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Abstract The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.

Abstract Background Maternal and Perinatal Death Surveillance and Response (MPDSR) systems provide an opportunity for health systems to understand the determinants of maternal and perinatal deaths in order to improve quality of care and prevent future deaths from occurring. While there has been broad uptake and learning from low- and middle-income countries, little is known on how to effectively implement MPDSR within humanitarian contexts – where disruptions in health service delivery are common, infrastructural damage and insecurity impact the accessibility of care, and severe financial and human resource shortages limit the quality and capacity to provide services to the most vulnerable. This study aimed to understand how contextual factors influence facility-based MPDSR interventions within five humanitarian contexts. Methods Descriptive case studies were conducted on the implementation of MPDSR in Cox’s Bazar refugee camps in Bangladesh, refugee settlements in Uganda, South Sudan, Palestine, and Yemen. Desk reviews of case-specific MPDSR documentation and in-depth key informant interviews with 76 stakeholders supporting or directly implementing mortality surveillance interventions were conducted between December 2021 and July 2022. Interviews were recorded, transcribed, and analyzed using Dedoose software. Thematic content analysis was employed to understand the adoption, penetration, sustainability, and fidelity of MPDSR interventions and to facilitate cross-case synthesis of implementation complexities. Results Implementation of MPDSR interventions in the five humanitarian settings varied in scope, scale, and approach. Adoption of the interventions and fidelity to established protocols were influenced by availability of financial and human resources, the implementation climate (leadership engagement, health administration and provider buy-in, and community involvement), and complex humanitarian-health system dynamics. Blame culture was pervasive in all contexts, with health providers often facing punishment or criminalization for negligence, threats, and violence. Across contexts, successful implementation was driven by integrating MPDSR within quality improvement efforts, improving community involvement, and adapting programming fit-for-context. Conclusions The unique contextual considerations of humanitarian settings call for a customized approach to implementing MPDSR that best serves the immediate needs of the crisis, aligns with stakeholder priorities, and supports health workers and humanitarian responders in providing care to the most vulnerable populations.

Objective: To describe two main pillars of the Maryland Maternal Health Innovation Program (MDMOM): (1) centering equity and (2) fostering broad stakeholder collaboration and trust. Methods: We summarized MDMOM?s key activities and used severe maternal morbidity (SMM) surveillance and program monitoring data to quantify MDMOM?s work on the two pillars. We developed measures of hospital engagement with MDMOM (participation in quality improvement [QI] activities, participation in check-in meetings, staff involvement) and with other partners (participation in QI activities, representation in state-level groups). We examined Bonferroni-adjusted correlations between these hospital engagement measures and with key hospital characteristics: level of maternity care, annual delivery volume, and SMM rate. Results: Over 100 national and state organizations and individual stakeholders contributed to our building the MDMOM program and implementing key activities centering equity: hospital-based SMM surveillance in 20 of Maryland?s 32 hospitals; almost 5,000 trainings offered to perinatal health care providers; two telemedicine/telehealth interventions; training of home visitors and community-based organization staff. Birthing hospitals represent MDMOM?s main implementation partners. The strength of their participation in MDMOM QI activities is positively correlated to their participation in check-in meetings and with the degree of involvement by physicians in such activities. Higher engagement in MDMOM QI activities is also positively correlated to hospitals? participation in other state-level maternal health initiatives or groups. Conclusion: Our experience with the MDMOM program demonstrates that an equity focus and broad stakeholder collaboration building strong relationships and providing implementation support can lead to high levels of engagement in innovative maternal health interventions.

