Learning from the End of the Public-Private Partnership for Lesotho's National Referral Hospital Network.

Background: Public-private partnerships (PPP) are one strategy to finance and deliver healthcare in lower-resourced settings. Lesotho's Queen 'Mamohato Memorial Hospital Integrated Network (QMMH-IN) was sub-Saharan Africa's first and largest integrated healthcare PPP. Objective: We assessed successes and challenges to performance of the QMMH-IN PPP. Methods: We conducted 26 semi-structured interviews among QMMH-IN executive leadership and staff in early 2020. Questions were guided by the WHO Health System Building Blocks Framework. We conducted a thematic analysis. Findings: Facilitators of performance included: 1) PPP leadership commitment to quality improvement supported by protocols, monitoring, and actions; 2) high levels of accountability and discipline; and 3) well-functioning infrastructure, core systems, workflows, and internal referral network. Barriers to performance included: 1) human resource management challenges and 2) broader health system and referral network limitations. Respondents anticipated the collapse of the PPP and suggested better investing in training incoming managerial staff, improving staffing, and expanding QMMH-IN's role as a training facility. Conclusions: The PPP contract was terminated approximately five years before its anticipated end date; in mid-2021 the government of Lesotho assumed management of QMMH-IN. Going forward, the Lesotho government and others making strategic planning decisions should consider fostering a culture of quality improvement and accountability; ensuring sustained investments in human resource management; and allocating resources in a way that recognizes the interdependency of healthcare facilities and overall system strengthening. Contracts for integrated healthcare PPPs should be flexible to respond to changing external conditions and include provisions to invest in people as substantively as infrastructure, equipment, and core systems over the full length of the PPP. Healthcare PPPs, especially in lower-resource settings, should be developed with a strong understanding of their role in the broader health system and be implemented in conjunction with efforts to ensure and sustain adequate capacity and resources throughout the health system.

Satisfaction with service delivery among HIV treatment clients enrolled in differentiated and conventional models of care in South Africa: a baseline survey.

INTRODUCTION: Differentiated service delivery (DSD) models aim to increase the responsiveness of HIV treatment programmes to the individual needs of antiretroviral therapy (ART) clients to improve treatment outcomes and quality of life. Little is known about how DSD client experiences differ from conventional care. METHODS: From May to November 2021, we interviewed adult (≥18) ART clients at 21 primary clinics in four districts of South Africa. Participants were enrolled consecutively at routine visits and stratified into four groups: conventional care-not eligible for DSD (conventional-not-eligible); conventional care eligible for but not enrolled in DSD (conventional-not-enrolled); facility pickup point DSD model; and external pickup point DSD model. Satisfaction was assessed using questions with 5-point Likert-scale responses. Mean scores were categorized as not satisfied (score ≤3) or satisfied (>3). We used logistic regression to assess differences and report crude and adjusted odds ratios (aORs). Qualitative themes were identified through content analysis. RESULTS: Eight hundred and sixty-seven participants (70% female, median age 39) were surveyed: 24% facility pick-up points; 27% external pick-up points; 25% conventional-not-eligible; and 24% conventional-not-enrolled. Seventy-four percent of all study participants expressed satisfaction with their HIV care. Those enrolled in DSD models were more likely to be satisfied, with an aOR of 6.24 (95% CI [3.18-12.24]) for external pick-up point versus conventional-not-eligible and an aOR of 3.30 (1.95-5.58) for facility pick-up point versus conventional-not-eligible. Conventional-not-enrolled clients were slightly but not significantly more satisfied than conventional-not-eligible clients (1.29, 0.85-1.96). Those seeking outside healthcare (crude OR 0.57, 0.41-0.81) or reporting more annual clinic visits (0.52, 0.29-0.93) were less likely to be satisfied. Conventional care participants reporting satisfaction with their current model of care perceived providers as helpful, respectful, and friendly and were satisfied with care despite long queues. DSD model participants emphasized ease and convenience, particularly not having to queue. CONCLUSIONS: Most adult ART clients in South Africa were satisfied with their care, but those enrolled in DSD models expressed slightly greater satisfaction than those remaining in conventional care. Efforts should focus on enrolling more eligible patients into DSD models, expanding eligibility criteria to cover a wider client base, and further improving the models' desirable characteristics.

