Severity and burden of sickle cell disease in France: a nationwide real-world study.

The burden of sickle cell disease (SCD) in France has been difficult to apprehend due to the paucity of reliable nationwide epidemiological data. We aimed to describe the epidemiology of SCD and evaluate its burden and costs. Patients with SCD and most severely affected patients were identified between 2012 and 2018 from the French National Health Data System database (SNDS, Système national des données de santé). Outcomes of interest included rates of acute and chronic complications, healthcare resource utilization and associated costs, and were compared in subpopulations of patients before and after hematopoietic stem cell transplantation, initiating hydroxyurea or a chronic transfusion program. Between 2012 and 2018, 22,619 patients with SCD were identified, among which 4,270 patients were defined as most severely affected. Rates of vaso-occlusion episodes and acute chest syndrome were 86.29 (95% confidence interval [CI]: 85.75-86.83] and 12.90 (95% CI: 12.69-13.11) per 100 person years in the study population and 166.9 (95% CI: 165.4- 168.4) and 22.71 (95% CI: 22.16-23.27) per 100 person years in most severely affected patients. Median (Q1-Q3) annualized total costs were €5,073.63 (range, €1,633.74-14,000.94) and €13,295.67 (range, €5,754.67-26,385.23) in the study population and most severely affected patients. Median annualized costs were ten times lower after treatment intensification for hematopoietic stem cell transplantation (€29,011.75 vs. €2,465.98; P<0.001), they slightly decreased after hydroxyurea initiation (€13,057.79 vs. €12,752.44; P=0.003) and were five times higher after chronic transfusion program initiation (€4,643.11 vs. €22,715.85; P<0.001). SCD still places a significant demand on health resources, even after therapeutic intensification.

Co-morbidities and mortality in patients with sickle cell disease in England: A 10-year cohort analysis using hospital episodes statistics (HES) data.

Patients with a primary diagnosis of sickle cell disease (SCD) with or without crisis during the 10-year period January 2009 to December 2018 were identified in the HES Admitted Patient Care (APC) dataset and matched with the Office for National Statistics (ONS) mortality dataset. Three sub-cohorts were defined: 'crises', 'transfusions' and 'other SCD'. APC records were examined for co-morbidities commonly associated with SCD and 10-year mortality rates compared with the general population. After data cleaning and exclusions, 9503 patients remained (entire cohort), with 1171, 201, and 8131 in crises, transfusions, and other SCD sub-cohorts, respectively. Median numbers of co-morbidities per patient were 2 (Interquartile range (IQR): 1-4), 2 (IQR: 1-3), and 1 (IQR: 0-2) in the crises, transfusions, and other SCD sub-cohorts, respectively. The majority of patients in the crises (63.2%) and transfusions (56.3%) cohorts had ≥2 co-morbidities, compared with 25.3% in the other SCD sub-cohort. Crude 10-year mortality rate was 5.3% (entire cohort), compared with 8.0% (crises) and 11.4% (transfusions) sub-cohorts; all rates were substantially higher than in age-sex matched general population. Our study adds further evidence that morbidity and mortality associated with SCD in England is high.

Contraceptive use among adolescent and young women in North and South Kivu, Democratic Republic of the Congo: A cross-sectional population-based survey.

