring system with resource prioritization and estimated excess mortality by race, ethnicity, and residence in a socially vulnerable area.This retrospective cohort analysis included adult patients in the intensive care unit during a regional COVID-19 surge from April 13 to May 22, 2020, at 6 hospitals in a health care network in greater Boston, Massachusetts. Participants were scored by acute severity of illness using the Sequential Organ Failure Assessment score and chronic severity of illness using comorbidity and life expectancy scores, and only participants with complete scores were included. The score was ordinal, with cutoff points suggested by the Massachusetts guidelines.Race, ethnicity, Social Vulnerability Index.The primary outcome was proportion of patients in the lowest priority score category stratified by self-reported race. Secondary outcomes were discrimination and calibration of the score overall and by race, ethnicity, and neighborhood Social Vulnerability Index. Projected excess deaths were modeled by race, using the priority scoring system and a random lottery.Of 608 patients in the intensive care unit during the study period, 498 had complete data and were included in the analysis; this population had a median (IQR) age of 67 (56-75) years, 191 (38.4%) female participants, 79 (15.9%) Black participants, and 225 patients (45.7%) with COVID-19. The area under the receiver operating characteristic curve for the priority score was 0.79 and was similar across racial groups. Black patients were more likely than others to be in the lowest priority group (12 [15.2%] vs 34 [8.1%]; P = .046). In an exploratory simulation model using the score for ventilator allocation, with only those in the highest priority group receiving ventilators, there were 43.9% excess deaths among Black patients (18 of 41 patients) and 28.6% (58 of 203 patients among all others (P = .05); when the highest and intermediate priority groups received ventilators, there were 4.9% (2 of 41 patients) excess deaths among Black patients and 3.0% (6 of 203) among all others (P = .53). A random lottery resulted in more excess deaths than the score.In this study, a CSOC priority score resulted in lower prioritization of Black patients to receive scarce resources. A model using a random lottery resulted in more estimated excess deaths overall without improving equity by race. CSOC policies must be evaluated for their potential association with racial disparities in health care.

ObjectiveThe WHO Safe Childbirth Checklist (SCC) is a promising initiative for safety in childbirth care, but the evidence about its impact on clinical outcomes is limited. This study analysed the impact of SCC on essential birth practices (EBPs), obstetric complications and adverse events (AEs) in hospitals of different profiles.DesignQuasi-experimental, time-series study and pre/post intervention.SettingTwo hospitals in North-East Brazil, one at a tertiary level (H1) and another at a secondary level (H2).Participants1440 women and their newborns, excluding those with congenital malformations.InterventionsThe implementation of the SCC involved its cross-cultural adaptation, raising awareness with videos and posters, learning sessions about the SCC and auditing and feedback on adherence indicators.Primary and secondary outcome measuresSimple and composite indicators related to seven EBPs, 3 complications and 10 AEs were monitored for 1 year, every 2 weeks, totalling 1440 observed deliveries.ResultsThe checklist was adopted in 83.3% (n=300) of deliveries in H1 and in 33.6% (n=121) in H2. The hospital with the highest adoption rate for SCC (H1) showed greater adherence to EBPs (improvement of 50.9%;pConclusionsA multifaceted SCC-based intervention can be effective in improving adherence to EBPs and clinical outcomes in childbirth. The context and adherence to the SCC seem to modulate its impact, working better in a hospital of higher complexity.

Robotic wheelchair research and development is a growing sector. This article introduces a robotic wheelchair taxonomy, and a readiness model supported by a mini-review. The taxonomy is constructed by power wheelchair and, mobile robot standards, the ICF and, PHAATE models. The mini-review of 2797 articles spanning 7 databases produced 205 articles and 4 review articles that matched inclusion/exclusion criteria. The review and analysis illuminate how innovations in robotic wheelchair research progressed and have been slow to translate into the marketplace.