Rapid Evolution of Multidrug Resistance in a Candida lusitaniae Infection during Micafungin Monotherapy.

Candida (Clavispora) lusitaniae is a rare, emerging non-albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood. Analyses of serial clinical isolates of any Candida species are uncommon and often analyze a limited number of samples collected over months of antifungal therapy with multiple drug classes, limiting the ability to understand relationships between drug classes and specific mutations. Here, we performed comparative genomic and phenotypic analysis of 20 serial C. lusitaniae bloodstream isolates collected daily from an individual patient treated with micafungin monotherapy during a single 11-day hospital admission. We identified isolates with decreased micafungin susceptibility 4 days after initiation of antifungal therapy and a single isolate with increased cross-resistance to micafungin and fluconazole, despite no history of azole therapy in this patient. Only 14 unique single nucleotide polymorphisms (SNPs) were identified between all 20 samples, including three different FKS1 alleles among isolates with decreased micafungin susceptibility and an ERG3 missense mutation found only in the isolate with increased cross-resistance to both micafungin and fluconazole. This is the first clinical evidence of an ERG3 mutation in C. lusitaniae that occurred during echinocandin monotherapy and is associated with cross-resistance to multiple drug classes. Overall, the evolution of multidrug resistance in C. lusitaniae is rapid and can emerge during treatment with only first-line antifungal therapy.

COVID-19 Knowledge and Prevention Behaviors in Rural Zambia: A Qualitative Application of the Information-Motivation-Behavioral Skills Model.

In early 2020, the Zambian Ministry of Health instituted prevention guidelines to limit spread of COVID-19. We assessed community knowledge, motivations, behavioral skills, and perceived community adherence to prevention behaviors (i.e., hand hygiene, mask wearing, social distancing, and limiting gatherings). Within a cluster-randomized controlled trial in four rural districts, in November 2020 and May 2021, we conducted in-depth interviews with health center staff (N = 19) and community-based volunteers (N = 34) and focus group discussions with community members (N = 281). A content analysis was conducted in Nvivo v12. Data were interpreted using the Information-Motivation-Behavioral Skills Model. Generally, respondents showed good knowledge of COVID-19 symptoms, spread, and high-risk activities, with some gaps. Prevention behavior performance was driven by personal and social factors. Respondents described institutional settings (e.g., clinics and church) having higher levels of perceived adherence due to stronger enforcement measures and clear leadership. Conversely, informal community settings (e.g., weddings, funerals, football matches) lacked similar social and leadership expectations for adherence and had lower perceived levels of adherence. These settings often involved higher emotions (excitement or grief), and many involved alcohol use, resulting in community members "forgetting" guidelines. Doubt about disease existence or need for precautions persisted among some community members and drove non-adherence more generally. Although COVID-19 information successfully penetrated these very remote rural communities, more targeted messaging may address persistent COVID-19 doubt and misinformation. Engaging local leaders in religious, civic, and traditional leadership positions could improve community behaviors without adding additional monitoring duties on an already overburdened, resource-limited health system.

A Qualitative Assessment of Community Acceptability and Use of a Locally Developed Children's Book to Increase Shared Reading and Parent-Child Interactions in Rural Zambia.

Introduction: Early reading interventions hold promise for increasing language and literacy development in young children and improving caregiver-child interactions. To engage rural caregivers and young children in home reading, Zambian child psychologists and education specialists developed a culturally representative, local language children's book targeted at pre-grade 1 children. Objectives: We qualitatively assessed community acceptability and use of the book distributed to households with young children in two provinces of Zambia. Methods: We conducted 15 focus group discussions (FGDs) with women (n=117) who received the "Zambian folktales adapted stories for young children" book. A codebook was created a priori, based on established themes in the guide; content analysis was conducted in Nvivo v12. Data were interpreted against the Theoretical Framework on Acceptability. Findings: Respondents described wide acceptability of the children's book across multiple framework constructs. Respondents believed the book was culturally appropriate for its folktale structure and appreciated the morals and lessons provided by the stories. Respondents described using the book in multiple ways including reading in one-on-one or group settings, asking the child questions about the narrative or pictures, and providing additional commentary on the actions or figures in the pictures. Respondents believed the books were helping children grow their vocabulary and early literacy skills. The book's simple vocabulary facilitated use by less educated caregivers. The primary concern voiced was the ability of low literacy caregivers to utilize the book for reading. Discussion: The children's book was widely considered acceptable by rural Zambian communities. It provided a platform for an additional method of caregiver-child interactions in these households for reading, dialogue, and oral storytelling. Shared reading experiences have potentially substantial benefits for the language development and emergent literacy of young children. Programs to develop and deliver culturally acceptable books to households with limited access should be considered by governments and funders.

