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We developed and tested a Centering-based group antenatal (ANC) model in Malawi, integrating health promotion for HIV prevention and mental health. We present effectiveness data and examine congruence with only the Group ANC theory of change model, which identifies key processes as supportive relationships, empowered partners in learning and care, and meaningful services, leading to better ANC experiences and outcomes. We conducted a hybrid effectiveness-implementation trial at seven clinics in Blantyre District, Malawi, comparing outcomes for 1887 pregnant women randomly assigned to Group ANC or Individual ANC. Group effects on outcomes were summarized and evaluated using t-tests, Mann-Whitney, or Chi-squared tests. Adjusted for seven individual and two clinic-level baseline covariates, point estimates are reported for continuous outcomes using multivariable linear regression models. Adjusted for the same covariates, odds ratios are reported for categorical outcomes using logistic regression models. All statistical tests were two-sided, controlling for a Type I error probability of 0.01 due to multiple testing. Women in Group ANC had higher peer connectedness and pregnancy-related empowerment, recalled receiving more services, and discussed more health promotion topics. They experienced less wait time, greater satisfaction with care (Estimate = 1.21, 99% CI = 0.07, 2.35), and had a higher mean number of ANC contacts (Estimate = 0.74, 99% CI = 0.50, 0.98). Most women preferred Group ANC for a future pregnancy (81% in Individual ANC; 95% in Group ANC). Women in Group ANC had more diverse diets (Estimate = 0.35, 99% CI = 0.17, 0.53), were better prepared for birth (Estimate 0.32, 99% CI = 0.16, 0.48), more likely to use condoms consistently (OR= 1.07, 99% CI = 1.00, 1.14) and communicated more with partners. They reported less mental distress in late pregnancy (Estimate = -0.61, 99% CI = -1.20, -0.02). Exclusive breastfeeding, partner HIV testing and disclosure, facility-based delivery, postnatal care attendance, postpartum family planning, and low birth weight did not differ by ANC type. This effectiveness study of Malawi Group ANC, the first trial with individual randomization in a low-income country, maps outcomes to the theory of change, enhancing our understanding of Group ANC's diverse positive impacts. The integration of typically neglected health promotion topics into the model highlights its flexibility to address changing local and global needs. Based on study results, the Malawi Ministry of Health is introducing Group ANC at district-level trainings and exploring the logistics for nationwide adoption. With momentum and political will, better care and a positive healthcare experience can be achieved for women, infants, and families in Malawi and globally. ClinicalTrials.gov NCT03673709.

Background Sub-Saharan Africa has the world’s highest rates of maternal and perinatal mortality and accounts for two-thirds of new HIV infections and 25% of preterm births. Antenatal care, as the entry point into the health system for many women, offers an opportunity to provide life-saving monitoring, health promotion, and health system linkages. Change is urgently needed, because potential benefits of antenatal care are not realized when pregnant women experience long wait times and short visits with inconsistent provisioning of essential services and minimal health promotion, especially for HIV prevention. This study answers WHO’s call for the rigorous study of group antenatal care as a transformative model that provides a positive pregnancy experience and improves outcomes. Methods Using a hybrid type 1 effectiveness-implementation design, we test the effectiveness of group antenatal care by comparing it to individual care across 6 clinics in Blantyre District, Malawi. Our first aim is to evaluate the effectiveness of group antenatal care through 6 months postpartum. We hypothesize that women in group care and their infants will have less morbidity and mortality and more positive HIV prevention outcomes. We will test hypotheses using multi-level hierarchical models using data from repeated surveys (four time points) and health records. Guided by the consolidated framework for implementation research, our second aim is to identify contextual factors related to clinic-level degree of implementation success. Analyses use within and across-case matrices. Discussion This high-impact study addresses three global health priorities, including maternal and infant mortality, HIV prevention, and improved quality of antenatal care. Results will provide rigorous evidence documenting the effectiveness and scalability of group antenatal care. If results are negative, governments will avoid spending on less effective care. If our study shows positive health impacts in Malawi, the results will provide strong evidence and valuable lessons learned for widespread scale-up in other low-resource settings. Positive maternal, neonatal, and HIV-related outcomes will save lives, impact the quality of antenatal care, and influence health policy as governments make decisions about whether to adopt this innovative healthcare model. Trial registration ClinicalTrials.gov registration number NCT03673709 . Registered on September 17, 2018.