Severe maternal morbidity (SMM) refers to any unexpected outcome directly related to pregnancy and childbirth that results in both short-term delivery complications and long-term consequences to a womens health. This affects about 60,000 women annually in the United States. Cardiovascular contributions to SMM including cardiac arrest, arrhythmia, and acute myocardial infarction are on the rise, probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. The utilization of SMM prediction tools and risk scores specific to cardiovascular disease in pregnancy has helped with risk stratification. Furthermore, health system data monitoring and reporting to identify and assess etiologies of cardiovascular complications has led to improvement in outcomes and greater standardization of care for mothers with cardiovascular disease. Improving cardiovascular disease-related SMM relies on a multipronged approach comprised of patient-level identification of risk factors, individualized review of SMM cases, and validation of risk stratification tools and system-wide improvements in quality of care. In this article, we review the epidemiology and cardiac causes of SMM, we provide a framework of risk prediction clinical tools, and we highlight need for organization of care to improve outcomes.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia.Methods: We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture.Results: Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir® Medium dried flowers (NC1) and Cannabixir® THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%–89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values.Discussion and Conclusion: Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.

Hepatic fibrosis is a common consequence of chronic liver diseases and necessitates accurate evaluation for optimal patient management. Traditional liver biopsy, the gold standard for fibrosis assessment, is invasive and can be associated with complications. Lately, considerable progress has been made in developing noninvasive markers for liver fibrosis evaluation.This comprehensive review presents a systematic analysis of the current noninvasive markers for hepatic fibrosis assessment. Serological markers, imaging techniques and novel technologies are thoroughly evaluated for their diagnostic accuracy and clinical applicability.The advantages and limitations of each noninvasive marker are discussed, highlighting their potential to replace or complement liver biopsy. Moreover, challenges and opportunities in standardization, validation, and clinical implementation of these markers are addressed.In conclusion, noninvasive markers play a significant role in hepatic fibrosis evaluation. As reliable alternatives to liver biopsy, these markers have the potential to enhance patient care, streamline disease monitoring, and drive personalized treatment strategies in liver diseases associated with fibrosis. However, further research and validation studies are required to establish their widespread use in routine clinical practice.

Melanoma is one of the most aggressive forms of skin cancer. While most melanomas have a discernible primary site, a small subset, approximately 3.2%, present as a metastatic disease without an identifiable primary origin, a condition known as melanoma of unknown primary (MUP). Unusual cases of primary melanoma have also been previously reported in the respiratory, gastrointestinal, and urogenital tracts. MUP typically is found in lymph nodes, subcutaneous sites, and visceral organs, with hypotheses about its origin including spontaneous primary tumor regression and ectopic melanocytes. MUP presents unique challenges in diagnosis and treatment due to the absence of a detectable primary tumor. Understanding its genetic and molecular features, epidemiology, prognostic factors, and treatment options is crucial for optimizing patient care and outcomes in this subset of melanoma patients. We conducted an extensive literature review triggered by a case report of a patient with suspected MUP. A 51-year-old woman was transferred from another hospital where an incision was performed for a suspected superinfected hematoma of the left thigh. Since the patient showed high leukocytosis and redness and swelling of the thigh, local debridement, drainage, and excisional biopsy of the tumor mass were performed in our unit in the emergency setting, and the tumor was taken for histopathology evaluation. Intraoperatively, the mass appeared nonspecific. The permanent histopathology report established a diagnosis of melanoma, with tumor proliferation also involving lymphoid tissue, and despite broad clinical and imagistic assessments, the primary melanoma could not be identified. Clinicians must be aware of the varied clinical manifestations of malignant melanoma, especially in cases of occult melanoma where the primary site is not evident.

Objectives: This study examines the relationship between integrated, person-centered maternity care (PCMC), the provision of postpartum family planning (PPFP) services, and postpartum contraceptive use among women delivering at health facilities in Ethiopia. Study design: We analyze 2019–2021 longitudinal data from a representative sample of pregnant and recently postpartum women in Ethiopia. This study examines baseline, 6-week, and 6-month survey data collected from women who delivered at a health facility. Results: Maternity patients who reported more person-centered care were more likely to be counseled on postpartum contraceptive methods before discharge. Overall, 27.5% of women delivering in a health facility received family planning counseling before discharge, ranging from 15.2% in the lowest PCMC quintile to 36.3% in the highest PCMC quintile. The receipt of PPFP counseling was associated with increased odds of postpartum contraceptive use. Conclusions: Findings suggest dimensions of quality care are interlinked, and person-centered care is associated with greater integration of recommended PPFP services into predischarge procedures. However, even among women who report relatively high levels of person-centered care, our results highlight that family planning is not routinely discussed prior to discharge from delivery, and very few women receive a contraceptive method or referral prior to discharge. Implications: While most postpartum women report they wish to limit or space future pregnancies, the uptake of modern contraceptive methods in the postpartum period is low. As women increasingly opt to deliver in health facilities, further integration of family planning services into predischarge procedures within maternity care can improve contraceptive access. Data statement: The data used in these analyses were collected as part of the PMA Ethiopia study. Data are publicly available at https://www.pmadata.org/data/request-access-datasets.

