ABSTRACT
BACKGROUND: Seasonal malaria chemoprevention (SMC) is a World Health Organization-recommended intervention for the prevention of malaria among children at high risk in areas with seasonal transmission. During the coronavirus disease 2019 (COVID-19) pandemic, SMC drug distribution was rapidly adapted to reduce contact and mitigate the risk of transmission between communities and community distributors, with caregivers administering doses. To address the challenges and find local solutions to improve administration and adherence, the role model approach was designed, implemented and evaluated in selected communities of Burkina Faso, Chad and Togo. This paper describes the results of this evaluation. METHODS: Focus group discussions were held with primary caregivers in all three countries to understand their perceptions of the approach's acceptability and feasibility. In Burkina Faso and Togo, household surveys assessed the characteristics of caregivers reached by role model activities. Key indicators on SMC coverage and adherence allowed for an assessment of caregiver engagement outcomes related to participation in activities. Statistical associations between participation in study's activities and caregiver beliefs related to SMC had been tested. RESULTS: The majority of caregivers believed the approach to have a positive effect on drug administration, with most adopting the promoted strategies. Greater involvement of fathers in drug administration and acknowledgement of their joint responsibility was a notable positive outcome. However, several barriers to participation were noted and there was criticism of the group approach. In Burkina Faso and Togo, end-of-round survey results revealed that 98.4% of respondents agreed the approach improved their knowledge and skills in malaria prevention, while 100% expressed a desire to continue practicing the behaviours learned. However, there was a relatively low level of awareness of the approach among communities. Participation was strongly associated with participants' self-reported belief in ease of remembering to administer, and ease of administering, SMC medicines. CONCLUSION: Caregivers perceived the role model approach to be beneficial in aiding drug administration, with other positive impacts also reported. Replication and scale-up should utilize the most popular communication channels and existing community structures to ensure activities are promoted effectively. A mixture of group and one-on-one approaches should be used where appropriate and feasible.
Subject(s)
Amodiaquine , Antimalarials , Caregivers , Drug Combinations , Malaria , Pyrimethamine , Sulfadoxine , Humans , Togo , Burkina Faso , Antimalarials/administration & dosage , Antimalarials/therapeutic use , Caregivers/psychology , Caregivers/statistics & numerical data , Child, Preschool , Infant , Malaria/prevention & control , Pyrimethamine/administration & dosage , Pyrimethamine/therapeutic use , Sulfadoxine/administration & dosage , Sulfadoxine/therapeutic use , Chad , Amodiaquine/administration & dosage , Amodiaquine/therapeutic use , Female , Male , Focus Groups , AdultABSTRACT
BACKGROUND: Recommended since 2012 by the World Health Organization (WHO), seasonal malaria chemoprevention (SMC) is a community-based intervention to prevent malaria in children in African regions where malaria transmission follows a seasonal pattern. Following the publication of consolidated WHO guidelines for malaria, SMC is expected to reach more children in new geographies in future years. Though SMC has been shown to reduce malaria-related morbidity and mortality, there is potential for quality improvement of the intervention implementation. Assisted by ten quality standards from a framework developed by Malaria Consortium, this paper aims to better understand the quality of SMC implementation and identify potential barriers to quality delivery of SMC. METHODS: A qualitative thematic analysis on data collected after the annual SMC rounds implemented in Burkina Faso and Chad in 2019 was conducted. Sixteen focus group discussions conducted with caregivers and community distributors were analysed. Three selected quality standards for SMC delivery; planning and enumeration; community engagement; and administration of SMC medicines provided overarching quality themes under which subthemes were identified. RESULTS: Eight subthemes relating to the three quality standards were identified. Although SMC was well accepted by communities in both settings, common barriers to the quality delivery of SMC were identified including difficulty ensuring adherence to the SMC administration protocol; difficulties reaching mobile populations; concerns around adverse drug reactions; rumours, and concerns about SMC safety; and community distributors' working conditions. Context-specific barriers included: the suboptimal timeliness of the SMC round in Burkina Faso, and the lack of involvement of female caregivers in mobilization activities in Chad. CONCLUSION: In the context of increased adoption of SMC, this paper provides relevant insights and recommendations for the improved implementation of SMC programmes. These include the integration of strategies addressing communities' concerns around adverse drug reactions, gender-specific mobilization strategies, and attention to community distributors' working conditions. It also highlights the importance and utility of further, robust research on the quality of SMC delivery.