BACKGROUND: Adolescent girls in humanitarian settings are especially vulnerable as their support systems are often disrupted. More than 20 years of violence in the Democratic Republic of the Congo (DRC) has weakened the health system, resulting in poor sexual and reproductive health (SRH) outcomes for women. Little evidence on adolescent contraceptive use in humanitarian settings is available. CARE, International Rescue Committee (IRC), and Save the Children, in collaboration with the Reproductive Health Access, Information and Services in Emergencies (RAISE) Initiative, Columbia University, have supported the Ministry of Health (MOH) since 2011 to provide good quality contraceptive services in public health facilities in conflict-affected North and South Kivu. In this study, we analyzed contraceptive use among sexually active young women aged 15-24 in the health zones served by the partners' programs. METHODS AND FINDINGS: The partners conducted cross-sectional population-based surveys in program areas of North and South Kivu using two-stage cluster sampling in six health zones in July-August 2016 and 2017. Twenty-five clusters were selected in each health zone, 22 households in each cluster, and one woman of reproductive age (15-49 years) was randomly selected in each household. This manuscript presents results from a secondary data analysis for 1,022 women aged 15-24 who reported ever having sex: 326 adolescents (15-19 years) and 696 young women (20-24 years), 31.7% (95% confidence interval [CI] 29.5-34.1), of whom were displaced at least once in the previous five years. Contraceptive knowledge was high, with over 90% of both groups able to name at least one modern contraceptive method. Despite this high knowledge, unmet need for contraception was also high: 31.7% (95%CI 27.9-35.7) among 15-19-year-olds and 40.1% (95% CI 37.1-43.1, p = 0.001) among 20-24-year-olds. Current modern contraceptive use (16.5%, 95% CI 14.7-18.4) was similar in both age groups, the majority of whom received their method from a supported health facility. Among current users, more than half of 15-19-year-olds were using a long-acting reversible contraceptive (LARC; 51.7%, 95% CI 41.1-61.9) compared to 36.5% of 20-24-year-olds (95% CI 29.6-43.9, p = 0.02). Age, younger age of sexual debut, having some secondary education, being unmarried, and having begun childbearing were associated with modern contraceptive use. The main limitations of our study are related to insecurity in three health zones that prevented access to some villages, reducing the representativeness of our data, and our defining sexually active women as those who have ever had sex. CONCLUSIONS: In this study, to our knowledge one of the first to measure contraceptive prevalence among adolescents in a humanitarian setting, we observed that adolescent and young women will use modern contraception, including long-acting methods. Meaningful engagement of adolescent and young women would likely contribute to even better outcomes. Creating an enabling environment by addressing gender and social norms, however, is key to reducing stigma and meeting the demand for contraception of young women. As we continue to build such supportive environments, we can see that they will use effective contraception when contraceptive services, including short- and long-acting methods, are available, even in protracted crisis settings.

"Provide care for everyone please": engaging community leaders as sexual and reproductive health advocates in North and South Kivu, Democratic Republic of the Congo.

BACKGROUND: Inadequate infrastructure, security threats from ongoing armed conflict, and conservative socio-cultural and gender norms that favour large families and patriarchal power structures contribute to poor sexual and reproductive health (SRH) outcomes in North and South Kivu provinces, Democratic Republic of the Congo (DRC). In order to expand contraceptive and post-abortion care (PAC) access in North and South Kivu, CARE, the International Rescue Committee and Save the Children provided technical support to the Ministry of Health and health facilities in these regions. Partners acknowledged that community leaders, given their power to influence local customs, could play a critical role as agents of change in addressing inequitable gender norms, stigma surrounding SRH service utilization, and topics traditionally considered taboo within Congolese society. As such, partners actively engaged with community leaders through a variety of activities such as community mapping exercises, values clarification and transformation (VCAT) activities, situational analyses, and education. METHODS: This manuscript presents findings from 12 key informant interviews (KIIs) with male political and non-political community leaders conducted in six rural health zones of North and South Kivu, DRC. Transcripts were analysed thematically to explore community leaders' perceptions of their role in addressing the issue of unintended pregnancy in their communities. RESULTS: While community leaders in this study expressed overall positive impressions of contraception and strong support for ensuring access to PAC services following spontaneous and induced abortions, the vast majority held negative beliefs concerning women who had induced abortion. Contrasting with their professed opposition to induced abortion, leaders' commitment to mediating interpersonal conflict arising between community members and women who had abortions was overwhelming. CONCLUSION: Results from this study suggest that when thoughtfully engaged by health interventions, community leaders can be empowered to become advocates for SRH. While study participants were strong supporters of contraception and PAC, they expressed negative perceptions of induced abortion. Given the hypothesized link between the presence of induced abortion stigma and care-avoidance behavior, further engagement and values clarification exercises with leaders must be integrated into community mobilization and engagement activities in order to increase PAC utilization.

Induction therapy with rabbit antithymocyte globulin versus basiliximab after kidney transplantation: a health economic analysis from a German perspective.