We developed and tested a Centering-based group antenatal (ANC) model in Malawi, integrating health promotion for HIV prevention and mental health. We present effectiveness data and examine congruence with only the Group ANC theory of change model, which identifies key processes as supportive relationships, empowered partners in learning and care, and meaningful services, leading to better ANC experiences and outcomes. We conducted a hybrid effectiveness-implementation trial at seven clinics in Blantyre District, Malawi, comparing outcomes for 1887 pregnant women randomly assigned to Group ANC or Individual ANC. Group effects on outcomes were summarized and evaluated using t-tests, Mann-Whitney, or Chi-squared tests. Adjusted for seven individual and two clinic-level baseline covariates, point estimates are reported for continuous outcomes using multivariable linear regression models. Adjusted for the same covariates, odds ratios are reported for categorical outcomes using logistic regression models. All statistical tests were two-sided, controlling for a Type I error probability of 0.01 due to multiple testing. Women in Group ANC had higher peer connectedness and pregnancy-related empowerment, recalled receiving more services, and discussed more health promotion topics. They experienced less wait time, greater satisfaction with care (Estimate = 1.21, 99% CI = 0.07, 2.35), and had a higher mean number of ANC contacts (Estimate = 0.74, 99% CI = 0.50, 0.98). Most women preferred Group ANC for a future pregnancy (81% in Individual ANC; 95% in Group ANC). Women in Group ANC had more diverse diets (Estimate = 0.35, 99% CI = 0.17, 0.53), were better prepared for birth (Estimate 0.32, 99% CI = 0.16, 0.48), more likely to use condoms consistently (OR= 1.07, 99% CI = 1.00, 1.14) and communicated more with partners. They reported less mental distress in late pregnancy (Estimate = -0.61, 99% CI = -1.20, -0.02). Exclusive breastfeeding, partner HIV testing and disclosure, facility-based delivery, postnatal care attendance, postpartum family planning, and low birth weight did not differ by ANC type. This effectiveness study of Malawi Group ANC, the first trial with individual randomization in a low-income country, maps outcomes to the theory of change, enhancing our understanding of Group ANC's diverse positive impacts. The integration of typically neglected health promotion topics into the model highlights its flexibility to address changing local and global needs. Based on study results, the Malawi Ministry of Health is introducing Group ANC at district-level trainings and exploring the logistics for nationwide adoption. With momentum and political will, better care and a positive healthcare experience can be achieved for women, infants, and families in Malawi and globally.

Postpartum hemorrhage (PPH), the leading cause of maternal mortality worldwide, is responsible for 35 percent of maternal deaths. Proximately, PPH results from the failure of the placenta to separate from the uterine wall properly, most often because of impairment of uterine muscle contraction. Despite its prevalence and its well-described clinical manifestations, the ultimate causes of PPH are not known and have not been investigated through an evolutionary lens. We argue that vulnerability to PPH stems from the intensely invasive nature of human placentation. The human placenta causes uterine vessels to undergo transformation to provide the developing fetus with a high plane of maternal resources; the degree of this transformation in humans is extensive. We argue that the particularly invasive nature of the human placenta increases the possibility of increased blood loss at parturition. We review evidence suggesting PPH and other placental disorders represent an evolutionary novel condition in hominins. La hemorragia posparto (HPP) es la principal causa de mortalidad materna en todo el mundo, responsable de 35% de las muertes maternas. Una causa de la HPP es la separación incompleta de la placenta de la pared uterina, principalmente debido a una contracción deficiente del músculo uterino. A pesar de su prevalencia, las causas exactas de la HPP no se conocen y aún no han sido investigadas usando una lente evolutiva. Sostenemos que la posibilidad para presentar HPP se debe a la naturaleza invasiva de la inserción placentaria humana. La placenta humana transforma los vasos uterinos incrementando el acceso fetal a nutrientes maternos; el grado de esta transformación en humanos es extenso. Sostenemos que la naturaleza particularmente invasiva de la placenta humana aumenta el riesgo de sangrado post partum. Finalmente, revisamos la evidencia que sugiere que la HPP y otros desórdenes placentarios representan una condición evolutiva sin precedente en humanos. Kutokwa na damu nyingi baada ya kijifungua (PPH) ni sababu kubwa ya vifo vya akina mama wakati wa uzazi duniani na ni 35% ya vifo hivyo. Kwa maelezo ya kisayansi sababu kubwa ya PPH hutokana na kondo la nyuma kushindwa kujiengua na mfuko wa uzazi, ambapo mará nyingi misuli ya mfuko huo hushindwa kubana i pasavyo. Pamoja na PPH kuwa ya kawaida na kuelezwa vizuri kitabibu, lakini tunaona sababu yake kwa msingi wa mtazamo mabadiliko ya maumbile (evolution) haijajulikana bado. Tunatoa hoja kuwa kondo la binadamu lina vyojikita na mabadiliko ya mishipa ya mfuko wa uzazi i naongeza uwezekano wa damu kutoka kwa wingi wakati wa uzazi ya kawaida kwa binadamu. Hatimaye tumepitia upya na kutafakari njia za asili za uzazi na mabadiliko ya jenetiki za kuzuia/punguza PPH.

