Africa South of the Sahara

撒哈拉以南非洲
  • 文章类型: Journal Article
    目的:了解三个低收入和中等收入国家的受伤患者在获得和接受优质伤害护理方面的共性和差异。
    方法:定性访谈研究。采访都有录音,转录和主题分析。
    方法:加纳的城乡环境,南非和卢旺达。
    方法:59例肌肉骨骼损伤患者。
    结果:我们发现了五种常见的障碍和六种常见的促进者,这些障碍是受伤患者获得和接受高质量伤害护理的经验。障碍包括服务和治疗可用性等问题,交通挑战,冷漠的护理,个人财政短缺和医疗保险覆盖面不足,除了低健康素养和信息提供。促进者包括有效的信息提供和知情同意做法,获得健康保险,提高健康素养,同情和反应灵敏的护理,综合多学科管理和出院计划,以及非正式和正式的交通选择,包括救护车服务。这些障碍和促进者在至少两个国家中普遍存在并共享,但在主题频率上显示出国家间和国家内部(城市化和乡村之间)的差异。
    结论:有影响患者获得和接受护理的普遍因素,独立于环境或医疗保健系统。重要的是要认识和理解这些障碍和促进者,以告知政策决定并制定可转让的干预措施,旨在提高撒哈拉以南非洲国家的伤害护理质量。
    OBJECTIVE: To understand commonalities and differences in injured patient experiences of accessing and receiving quality injury care across three lower-income and middle-income countries.
    METHODS: A qualitative interview study. The interviews were audiorecorded, transcribed and thematically analysed.
    METHODS: Urban and rural settings in Ghana, South Africa and Rwanda.
    METHODS: 59 patients with musculoskeletal injuries.
    RESULTS: We found five common barriers and six common facilitators to injured patient experiences of accessing and receiving high-quality injury care. The barriers encompassed issues such as service and treatment availability, transportation challenges, apathetic care, individual financial scarcity and inadequate health insurance coverage, alongside low health literacy and information provision. Facilitators included effective information giving and informed consent practices, access to health insurance, improved health literacy, empathetic and responsive care, comprehensive multidisciplinary management and discharge planning, as well as both informal and formal transportation options including ambulance services. These barriers and facilitators were prevalent and shared across at least two countries but demonstrated intercountry and intracountry (between urbanity and rurality) variation in thematic frequency.
    CONCLUSIONS: There are universal factors influencing patient experiences of accessing and receiving care, independent of the context or healthcare system. It is important to recognise and understand these barriers and facilitators to inform policy decisions and develop transferable interventions aimed at enhancing the quality of injury care in sub-Saharan African nations.
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  • 文章类型: Journal Article
    背景:社区卫生工作者(CHW)的激励和报酬是影响CHW和健康计划绩效的核心问题。关于撒哈拉以南非洲国家使用的CHW财政补偿计划的实施细节的文件有限,包括其交付机制和有效性。我们旨在记录CHW的经济补偿计划,并了解CHW,政府,以及其他利益相关者对其有效性的看法。
    方法:共进行了68次半结构化访谈,对7个国家/地区的一系列有目的地选择的关键线人进行了访谈:贝宁,布基纳法索,加纳,马拉维,马里,尼日尔,赞比亚。对编码访谈数据进行了主题分析,并审查了相关的国家文件,包括关键线人引用的任何文件,为定性解释提供语境背景。
    结果:主要信息提供者描述了补偿计划在定期付款时有效,分布是一致的,和金额足以支持卫生工作者的表现和服务提供的连续性。与雇用工人身份和政府工资机制相关的CHW补偿计划通常被利益相关者视为有效。发现与志愿者身份相关的补偿计划在其交付机制上差异很大(例如,现金或手机分销),并被认为效果较差。实施CHW补偿计划的经验教训涉及政府领导的需要,部长级协调,社区参与,合作伙伴协调,和现实的过渡性融资计划。
    结论:政策制定者在为从事日常工作的CHW设计补偿计划时应考虑这些发现,在本国卫生服务提供模式的背景下,持续提供卫生服务。关于志愿者身份CHWs的任务和时间承诺的系统文件可以支持更多地承认他们的卫生系统贡献,并根据2018年世界卫生组织《卫生政策和系统支持优化社区卫生工作者计划指南》的建议,更好地确定相应的补偿。
    BACKGROUND: Community health worker (CHW) incentives and remuneration are core issues affecting the performance of CHWs and health programs. There is limited documentation on the implementation details of CHW financial compensation schemes used in sub-Saharan African countries, including their mechanisms of delivery and effectiveness. We aimed to document CHW financial compensation schemes and understand CHW, government, and other stakeholder perceptions of their effectiveness.