This anthropological study explores why more women in the rural Sierra Madre region of Chiapas, Mexico birth at home rather than at the hospital. Between January and May of 2014, the primary investigator conducted in-depth, semi-structured interviews with twenty-six interlocutors: six parteras (home birth attendants), nine pregnant women, four mothers, four healthcare providers, and three local government leaders. Participant observation occurred in the health clinic, participants' homes, and other spaces in a community with a population of 1,188 people. Drawing from narrative analysis, the findings suggest that women face structural obstacles to accessing high-quality childbirth care, which lead them to give birth at home instead of the hospital. These obstacles include financial barriers in obtaining facility-based care and poor quality of care, such as mistreatment in the facility. The study highlights the importance of centreing community narratives in healthcare programming in order to bridge the implementation gap between women in rural communities, healthcare workers, and policymakers.

Transforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-β signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-β pathway is critical in endothelial-to-mesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-β and related signaling in the endothelium. This study applied a gain- and loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-β signaling and has a key role in EndMT, targeting TGFB2 and SMAD2. Overexpression of miR-148b increased EC migration, proliferation, and angiogenesis, whereas its inhibition promoted EndMT. Cytokine challenge decreased miR-148b levels in ECs while promoting EndMT through the regulation of SMAD2. Finally, in a mouse model of skin wound healing, delivery of miR-148b mimics promoted wound vascularization and accelerated closure. In contrast, inhibition of miR-148b enhanced EndMT in wounds, resulting in impaired wound closure that was reversed by SMAD2 silencing. Together, these results demonstrate for the first time that miR-148b is a key factor controlling EndMT and vascularization. This opens new avenues for therapeutic application of miR-148b in vascular and tissue repair., Graphical Abstract, The TGF-β pathway is deemed to be critical for endothelial cell function. Herein, Miscianinov et al. demonstrated that miR-148b is a novel regulator of the TGF-β signaling. Delivery of miR-148b mimics promotes angiogenesis and accelerates skin wound healing. Conversely, inhibition of miR-148b enhances endothelial-mesenchymal transition leading to impaired wound closure.

Maternal morbidity and mortality, important indicators of healthcare quality both nationally and internationally, have gained increasing public attention in the United States (U.S.). The U.S. has the highest rate of maternal mortality among high-income countries; notably, this rate has more than doubled since 1990. Black women in the U.S. die at three to four times the rate of white women from pregnancy-related complications, one of the widest of all racial disparities in women's health. Medical complications, including cardiovascular disease and hypertensive disorders in pregnancy, remain leading contributors to disparities in maternal outcomes including pregnancy-related deaths. However, an under-explored opportunity for improvement is the failure to transition from obstetrical to primary care, which limits optimizing postpartum health. Health system approaches, community-based interventions, and policy solutions that facilitate transitions of care may be critical to eliminating persistent disparities in maternal outcomes.

The political environment and legal decisions in the United States (US) can impact lives around the globe. A recent attack on women’s sexual and reproductive health and rights (SRHR) occurred in Ju...

OBJECTIVE To describe various work models for obstetrics and gynecology global health faculty affiliated with academic medical centers and to identify barriers and opportunities for pursuing global health work. METHODS A mixed-methods study was conducted in 2016 among obstetrics and gynecology faculty and leaders from seven academic medical institutions in Boston, Massachusetts. Global health faculty members were invited to complete an online survey about their work models and to participate in semistructured interviews about barriers and facilitators of these models. Department chairs and residency directors were asked to participate in interviews. RESULTS The survey response rate among faculty was 65.6% (21/32), of which 76.2% (16/21) completed an interview. Five department leaders (45.5% [5/11]) participated in an interview. Faculty described a range of work models with varied time and compensation, but only one third reported contracted time for global health work. The most common barriers to global health work were financial constraints, time limitations, lack of mentorship, need for specialized training, and maintenance of clinical skills. Career satisfaction, creating value for the obstetrics and gynecology department, and work model flexibility were the most important facilitators of sustainable global health careers. CONCLUSION The study identified challenges and opportunities to creating flexible and sustainable work models for academic obstetrics and gynecology clinicians engaged in global health work. Additional research and innovation are needed to identify work models that allow for sustainable careers in global women's health. There are opportunities to create professional standards and models for academic global health work in the obstetrics and gynecology specialty.