We developed and tested a Centering-based group antenatal (ANC) model in Malawi, integrating health promotion for HIV prevention and mental health. We present effectiveness data and examine congruence with only the Group ANC theory of change model, which identifies key processes as supportive relationships, empowered partners in learning and care, and meaningful services, leading to better ANC experiences and outcomes. We conducted a hybrid effectiveness-implementation trial at seven clinics in Blantyre District, Malawi, comparing outcomes for 1887 pregnant women randomly assigned to Group ANC or Individual ANC. Group effects on outcomes were summarized and evaluated using t-tests, Mann-Whitney, or Chi-squared tests. Adjusted for seven individual and two clinic-level baseline covariates, point estimates are reported for continuous outcomes using multivariable linear regression models. Adjusted for the same covariates, odds ratios are reported for categorical outcomes using logistic regression models. All statistical tests were two-sided, controlling for a Type I error probability of 0.01 due to multiple testing. Women in Group ANC had higher peer connectedness and pregnancy-related empowerment, recalled receiving more services, and discussed more health promotion topics. They experienced less wait time, greater satisfaction with care (Estimate = 1.21, 99% CI = 0.07, 2.35), and had a higher mean number of ANC contacts (Estimate = 0.74, 99% CI = 0.50, 0.98). Most women preferred Group ANC for a future pregnancy (81% in Individual ANC; 95% in Group ANC). Women in Group ANC had more diverse diets (Estimate = 0.35, 99% CI = 0.17, 0.53), were better prepared for birth (Estimate 0.32, 99% CI = 0.16, 0.48), more likely to use condoms consistently (OR= 1.07, 99% CI = 1.00, 1.14) and communicated more with partners. They reported less mental distress in late pregnancy (Estimate = -0.61, 99% CI = -1.20, -0.02). Exclusive breastfeeding, partner HIV testing and disclosure, facility-based delivery, postnatal care attendance, postpartum family planning, and low birth weight did not differ by ANC type. This effectiveness study of Malawi Group ANC, the first trial with individual randomization in a low-income country, maps outcomes to the theory of change, enhancing our understanding of Group ANC's diverse positive impacts. The integration of typically neglected health promotion topics into the model highlights its flexibility to address changing local and global needs. Based on study results, the Malawi Ministry of Health is introducing Group ANC at district-level trainings and exploring the logistics for nationwide adoption. With momentum and political will, better care and a positive healthcare experience can be achieved for women, infants, and families in Malawi and globally.

The Covid-19 pandemic has exposed and exacerbated weaknesses in the U.S. health care system. Many patients are losing their health insurance when they lose their jobs. Declining revenues are threatening the financial viability of some hospitals and medical practices. The authors propose policy solutions to address these challenges.