A cost description of the setup costs of community-owned maternity waiting homes in rural Zambia.

Maternity waiting homes (MWHs) are one strategy to improve access to skilled obstetric care in low resource settings such as Zambia. The Maternity Homes Access in Zambia project built 10 MWHs at rural health centers in Zambia for women awaiting delivery and postnatal care (PNC) visits. The objective of this paper is to summarize the costs associated with setup of 10 MWHs, including infrastructure, furnishing, stakeholder engagement, and activities to build the capacity of local communities to govern MWHs. We do not present operational costs after setup was complete. We used a retrospective, top-down program costing approach. We reviewed study documentation to compile planned and actual costs by site. All costs were annuitized using a 3% discount rate and organized by cost categories: (1) Capital: infrastructure and furnishing, and (2) Installation: capacity building activities and stakeholder engagement. We assumed lifespans of 30 years for infrastructure; 5 years for furnishings; and 3 years for installation activities. Annuitized costs were used to estimate cost per night stayed and per visit for delivery and PNC-related stays. We also modeled theoretical utilization and cost scenarios. The average setup cost of one MWH was $85,284 (capital: 76%; installation: 24%). Annuitized setup cost per MWH was USD$12,516 per year. At an observed occupancy rate of 39%, setup cost per visit to the MWH was USD$70, while setup cost per night stayed was USD$6. The cost of stakeholder engagement activities was underbudgeted by half at the beginning of this project.This analysis serves as a planning resource for governments and implementers that are considering MWHs as a component of their overall maternal and child health strategy. Planning considerations should include the annuitized cost, value of capacity building and stakeholder engagement, and that cost per bed night and visit are dependent upon utilization.

Trends in maternal mental health during the COVID-19 pandemic-evidence from Zambia.

The COVID-19 pandemic has increased social and emotional stressors globally, increasing mental health concerns and the risk of psychiatric illness worldwide. To date, relatively little is known about the impact of the pandemic on vulnerable groups such as women and children in low-resourced settings who generally have limited access to mental health care. We explore two rounds of data collected as part of an ongoing trial of early childhood development to assess mental health distress among mothers of children under 5-years-old living in two rural areas of Zambia during the COVID-19 pandemic. We examined the prevalence of mental health distress among a cohort of 1105 mothers using the World Health Organization's Self-Reporting Questionnaire (SRQ-20) before the onset of the COVID-19 pandemic in August 2019 and after the first two infection waves in October-November 2021. Our primary outcome was mental health distress, defined as SRQ-20 score above 7. We analyzed social, economic and family level characteristics as factors modifying to the COVID-19 induced changes in the mental health status. At baseline, 22.5% of women were in mental health distress. The odds of mental health distress among women increased marginally over the first two waves of the pandemic (aOR1.22, CI 0.99-1.49). Women under age 30, with lower educational background, with less than three children, and those living in Eastern Province (compared to Southern Province) of Zambia, were found to be at highest risk of mental health deterioration during the pandemic. Our findings suggest that the prevalence of mental health distress is high in this population and has further worsened during COVID-19 pandemic. Public health interventions targeting mothers' mental health in low resource settings may want to particularly focus on young mothers with limited educational attainment.

Postnatal care services in rural Zambia: a qualitative exploration of user, provider, and community perspectives on quality of care.