The Communities Advancing Resilience Toolkit (CART)©* is a community-driven, publicly available, theory-based, and evidence-informed community intervention designed to build community resilience to disasters and other adversities. Based on principles of participatory action research, CART applications contribute to community resilience by encouraging and supporting community participation and cooperation, communication, self-awareness, and critical reflection. The primary value of CART lies in its ability to stimulate analysis, collaboration, skill building, resource sharing, and purposeful action. In addition to generating community assessment data, CART can be used as a vehicle for delivering other interventions and creating sustainable capacity within communities. Two models for CART implementation are described.

We live in a world of incredible linguistic diversity; nearly 7000 languages are spoken globally and at least 350 are spoken in the United States. Language-concordant care enhances trust between patients and physicians, optimizes health outcomes, and advances health equity for diverse populations. However, historical and contemporary trauma have impaired trust between communities of color, including immigrants with limited English proficiency, and physicians in the U.S. Threats to informed consent among patients with limited English proficiency persist today. Language concordance has been shown to improve care and serves as a window to broader social determinants of health that disproportionately yield worse health outcomes among patients with limited English proficiency. Language concordance is also relevant for medical students engaged in health care around the world. Global health experiences among medical and dental students have quadrupled in the last 30 years. Yet, language proficiency and skills to address cultural aspects of clinical care, research and education are lacking in pre-departure trainings. We call on medical schools to increase opportunities for medical language courses and integrate them into the curriculum with evidence-based teaching strategies, content about health equity, and standardized language assessments. The languages offered should reflect the needs of the patient population both where the medical school is located and where the school is engaged globally. Key content areas should include how to conduct a history and physical exam; relevant health inequities that commonly affect patients who speak different languages; cultural sensitivity and humility, particularly around beliefs and practices that affect health and wellbeing; and how to work in language-discordant encounters with interpreters and other modalities. Rigorous language assessment is necessary to ensure equity in communication before allowing students or physicians to use their language skills in clinical encounters. Lastly, global health activities in medical schools should assess for language needs and competency prior to departure. By professionalizing language competency in medical schools, we can improve patients’ trust in individual physicians and the profession as a whole; improve patient safety and health outcomes; and advance health equity for those we care for and collaborate with in the U.S. and around the world.

Celiac disease (CD) is a common chronic condition with potential adverse physical and psychosocial implications for affected children. The study purpose was to characterize health-related quality of life (HRQOL) in a large sample of pediatric patients with newly diagnosed CD using the PedsQL 4.0 Generic Core Scales, and compare it to that of healthy children and children with nonceliac gastrointestinal (GI) conditions using historic data.The PedsQL was administered to 159 children with newly diagnosed CD and their parents at either the time of diagnostic esophagogastroduodenoscopy or before their initial dietitian appointment for gluten-free diet teaching. Mean parent-report and self-report PedsQL summary and subscale scores were calculated, then compared to published means from a sample of healthy children and a sample of children with nonceliac GI symptoms using 1-sample t tests.Compared to the healthy children, those with newly diagnosed CD had lower Total Scores, Physical Health, Psychosocial Health, Emotional Functioning, and School Functioning on parent report (P 0.008) with similar findings on self-report. Within the CD sample, clinically significant scores were found in 55.9% for School Functioning, 62.7% for Physical Health, 54.4% for Emotional Functioning, 43.7% for Social Functioning, and 49% for Total Score.Children and adolescents with newly diagnosed CD had lower HRQOL than healthy children and similar HRQOL to that of patients with nonceliac GI conditions. Patients with deficits in domains such as school or emotional functioning may benefit from early interventions including a Section 504 plan or meeting with a psychologist or social worker.