RéSUMé EN FRANçAIS: BACKGROUND: Recommandée depuis 2012 par l'Organisation mondiale de la santé (OMS), la chimioprévention du paludisme saisonnier (CPS) est une intervention communautaire visant à prévenir le paludisme chez les enfants dans les régions d'Afrique où la transmission du paludisme suit un schéma saisonnier. Suite à la publication des lignes directrices consolidées de l'OMS sur le paludisme, la CPS devrait toucher davantage d'enfants dans de nouvelles zones géographiques dans les années à venir. Bien qu'il ait été démontré que la CPS réduisait la morbidité et la mortalité liées au paludisme, il y a du potentiel pour améliorer la qualité de l'implémentation l'intervention. En s'appuyant sur un cadre de normes de qualité de la CPS développé par le Malaria Consortium, cette publication vise à mieux comprendre la qualité de la mise en Åuvre de la CPS et à identifier les obstacles potentiels à la qualité de la mise en Åuvre de la CPS. METHODS: Une étude qualitative basée sur l'analyse secondaire des données collectées après les tournées annuelles du SMC mises en Åuvre au Burkina Faso et au Tchad en 2019 a été menée. Une analyse thématique de 16 discussions de groupe menées avec des parents/tuteurs et des distributeurs communautaires a été faite. Trois des éléments clés du cadre des normes de qualité pour le déploiement de la CPS ont fourni les thèmes de qualité principaux sous lesquels les sous-thèmes identifiés ont été placés. RéSULTATS: Huit sous-thèmes relatifs aux normes de qualité ; la planification, la sensibilisation et l'engagement des communautés ainsi que l'administration des médicaments de la CPS ont été identifiés. Bien que la CPS ait été bien acceptée par les communautés dans les deux contextes, des obstacles communs à la qualité du déploiement de la CPS ont été identifiés, notamment : la difficulté d'assurer le respect du protocole d'administration de la CPS; atteindre les populations mobiles ; les préoccupations concernant les effets indésirables des médicaments ; les rumeurs et les préoccupations concernant le SMC; et les conditions de travail des distributeurs communautaires. D'autres barrières spécifiques au contexte de déploiement ont été identifiées, telles que le choix sous-optimal de la période de déploiement au Burkina Faso ou le manque d'implication des mères/tutrices dans les activités de mobilisation au Tchad. CONCLUSION: Dans le contexte de l'adoption croissante de la CPS, cette publication fournit des informations et des recommandations pertinentes pour l'amélioration de la mise en Åuvre des programmes de CMS, telles que l'intégration de stratégies répondant aux préoccupations des communautés concernant les effets indésirables des médicaments, les stratégies de mobilisation spécifiques au genre, et/ou l'attention portée aux conditions de travail des distributeurs communautaires. Cette publication souligne également l'importance et l'utilité des recherches en cours sur la qualité du déploiement de la CPS.
RESUMO EM PORTUGUêS: INTRODUçãO: Recomendada desde 2012 pela Organização Mundial de Saúde (OMS), a quimioprevenção sazonal do paludismo (SMC) é uma intervenção de base comunitária para prevenir o paludismo em crianças em zonas da África onde a transmissão do paludismo segue um padrão sazonal. Após a publicação das diretrizes consolidadas da OMS sobre o paludismo, espera-se que a SMC chegue a mais crianças em novas zonas geográficas nos próximos anos. Embora se tenha demonstrado que a SMC reduz a morbilidade e a mortalidade causadas pelo paludismo, há potencial para melhorar a qualidade da implementação da intervenção. Com ajuda dum quadro de padrões de qualidade para a SMC desenvolvido pelo Malaria Consortium, a presente publicação visa compreender melhor a qualidade da implementação da SMC e identificar potenciais barreiras à qualidade da implementação da SMC. MéTODOS: Foi realizado um estudo qualitativo baseado na análise secundária dos dados recolhidos após as rondas anuais da SMC implementadas no Burkina Faso e no Chade em 2019. Foi efectuado uma análise temática de 16 discussões de grupos focais realizadas com cuidadores e distribuidores comunitários. Tres padrões do quadro de normas de qualidade para a implementação da SMC forneceu os principais temas de qualidade sob os quais os subtemas identificados foram colocados. RESULTADOS: Foram identificados oito sub-temas relacionados com padrões de qualidade; planeamento; sensibilização e envolvimento da comunidade; e administração de drogas da SMC. Embora a SMC tenha sido bem aceita pelas comunidades em ambos os contextos, foram identificadas barreiras comuns à implementação duma SMC de qualidade, incluindo: a dificuldade de assegurar o cumprimento do protocolo de administração da SMC; atingir populações móveis; preocupações com reacções adversas aos medicamentos; rumores e preocupações com a SMC; e as condições de trabalho dos distribuidores comunitários. Foram identificados outros obstáculos específicos ao contexto de implantação, tais como a escolha subaproveitada do período de implantação no Burkina Faso ou a falta de envolvimento das cuidadoras femininas nas actividades de mobilização no Chade. CONCLUSãO: No contexto do aumento da adopção da SMC, esta publicação fornece informações e recomendações relevantes para melhorar a implementação de programas de SMC, tais como estratégias integradoras que abordam as preocupações da comunidade sobre reacções adversas aos medicamentos, estratégias de mobilização específicas de género, e/ou atenção às condições de trabalho dos distribuidores comunitários. Salienta igualmente a importância e a utilidade das investigaçãos em curso sobre a qualidade da implementação da SMC.