    METHODS: A total of 68 semistructured interviews were conducted with a range of purposefully selected key informants in 7 countries: Benin, Burkina Faso, Ghana, Malawi, Mali, Niger, and Zambia. Thematic analysis of coded interview data was conducted, and relevant country documentation was reviewed, including any documents referenced by key informants, to provide contextual background for qualitative interpretation.
    RESULTS: Key informants described compensation schemes as effective when payments are regular, distributions are consistent, and amounts are sufficient to support health worker performance and continuity of service delivery. CHW compensation schemes associated with an employed worker status and government payroll mechanisms were most often perceived as effective by stakeholders. Compensation schemes associated with a volunteer status were found to vary widely in their delivery mechanisms (e.g., cash or mobile phone distribution) and were perceived as less effective. Lessons learned in implementing CHW compensation schemes involved the need for government leadership, ministerial coordination, community engagement, partner harmonization, and realistic transitional financing plans.
    CONCLUSIONS: Policymakers should consider these findings in designing compensation schemes for CHWs engaged in routine, continuous health service delivery within the context of their country\'s health service delivery model. Systematic documentation of the tasks and time commitment of volunteer status CHWs could support more recognition of their health system contributions and better determination of commensurate compensation as recommended by the 2018 World Health Organization Guidelines on Health Policy and System Support to Optimize Community Health Worker Programs.
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  • 文章类型: Journal Article
    非传染性疾病全球死亡的主要原因,估计将超过撒哈拉以南非洲的传染病,医护人员(HCWs)在预防和治疗中起着至关重要的作用,但是极度短缺,从而增加了这一特定人群的非传染性疾病负担。为决策提供证据,我们评估了非传染性疾病的负担,四个撒哈拉以南非洲国家的HCWs的相关因素和治疗。
    我们在四个撒哈拉以南非洲国家[科特迪瓦(CIV),刚果民主共和国(DRC)马达加斯加(MDG),和尼日利亚(NIG)]2022年2月至12月。在标准化问卷中,社会人口统计学,慢性病和治疗数据为自我报告.我们估计(1)至少一种慢性疾病的患病率,(2)高血压,并采用反向消除logistic回归模型识别危险因素。
    我们总共招募了6848名医务人员。至少一种慢性病的患病率在NIG的9.7%和MDG的20.6%之间,高血压的患病率在CIV的5.4%和MDG的11.3%之间。最多,报告的治疗率达到36.5%。两种结局的赔率均随年龄增加(至少一种慢性疾病调整的赔率比:CIV:1.04;DRC:1.09;MDG:1.06;NIG:1.10;高血压:CIV:1.10;DRC:1.31;MDG:1.11;NIG:1.11)和BMI(至少一种慢性疾病:CIV:1.10;DRC:1.07;MDG:1.66;NIG:1.两种结果的几率在男性中都较低,除了在CIV.在NIG,在医生中,两种结局的几率较高,在二级保健工作者中,高血压的几率较高.在千年发展目标中,在二级保健中的工作增加,而作为辅助人员的工作减少了至少一种慢性疾病的几率。
    在四个撒哈拉以南的国家中,自我报告的慢性病的患病率各不相同,治疗率可能非常低。我们确定了几个人(年龄,性别,和BMI)和职业(职业,医疗保健水平)影响非传染性疾病几率的因素。在制定干预措施时,应考虑到这些因素,以解决HCWs中的非传染性疾病的负担和管理。
    UNASSIGNED: Non-communicable diseases (NCDs), the leading cause of death globally, are estimated to overtake communicable diseases in sub-Sahara Africa, where healthcare workers (HCWs) play a crucial role in prevention and treatment, but are in extreme shortage, thereby increasing the burden of NCDs among this specific population. To provide evidence for policy-making, we assessed the NCD burden, associated factors and treatment among HCWs in four sub-Saharan African countries.