A health economic analysis was undertaken based on the 1-year database from a randomized study of rabbit anti-human thymocyte immunoglobulin (rATG) versus basiliximab, in kidney transplantation using resource utilization data and cost estimates from three German hospitals. A three-state Markov model was applied to estimate cost-effectiveness to 10 years post-transplant. Total mean treatment cost per patient to year 1 post-transplant was €62 075 vs. €59 767 for rATG versus basiliximab (P < 0.01). rATG therapy was associated with similar treatment costs to basiliximab by year 2, and a predicted cumulative treatment cost saving of €4 259 under rATG versus basiliximab by year 10 post-transplant. The mean number of quality-adjusted life years (QALYs) per patient by year 1 was 0.809 vs. 0.802 in the rATG and basiliximab cohorts, respectively (P = 0.38), with cumulative QALYs of 6.161 and 6.065 per patient by year 10. By year 2, the cumulative cost per QALY was slightly lower under rATG (€35 378) than basiliximab (€35 885), progressing to a saving of €1 041 under rATG for the cumulative cost per QALY by year 10. In conclusion, this model indicates that rATG induction provides a modest increase in QALYs with lower long-term costs than basiliximab in deceased-donor high-risk kidney transplant patients.

Uptake of postabortion care services and acceptance of postabortion contraception in Puntland, Somalia.

Unsafe abortion is responsible for at least 9% of all maternal deaths worldwide; however, in humanitarian emergencies where health systems are weak and reproductive health services are often unavailable or disrupted, this figure is higher. In Puntland, Somalia, Save the Children International (SCI) implemented postabortion care (PAC) services to address the issue of high maternal morbidity and mortality due to unsafe abortion. Abortion is explicitly permitted by Somali law to save the life of a woman, but remains a sensitive topic due to religious and social conservatism that exists in the region. Using a multipronged approach focusing on capacity building, assurance of supplies and infrastructure, and community collaboration and mobilisation, the demand for PAC services increased as did the proportion of women who adopted a method of family planning post-abortion. From January 2013 to December 2015, a total of 1111 clients received PAC services at the four SCI-supported health facilities. The number of PAC clients increased from a monthly average of 20 in 2013 to 38 in 2015. During the same period, 98% (1090) of PAC clients were counselled for postabortion contraception, of which 955 (88%) accepted a contraceptive method before leaving the facility, with 30% opting for long-acting reversible contraception. These results show that comprehensive PAC services can be implemented in politically unstable, culturally conservative settings where abortion and modern contraception are sensitive and stigmatised matters among communities, health workers, and policy makers. However, like all humanitarian settings, large unmet needs exist for PAC services in Somalia.

Cost-Effectiveness of Lovotibeglogene Autotemcel (Lovo-Cel) Gene Therapy for Patients with Sickle Cell Disease and Recurrent Vaso-Occlusive Events in the United States.

BACKGROUND AND OBJECTIVE: Gene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥ 12 years with ≥ 4 vaso-occlusive events (VOEs) in the past 24 months. METHODS: We developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase 1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses. RESULTS: Patients treated with lovo-cel were predicted to survive 23.84 years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40 years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs. CONCLUSIONS: Our analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden.

Nutritional status of haemodialysis patients: comparison of Australian cohorts of Aboriginal and European descent.

AIM: It is not known whether nutritional status differs between Australian Aboriginal and non Aboriginal haemodialysis subjects. The aim of this study was to investigate the nutritional status of Australian Aboriginal and non-Aboriginal haemodialysis subjects at satellite dialysis centres. METHOD: Seventy-six (25 Aboriginal, 51 non-Aboriginal) prevalent haemodialysis patients were enrolled in a 3-month cross-sectional study. Each month anthropometric and biochemical measurements were collected. Nutritional status (diet history, patient-generated subjective global assessment (PG-SGA), handgrip strength) was assessed by a dietitian. RESULTS: PG-SGA detected mild to moderate malnutrition in 35% of Aboriginal patients and 25% of non-Aboriginal patients. The overall physical rating on the PG-SGA was significantly higher in Aboriginal patients, indicating the presence of a greater deficit in muscle mass in this population. Inter-dialytic weight gain was significantly greater in Aboriginal subjects (median [range] 3.0 [2.1-5.7] vs 2.5 [-0.3-5.0] kg, P<0.001). Glucose and HbA1c were significantly higher in Aboriginal subjects with diabetes than in non-Aboriginal patients with diabetes (median [range] 9.4 [4.9-23.4] vs 5.7 [3.1-12.9], P=0.002; 7.0 [5.2-11.0] vs 5.8 [4.6-9.0], P<0.000; respectively). These findings occurred in the setting of each cohort having adequate dialysis parameters (median Kt/V of >1.6 and median normalized protein catabolic rate 1.5). Difficulties were encountered in obtaining dietary information from Aboriginal subjects using the diet history method. CONCLUSION: Subjects had acceptable parameters of dialysis adequacy; however, 35% had evidence of malnutrition. Further research should focus on establishing a knowledge base for the nutritional management for Aboriginal dialysis subjects, and the development of a validated individual dietary assessment method for use in this population group.