As part of an investment by the Bill & Melinda Gates Foundation to support the Government of Bihar to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) statewide, BBC Media Action implemented multiple communication tools to support front-line worker (FLW) outreach. We analyse the impacts of a package of mHealth audio messaging and paper-based job aids used by FLWs during government-sponsored village health, sanitation and nutrition days (VHSNDs) on knowledge and practices of childbearing women across the RMNCHN continuum of care. Data from two surveys collected between July and September 2016 were analysed using logistic regression to compare health-related knowledge and behaviours between women who had been exposed at VHSNDs to the mHealth GupShup Potli (GSP) audio recordings or interpersonal communication (IPC) tools versus those who were unexposed. Exposure to GSP recordings (n=2608) was associated with improved knowledge across all continuum-of-care domains, as well as improved health-related behaviours in some domains. The odds of having taken iron-folic acid (IFA) tablets were significantly higher in exposed women (OR 1.5, 95% CI 1.1 to 2.2), as was contraceptive use (OR 2.0, 95% CI 1.2 to 3.2). There were no differences in birth preparedness or complementary feeding practices between groups. Exposure to IPC paper-based tools (n=2002) was associated with a twofold increased odds of IFA consumption (OR 2.3, 95% CI 1.7 to 3.2) and contraceptive use (OR 1.8, 95% CI 1.2 to 2.8). Women exposed to both tools were generally at least twice as likely to subsequently discuss the messages with others. BBC Media Action's mHealth audio messaging job aids and paper-based IPC tools were associated with improved knowledge and practices of women who were exposed to them across multiple domains, suggesting their important potential for improving health outcomes for beneficiaries at scale in low-resource settings. NCT02726230.

Purpose: The main research goal was to address the critical need for an objective and quantitative index to describe the nature and extent of radiographic features of medication-related osteonecrosis of the jaw (MRONJ) lesions and complement the descriptive radiographic interpretation of the lesion and its clinical assessment. Method and Materials: A retrospective review of MRONJ patients assessed at our institution was performed to compare the Composite Radiographic Index (CRI), identified from a prior scoping review, with a proposed modification, the Modified CRI index (‘Mod-CRI’). The Mod-CRI index was weighted to assign a higher score for diffuse radiographic involvement of a given lesion, and delineated MRONJ lesions into those with ‘high’ and ‘low’ severity. Twenty-two MRONJ cases imaged with CBCT were retrospectively assessed with both CRI and Mod-CRI indices and the two indices were compared for their ability to quantitatively describe cone-beam computerized tomography (CBCT) radiographic features and complement the clinical staging of the MRONJ lesion. Results: There was a statistically significant association between increased clinical stage and higher mod-CRI score (p = 0.040). The Mod-CRI index sorted the patients who scored intermediate scores with the CRI (n = 15) into either the low (n = 8) or high categories (n = 7). Conclusion: The Mod-CRI index eliminated the ambiguous intermediate-category-scores in the previously published CRI index and provided greater clarity to the interpretation of a given index score. Adopting the Mod-CRI could improve MRONJ assessment and enhance communication between the radiologist and the clinician.