Subject(s)
Caregivers , Chemoprevention , Malaria , Burkina Faso , Chad , Malaria/prevention & control , Chemoprevention/statistics & numerical data , Humans , Caregivers/psychology , Caregivers/statistics & numerical data , Antimalarials/administration & dosage , Antimalarials/therapeutic use , Seasons , Community Health Workers , Female , Male , Child, Preschool , Focus GroupsABSTRACT
Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al.1.
Subject(s)
Brain Neoplasms , Immunotherapy, Adoptive , Xenograft Model Antitumor Assays , Humans , Brain Neoplasms/therapy , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Animals , Mice , Immunotherapy, Adoptive/methods , T-Lymphocytes/immunology , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/immunology , Receptors, Chimeric Antigen/immunologyABSTRACT
BACKGROUND: Cameroon is one of the countries with the highest burden of malaria. Since 2018, there has been an ongoing conflict in the country, which has reduced access to healthcare for populations in affected regions, and little is known about the impact on access to malaria services. The objective of this study was to understand the current situation regarding access to malaria services in Cameroon to inform the design of interventions to remove barriers and encourage the use of available services. METHODS: A qualitative research study was carried out to understand the barriers preventing communities accessing care, the uptake of community health worker (CHW) services, and to gather perceptions on community engagement approaches, to assess whether these could be an appropriate mechanism to encourage uptake of community health worker (CHW) services. Twenty-nine focus group discussions and 11 in-depth interviews were carried out between May and July 2021 in two regions of Cameroon, Southwest and Littoral. Focus group discussions were held with CHWs and community members and semi-structured, in-depth interviews were conducted with key stakeholders including regional government staff, council staff, community leaders and community-based organisations. The data were analysed thematically; open, descriptive coding was combined with exploration of pre-determined investigative areas. RESULTS: The study confirmed that access to healthcare has become increasingly challenging in conflict-affected areas. Although the Ministry of Health are providing CHWs to improve access, several barriers remain that limit uptake of these services including awareness, availability, cost, trust in competency, and supply of testing and treatment. This study found that communities were supportive of community engagement approaches, particularly the community dialogue approach. CONCLUSION: Communities in conflict-affected regions of Cameroon continue to have limited access to healthcare services, in part due to poor use of CHW services provided. Community engagement approaches can be an effective way to improve the awareness and use of CHWs. However, these approaches alone will not be sufficient to resolve all the challenges faced by conflict-affected communities when accessing health and malaria services. Additional interventions are needed to increase the availability of CHWs, improve the supply of diagnostic tests and treatments and to reduce the cost of treatment for all.