Background The BetterBirth trial tested the effect of a peer coaching program around the WHO Safe Childbirth Checklist for birth attendants in primary-level facilities in Uttar Pradesh, India on a composite measure of perinatal and maternal mortality and maternal morbidity. This study aimed to examine the adherence to essential birth practices between two different cadres of birth attendants—nurses and auxiliary nurse midwives (ANMs)—during and after a peer coaching intervention for the WHO Safe Childbirth Checklist. Methods This is a secondary analysis of birth attendant characteristics, coaching visits, and behavior uptake during the BetterBirth trial through birth attendant surveys, coach observations, and independent observations. Descriptive statistics were calculated overall, and by staffing cadre (staff nurses and ANMs) for demographic characteristics. Logistic regression using the Pearson overdispersion correction (to account for clustering by site) was used to assess differences between staff nurses and ANMs in the intervention group during regular coaching (2-month time point) and 4 months after the coaching program ended (12-month time point). Results Of the 570 birth attendants who responded to the survey in intervention and control arms, 474 were staff nurses (83.2%) and 96 were ANMs (16.8%). In the intervention arm, more staff nurses (240/260, 92.3%) received coaching at all pause points compared to ANMs (40/53, 75.5%). At baseline, adherence to practices was similar between ANMs and staff nurses (~ 30%). Overall percent adherence to essential birth practices among ANMs and nurses was highest at 2 months after intervention initiation, when frequent coaching visits occurred (68.1% and 64.1%, respectively, p = 0.76). Practice adherence tapered to 49.2% among ANMs and 56.1% among staff nurses at 12 months, which was 4 months after coaching had ended (p = 0.68). Conclusions Overall, ANMs and nurses responded similarly to the coaching intervention with the greatest increase in percent adherence to essential birth practices after 2 months of coaching and subsequent decrease in adherence 4 months after coaching ended. While coaching is an effective strategy to support some aspects of birth attendant competency, the structure, content, and frequency of coaching may need to be customized according to the birth attendant training and competency. Trial registration ClinicalTrials.gov: NCT2148952; Universal Trial Number: U1111–1131-5647.

This paper reviews the extant research on the effects of contact with terrorism media coverage on psychological outcomes in youth in the context of chronic threat and conflict in Israel. The extant research is inconclusive with respect to the relationship between media contact and a variety of psychological outcomes in Israeli studies of youth exposed to ongoing threat and repeated terrorist attacks. Additional research is needed to examine potential differences in outcomes and the factors that influence youth coping and adaptation in an environment of chronic threat and extensive media coverage. Moreover, studies are needed to identify and evaluate potential parental, professional, and social strategies to enhance youth adjustment. Because political conflict in Israel is not likely to abate in the near future, the setting is ideal to conduct methodologically rigorous research including research using representative samples, prospective reporting, and longitudinal design.

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to-0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P

Objective This study explored the effects of media coverage of a terrorist incident in individuals remote from the location of a major attack who had directly experienced a prior terrorist incident. Method Directly-exposed survivors of the 1995 Oklahoma City bombing, initially studied six months after the incident, and indirectly-affected Oklahoma City community residents were assessed two to seven months after the September 11, 2001, attacks. Survivors were assessed for a diagnosis of bombing-related posttraumatic stress disorder (PTSD) at index and follow up, and emotional reactions and September 11 media behavior were assessed in all participants. Results Among the three investigated forms of media (television, radio, and newspaper), only television viewing was associated with 9/11-related posttraumatic stress reactions. Exposure to the Oklahoma City bombing was associated with greater arousal in relation to the September 11 attacks, and among survivors, having developed bombing-related PTSD was associated with higher scores on all three September 11 posttraumatic stress response clusters (intrusion, avoidance, and arousal). Although time spent watching television coverage of the September 11 attacks and fear-related discontinuation of media contact were not associated with Oklahoma City bombing exposure, discontinuing September 11 media contact due to fear was associated with avoidance/numbing in the full sample and in the analysis restricted to the bombing survivors. Conclusion Surviving a prior terrorist incident and developing PTSD in relation to that incident may predispose individuals to adverse reactions to media coverage of a future terrorist attack.