BACKGROUND: Postnatal care (PNC) is an important set of services offered to the mother and her newborn baby immediately after birth for the first six weeks to prevent maternal and neonatal complications and death. This qualitative study explored user and provider perspectives on quality of PNC services in the selected health facilities within the context of the Maternity Homes Access in Zambia project in the Saving Mothers Giving Life districts in rural Zambia. METHODS: Between October 2018 and February 2019, forty focus group discussions (FGDs) (n = 160 participants) and twelve in-depth interviews (IDIs) were conducted in four districts in Southern and Eastern provinces. FGDs comprised women who delivered within the last year, fathers, community elders, and volunteers. IDIs comprised health workers at facility, district, and provincial levels. Data were analysed using content analysis guided by the international quality of care domains derived from the World Health Organization quality of care framework. Findings were triangulated to understand perceptions. RESULTS: Overall, study participants perceived PNC services to be beneficial. Nevertheless, respondents had mixed feelings on the quality of PNC services and expressed a stark difference in their perception of factors affecting service quality. Service users described challenges arising from ineffective communication about the new PNC guidelines, and non-adherence of service providers to quality standards regarding respect, preservation of dignity and emotional support. Other factors were long waiting hours, small examination rooms providing inadequate privacy, and low levels of confidentiality. In contrast, service providers attributed poor service quality to various health system-related factors including low staffing levels, dysfunctional referral services, low supply of essential medicines, supplies, vaccines and equipment for optimal routine emergency obstetric and newborn care and management of complications. CONCLUSION: These findings highlight important intervention opportunities to improve quality of PNC services in Zambia through better communication and raising awareness on PNC guidelines, respect, preservation of dignity and emotional support to mothers. Interventions should also focus on addressing contextual health system challenges including staffing levels, supply chain for essential medicines and commodities, shortening waiting time, and ensuring functional referral system.

Lessons from a Year of COVID-19 in Zambia: Reported Attendance and Mask Wearing at Large Gatherings in Rural Communities.

Zambia instituted prevention behavior guidelines for social gatherings before the first case of COVID-19 was confirmed on March 18, 2020. Guidelines included nonpharmaceutical interventions (NPIs) including mask wearing, social distancing, and reducing sizes of gatherings. Within a larger cluster randomized trial of community-based parenting groups in four rural districts (three in Southern Province, one in Eastern Province), we collected 5,711 questionnaires from intervention participants between August 2020 and September 2021, during which the country saw two COVID-19 waves. Questionnaires asked about participation and behaviors at community gatherings. Generally, perception of risk of contracting COVID-19 was low for respondents in districts in Southern Province but higher for those in Eastern Province. The highest compliance to mask wearing was reported at clinics (84%) and church services (81%), which were the most frequently attended gatherings. Many funerals were attended by 200 to 300 people, but individuals were 30% less likely to report wearing masks (odds ratio [OR] = 0.71, 95% confidence ratio [CI]: 0.6-0.8) than those attending a clinic visit. After controlling for other variables, the odds of self-reported mask wearing at events were higher in January to March 2021 (adjusted OR = 1.5, 95% CI: 1.3, 1.7) and July and September of 2021 (adjusted OR = 3.0, 95% CI: 2.5-3.5), timepoints that broadly overlay with two COVID-19 peaks observed in Zambia. Results suggest guideline dissemination penetrated the rural areas. However, there is need to optimize the messaging to increase compliance to NPIs at high-risk gatherings, including funerals. The findings from this analysis should be considered as the COVID-19 pandemic continues to evolve.

Preferences for services in a patient's first six months on antiretroviral therapy for HIV in South Africa and Zambia (PREFER): research protocol for a prospective observational cohort study.

Background: For patients on HIV treatment in sub-Saharan Africa, the highest risk for loss from care remains the first six months after antiretroviral (ART) initiation, when patients are not yet eligible for differentiated service delivery (DSD) models that offer lower-burden, patient-centred care and thus improve treatment outcomes. To reduce early disengagement from care, the PREFER study will use a sequential mixed-methods approach to describe the characteristics, needs, concerns, and preferences of patients in South Africa and Zambia 0-6 months after ART initiation or re-initiation. Protocol: PREFER is an observational, prospective cohort study of adults on ART for ≤6 months at 12 public healthcare facilities in Zambia and 18 in South Africa. Its objective is to describe and understand the needs and preferences of initiating and re-initiating ART clients to inform the design of DSD models for the early HIV treatment period, improve early treatment outcomes, and distinguish the barriers encountered by naïve patients from those facing re-initiators. It has four components: 1) survey of clients 0-6 months after ART initiation (identify characteristics and preferences of clients starting ART); 2) follow up through routinely collected medical records for <24 months after enrollment (describe resource utilization and patterns and predictors of engagement in care); 3) focus group discussions and discrete choice experiment (explore reported barriers to and facilitators of retention); and 4) in South Africa only, collection of blood samples (assess the prevalence of ARV metabolites indicating prior ART use). Conclusions: PREFER aims to understand why the early treatment period is so challenging and how service delivery can be amended to address the obstacles that lead to early disengagement from care. It will generate information about client characteristics and preferences to help respond to patients' needs and design better strategies for service delivery and improve resource allocation going forward.