Measuring supply-side service disruption: a systematic review of the methods for measuring disruption in the context of maternal and newborn health services in low and middle-income settings.

OBJECTIVES: During the COVID-19 pandemic, most essential services experienced some level of disruption. Disruption in LMICs was more severe than in HICs. Early reports suggested that services for maternal and newborn health were disproportionately affected, raising concerns about health equity. Most disruption indicators measure demand-side disruption, or they conflate demand-side and supply-side disruption. There is currently no published guidance on measuring supply-side disruption. The primary objective of this review was to identify methods and approaches used to measure supply-side service disruptions to maternal and newborn health services in the context of COVID-19. DESIGN: We carried out a systematic review and have created a typology of measurement methods and approaches using narrative synthesis. DATA SOURCES: We searched MEDLINE, EMBASE and Global Health in January 2023. We also searched the grey literature. ELIGIBILITY CRITERIA: We included empirical studies describing the measurement of supply-side service disruption of maternal and newborn health services in LMICs in the context of COVID-19. DATA EXTRACTION AND SYNTHESIS: We extracted the aim, method(s), setting, and study outcome(s) from included studies. We synthesised findings by type of measure (ie, provision or quality of services) and methodological approach (ie, qualitative or quantitative). RESULTS: We identified 28 studies describing 5 approaches to measuring supply-side disruption: (1) cross-sectional surveys of the nature and experience of supply-side disruption, (2) surveys to measure temporal changes in service provision or quality, (3) surveys to create composite disruption scores, (4) surveys of service users to measure receipt of services, and (5) clinical observation of the provision and quality of services. CONCLUSION: Our review identified methods and approaches for measuring supply-side service disruption of maternal and newborn health services. These indicators provide important information about the causes and extent of supply-side disruption and provide a useful starting point for developing specific guidance on the measurement of service disruption in LMICs.

Heterogeneity of the long-term economic burden of severe sickle cell disease: a 5-year longitudinal analysis.

BACKGROUND: Sickle cell disease (SCD) is a lifelong burdensome disorder of heterogenic expression. This study investigated the longer-term economic burden of severe presentation of SCD. As SCD treatment landscapes evolve toward curative intent gene therapies, understanding how SCD-associated costs may change over the patient lifetime will be important for medical decision-making. METHODS: Patients with severe presentation of SCD (presence of acute vaso-occlusive events [VOEs] or history of stroke and/or other disease-related sequelae), were identified within the MarketScan Commercial and Medicare Supplemental and Multi-state Medicaid Databases from 1/1/2010 to 12/31/2018. The first SCD claim served as the index date and patients were followed over a 5-year post-period. Clinical characteristics and healthcare resource utilization and costs were assessed over follow-up for eligible cohorts of commercial and Medicaid patients with severe SCD presentation and age-based subgroups (<18, 18-30, and ≥31). RESULTS: A total of 4,487 patients, primarily insured via Medicaid (79.2%), qualified for the analysis. Patients evidenced persistent VOEs over follow-up; prevalence of most comorbidities increased with age. Mean total healthcare costs over the 5-year follow-up were $275,143 (SD± $406,770) and $362,728 (SD± $620,189) in the commercial and Medicaid samples, respectively. Disease severity, assessed by the number of VOEs and utilization of inpatient and emergency services, peaked in the 18-30 year group in both samples. These groups also evidenced the highest mean healthcare costs over the 5-year follow-up at $344,776 (SD± $434,521) and $671,321 (SD± $938,764) in the commercial and Medicaid samples respectively. CONCLUSION: Results indicate high clinical need and economic burden among patients with severe presentation of SCD. These findings not only highlight the need for improved therapeutic options to limit or prevent disease progression, but also start to provide insight on lifetime costs of SCD that will be needed in the evaluation of emerging curative intent therapies.