Key Points Question What is the association between delays in treatment initiation for common cancers, as are necessary in resource-limited settings and pandemic conditions, with mortality? Findings In this cohort study including 2 241 706 patients with breast, prostate, non-small cell lung, and colon cancer, generally higher all-cause mortality was associated with increasing time to treatment, although the degree varied by cancer type and stage. Patients with colon and lung cancer had the highest mortality associated with increased time to treatment. Meaning These findings emphasize the importance of timely cancer treatment, and, in contrast to current pandemic-related guidelines, support more prompt definitive treatment for intermediate-risk and high-risk prostate cancer., This cohort study of patients with breast, prostate, non-small cell lung, and colon cancer assesses the association of time from diagnosis to treatment with all-cause mortality., Importance Resource limitations because of pandemic or other stresses on infrastructure necessitate the triage of time-sensitive care, including cancer treatments. Optimal time to treatment is underexplored, so recommendations for which cancer treatments can be deferred are often based on expert opinion. Objective To evaluate the association between increased time to definitive therapy and mortality as a function of cancer type and stage for the 4 most prevalent cancers in the US. Design, Setting, and Participants This cohort study assessed treatment and outcome information from patients with nonmetastatic breast, prostate, non-small cell lung (NSCLC), and colon cancers from 2004 to 2015, with data analyzed January to March 2020. Data on outcomes associated with appropriate curative-intent surgical, radiation, or medical therapy were gathered from the National Cancer Database. Exposures Time-to-treatment initiation (TTI), the interval between diagnosis and therapy, using intervals of 8 to 60, 61 to 120, 121 to 180, and greater than 180 days. Main Outcomes and Measures 5-year and 10-year predicted all-cause mortality. Results This study included 2 241 706 patients (mean [SD] age 63 [11.9] years, 1 268 794 [56.6%] women, 1 880 317 [83.9%] White): 1 165 585 (52.0%) with breast cancer, 853 030 (38.1%) with prostate cancer, 130 597 (5.8%) with NSCLC, and 92 494 (4.1%) with colon cancer. Median (interquartile range) TTI by cancer was 32 (21-48) days for breast, 79 (55-117) days for prostate, 41 (27-62) days for NSCLC, and 26 (16-40) days for colon. Across all cancers, a general increase in the 5-year and 10-year predicted mortality was associated with increasing TTI. The most pronounced mortality association was for colon cancer (eg, 5 y predicted mortality, stage III: TTI 61-120 d, 38.9% vs. 181-365 d, 47.8%), followed by stage I NSCLC (5 y predicted mortality: TTI 61-120 d, 47.4% vs 181-365 d, 47.6%), while survival for prostate cancer was least associated (eg, 5 y predicted mortality, high risk: TTI 61-120 d, 12.8% vs 181-365 d, 14.1%), followed by breast cancer (eg, 5 y predicted mortality, stage I: TTI 61-120 d, 11.0% vs. 181-365 d, 15.2%). A nonsignificant difference in treatment delays and worsened survival was observed for stage II lung cancer patients—who had the highest all-cause mortality for any TTI regardless of treatment timing. Conclusions and Relevance In this cohort study, for all studied cancers there was evidence that shorter TTI was associated with lower mortality, suggesting an indirect association between treatment deferral and mortality that may not become evident for years. In contrast to current pandemic-related guidelines, these findings support more timely definitive treatment for intermediate-risk and high-risk prostate cancer.