The role of Savings and Internal Lending Communities (SILCs) in improving community-level household wealth, financial preparedness for birth, and utilization of reproductive health services in rural Zambia: a secondary analysis.

BACKGROUND: Savings and Internal Lending Communities (SILCs) are a type of informal microfinance mechanism widely adapted in Zambia. The benefits of SILCs paired with other interventions have been studied in many countries. However, limited studies have examined SILCs in the context of maternal health. This study examined the association between having access to SILCs and: 1) household wealth, 2) financial preparedness for birth, and 3) utilization of various reproductive health services (RHSs). METHODS: Secondary analysis was conducted on baseline and endline household survey data collected as part of a Maternity Waiting Home (MWH) intervention trial in 20 rural communities across seven districts of Zambia. Data from 4711 women who gave birth in the previous year (baseline: 2381 endline: 2330) were analyzed. The data were stratified into three community groups (CGs): CG1) communities with neither MWH nor SILC, CG2) communities with only MWH, and CG3) communities with both MWH and SILC. To capture the community level changes with the exposure to SILCs, different women were randomly selected from each of the communities for baseline and endline data, rather than same women being surveyed two times. Interaction effect of CG and timepoint on the outcome variables - household wealth, saving for birth, antenatal care visits, postnatal care visits, MWH utilization, health facility based delivery, and skilled provider assisted delivery - were examined. RESULTS: Interaction effect of CGs and timepoint were significantly associated only with MWH utilization, health facility delivery, and skilled provider delivery. Compared to women from CG3, women from CG1 had lower odds of utilizing MWHs and delivering at health facility at endline. Additionally, women from CG1 and women from CG2 had lower odds of delivering with a skilled provider compared to women from CG3. CONCLUSION: Access to SILCs was associated with increased MWH use and health facility delivery when MWHs were available. Furthermore, access to SILCs was associated with increased skilled provider delivery regardless of the availability of MWH. Future studies should explore the roles of SILCs in improving the continuity of reproductive health services. TRIAL REGISTRATION: NCT02620436.

Observational study of the clinical performance of a public-private partnership national referral hospital network in Lesotho: Do improvements last over time?

Public-private partnerships (PPP) may increase healthcare quality but lack longitudinal evidence for success. The Queen 'Mamohato Memorial Hospital (QMMH) in Lesotho is one of Africa's first healthcare PPPs. We compare data from 2012 and 2018 on capacity, utilization, quality, and outcomes to understand if early documented successes have been sustained using the same measures over time. In this observational study using administrative and clinical data, we assessed beds, admissions, average length of stay (ALOS), outpatient visits, and patient outcomes. We measured triage time and crash cart stock through direct observation in 2013 and 2020. Operational hospital beds increased from 390 to 410. Admissions decreased (-5.3%) while outpatient visits increased (3.8%). ALOS increased from 5.1 to 6.5 days. Occupancy increased from 82% to 99%; half of the wards had occupancy rates ≥90%, and Neonatal ward occupancy was 209%. The proportion of crash cart stock present (82.9% to 73.8%) and timely triage (84.0% to 27.6%) decreased. While overall mortality decreased (8.0% to 6.5%) and neonatal mortality overall decreased (18.0% to 16.3%), mortality among very low birth weight neonates increased (30.2% to 36.8%). Declines in overall hospital mortality are promising. Yet, continued high occupancy could compromise infection control and impede response to infections, such as COVID-19. High occupancy in the Neonatal ward suggests that the population need for neonatal care outpaces QMMH capacity; improvements should be addressed at the hospital and systemic levels. The increase in ALOS is acceptable for a hospital meant to take the most critical cases. The decline in crash cart stock completeness and timely triage may affect access to emergency treatment. While the partnership itself ended earlier than anticipated, our evaluation suggests that generally the hospital under the PPP was operational, providing high-level, critically needed services, and continued to improve patient outcomes. Quality at QMMH remained substantially higher than at the former Queen Elizabeth II hospital.