Subject(s)
Health Services Accessibility , Malaria , Qualitative Research , Cameroon , Malaria/prevention & control , Humans , Health Services Accessibility/statistics & numerical data , Community Health Workers/statistics & numerical data , Focus Groups , Community Participation/statistics & numerical data , Male , Female , AdultABSTRACT
BACKGROUND: Malaria remains a major global health problem often worsened by political instability and armed conflict. The purpose of the study was to explore community knowledge, attitudes and practices on malaria prevention, and to understand the burden of malaria and health-seeking behaviours of caregivers of children under-five in conflict-affected communities of the South West and Littoral Regions of Cameroon. METHODS: A cross-sectional survey involving internally displaced persons (IDPS), host population, and their children under-five was conducted across 80 communities. The survey was conducted from May to June 2021. Participants were interviewed using a structured questionnaire. Malaria prevalence for children under-five was determined using rapid diagnostic tests (RDT) on blood samples. Association between variables and displacement status was measured using chi square test and multivariate logistic regression model was fitted to identify factors associated with adequate knowledge on malaria prevention. RESULTS: A total of 2386 adults participated in the study and 1543 RDTs were conducted for children under-five. Adequate levels of knowledge and attitudes on malaria prevention was recorded among 1258 (52.9%) of the participants, with very strong evidence to suggest the level to be higher among the host (59.5%) compared to the IDPs (49.5%) and returnees (39.7%) (p < 0.001). Good practices towards malaria prevention was 43.3%, with very strong evidence indicating lower levels among IDPs (42.8%) and returnees (28.5%) compared to the host (49.4%) (p < 0.001). Malaria prevalence for children under-five was 54.0% and adequate health-seeking for suspected episodes of malaria was 53.0%, without any difference among IDPs (51.78%) and returnees (48.7%) compared to host populations (55.4%) (p = 0.154). Multivariate logistic regression model showed that there was quite strong evidence to suggest primary and secondary levels of education have higher odds of having correct knowledge of malaria prevention (adjusted odds ratio (AOR) 1.71, 95% confidence interval (CI): 1.11-2.64, p = 0.015 and AOR 1.80, 95% CI 1.15-2.82, p = 0.010 respectively). There was very strong evidence to suggest that owning a radio or a television was associated with greater odds of having a higher knowledge on malaria prevention (AOR 1.49, 95% CI 1.233-1.81, p = 0.000 and AOR 1.47, 95% CI 1.18-1.84, p = 0.001). CONCLUSION: Over half of the population have correct knowledge and attitudes towards malaria prevention but gaps in complete knowledge remained. Some of the caregivers know the correct malaria preventive practices coupled with largely unsatisfactory treatment approaches and reflected by the high prevalence of malaria among their children. In order to effectively treat malaria, innovative strategies should target community participation.
Subject(s)
Caregivers , Malaria , Adult , Child , Humans , Cross-Sectional Studies , Cameroon/epidemiology , Malaria/epidemiology , Malaria/prevention & control , Malaria/diagnosis , Health Knowledge, Attitudes, Practice , Patient Acceptance of Health CareABSTRACT
SUMMARY: We are building the world's first Virtual Child-a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will "develop cancer" that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life.
Subject(s)
Neoplasms , Humans , Neoplasms/geneticsABSTRACT
Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies.
Subject(s)
Cerebellar Neoplasms , Medulloblastoma , Humans , Hedgehog Proteins/genetics , Medulloblastoma/genetics , Proteomics , Cerebellum , Cerebellar Neoplasms/geneticsABSTRACT
BACKGROUND: Seasonal malaria chemoprevention (SMC) is a safe and effective intervention for preventing malaria in children under 5 years of age. Lead mothers are community health volunteers that help caregivers comply with monthly administration of anti-malarial drugs during SMC campaigns. The lead mother approach is used in several SMC implementing states across Nigeria, but there is lack of evidence about their roles and how effective they are. This study sought to better understand the current role of lead mothers, identify areas for improvement and ways to optimize the role of lead mothers during SMC campaigns. METHODS: This paper reports the formative phase of a three-phased intervention development study. The formative phase involved semi-structured interviews with stakeholders from national, state, local government and community levels (n = 20). Thematic analysis was used to identify key themes, forming the basis of a subsequent co-design workshop with stakeholders routinely involved in SMC campaigns. RESULTS: The findings of the formative phase converged around four overarching themes: skills and attributes required of lead mothers; factors that affect lead mother's roles; how lead mothers interact with Community Health Influencers Promoters Services (CHIPS) agents and re-imagining the role of lead mothers during SMC campaigns. CONCLUSION: This formative work in Kano state indicates that through their strong connection to communities and unique relationship with caregivers, lead mothers can and do influence caregivers to adopt healthy behaviours during SMC campaigns. However, there is room for improvement in how they are recruited, trained and supervised. There is need to improve lead mothers' knowledge and skills through adequate training and supporting materials, so they can deliver targeted health messages to caregivers. Sustainability of the lead mother approach is at risk if policymakers do not find a way of transitioning their role into the existing community health worker infrastructure, for example by using CHIPs agents, and ensuring less reliance on external donor support.