Caesarean delivery rates in Mexico are among the highest in the world. Given heightened public and professional awareness of this problem and the updated 2014 national guidelines to reduce the frequency of caesarean delivery, we analysed trends in caesarean delivery by type of facility in Mexico from 2008 to 2017. We obtained birth-certificate data from the Mexican General Directorate for Health Information and grouped the total number of vaginal and caesarean deliveries into five categories of facility: health-ministry hospitals; private hospitals; government employment-based insurance hospitals; military hospitals; and other facilities. Delivery rates were calculated for each category nationally and for each state. On average, 2 114 630 (95% confidence interval, CI: 2 061 487-2 167 773) live births occurred nationally each year between 2008 and 2017. Of these births, 53.5% (1 130 570; 95% CI: 1 108 068-1 153 072) were vaginal deliveries, and 45.3% (957 105; 95% CI: 922 936-991 274) were caesarean deliveries, with little variation over time. During the study period, the number of live births increased by 4.4% (from 1 978 380 to 2 064 507). The vaginal delivery rate decreased from 54.8% (1 083 331/1 978 380) to 52.9% (1 091 958/2 064 507), giving a relative percentage decrease in the rate of 3.5%. The caesarean delivery rate increased from 43.9% (869 018/1 978 380) to 45.5% (940 206/2 064 507), giving a relative percentage increase in the rate of 3.7%. The biggest change in delivery rates was in private-sector hospitals. Since 2014, rates of caesarean delivery have fallen slightly in all sectors, but they remain high at 45.5%. Policies with appropriate interventions are needed to reduce the caesarean delivery rate in Mexico, particularly in private-sector hospitals.Les taux d'accouchements par césarienne au Mexique sont parmi les plus élevés au monde. Au vu de la sensibilisation accrue de la population et des professionnels à ce problème et de la mise à jour des directives nationales de 2014 visant à diminuer la fréquence des accouchements par césarienne, nous avons analysé l'évolution des accouchements par césarienne selon le type d'établissement entre 2008 et 2017 au Mexique. Nous avons obtenu des données issues d'actes de naissance auprès de la Direction générale mexicaine des informations sur la santé et regroupé le nombre total d'accouchements par voie basse et par césarienne en cinq catégories d'établissement: hôpitaux relevant du ministère de la Santé, hôpitaux publics, hôpitaux relevant de l'assurance liée à l'emploi public, hôpitaux militaires et autres établissements. Les taux d'accouchements ont été calculés pour chaque catégorie à l'échelle nationale et pour chaque État. En moyenne, 2 114 630 (intervalle de confiance, IC, à 95%: 2 061 487-2 167 773) naissances vivantes ont eu lieu chaque année entre 2008 et 2017 à l'échelle nationale. Parmi ces naissances, 53,5% (1 130 570; IC à 95%: 1 108 068-1 153 072) étaient des accouchements par voie basse, et 45,3% (957 105; IC à 95%: 922 936-991 274) étaient des accouchements par césarienne, avec peu de variations dans le temps. Au cours de la période étudiée, le nombre de naissances vivantes a augmenté de 4,4% (de 1 978 380 à 2 064 507). Le taux d'accouchements par voie basse est passé de 54,8% (1 083 331/1 978 380) à 52,9% (1 091 958/2 064 507), ce qui correspond à une diminution relative du taux de 3,5%. Le taux d'accouchements par césarienne est passé de 43,9% (869 018/1 978 380) à 45,5% (940 206/2 064 507), ce qui correspond à une augmentation relative du taux de 3,7%. Le changement le plus important concernant les taux d'accouchements a été constaté dans les hôpitaux du secteur privé. Depuis 2014, les taux d'accouchements par césarienne ont légèrement diminué dans tous les secteurs, mais demeurent élevés (45,5%). Des politiques et des interventions appropriées sont nécessaires pour réduire le taux d'accouchements par césarienne aux Mexique, en particulier dans les hôpitaux de secteur privé.Las tasas de parto por cesárea en México están entre las más altas del mundo. Dada la creciente concienciación pública y profesional sobre este problema y las directrices nacionales actualizadas de 2014 para reducir la frecuencia de los partos por cesárea, se analizaron las tendencias de los partos por cesárea según el tipo de establecimiento en México entre 2008 y 2017. Se obtuvieron datos de los certificados de nacimiento de la Dirección General de Información Sanitaria de México y se agrupó el número total de partos vaginales y por cesárea en cinco categorías de establecimientos: hospitales del ministerio de salud pública, hospitales privados, hospitales gubernamentales para asegurados por empleo, hospitales militares y otras instalaciones. Se calcularon los índices de partos para cada categoría a nivel nacional y según cada estado. De media, 2 114 630 (intervalo de confianza, IC, del 95 %: 2 061 487–2 167 773) nacimientos vivos se produjeron a nivel nacional al año entre 2008 y 2017. De estos nacimientos, el 53,5 % (1 130 570; IC del 95 %: 1 108 068–1 153 072) fueron partos vaginales y el 45,3 % (957 105; IC del 95 %: 922 936–991 274) fueron partos por cesárea, con poca variación a lo largo del tiempo. Durante el periodo de estudio, el número de nacidos vivos aumentó un 4,4 % (de 1 978 380 a 2 064 507). La tasa de partos vaginales disminuyó del 54,8 % (1 083 331/1 978 380) al 52,9 % (1 091 958/2 064 507), lo que supone una disminución porcentual relativa de la tasa del 3,5 %. La tasa de partos por cesárea aumentó del 43,9 % (869 018/1 978 380) al 45,5 % (940 206/2 064 507), lo que representa un aumento porcentual relativo de la tasa del 3,7 %. El mayor cambio en las tasas de partos se produjo en los hospitales del sector privado. Desde 2014, las tasas de parto por cesárea se han reducido ligeramente en todos los sectores, pero siguen siendo elevadas (45,5 %). Se necesitan políticas con intervenciones apropiadas para reducir la tasa de partos por cesárea en México, especialmente en los hospitales del sector privado.