In 2010, the Bill and Melinda Gates Foundation (BMGF) partnered with the Government of Bihar (GoB), India to launch the Ananya program to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) outcomes. The program sought to address supply- and demand-side barriers to the adoption, coverage, quality, equity and health impact of select RMNCHN interventions. Approaches included strengthening frontline worker service delivery; social and behavior change communications; layering of health, nutrition and sanitation into women's self-help groups (SHGs); and quality improvement in maternal and newborn care at primary health care facilities. Ananya program interventions were piloted in approximately 28 million population in eight innovation districts from 2011-2013, and then beginning in 2014, were scaled up by the GoB across the rest of the state's population of 104 million. A Bihar Technical Support Program provided techno-managerial support to governmental Health as well as Integrated Child Development Services, and the JEEViKA Technical Support Program supported health layering and scale-up of the GoB's SHG program. The level of support at the block level during statewide scale-up in 2014 onwards was approximately one-fourth that provided in the pilot phase of Ananya in 2011-2013. This paper - the first manuscript in an 11-manuscript and 2-viewpoint collection on Learning from Ananya: Lessons for primary health care performance improvement - seeks to provide a broad description of Ananya and subsequent statewide adaptation and scale-up, and capture the background and context, key objectives, interventions, delivery approaches and evaluation methods of this expansive program. Subsequent papers in this collection focus on specific intervention delivery platforms. For the analyses in this series, Stanford University held key informant interviews and worked with the technical support and evaluation grantees of the Ananya program, as well as leadership from the India Country Office of the BMGF, to analyse and synthesise data from multiple sources. Capturing lessons from the Ananya pilot program and statewide scale-up will assist program managers and policymakers to more effectively design and implement RMNCHN programs at scale through technical assistance to governments.

BackgroundThe objective of this study was to assess the impact of self-help groups (SHGs) and subsequent scale-up on reproductive, maternal, newborn, child health, and nutrition (RMNCHN) and sanitation outcomes among marginalised women in Bihar, India from 2014-2017.MethodsWe examined RMNCHN and sanitation behaviors in women who were members of any SHGs compared to non-members, without differentiating between types of SHGs. We analysed annual surveys across 38 districts of Bihar covering 62 690 women who had a live birth in the past 12 months. All analyses utilised data from Community-based Household Surveys (CHS) rounds 6-9 collected in 2014-2017 by CARE India as part of the Bihar Technical Support Program funded by the Bill & Melinda Gates Foundation. We examined 66 RMNCHN and sanitation indicators using survey logistic regression; the comparison group in all cases was age-comparable women from the geographic contexts of the SHG members but who did not belong to SHGs. We also examined links between discussion topics in SHGs and changes in relevant behaviours, and stratification of effects by parity and mother's age.ResultsSHG members had higher odds compared to non-SHG members for 60% of antenatal care indicators, 22% of delivery indicators, 70% of postnatal care indicators, 50% of nutrition indicators, 100% of family planning and sanitation indicators and no immunisation indicators measured. According to delivery platform, most FLW performance indicators (80%) had increased odds, followed by maternal behaviours (57%) and facility care and outreach service delivery (22%) compared to non-SHG members. Self-report of discussions within SHGs on specific topics was associated with increased related maternal behaviours. Younger SHG members (

BackgroundSelf-help group (SHG) interventions have been widely studied in low and middle income countries. However, there is little data on specific impacts of health layering, or adding health education modules upon existing SHGs which were formed primarily for economic empowerment. We examined three SHG interventions from 2012-2017 in Bihar, India to test the hypothesis that health-layering of SHGs would lead to improved health-related behaviours of women in SHGs.MethodsA model for health layering of SHGs - Parivartan - was developed by the non-governmental organisation (NGO), Project Concern International, in 64 blocks of eight districts. Layering included health modules, community events and review mechanisms. The health layering model was adapted for use with government-led SHGs, called JEEViKA+HL, in 37 other blocks of Bihar. Scale-up of government-led SHGs without health layering (JEEViKA) occurred contemporaneously in 433 other blocks, providing a natural comparison group. Using Community-based Household Surveys (CHS, rounds 6-9) by CARE India, 62 reproductive, maternal, newborn and child health and nutrition (RMNCHN) and sanitation indicators were examined for SHGs with health layering (Pavivartan SHGs and JEEViKA+HL SHGs) compared to those without. We calculated mean, standard deviation and odds ratios of indicators using surveymeans and survey logistic regression.ResultsIn 2014, 64% of indicators were significantly higher in Parivartan members compared to non-members residing in the same blocks. During scale up, from 2015-17, half (50%) of indicators had significantly higher odds in health layered SHG members (Parivartan or JEEViKA+HL) in 101 blocks compared to SHG members without health layering (JEEViKA) in 433 blocks.ConclusionsHealth layering of SHGs was demonstrated by an NGO-led model (Parivartan), adapted and scaled up by a government model (JEEViKA+HL), and associated with significant improvements in health compared to non-health-layered SHGs (JEEViKA). These results strengthen the evidence base for further layering of health onto the SHG platform for scale-level health change.Study registrationClinicalTrials.gov number NCT02726230.