Subject(s)
Antimalarials , Malaria , Child , Female , Humans , Infant , Child, Preschool , Mothers , Nigeria , Seasons , Malaria/prevention & control , Malaria/drug therapy , Antimalarials/therapeutic use , ChemopreventionABSTRACT
BACKGROUND AIMS: The targeting of solid cancers with chimeric antigen receptor (CAR) T cells faces many technological hurdles, including selection of optimal target antigens. Promising pre-clinical and clinical data of CAR T-cell activity have emerged from targeting surface antigens such as GD2 and B7H3 in childhood cancer neuroblastoma. Anaplastic lymphoma kinase (ALK) is expressed in a majority of neuroblastomas at low antigen density but is largely absent from healthy tissues. METHODS: To explore an alternate target antigen for neuroblastoma CAR T-cell therapy, the authors generated and screened a single-chain variable fragment library targeting ALK extracellular domain to make a panel of new anti-ALK CAR T-cell constructs. RESULTS: A lead novel CAR T-cell construct was capable of specific cytotoxicity against neuroblastoma cells expressing low levels of ALK, but with only weak cytokine and proliferative T-cell responses. To explore strategies for amplifying ALK CAR T cells, the authors generated a co-CAR approach in which T cells received signal 1 from a first-generation ALK construct and signal 2 from anti-B7H3 or GD2 chimeric co-stimulatory receptors. The co-CAR approach successfully demonstrated the ability to avoid targeting single-antigen-positive targets as a strategy for mitigating on-target off-tumor toxicity. CONCLUSIONS: These data provide further proof of concept for ALK as a neuroblastoma CAR T-cell target.
Subject(s)
Neuroblastoma , Receptors, Antigen, T-Cell , Humans , Receptors, Antigen, T-Cell/genetics , Cell Line, Tumor , Xenograft Model Antitumor Assays , Gangliosides , Neuroblastoma/genetics , Neuroblastoma/therapy , T-Lymphocytes , Immunotherapy, Adoptive , Antibodies , LogicABSTRACT
Major obstacles in brain cancer treatment include the blood-tumor barrier (BTB), which limits the access of most therapeutic agents, and quiescent tumor cells, which resist conventional chemotherapy. Here, we show that Sox2+ tumor cells project cellular processes to ensheathe capillaries in mouse medulloblastoma (MB), a process that depends on the mechanosensitive ion channel Piezo2. MB develops a tissue stiffness gradient as a function of distance to capillaries. Sox2+ tumor cells perceive substrate stiffness to sustain local intracellular calcium, actomyosin tension, and adhesion to promote cellular process growth and cell surface sequestration of ß-catenin. Piezo2 knockout reverses WNT/ß-catenin signaling states between Sox2+ tumor cells and endothelial cells, compromises the BTB, reduces the quiescence of Sox2+ tumor cells, and markedly enhances the MB response to chemotherapy. Our study reveals that mechanosensitive tumor cells construct the BTB to mask tumor chemosensitivity. Targeting Piezo2 addresses the BTB and tumor quiescence properties that underlie treatment failures in brain cancer.
Subject(s)
Brain Neoplasms , beta Catenin , Mice , Animals , beta Catenin/metabolism , beta Catenin/therapeutic use , Endothelial Cells/metabolism , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain/metabolism , Ion Channels/metabolism , Blood-Brain Barrier/metabolismABSTRACT
Uterine transplantation (UTx) is a programme of treatment aimed at providing a unique solution to absolute uterine factor infertility, enabling patients to have children as a result of their own pregnancies. As a transplant procedure performed for fertility purposes it may be thought obvious that the welfare of any children created should be assessed prior to treatment provision. However, major concerns about the breadth and scope of such requirements, and the potential threat they pose to patients' reproductive autonomy, have been raised. In this paper, I analyse novel questions regarding the role of the pre-conception welfare principle in UTx. After outlining traditional critiques of the principle, I focus on the unique issues raised by its application in the two areas of medicine occupied by UTx. As a treatment for a particular form of infertility, I explore whether law and policy regulating traditional assisted reproductive technologies applies equally to the case of UTx, and whether a distinction (in welfare terms) does and should exist between fertility treatment involving gametes and embryos and gynaecological surgery for fertility purposes. As a quality-of-life-enhancing transplant, I consider and reject proposals in favour of using pre-conception welfare considerations to inform patient listing and the allocation of deceased donor uteri on the grounds that such assessments may both compromise patient autonomy and lead to unjust discrimination against particular patients or groups of patients.