تعد معدلات الولادة القيصرية في المكسيك واحدة من أعلى المعدلات على مستوى العالم. في ظل ارتفاع الوعي لدى العامة والمهنيين بهذه المشكلة وبالمبادئ التوجيهية الوطنية التي تم تعديلها عام 2014 للحد من وتيرة الولادة القيصرية، فقد قمنا بتحليل الاتجاهات في الولادة القيصرية حسب نوع المنشأة في المكسيك من عام 2008 إلى عام 2017. وحصلنا على بيانات شهادات الميلاد من الإدارة المكسيكية العامة للمعلومات الصحية، كما قمنا بتقسيم العدد الإجمالي من الولادات الطبيعية والقيصرية إلى خمس فئات من المرافق: مستشفيات وزارة الصحة؛ والمستشفيات الخاصة؛ ومستشفيات التأمين ذات فرق العمل الحكومية؛ والمستشفيات العسكرية، وغيرها من المرافق. تم حساب معدلات الولادة لكل فئة على المستوى الوطني ولكل ولاية. بمعدل متوسط، 2114630 (فاصل الثقة 95%: 2061487 إلى 2167773) حالة مواليد أحياء حدثت على المستوى الوطني كل عام ما بين عامي 2008 و2017. ونسبة 53.5% من هذه الولادات (1130570؛ فاصل الثقة 95%: 1108068 إلى 1153072) كانت ولادات طبيعية، ونسبة 45.3% منها (957105؛ فاصل الثقة 95%: 922936 إلى 991274) كانت ولادات قصية، فضلاً عن قليل من التنوع بمرور الوقت. وخلال فترة الدراسة، زاد عدد المواليد الأحياء بنسبة 4.4% (من 1978380 إلى 2064507). انخفض معدل الولادة الطبيعية من 54.8% (1083331/1978380) إلى 52.9% (1091958/2064507)، مما أدى بدوره إلى انخفاض نسبي في النسبة المئوية بمعدل 3.5%. كما انخفض معدل الولادة القيصرية من 43.9% (869018/1978380) إلى 45.5% (940206/2064507)، مما أدى بدوره إلى ارتفاع نسبي في النسبة المئوية بمعدل 3.7%. وكان أكبر تغيير في معدلات الولادة في مستشفيات القطاع الخاص. منذ عام 2014، تعرضت معدلات الولادة القيصرية للانخفاض بشكل طفيف في جميع القطاعات، لكنها لا تزال مرتفعة عند مستوى 45.5%. هناك حاجة إلى سياسات تنطوي على تدخلات مناسبة، وذلك للحد من معدل الولادة القيصرية في المكسيك، وخاصة في مستشفيات القطاع الخاص.墨西哥剖腹产分娩率居世界首位。鉴于公众和专业人员对此问题的日益重视，以及修订后的 2014 年版国家指南旨在减少剖腹产手术发生率，我们按照机构类型对墨西哥 2008 年至 2017 年的剖腹产手术趋势进行了分析。我们从墨西哥卫生信息总局 (Mexican General Directorate for Health Information) 处获得了出生证明的数据，并将阴道分娩和剖腹产分娩的总数按照机构类型分为五类：卫生部下辖医院；私立医院；政府就业保险医院；军队医院；以及其它医院。计算全国以及各州各类型机构的分娩率。2008 年至 2017 年期间，全国年均活产儿为 2 114 630（95％ 置信区间，CI：2 061 487-2 167 773）。在这些活产儿中，53.5％（1 130 570；95％ 置信区间，CI：1 108 068-1 153 072）为阴道分娩，45.3％（957 105；95％ CI：922 936-991 274）为剖腹产分娩，数据随时间变化极小。研究期间，活产儿数量增加了 4.4％（从 1 978 380 增加至 2 064 507 ）。阴道分娩率从 54.8％（1 083 331/1 978 380）降至 52.9％（1 091 958/2 064 507），相对百分比下降 3.5％。剖腹产率从 43.9％（869 018/1 978 380）上升至 45.5％（940 206/2 064 507），相对百分比上升 3.7％。分娩率上的最大变化出现在私营医院。自 2014 年以来，虽然所有机构的剖腹产分娩率略有下降，但仍高达 45.5％。需施行政策，采取适当干预措施降低墨西哥（尤其是私营医院）的剖腹产分娩率Мексика характеризуется одним из самых высоких показателей родоразрешения с помощью кесарева сечения в мире. С учетом признания этой проблемы специалистами и общественностью и с учетом обновленных национальных рекомендаций от 2014 года, направленных на снижение количества кесаревых сечений, авторы статьи анализируют тенденции в использовании кесарева сечения в зависимости от типа медицинского учреждения в Мексике в период с 2008 по 2017 год. От Главного управления здравоохранения Мексики были получены данные свидетельств о рождении, которые затем были сгруппированы с разделением общего количества вагинальных родов и родов с использованием кесарева сечения в пять категорий по типу медицинского учреждения: больницы Министерства здравоохранения, частные больницы, государственные больницы, предоставляющие услуги по страховке для работающих, военные госпитали и прочие медицинские учреждения. Были рассчитаны показатели родов для каждой категории в национальном масштабе и отдельно по штатам. В среднем ежегодно в период между 2008 и 2017 годами регистрировалось 2 114 630 живорожденных младенцев (95%-й ДИ: 2 061 487–2 167 773). Из них 53,5% (1 130 570; 95%-й ДИ: 1 108 068–1 153 072) приходилось на вагинальные роды и 45,3% (957 105; 95%-й ДИ: 922 936–991 274) родились с помощью кесарева сечения; вариации по годам были незначительными. В период исследования количество живорожденных выросло на 4,4% (с 1 978 380 до 2 064 507). Количество вагинальных родов снизилось с 54,8% (1 083 331 из 1 978 380) до 52,9% (1 091 958 из 2 064 507), что дает относительное процентное уменьшение на 3,5%. Частота кесарева сечения выросла с 43,9% (869 018 из 1 978 380) до 45,5% (940 206 из 2 064 507), что дает относительное процентное увеличение на 3,7%. Максимальное изменение показателей отмечалось в частных больницах. С 2014 года частота кесарева сечения слегка снизилась во всех учреждениях, но остается по-прежнему высокой (на уровне 45,5%). Необходимо разработать стратегию и соответствующие меры, которые позволили бы снизить частоту использования кесарева сечения в Мексике, особенно в больницах частного сектора.