Keeping Patients Safer: Reviewing Predictors of Success and Failure of Short Peripheral Intravenous Catheters.

In 2014, a large urban community hospital adopted protected clinical indication practices as a quality improvement project. It then undertook a research study to examine bedside practices with short peripheral catheters, which included direct observation at the bedside once weekly for 6 months. A total of 4305 catheters were observed and remained in place for a total of 23 423 days. Fifty six percent of devices remained in place beyond 96 hours. The overall rate of peripheral bloodstream infection in patients enrolled in the study was 0.12/1000 peripheral intravenous days. Significant differences were noted based on which department placed the catheter, as well as which department cared for the patient during hospitalization. Patients admitted to step-down critical care units had the highest completion of therapy rates; however, those being cared for in medical/surgical units had the best outcomes. Devices placed in the emergency department had a higher successful dwell rate than those placed in critical care units. Twenty-gauge catheters were found to have the highest successful dwell rate, as well as insertion sites that were observed to be within normal limits during the weekly observation. Dressings that were noted to be clean, dry, and intact had a stronger association with completion of therapy than those that were not fully intact. Emphasis was placed on ensuring consistent practices with insertion, care, and maintenance, which contributed to more consistent outcomes between settings that insert, care for, and maintain devices. Nonmodifiable risk factors may remain.

Barriers and facilitators to facility-based delivery in rural Zambia: a qualitative study of women's perceptions after implementation of an improved maternity waiting homes intervention.

OBJECTIVES: Women in sub-Saharan Africa face well-documented barriers to facility-based deliveries. An improved maternity waiting homes (MWH) model was implemented in rural Zambia to bring pregnant women closer to facilities for delivery. We qualitatively assessed whether MWHs changed perceived barriers to facility delivery among remote-living women. DESIGN: We administered in-depth interviews (IDIs) to a randomly selected subsample of women in intervention (n=78) and control (n=80) groups who participated in the primary quasi-experimental evaluation of an improved MWH model. The IDIs explored perceptions and preferences of delivery location. We conducted content analysis to understand perceived barriers and facilitators to facility delivery. SETTING AND PARTICIPANTS: Participants lived in villages 10+ km from the health facility and had delivered a baby in the previous 12 months. INTERVENTION: The improved MWH model was implemented at 20 rural health facilities. RESULTS: Over 96% of participants in the intervention arm and 90% in the control arm delivered their last baby at a health facility. Key barriers to facility delivery were distance and transportation, and costs associated with delivery. Facilitators included no user fees, penalties for home delivery, desire for safe delivery and availability of MWHs. Most themes were similar between study arms. Both discussed the role MWHs have in improving access to facility-based delivery. Intervention arm participants expressed that the improved MWH model encourages use and helps overcome the distance barrier. Control arm participants either expressed a desire for an improved MWH model or did not consider it in their decision making. CONCLUSIONS: Even in areas with high facility-based delivery rates in rural Zambia, barriers to access persist. MWHs may be useful to address the distance challenge, but no single intervention is likely to address all barriers experienced by rural, low-resourced populations. MWHs should be considered in a broader systems approach to improving access in remote areas. TRIAL REGISTRATION NUMBER: NCT02620436.

Planning for Maternity Waiting Home Bed Capacity: Lessons from Rural Zambia.