ABSTRACT
PURPOSE: Health related quality of life (HRQoL) is often used as an outcome measure of cancer treatment. Stereotactic radiosurgery (SRS) is a mainstay treatment of brain metastases (BMs) with constantly improving treatment envelope. The goal of this systematic review was to evaluated HRQoL trajectories after SRS, identify important predictors of HRQoL after SRS, and to evaluate clinical importance of post-SRS HRQoL trajectories of BM patients treated with SRS. METHODS: A systematic literature review according to the PRISMA guidelines analyzing HRQoL trajectories after SRS for BM published in the Pubmed/MEDLINE database before January, 2022. RESULTS: We identified 18 studies that evaluated HRQoL before and at least once after SRS for BMs. The majority of studies were single-institution retrospective series and included patients with different cancer types. Different instruments were used to assess HRQoL. In the majority of studies (n = 10) at group level, there was no significant change in global HRQoL after SRS. Stability, improvement, and deterioration of HRQoL global and subscale scores at individual patient level were common. Post-SRS HRQoL deterioration was predicted by worse functional status, greater number of BMs, delayed SRS, symptomatic BMs, and presence of seizures and cognitive impairment. Shorter post-SRS survival and adverse radiation effects (AREs) were associated with worse HRQoL. CONCLUSIONS: SRS for BMs is often associated with sustained preservation of HRQoL. Individual variation of HRQoL domains after SRS is common. Shorter survival and AREs are associated with worse HRQoL. Worse functional status and greater disease burden predict unfavorable HRQoL trajectories after SRS for BMs.
Subject(s)
Brain Neoplasms , Radiosurgery , Humans , Quality of Life , Retrospective StudiesSubject(s)
Immunotherapy , Neoplasms , Cell Line, Tumor , Humans , Immunologic Factors , Neoplasms/therapyABSTRACT
BACKGROUND: To prevent malaria among children aged 3-59 months in areas with high seasonal transmission, seasonal malaria chemoprevention (SMC) is recommended. In Chad, there is evidence of SMC administration to children aged older than 5 years (referred to as "leakage"). This study aimed to understand the reasons for leakage and explore the feasibility and acceptability of extending the delivery of SMC to children aged 5-10 years in Chad. METHODS: We conducted a mixed-methods study in Massaguet health district with a cross-sectional survey to determine SMC coverage for children aged up to 10 years after SMC cycles 1 and 3 (n=90 and n=100 caregivers surveyed, respectively) and at the end of cycle 4 (n=101 caregivers surveyed). We conducted 14 key informant interviews at the national and district level and 8 focus group discussions with community distributors and caregivers. RESULTS: In the compounds surveyed, there were no children aged 5-10 years in cycle 1. In cycles 3 (n=1 children) and 4 (n=16 children), there was 100% (95% confidence interval [CI]=2.5, 100.0) and 62.5% (95% CI=35.4, 84.8) coverage of SMC in children aged 5-10 years, respectively. Extension of SMC to older children was considered acceptable, but there were concerns about feasibility and ensuring the sustainability of the current program in children aged 3-59 months. Key informants acknowledged the need to secure additional funding to pilot SMC in older age groups and were uncertain about the impact of the current SMC program at scale. CONCLUSION: Key informants considered extending SMC to children aged 5-10 years acceptable but did not deem it a current priority. They expressed an urgent need to address leakage and reinforce both the sustainability and quality of the current SMC program.
Subject(s)
Antimalarials , Malaria , Adolescent , Aged , Antimalarials/therapeutic use , Chad , Chemoprevention/methods , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Malaria/prevention & control , SeasonsABSTRACT
BACKGROUND: Seasonal malaria chemoprevention (SMC) is a WHO-recommended intervention for children aged 3-59 months living in areas of high malaria transmission to provide protection against malaria during the rainy season. Operational guidelines were developed, based on WHO guidance, to support countries to mitigate the risk of coronavirus disease 2019 (COVID-19) transmission within communities and among community distributors when delivering SMC. METHODS: A cross-sectional study to determine adherence to infection prevention and control (IPC) measures during two distribution cycles of SMC in Nigeria, Chad and Burkina Faso. Community distributors were observed receiving equipment and delivering SMC. Adherence across six domains was calculated as the proportion of indications in which the community distributor performed the correct action. Focus group discussions were conducted with community distributors to understand their perceptions of the IPC measures and barriers and facilitators to adherence. RESULTS: Data collectors observed community distributors in Nigeria (n = 259), Burkina Faso (n = 252) and Chad (n = 266) receiving IPC equipment and delivering SMC. Adherence to IPC indications varied. In all three countries, adherence to mask use was the highest (ranging from 73.3% in Nigeria to 86.9% in Burkina Faso). Adherence to hand hygiene for at least 30 s was low (ranging from 3.6% in Nigeria to 10.3% in Burkina Faso) but increased substantially when excluding the length of time spent hand washing (ranging from 36.7% in Nigeria to 61.4% in Burkina Faso). Adherence to safe distancing in the compound ranged from 5.4% in Chad to 16.4% in Nigeria. In Burkina Faso and Chad, where disinfection wipes widely available compliance with disinfection of blister packs for SMC was low (17.4% in Burkina Faso and 16.9% in Chad). Community distributors generally found the IPC measures acceptable, however there were barriers to optimal hand hygiene practices, cultural norms made social distancing difficult to adhere to and caregivers needed assistance to administer the first dose of SMC. CONCLUSION: Adherence to IPC measures for SMC delivery during the COVID-19 pandemic varied across domains of IPC, but was largely insufficient, particularly for hand hygiene and safe distancing. Improvements in provision of protective equipment, early community engagement and adaptations to make IPC measures more feasible to implement could increase adherence.