Virulence of Yersinia pestis in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across Y. pestis strains, but three, YopJ, YopT, and YpkA, are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a Y. pestis strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death in vitro and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each effector enhances Y. pestis virulence and that YopT and YpkA act through a mechanism distinct from that of YopJ.

Objectives. The current study seeks to determine if a sample of foragers, farmers, and pastoralists can be distinguished by their dental microwear texture signatures. Materials and Methods. The study included a sample of 719 individuals from 51 archaeological sites (450 farmers, 192 foragers, 77 pastoralists). All were over age 12 and sexes were pooled. Using a Sensofar® white-light confocal profiler we collected dental microwear texture analysis (DMTA) data from a single first or second molar from each individual. We leveled and cleaned data clouds following standard procedures and analyzed the data with Sfrax® and Toothfrax® software. The DMTA variables were complexity and anisotropy. Statistics included ANOVA with partial eta squared and Hedges's g. We also performed a follow-up K-means cluster analysis. Results. We found significant differences between foragers and farmers and pastoralists for complexity and anisotropy, with foragers having greater complexity than either the farmers or the pastoralists. The farmers and pastoralists had greater anisotropy than the foragers. The Old World foragers had significantly higher anisotropy values than New World foragers. Old and New World farmers did not differ. Among the Old World farmers, those dating from the Neolithic through the Late Bronze Age had higher complexity values than those from the Iron Age through the medieval period. The cluster analysis discerned foragers and farmers but also indicated similarity between hard food foragers and hard food farmers. Discussion. Our findings reaffirm that DMTA is capable of distinguishing human diets. We found that foragers and farmers, in particular, differ in their microwear signatures across the globe. There are some exceptions, but nothing that would be unexpected given the range of human diets and food preparation techniques. This study indicates that in general DMTA is an efficacious means of paleodietary reconstruction in humans.