BackgroundThe Ananya program in Bihar implemented household and community-level interventions to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) in two phases: a first phase of intensive ancillary support to governmental implementation and innovation testing by non-government organisation (NGO) partners in eight focus districts (2012-2014), followed by a second phase of state-wide government-led implementation with techno-managerial assistance from NGOs (2014 onwards). This paper examines trends in RMNCHN indicators in the program's implementation districts from 2012-2017.MethodsEight consecutive rounds of cross-sectional Community-based Household Surveys conducted by CARE India in 2012-2017 provided comparable data on a large number of indicators of frontline worker (FLW) performance, mothers' behaviours, and facility-based care and outreach service delivery across the continuum of maternal and child care. Logistic regression, considering the complex survey design and sample weights generated by that design, was used to estimate trends using survey rounds 2-5 for the first phase in the eight focus districts and rounds 6-9 for the second phase in all 38 districts statewide, as well as the overall change from round 2-9 in focus districts. To aid in contextualising the results, indicators were also compared amongst the formerly focus and the non-focus districts at the beginning of the second phase.ResultsIn the first phase, the levels of 34 out of 52 indicators increased significantly in the focus districts, including almost all indicators of FLW performance in antenatal and postnatal care, along with mother's birth preparedness, some breastfeeding practices, and immunisations. Between the two phases, 33 of 52 indicators declined significantly. In the second phase, the formerly focus districts experienced a rise in the levels of 14 of 50 indicators and a decline in the levels of 14 other indicators. There was a rise in the levels of 22 out of 50 indicators in the non-focus districts in the second phase, with a decline in the levels of 13 other indicators.ConclusionsImprovements in indicators were conditional on implementation support to program activities at a level of intensity that was higher than what could be achieved at scale so far. Successes during the pilot phase of intensive support suggests that RMNCHN can be improved statewide in Bihar with sufficient investments in systems performance improvements.Study registrationClinicalTrials.gov number NCT02726230.

BackgroundDespite increasing focus on health inequities in low- and middle income countries, significant disparities persist. We analysed impacts of a statewide maternal and child health program among the most compared to the least marginalised women in Bihar, India.MethodsUtilising survey-weighted logistic regression, we estimated programmatic impact using difference-in-difference estimators from Mathematica data collected at the beginning (2012, n = 10 174) and after two years of program implementation (2014, n = 9611). We also examined changes in disparities over time using eight rounds of Community-based Household Surveys (CHS) (2012-2017, n = 48 349) collected by CARE India.ResultsAt baseline for the Mathematica data, least marginalised women generally performed desired health-related behaviours more frequently than the most marginalised. After two years, most disparities persisted. Disparities increased for skilled birth attendant identification [+16.2% (most marginalised) vs +32.6% (least marginalized), P