Subject(s)
Antimalarials , COVID-19 , Malaria , Antimalarials/therapeutic use , Burkina Faso/epidemiology , COVID-19/prevention & control , Chad , Chemoprevention , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Malaria/prevention & control , Nigeria/epidemiology , Pandemics/prevention & control , SeasonsABSTRACT
BACKGROUND: Seasonal malaria chemoprevention (SMC) involves administering antimalarial drugs at monthly intervals during the high malaria transmission period to children aged 3 to 59 months as recommended by the World Health Organization. Typically, a full SMC course is administered over four monthly cycles from July to October, coinciding with the rainy season. However, an analysis of rainfall patterns suggest that the malaria transmission season is longer and starting as early as June in the south of Burkina Faso, leading to a rise in cases prior to the first cycle. This study assessed the acceptability and feasibility of extending SMC from four to five cycles to coincide with the earlier rainy season in Mangodara health district. METHODS: The mixed-methods study was conducted between July and November 2019. Quantitative data were collected through end-of-cycle and end-of-round household surveys to determine the effect of the additional cycle on the coverage of SMC in Mangodara. The data were then compared with 22 other districts where SMC was implemented by Malaria Consortium. Eight focus group discussions were conducted with caregivers and community distributors and 11 key informant interviews with community, programme and national-level stakeholders. These aimed to determine perceptions of the acceptability and feasibility of extending SMC to five cycles. RESULTS: The extension was perceived as acceptable by caregivers, community distributors and stakeholders due to the positive impact on the health of children under five. However, many community distributors expressed concern over the feasibility, mainly due to the clash with farming activities in June. Stakeholders highlighted the need for more evidence on the impact of the additional cycle on parasite resistance prior to scale-up. End-of-cycle survey data showed no difference in coverage between five SMC cycles in Mangodara and four cycles in the 22 comparison districts. CONCLUSIONS: The additional cycle should begin early in the day in order to not coincide with the agricultural activities of community distributors. Continuous sensitisation at community level is critical for the sustainability of SMC and acceptance of an additional cycle, which should actively engage male caregivers. Providing additional support in proportion to the increased workload from a fifth cycle, including timely remuneration, is critical to avoid the demotivation of community distributors. Further studies are required to understand the effectiveness, including cost-effectiveness, of tailoring SMC according to the rainy season. Understanding the impact of an additional cycle on parasite resistance to SPAQ is critical to address key informants' concerns around the deviation from the current four-cycle policy recommendation.
Subject(s)
Antimalarials , Malaria , Antimalarials/therapeutic use , Burkina Faso , Chemoprevention/methods , Child , Feasibility Studies , Humans , Infant , Malaria/drug therapy , Malaria/prevention & control , Male , Pilot Projects , SeasonsABSTRACT
It is often claimed that a legitimate approach to organ donation is an opt-out system, also known as 'presumed consent', 'deemed consent', or 'deemed authorisation', whereby individuals are presumed or deemed willing to donate at least some of their organs and tissues after death unless they have explicitly refused permission. While sharing a default in favour of donation, such systems differ in several key respects, such as the role and importance assigned to the family members of prospective donors and their preferences, and exclusions and safeguards which often specify the demographic groups, purposes, or organs and tissues that will remain outside the scope of the opt-out system. Using the recent shift to opt-out in England, Scotland, and Northern Ireland as case studies, and by reference to the key goals motivating this shift across the UK, this article asks whether and, if so, why, and how, opt-out systems for post-mortem organ donation should restrict the types of organs and tissues for which consent is deemed. In other words, ought opt-out systems for PMOD presume dissent regarding the donation of certain organs and tissues?