Understanding the Sexual and Reproductive Health Experiences of Refugee and Host Community Adolescents and Youth in Rwanda During COVID-19: Needs, Barriers, and Opportunities.

Background: COVID-19 has exacerbated the sexual and reproductive health (SRH) needs of those affected by humanitarian emergencies, particularly affecting adolescents and youth, whose needs are often neglected during crises. In Rwanda, the situation for refugees in Mahama Refugee Camp has worsened, as COVID-19 lockdown measures have increased needs while restricting access to basic services. Few assessments have been conducted on the SRH needs of refugees in Mahama camp, including adolescents and youth, since COVID-19. To address this gap, Save the Children (SC) undertook research utilizing SenseMaker to collect data on the SRH needs of adolescents and youth in Mahama camp, as well as in the surrounding host community. Methodology: SC used SenseMaker to collect 745 data entries from adolescents and youth in Mahama camp and the surrounding host community. The application was pretested with adolescents and youth in Mahama camp before initiating the research. SenseMaker asks participants to share their stories in response to a prompt; our prompt asked participants to describe their experience seeking help with their health during COVID-19. The research team analyzed the data using simultaneous coding to examine key themes. The results were discussed with SC staff to validate the coding analysis results before conducting four focus group discussions to further clarify results and propose action steps in response to the findings. Results: Many adolescents and youth reported significant difficulties accessing SRH information and services, including stigmatization among service providers. Provider biases and negative attitudes were repeatedly cited as barriers. Stories collected during COVID-19 show how these biases and judgmental attitudes continue to adversely affect access and use of SRH services for young people. Coercive, non-consensual, and transactional sexual incidents were reported from adolescents and youth. They cited reduced time in education spaces as a source of distress as well as increasing their level of sexual activity and associated risks. Limited data exists for SRH needs among adolescents and youth during COVID-19 in humanitarian settings. This study adds to the evidence, making the case for increased SRH prioritization for adolescents and youth in humanitarian settings, particularly when facing overlapping crises like during the COVID-19 pandemic.

Adapting High Impact Practices in Family Planning During the COVID-19 Pandemic: Experiences From Kenya, Nigeria, and Zimbabwe.

BACKGROUND: We describe how High Impact Practices (HIPs) in family planning (FP) were adapted across Kenya, Nigeria, and Zimbabwe to maintain access to services in response to the coronavirus disease (COVID-19) pandemic. METHODS: Using a qualitative data collection tool structured around 3 HIP categories (service delivery, demand creation, and enabling environment), adaptations in FP programs during the pandemic were documented. We describe adaptations made to 3 specific HIPs: mobile outreach, community health workers, and digital health for social and behavior change. PROGRAM EXPERIENCES: In Zimbabwe, the Mhuri/Imuli project adapted its mobile outreach model integrating community-based outreach with facility-based outreach. The number of outreach clients served per week peaked at 1,759 (July 2020) from a low of 203 (May 2020). Clients choosing long-acting reversible methods increased from 22% to 59% during the 3 months before and after lockdown, respectively.In Kenya, a program addressed youth's hesitation to visit health facilities through youth community health volunteers, who provided counseling, community dialogues, contraceptive pills, and condoms. Over 6 months, the program reached 1,048 youth with community dialogues, and 4,656 youth received FP services. In Nigeria, peer mobilizers provided services through a socially distanced community-based program to help adolescent girls access contraceptive self-injection when movement restrictions limited youth's ability to travel to facilities.In Nigeria, Adolescents 360 adapted sexual and reproductive health information programs for virtual delivery through WhatsApp. A contraceptive education Facebook campaign gained more than 80,000 followers, reached 5.9 million adolescents, and linked 330 adolescents to program-supported facilities from January to March 2021. In Kenya, the Kibera-based project used WhatsApp to reach youth with discussion groups and health workers with skills strengthening. CONCLUSION: Monitoring how projects adapt HIPs to ensure continuity of care during the COVID-19 pandemic can help inform the implementation of successful adaptations in the face of present and future challenges.