Youth-led strategies remain untested in clinic-based programs to improve viral suppression (VS) and reduce stigma among HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. In response, Project YES! placed paid HIV-positive youth peer mentors (YPM) in four HIV clinics in Ndola, Zambia including a Children's Hospital (pediatric setting), an adult Hospital and two primary care facilities (adult settings). A randomized controlled trial was conducted from December 2017 to February 2019. Consecutively recruited 15 to 24-year-olds were randomly assigned to an intervention arm with monthly YPM one-on-one and group sessions and optional caregiver support groups, or a usual care comparison arm. Survey data and blood samples were collected at baseline and at the six-month midline. Generalized estimating equation models evaluated the effect of study arm over time on VS, antiretroviral treatment (ART) adherence gap, and internalized stigma. Out of 276 randomized youth, 273 were included in the analysis (Intervention n = 137, Comparison n = 136). VS significantly improved in both arms (I:63.5% to 73.0%; C:63.7% to 71.3.0%) [OR:1.49, 95% CI:1.08, 2.07]. In a stratified analysis intervention (I:37.5% to 70.5%) versus the comparison (C:60.3% to 59.4%) participants from the pediatric clinic experienced a relative increase in the odds of VS by a factor of 4.7 [interaction term OR:4.66, 95% CI:1.84, 11.78]. There was no evidence of a study arm difference in VS among AYA in adult clinics, or in ART adherence gaps across clinics. Internalized stigma significantly reduced by a factor of 0.39 [interaction term OR:0.39, 95% CI:0.21,0.73] in the intervention (50.4% to 25.4%) relative to the comparison arm (45.2% to 39.7%). Project YES! engaged AYA, improving VS in the pediatric clinic and internalized stigma in the pediatric and adult clinics. Further research is needed to understand the intersection of VS and internalized stigma among AYA attending adult HIV clinics. ClinicalTrials.gov NCT04115813.

Catecholamines released by sympathetic nerves can activate adrenergic receptors present on nearly every cell type, including myeloid-derived suppressor cells (MDSCs). Using in vitro systems, murine tumor models in wild-type and genetically modified (β2-AR-/-) mice, and adoptive transfer approaches, we found that the degree of β2-AR signaling significantly influences MDSC frequency and survival in tumors and other tissues. It also modulates their expression of immunosuppressive molecules such as arginase-I and PD-L1 and alters their ability to suppress the proliferation of T cells. The regulatory functions of β2-AR signaling in MDSCs were also found to be dependent upon STAT3 phosphorylation. Moreover, we observed that the β2-AR-mediated increase in MDSC survival is dependent upon Fas-FasL interactions, and this is consistent with gene expression analyses, which reveal a greater expression of apoptosis-related genes in β2-AR-/- MDSCs. Our data reveal the potential of β2-AR signaling to increase the generation of MDSCs from both murine and human peripheral blood cells and that the immunosuppressive function of MDSCs can be mitigated by treatment with β-AR antagonists, or enhanced by β-AR agonists. This strongly supports the possibility that reducing stress-induced activation of β2-ARs could help to overcome immune suppression and enhance the efficacy of immunotherapy and other cancer therapies.

Little is known about youth-led approaches to addressing HIV-related outcomes among adolescents and young adults (AYA) living with HIV. In response, Project YES! hired and trained youth living with HIV as peer mentors (YPMs) in four HIV clinics in Ndola, Zambia to hold meetings with 276 15-24-year-olds living with HIV. Within this randomized controlled trial, a qualitative sub-study was conducted to explore YPMs' implementing experiences. In-depth interviews were conducted with the eight YPMs (50% female) ages 21-26 years. YPMs were asked about their experiences working with clients, their feedback on program components, and what the experience meant to them personally and professionally. Interviews were audio-recorded, transcribed verbatim, and thematic analysis was performed. YPMs connected with AYA clients by discussing shared struggles, modeling positive health behaviors, and establishing judgement-free environments. YPMs experienced powerful personal transformations in HIV-related health behaviors, conceptions of self, and plans for the future. Many expressed now seeing themselves as community leaders-\"ambassadors\", \"game changers\"-and \"not just alone in this world.\" They described newfound commitments to reaching personal and professional goals. YPMs were adamant that Project YES! should expand so other HIV-positive AYA might benefit. Well-trained and compensated YPMs who are integrated into HIV clinics can support AYA in unique and important ways due to their shared experiences. The transformational experience of becoming YPMs empowers youth to see themselves as role models and leaders. Future programs should engage youth living with HIV as partners in efforts to end the HIV epidemic.