BackgroundMobile health (mHealth) tools have potential for improving the reach and quality of health information and services through community health workers in low- and middle-income countries. This study evaluates the impact of an mHealth tool implemented at scale as part of the statewide reproductive,maternal, newborn and child health and nutrition (RMNCHN) program in Bihar, India.MethodsThree survey-based data sets were analysed to compare the health-related knowledge, attitudes and behaviours amongst childbearing women exposed to the Mobile Kunji and Dr. Anita mHealth tools during their visits with frontline workers compared with those who were unexposed.ResultsAn evaluation by Mathematica (2014) revealed that exposure to Mobile Kunji and Dr. Anita recordings were associated with significantly higher odds of consuming iron-folic acid tablets (odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.8-3.1) as well as taking a set of three measures for delivery preparedness (OR = 2.8, 95% CI = 1.9-4.2) and appropriate infant complementary feeding (OR = 1.9, 95% CI = 1.0-3.5). CARE India's Community-based Household Surveys (2012-2017) demonstrated significant improvements in early breastfeeding (OR = 1.64, 95% CI = 1.5-1.78) and exclusive breastfeeding (OR = 1.46, 95% CI = 1.33-1.62) in addition to birth preparedness practices. BBC Media Action's Usage & Engagement Survey (2014) demonstrated a positive association between exposure to Mobile Kunji and Dr. Anita and exclusive breastfeeding (58% exposed vs 43% unexposed, P

BackgroundThe Government of Bihar (GoB) in India, the Bill and Melinda Gates Foundation and several non-governmental organisations launched the Ananya program aimed to support the GoB to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) statewide. Here we summarise changes in indicators attained during the initial two-year pilot phase (2012-2013) of implementation in eight focus districts of approximately 28 million population, aimed to inform subsequent scale-up.MethodsThe quasi-experimental impact evaluation included statewide household surveys at two time points during the pilot phase: January-April 2012 ("baseline") including an initial cohort of beneficiaries and January-April 2014 ("midline") with a new cohort. The two arms were: 1) eight intervention districts, and 2) a comparison arm comprised of the remaining 30 districts in Bihar where Ananya interventions were not implemented. We analysed changes in indicators across the RMNCHN continuum of care from baseline to midline in intervention and comparison districts using a difference-in-difference analysis.ResultsIndicators in the two arms were similar at baseline. Overall, 40% of indicators (20 of 51) changed significantly from baseline to midline in the comparison districts unrelated to Ananya; two-thirds (n = 13) of secular indicator changes were in a direction expected to promote health. Statistically significant impact attributable to the Ananya program was found for 10% (five of 51) of RMNCHN indicators. Positive impacts were most prominent for mother's behaviours in contraceptive utilisation.ConclusionsThe Ananya program had limited impact in improving health-related outcomes during the first two-year period covered by this evaluation. The program's theories of change and action were not powered to observe statistically significant differences in RMNCHN indicators within two years, but rather aimed to help inform program improvements and scale-up. Evaluation of large-scale programs such as Ananya using theory-informed, equity-sensitive (including gender), mixed-methods approaches can help elucidate causality and better explain pathways through which supply- and demand-side interventions contribute to changes in behaviour among the actors involved in the production of population-level health outcomes. Evidence from Bihar indicates that deep structural constraints in health system organisation and delivery of interventions pose substantial limitations on behaviour change among health care providers and beneficiaries.Study registrationClinicalTrials.gov number NCT02726230.

Objectives: It is not unusual for Medication-related osteonecrosis of the jaw (MRONJ) lesions that have similar clinical presentation and staging to have dissimilar radiographic extent of disease. The aim of this review was to explore the published scientific literature for quantitative indices that describe the cone-beam computerized tomography (CBCT) radiographic features of MRONJ lesions and assess their clinical utility. Method and Materials: A scoping review of the literature was performed to identify quantitative indices developed to describe the CBCT radiographic features of MRONJ lesions. Five electronic databases were included in the review: PubMed, Scopus, Web of Science, Trip medical database, and Cochrane Library. Articles published from the year 2003 onward were included in the review. Results: 367 articles were initially included in the review. 39 abstracts were screened for full-text assessment. The scoping review yielded 12 full length articles with169 cases reported. The Composite Radiographic Index score (CRI score) was identified as the most meaningful index in published literature that attempted to quantify qualitative radiographic changes (Walton, Grogan et al. 2019). However, lesions with similar CRI scores that corresponded to intermediate severity (3–5) may be very dissimilar radiographically in both nature and extent of radiographic changes, undercutting its clinical value. Conclusion: The CRI index score was the only relevant index for cross-sectional (one-time) assessment of established MRONJ lesions (non-stage 0). This scoping review yielded several critical questions regarding the clinical significance and prognostic implications of various radiographic changes in MRONJ, thereby identifying focus areas for future research.