Background: Maternity waiting homes (MWH) allow pregnant women to stay in a residential facility close to a health center while awaiting delivery. This approach can improve health outcomes for women and children. Health planners need to consider many factors in deciding the number of beds needed for an MWH. Objective: The objective of the study is to review experience in Zambia in planning and implementing MWHs, and consider lessons learned in determining optimal capacity. Methods: We conducted a study of 10 newly built MWH in Zambia over 12 months. For this case study analysis, data on beds, service volume, and catchment area population were examined, including women staying at the homes, bed occupancy, and average length of stay. We analyzed bed occupancy by location and health facility catchment area size, and categorized occupancy by month from very low to very high. Findings: Most study sites were rural, with 3 of the 10 study sites rural-remote. Four sites served small catchment areas (<9 000), 3 had medium (9 000-11 000), and 3 had large (>11 000) size populations. Annual occupancy was variable among the sites, ranging from 13% (a medium rural site) to 151% (a large rural-remote site). Occupancy higher than 100% was accommodated by repurposing the MWH postnatal beds and using extra mattresses. Most sites had between 26-69% annual occupancy, but monthly occupancy was highly variable for reasons that seem unrelated to catchment area size, rural or rural-remote location. Conclusion: Planning for MWH capacity is difficult due to high variability. Our analysis suggests planners should try to gather actual recent monthly birth data and estimate capacity using the highest expected utilization months, anticipating that facility-based deliveries may increase with introduction of a MWH. Further research is needed to document and share data on MWH operations, including utilization statistics like number of beds, mattresses, occupancy rates and average length of stay.

Addressing Inequities in SARS-CoV-2 Vaccine Uptake: The Boston Medical Center Health System Experience.

Academic medical centers could play an important role in increasing access to and uptake of SARS-CoV-2 vaccines, especially in Black and Latino communities that have been disproportionately affected by the pandemic. This article describes the vaccination program developed by the Boston Medical Center (BMC) health system (New England's largest safety-net health system), its affiliated community health centers (CHCs), and community partners. The program was based on a conceptual framework for community interventions and aimed to increase equitable access to vaccination in the hardest-hit communities through community-based sites in churches and community centers, mobile vaccination events, and vaccination on the BMC campus. Key strategies included a communication campaign featuring trusted messengers, a focus on health equity, established partnerships with community leaders and CHCs, and strong collaboration with local health departments and the Commonwealth of Massachusetts to ensure equitable allocation of the vaccine supply. Process factors involved the use of robust analytics relying on the Centers for Disease Control and Prevention's Social Vulnerability Index (SVI). The vaccination program administered 109 938 first doses, with 94 703 (86%) given at community sites and 2466 (2%) given at mobile sites. Mobile vaccination events were key in reaching younger people living in locations with the highest SVIs. Challenges included the need for a robust operational infrastructure and mistrust of the health system given the long history of economic disinvestment in the surrounding community. The BMC model could serve as a blueprint for other medical centers interested in implementing programs aimed at increasing vaccine uptake during a pandemic and in developing an infrastructure to address other health-related disparities.

GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity.

Inhibitory myeloid cells and their cytokines play critical roles in limiting chimeric antigen receptor T (CART) cell therapy by contributing to the development of toxicities and resistance following infusion. We have previously shown that neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF) prevents these toxicities and enhances CART cell functions by inhibiting myeloid cell activation. In this report, we study the direct impact of GM-CSF disruption during the production of CD19-directed CART cells on their effector functions, independent of GM-CSF modulation of myeloid cells. In this study, we show that antigen-specific activation of GM-CSFKO CART19 cells consistently displayed reduced early activation, enhanced proliferation, and improved anti-tumor activity in a xenograft model for relapsed B cell malignancies. Activated CART19 cells significantly upregulate GM-CSF receptors. However, the interaction between GM-CSF and its upregulated receptors on CART cells was not the predominant mechanism of this activation phenotype. GM-CSFKO CART19 cell had reduced BH3 interacting-domain death agonist (Bid), suggesting an interaction between GM-CSF and intrinsic apoptosis pathways. In conclusion, our study demonstrates that CRISPR/Cas9-mediated GM-CSF knockout in CART cells directly ameliorates CART cell early activation and enhances anti-tumor activity in preclinical models.

A systemic review of the role of enterotoxic Bacteroides fragilis in colorectal cancer.