Care-seeking behavior by survivors of sexual assault in the Democratic Republic of the Congo.

In February 2008, trained female interviewers collected data on sexual violence and use of medical services following sexual assault from 607 women in the Democratic Republic of the Congo (DRC). Exposure to sexual violence during the DRC's civil war was reported by 17.8% of the women; 4.8% of the women reported exposure to sexual violence after the war. Few sexual-assault survivors accessed timely medical care. Facility assessments showed that this care was rarely available. Clinical care for sexual-assault survivors must be integrated into primary health care for DRC women.

Evaluating the mental health of Jordanian women in relationships with intimate partner abuse.

This study evaluated the mental health consequences of abuse among Jordanian women and tested the effectiveness of using cognitive behavioral interventions to change the level of depression and level of stress among Jordanian women experiencing intimate partner abuse (IPA). A mixed methods design using phenomenology and quasi-experimental research data collection and analysis was implemented. The most commonly reported form of abuse was psychological abuse. Prior to cognitive behavioral intervention, participants demonstrated moderate to severe levels of depression, low levels of perceived social support, moderate to high levels of self-efficacy, and used approach coping skills more frequently than avoidance coping. Cognitive behavioral interventions resulted in decreased depression (p = .003) and decreased stress levels, although this finding did not reach significance (p > .05). Cognitive behavioral interventions are effective interventions when working with women experiencing IPA.

Immediate Postpartum Long-Acting Reversible Contraception: A Comparison Across Six Humanitarian Country Contexts.

Postpartum family planning (FP) could prevent more than 30% of maternal deaths by effectively spacing births; this is particularly relevant in humanitarian contexts given that disproportionate maternal death occurs in countries affected by crises. In humanitarian settings, where accessing functional facilities is challenging with security risks that constrain movement, many women are unable to return for their 6-week postpartum visits and thus unable to receive FP counseling and adopt a method that suits their fertility intentions. Thus, immediate postpartum family planning (IPPFP) interventions, focused on long-acting reversible contraception (LARC) and tailored toward humanitarian contexts, could contribute to healthy timing and spacing of pregnancy, particularly among postpartum women, and improve maternal and newborn health. In 2014, Save the Children integrated postpartum intrauterine device (IUD) services into its FP package in emergency settings. In 2017, this expanded to include postpartum implant uptake as well, given updated World Health Organization guidelines. Three countries (Democratic Republic of Congo, Somalia, and Pakistan) opted for higher-intensity programming for IPPFP with a specific focus on LARC. This involved training delivery-room providers on counseling and provision of IPPFP, as well as training antenatal care nurses in counseling pregnant women on IPPFP options. Three countries (Rwanda, Syria, and Yemen) did not implement notable IPPFP interventions, although they provided the standard of care and monitored provision via monthly service delivery data. Using data from 2016 to 2019, we examined trends in immediate postpartum LARC (IPP LARC) uptake and compared countries with higher-intensity IPP LARC interventions to countries providing standard care. Tests of association were performed to assess the significance of these differences. In the country programs with higher-intensity IPPFP interventions, IPP LARC as a percentage of all deliveries was much higher overall during the July 2016-December 2019 period. The IPP LARC intervention had a significant impact on the overall proportion of women and girls who adopted an IUD or implant within the first 48 h of delivery, F (1, 250) = 523.16, p < 0.001. The mean percentage of IPP LARC among all deliveries in intervention country programs was 10.01% as compared to 0.77% in countries providing standard care. Results suggest that there is demand for IPP LARC in humanitarian contexts and that uptake increases when multipronged solutions focusing on provider training, community outreach, and service integration are applied.

Strengthening Health Systems in Humanitarian Settings: Multi-Stakeholder Insights on Contraception and Postabortion Care Programs in the Democratic Republic of Congo and Somalia.