Subject(s)
Organ Transplantation , Tissue and Organ Procurement , Dissent and Disputes , Humans , Presumed Consent , Prospective Studies , Tissue DonorsABSTRACT
BACKGROUND AND OBJECTIVES: To understand patterns of care and circumstances surrounding end of life in patients with intracranial gliomas. METHODS: We retrospectively analyzed end-of-life circumstances in patients with intracranial high-grade gliomas at Columbia University Irving Medical Center who died from January 2014 to February 2019, including cause of death, location of death, and implementation of comfort measures and resuscitative efforts. RESULTS: There were 152 patients (95 men, 57 women; median age at death 61.5 years, range 24-87 years) who died from January 2014 to February 2019 with adequate data surrounding end-of-life circumstances. Clinical tumor progression (n = 117, 77.0%) was the most common cause of death, with all patients transitioned to comfort measures. Other causes included, but were not limited to, infection (19, 12.5%); intratumoral hemorrhage (5, 3.3%); seizures (8, 5.3%); cerebral edema (4, 2.6%); pulmonary embolism (4, 2.6%); autonomic failure (2, 1.3%); and hemorrhagic shock (2, 1.3%). Multiple mortal events were identified in 10 (8.5%). Seventy-three patients (48.0%) died at home with hospice. Other locations were inpatient hospice (40, 26.3%); acute care hospital (34, 22.4%), including 27 (17.8%) with and 7 (4.6%) without comfort measures; skilled nursing facility (4, 3.3%), including 3 (2.0%) with and 1 (0.7%) without comfort measures; or religious facility (1, 0.7%) with comfort measures. Acute cardiac or pulmonary resuscitation was performed in 20 patients (13.2%). DISCUSSION: Clinical tumor progression was the most common (77.0%) cause of death, followed by infection (12.5%). Hospice or comfort measures were ultimately implemented in 94.7% of patients, although resuscitation was performed in 13.2%. Improved understanding of circumstances surrounding death, frequency of use of hospice services, and frequency of resuscitative efforts in patients with gliomas may allow physicians to more accurately discuss end-of-life expectations with patients and caregivers, facilitating informed care planning.
Subject(s)
Glioma , Hospice Care , Terminal Care , Adult , Aged , Aged, 80 and over , Cause of Death , Female , Glioma/therapy , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Quality data from Health Management Information Systems (HMIS) are important for tracking the effectiveness of malaria control interventions. However, HMIS data in many resource-limited settings do not currently meet standards set by the World Health Organization (WHO). We aimed to assess HMIS data quality and associated factors in Chad. METHODS: A cross-sectional study was conducted in 14 health facilities in Massaguet district. Data on children under 15 years were obtained from the HMIS and from the external patient register covering the period January-December 2018. An additional questionnaire was administered to 16 health centre managers to collect data on contextual variables. Patient registry data were aggregated and compared with the HMIS database at district and health centre level. Completeness and accuracy indicators were calculated as per WHO guidelines. Multivariate logistic regressions were performed on the Verification Factor for attendance, suspected and confirmed malaria cases for three age groups (1 to < 12 months, 1 to < 5 years and 5 to < 15 years) to identify associations between health centre characteristics and data accuracy. RESULTS: Health centres achieved a high level of data completeness in HMIS. Malaria data were over-reported in HMIS for children aged under 15 years. There was an association between workload and higher odds of inaccuracy in reporting of attendance among children aged 1 to < 5 years (Odds ratio [OR]: 10.57, 95% CI 2.32-48.19) and 5- < 15 years (OR: 6.64, 95% CI 1.38-32.04). Similar association was found between workload and stock-outs in register books, and inaccuracy in reporting of malaria confirmed cases. Meanwhile, we found that presence of a health technician, and of dedicated staff for data management, were associated with lower inaccuracy in reporting of clinic attendance in children aged under five years. CONCLUSION: Data completeness was high while the accuracy was low. Factors associated with data inaccuracy included high workload and the unavailability of required data collection tools. The results suggest that improvement in working conditions for clinic personnel may improve HMIS data quality. Upgrading from paper-based forms to a web-based HMIS may provide a solution for improving data accuracy and its utility for future evaluations of health interventions. Results from this study can inform the Ministry of Health and it partners on the precautions to be taken in the use of HMIS data and inform initiatives for improving its quality.