Cannabis enjoyed a “golden age” as a medicinal product in the late 19th, early 20th century, but the increased risk of overdose and abuse led to its criminalization. However, the 21st century have witnessed a resurgence of interest and a large body of literature regarding the benefits of cannabinoids have emerged. As legalization and decriminalization have spread around the world, cancer patients are increasingly interested in the potential utility of cannabinoids. Although eager to discuss cannabis use with their oncologist, patients often find them to be reluctant, mainly because clinicians are still not convinced by the existing evidence-based data to guide their treatment plans. Physicians should prescribe cannabis only if a careful explanation can be provided and follow up response evaluation ensured, making it mandatory for them to be up to date with the positive and also negative aspects of the cannabis in the case of cancer patients. Consequently, this article aims to bring some clarifications to clinicians regarding the sometimes-confusing various nomenclature under which this plant is mentioned, current legislation and the existing evidence (both preclinical and clinical) for the utility of cannabinoids in cancer patients, for either palliation of the associated symptoms or even the potential antitumor effects that cannabinoids may have.

# Background Facility readiness is an important prerequisite for providing safe, effective childbirth care. This study assesses the readiness of health facilities in Ethiopia to provide childbirth services, describes variations in geographic access to service-ready facilities, and evaluates how facility readiness relates to childbirth service usage with a lens on equity. # Methods The study used cross-sectional data from a nationally representative sample of households in Ethiopia linked with data from health facilities serving the same areas. We explored variation in childbirth service readiness across facilities and classified facilities as "service-ready" if they had a readiness score of 0.75 or higher on a 0-1 scale. We used logistic regression modeling to examine the odds of residing within 10 kilometers of a service-ready facility by socioeconomic and geographic characteristics, and the odds of a facility delivery given the readiness of nearby facilities. # Results Childbirth service readiness was generally high for hospitals (median score: 0.92) with minimal variation (interquartile range, IQR: 0.88 to 0.96). Health centers and clinics displayed lower and more variable readiness (median: 0.75, IQR: 0.66 to 0.84). In both crude and adjusted regression analyses, odds of residing within 10 kilometers of a service-ready facility were significantly greater for women with higher education levels, greater wealth, and urban residence. We found the adjusted odds of using facility childbirth services were 1.23 (95% CI: 1.03, 1.48) times greater for each 0.10-unit increase in the readiness level of nearby facilities. # Conclusions Access to childbirth care is not equal for Ethiopian women. Those living in rural areas and the poor must travel farther to reach facility childbirth services, and the nearest facilities serving these women were less prepared to provide quality care. This may contribute to lower service utilization by such disadvantaged groups of women.

IntroductionWe evaluated the impact of a 'Team-Based Goals and Incentives' (TBGI) intervention in Bihar, India, designed to improve front-line (community health) worker (FLW) performance and health-promoting behaviours related to reproductive, maternal, newborn and child health and nutrition.MethodsThis study used a cluster randomised controlled trial design and difference-in-difference analyses of improvements in maternal health-related behaviours related to the intervention's team-based goals (primary), and interactions of FLWs with each other and with maternal beneficiaries (secondary). Evaluation participants included approximately 1300 FLWs and 3600 mothers at baseline (May to June 2012) and after 2.5 years of implementation (November to December 2014) who had delivered an infant in the previous year.ResultsThe TBGI intervention resulted in significant increases in the frequency of antenatal home visits (15 absolute percentage points (PP), p=0.03) and receipt of iron-folic acid (IFA) tablets (7 PP, p=0.02), but non-significant changes in other health behaviours related to the trial's goals. Improvements were seen in selected attitudes related to coordination and teamwork among FLWs, and in the provision of advice to beneficiaries (ranging from 8 to 14 PP) related to IFA, cord care, breast feeding, complementary feeding and family planning.ConclusionResults suggest that combining an integrated set of team-based coverage goals and targets, small non-cash incentives for teams who meet targets and team building to motivate FLWs resulted in improvements in FLW coordination and teamwork, and in the quality and quantity of FLW-beneficiary interactions. These improvements represent programmatically meaningful steps towards improving health behaviours and outcomes.Trial registration numberNCT03406221.