Enterotoxigenic Bacteroides fragilis (ETBF) has received significant attention for a possible association with, or causal role in, colorectal cancer (CRC). The goal of this review was to assess the status of the published evidence supporting (i) the association between ETBF and CRC and (ii) the causal role of ETBF in CRC. PubMed and Scopus searches were performed in August 2021 to identify human, animal, and cell studies pertaining to the role of ETBF in CRC. Inclusion criteria included the use of cell lines, mice, exposure to BFT or ETBF, and detection of bft. Review studies were excluded, and studies were limited to the English language. Quality of study design and risk of bias analysis was performed on the cell, animal, and human studies using ToxRTools, SYRCLE, and NOS, respectively. Ninety-five eligible studies were identified, this included 22 human studies, 24 animal studies, 43 cell studies, and 6 studies that included both cells and mice studies. We found that a large majority of studies supported an association or causal role of ETBF in CRC, as well as high levels of study bias was detected in the in vitro and in vivo studies. The high-level heterogeneity in study design and reporting made it difficult to synthesize these findings into a unified conclusion, suggesting that the need for future studies that include improved mechanistic models, longitudinal in vitro and in vivo evidence, and appropriate control of confounding factors will be required to confirm whether ETBF has a direct role in CRC etiopathogenesis.

Using Open Public Meetings and Elections to Promote Inward Transparency and Accountability: Lessons From Zambia.

BACKGROUND: Community-led governance can ensure that leaders are accountable to the populations they serve and strengthen health systems for maternal care. A key aspect of democratic accountability is electing respective governance bodies, in this case community boards, and holding public meetings to inform community members about actions taken on their behalf. After helping build and open 10 maternity waiting homes (MWHs) in rural Zambia as part of a randomized controlled trial, we assisted community governance committees to plan and execute annual meetings to present performance results and, where needed, to elect new board members. METHODS: We applied a principally qualitative design using observation and analysis of written documentation of public meetings to answer our research question: how do governance committees enact inward transparency and demonstrate accountability to their communities. The analysis measured participation and stakeholder representation at public meetings, the types and purposes of accountability sought by community members as evidenced by questions asked of the governance committee, and responsiveness of the governance committee to issues raised at public meetings. RESULTS: Public meetings were attended by 6 out of 7 possible stakeholder groups, and reports were generally transparent. Stakeholders asked probing questions focused mainly on financial performance. Governance committee members were responsive to questions raised by participants, with 59% of answers rated as fully or mostly responsive (showing understanding of and answering the question). Six of the 10 sites held elections to re-elect or replace governance committee members. Only 2 sites reached the target set by local stakeholder committees of 50% female membership, down from 3 at formation. To further improve transparency and accountability, community governance committees need to engage in advance preparation of reports, and should consult with stakeholders on broader measures for performance assessment. Despite receiving training, community-level governance committees lacked understanding of the strategic purpose of open public meetings and elections, and how these relate to democratic accountability. They were therefore not motivated to engage in tactics to manage stakeholders effectively. CONCLUSION: While open meetings and elections have potential to enhance good governance at the community level, continuous training and mentoring are needed to build capacity and enhance sustainability.

Out-of-Pocket Expenditures for Delivery for Maternity Waiting Home Users and Non-users in Rural Zambia.

BACKGROUND: Utilizing maternity waiting homes (MWHs) is a strategy to improve access to skilled obstetric care in rural Zambia. However, out-of-pocket (OOP) expenses remain a barrier for many women. We assessed delivery-related expenditure for women who used MWHs and those who did not who delivered at a rural health facility. METHODS: During the endline of an impact evaluation for an MWH intervention, household surveys (n = 826) were conducted with women who delivered a baby in the previous 13 months at a rural health facility and lived >10 km from a health facility in seven districts of rural Zambia. We captured the amount women reported spending on delivery. We compared OOP spending between women who used MWHs and those who did not. Amounts were converted from Zambian kwacha (ZMW) to US dollar (USD). RESULTS: After controlling for confounders, there was no significant difference in delivery-related expenditure between women who used MWHs (US$40.01) and those who did not (US$36.66) (P=.06). Both groups reported baby clothes as the largest expenditure. MWH users reported spending slightly more on accommodation compared to those did not use MWHs, but this difference represents only a fraction of total costs associated with delivery. CONCLUSION: Findings suggest that for women coming from far away, utilizing MWHs while awaiting delivery is not costlier overall than for women who deliver at a health facility but do not utilize a MWH.