Background: In humanitarian settings, strengthening health systems while responding to the health needs of crisis-affected populations is challenging and marked with evidence gaps. Drawing from a decade of family planning and postabortion care programming in humanitarian settings, this paper aims to identify strategic components that contribute to health system strengthening in such contexts. Materials and Methods: A diverse range of key informants from North Kivu (Democratic Republic of Congo, DRC) and Puntland (Somalia), including female and male community members, adolescents and adults, healthcare providers, government and community leaders, participated in qualitative interviews, which applied the World Health Organization health system building blocks framework. Data were thematically analyzed according to this framework. Results: Findings from the focus group discussions (11 in DRC, 7 in Somalia) and key informant interviews (seven in DRC, four in Somalia) involving in total 54 female and 72 male participants across both countries indicate that health programs in humanitarian settings, such as Save the Children's initiative on family planning and postabortion care, could contribute to strengthening health systems by positively influencing national policies and guidance, strengthening local coordination mechanisms, capacitating the healthcare workforce with competency-based training and supportive supervision (benefiting facilities supported by the project and beyond), developing the capacity of Ministry of Health staff in the effective management of the supply chain, actively and creatively mobilizing the community to raise awareness and create demand, and providing quality and affordable services. Financial sustainability is challenged by the chronically limited healthcare expenditure experienced in both humanitarian contexts. Conclusions: In humanitarian settings, carefully designed healthcare interventions, such as those that address the family planning and postabortion care needs of crisis-affected populations, have the potential not only to increase access to essential services but also contribute to strengthening several components of the health system while increasing the government capacity, ownership, and accountability.

AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer.

PURPOSE: Radiation and cetuximab are therapeutics used in management of head and neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development of both intrinsic and acquired resistance is an emerging problem in the management of this disease. The purpose of this study was to investigate signaling of the receptor tyrosine kinase AXL in resistance to radiation and cetuximab treatment. EXPERIMENTAL DESIGN: To study AXL signaling in the context of treatment-resistant HNSCC, we used patient-derived xenografts (PDXs) implanted into mice and evaluated the tumor response to AXL inhibition in combination with cetuximab or radiation treatment. To identify molecular mechanisms of how AXL signaling leads to resistance, three tyrosine residues of AXL (Y779, Y821, Y866) were mutated and examined for their sensitivity to cetuximab and/or radiation. Furthermore, reverse phase protein array (RPPA) was employed to analyze the proteomic architecture of signaling pathways in these genetically altered cell lines. RESULTS: Treatment of cetuximab- and radiation-resistant PDXs with AXL inhibitor R428 was sufficient to overcome resistance. RPPA analysis revealed that such resistance emanates from signaling of tyrosine 821 of AXL via the tyrosine kinase c-ABL. In addition, inhibition of c-ABL signaling resensitized cells and tumors to cetuximab or radiotherapy even leading to complete tumor regression without recurrence in head and neck cancer models. CONCLUSIONS: Collectively, the studies presented herein suggest that tyrosine 821 of AXL mediates resistance to cetuximab by activation of c-ABL kinase in HNSCC and that targeting of both EGFR and c-ABL leads to a robust antitumor response.

When political solutions for acute conflict in Yemen seem distant, demand for reproductive health services is immediate: a programme model for resilient family planning and post-abortion care services.

The political situation in Yemen has been precarious since 2011 when popular protest broke out amid the Arab Spring, calling for President Saleh to step down. In March 2015, a Houthi insurgency took control of the capital, Sana'a and ignited a civil conflict that is now characterised by foreign political and military involvement. Since 2015, health facilities have been a primary target for airstrikes and bombing. Seaports have been blockaded barring the delivery of essential medicines and supplies, contributing to the near collapse of an already fragile health system. Since 2012, Save the Children (SC) has been implementing a Family Planning (FP) and Post-abortion Care (PAC) programme in two governorates heavily affected by the conflict. Despite the risks associated with the conflict, there remains a strong demand for SC's FP and PAC services. Ongoing programmatic support and capacity strengthening have allowed quality FP and PAC services to continue for Yemenis even when humanitarian access is impeded. Since the onset of conflict in March 2015, 16 facilities provided services to 43,218 new FP clients (with 23% accepting a long-acting method) and treated 3627 women with PAC. Over 93% of FP clients would recommend FP services at the facility to a friend or family member. Findings support growing evidence that women affected by conflict require family planning services, and that demand does not decline as long as quality services remain accessible. An adaptable reproductive health programme model that embraces innovative approaches is necessary for establishing services and maintaining quality during acute conflict.