Background: Maternal mortality rate reviews have identified the need for improved patient education regarding the warning signs of maternal complications to reduce preventable deaths. Maternal and child home visiting programs have the potential to deliver this education in communities. Aims: This study sought to evaluate the baseline provision of warning signs education among home visiting programs in Maryland and to assess the acceptability of and preferences for warning signs education materials among program staff. Materials and Methods: This sequential exploratory, mixed-methods study included qualitative interviews and focus group discussions followed by a web-based survey of all home visiting programs providing early postpartum visits in Maryland. Results: Twenty-five home visiting program staff took part in qualitative data collection, and survey responses were submitted by a manager from 40 of 58 eligible home visiting programs (69% response rate). All survey respondents agreed that home visiting programs should provide warning signs education and more than 80% of programs provided some warning signs education during pregnancy and the postpartum period. Printed pamphlets were provided by 68% of programs for pregnancy complications and 43% for postpartum complications. Only 33% of respondents were satisfied with their existing warnings signs education materials; 98% were interested in new illustrated pamphlets and 88% were interested in education videos. Qualitative participants considered pamphlets with simple designs, limited text, and visuals, as the most accessible for home visiting clients. Conclusions: There are opportunities to strengthen and expand warning signs education in Maryland through home visiting programs using new printed and video education materials.

Antibiotic administration commonly induces allergic reactions, dysmicrobism and microbial resistance, but longterm effects due to changes in gut microbiota composition are difficult to assess. This paper aims to identify in the literature adverse effects induced by changes in gut microbiota composition after perinatal administration of antibiotics. Antibiotic administration during pregnancy is a predisposing factor for the development of bronchial asthma, eczema, or allergic rhinitis in children, but does not support the hypothesis as being a risk factor for childhood obesity/overweight. The effect on the newborn’s microbiota of prophylactic administration of antibiotics during caesarean section is controversial. Postnatal treatments with antibiotics frequently causes intestinal dysmicrobism, the most severe form being necrotizing enterocolitis, especially among premature infants, but effects on the changes in body weight are controversial. Early administration of broad-spectrum antibiotics, particularly macrolides and cephalosporins, is strongly associated with the development of bronchial asthma at age 5 years. Recently, altered auditory processing and changes in recognition memory were described in newborn exposed to antibiotics in the absence of infection. More studies are needed to clarify the association between the type of antibiotic, the frequency, respectively period (both prenatal and intrapartum) of administration and long-term effects.

# Background Well-functioning health management information systems (HMIS) enable decision-making at all health system levels. This study develops an index to measure the use of HMIS data at the facility level. # Methods We used two rounds of cross-sectional data collected from 305 health facilities in Ethiopia in 2019 (pre-COVID-19) and 2020 (post-COVID-19). We constructed a summative, 10-item index using exploratory factor analysis and 2019 index development data; and used Cronbach's alpha to assess reliability. To examine content validity, we mapped items against a previously published conceptual framework and consulted Ethiopian experts. We then employed one-way ANOVA and t-tests comparing the mean index scores overall and by key facility characteristics between 2019 and 2020. # Results The 10-item index loaded on one factor (Cronbach's alpha=0.74), and the index scores did not differ significantly by facility characteristics in 2019. The mean index score increased from 7.2 in 2019 to 7.9 in 2020 (*P*\

Influenza virus neuraminidase (NA) is a drug target and a potential vaccine antigen. Here, the authors provide a detailed analysis of the conformational stability of NA, and show how expression and stability of recombinant NA antigens can be strengthened through structure-based design.