    UNASSIGNED: We conducted a cross-sectional study across four sub-Saharan African countries [Côte d\'Ivoire (CIV), Democratic Republic of the Congo (DRC), Madagascar (MDG), and Nigeria (NIG)] between February and December 2022. In a standardized questionnaire, sociodemographic, chronic disease and treatment data were self-reported. We estimated the prevalence of (1) at least one chronic disease, (2) hypertension, and used backward elimination logistic regression model to identify risk factors.
    UNASSIGNED: We recruited a total of 6,848 HCWs. The prevalence of at least one chronic disease ranged between 9.7% in NIG and 20.6% in MDG, the prevalence of hypertension between 5.4% in CIV and 11.3% in MDG. At most, reported treatment rates reached 36.5%. The odds of each of both outcomes increased with age (at least one chronic disease adjusted odds ratio: CIV: 1.04; DRC: 1.09; MDG: 1.06; NIG: 1.10; hypertension: CIV: 1.10; DRC: 1.31; MDG: 1.11; NIG: 1.11) and with BMI (at least one chronic disease: CIV: 1.10; DRC: 1.07; MDG: 1.06; NIG: 1.08; hypertension: CIV: 1.10; DRC: 1.66; MDG: 1.13; NIG: 1.07). Odds of both outcomes were lower among males, except in CIV. In NIG, the odds of both outcomes were higher among medical doctors and odds of hypertension were higher among those working in secondary care. In MDG, working in secondary care increased and working as auxiliary staff decreased the odds of at least one chronic disease.
    UNASSIGNED: The prevalence of self-reported chronic disease varied across the four sub-Saharan countries with potentially very low treatment rates. We identified several individual (age, sex, and BMI) and occupational (profession, level of healthcare) factors that influence the odds of NCDs. These factors should be taken into account when developing interventions addressing the burden and management of NCDs among HCWs.
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  • 文章类型: Journal Article
    背景:迫切需要提高撒哈拉以南非洲的乳腺癌生存率。地理空间障碍延迟诊断和治疗,但是它们在这些环境中对生存的影响还没有得到很好的理解。我们研究了非洲乳腺癌-结果差异队列中4年生存率的地理空间差异。
    方法:在这项前瞻性队列研究中,从纳米比亚的八家医院招募了新诊断为乳腺癌的女性(年龄≥18岁),尼日利亚,南非,乌干达,赞比亚。他们在面试官管理的问卷中报告了社会人口统计信息,他们的临床和治疗数据是从医疗记录中收集的。通过每3个月联系参与者或他们的近亲来确定生命状态。主要结果是与农村和城市居住有关的全因死亡率,直线距离,模拟了去医院的旅行时间,使用受限平均生存时间进行分析,Cox比例危险,和灵活的参数生存模型。
    结果:在2014年9月8日至2017年12月31日之间招募了2228名患有乳腺癌的女性。127人被排除在分析之外(58人患有潜在复发癌症,以前接受过治疗,或没有随访;14个来自少数族裔,样本量小;55个缺少地理编码的家庭地址)。在分析的2101名女性中,928(44%)居住在农村地区。1042例患者在诊断后4年内死亡;农村地区女性的4年生存率为39%(95%CI36-42),城市地区为49%(46-52)(未调整的风险比[HR]1·24[95%CI1·09-1·40])。在734名离医院超过1小时的妇女中,农村地区女性的粗4年生存率为37%(95%CI32-42),城市地区女性为54%(46-62)(HR1·35[95%CI1·07-1·71],舞台,和治疗状态)。在农村地区的妇女中,死亡率随距离(调整后HR/50km1·04,1·01-1·07)和旅行时间(调整后HR/h1·06,1·02-1·10)而增加.在接受治疗的早期乳腺癌女性中,农村地区的女性有很强的生存劣势(总体HR1·54,1·14-2·07,经年龄和分期调整;>1小时距离调整HR2·14,1·21-3·78).
    结论:地理空间障碍降低了撒哈拉以南非洲乳腺癌患者的生存率。需要特别注意支持生活在远离癌症治疗设施的农村地区的早期乳腺癌患者。
    背景:美国国立卫生研究院(国家癌症研究所),苏珊·G·科曼的治疗,和国际癌症研究机构。
    BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort.
    METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models.
    RESULTS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78).
    CONCLUSIONS: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities.
    BACKGROUND: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.
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  • 文章类型: Journal Article
    背景:非洲的癌症生存,亚洲,国际癌症研究机构的南美项目(SURVCAN-3)旨在填补这些地区国家的人口水平癌症生存率估计的空白。这里,我们使用来自撒哈拉以南非洲11个国家的非洲癌症登记网络成员登记处的数据,分析了18种癌症的生存率.
    方法:我们纳入了2005年1月1日至2014年12月31日之间诊断为18种癌症类型的患者的数据,来自科托努(贝宁)的13个基于人群的癌症登记处,阿比让(科特迪瓦),亚的斯亚贝巴(埃塞俄比亚),埃尔多雷特和内罗毕(肯尼亚),巴马科(马里),毛里求斯,纳米比亚,塞舌尔,东开普省(南非),坎帕拉(乌干达),布拉瓦约和哈拉雷(津巴布韦)。患者随访至2018年12月31日。患者级数据,包括癌症地形和形态学,诊断时的年龄和日期,生命状态,并收集死亡日期(如适用)。随访(生存)时间从发病日期到最后一次接触日期,死亡日期,或者直到研究结束,以先发生者为准。我们估计了一年,3年,和5年生存率(观察,net,和年龄标准化的净存活率)按性别划分,癌症类型,注册表,国家,人类发展指数(HDI)。1年和3年的生存数据可用于所有注册和所有癌症地点,而5年生存数据的可得性稍有变化;因此,为了提供中期生存前景,我们在结果部分重点关注了3年生存率.
    结果:来自11个国家的13个基于人群的癌症登记处的10500名个体被纳入生存分析。10500例中的9177例(87·4%)进行了形态学验证。高负担且易于预防的癌症生存率较差:宫颈癌的3岁标准化净生存率为52·3%(95%CI49·4-55·0),18·1%(11·5-25·9)用于肝癌,32·4%(27·5-37·3)为肺癌。不到一半的纳入患者在癌症诊断为八种癌症类型(口腔,食管,胃,喉部,肺,肝脏,非霍奇金淋巴瘤,和白血病)。某些癌症的生存率因性别而异:患有胃癌或肺癌的女性比患有胃癌或肺癌的男性更长,非霍奇金淋巴瘤的男性比非霍奇金淋巴瘤的女性更长。口腔癌的国家/地区HDI生存率没有差异,食管,肝脏,甲状腺,还有霍奇金淋巴瘤.
    结论:对于存在人群水平预防策略的癌症,预后相对较差,这些估计突出表明,迫切需要在撒哈拉以南非洲扩大人口一级的预防活动。这些数据对于为宣传提供知识库以改善获得预防的机会至关重要,诊断,并为撒哈拉以南非洲的癌症患者提供护理。
    背景:重要策略,马丁-路德大学哈雷-维滕贝格,和国际癌症研究机构。
    有关摘要的法语和葡萄牙语翻译,请参见补充材料部分。
    BACKGROUND: The Cancer Survival in Africa, Asia, and South America project (SURVCAN-3) of the International Agency for Research on Cancer aims to fill gaps in the availability of population-level cancer survival estimates from countries in these regions. Here, we analysed survival for 18 cancers using data from member registries of the African Cancer Registry Network across 11 countries in sub-Saharan Africa.
    METHODS: We included data on patients diagnosed with 18 cancer types between Jan 1, 2005, and Dec 31, 2014, from 13 population-based cancer registries in Cotonou (Benin), Abidjan (CÔte d\'Ivoire), Addis Ababa (Ethiopia), Eldoret and Nairobi (Kenya), Bamako (Mali), Mauritius, Namibia, Seychelles, Eastern Cape (South Africa), Kampala (Uganda), and Bulawayo and Harare (Zimbabwe). Patients were followed up until Dec 31, 2018. Patient-level data including cancer topography and morphology, age and date at diagnosis, vital status, and date of death (if applicable) were collected. The follow-up (survival) time was measured from the date of incidence until the date of last contact, the date of death, or until the end of the study, whichever occurred first. We estimated the 1-year, 3-year, and 5-year survival (observed, net, and age-standardised net survival) by sex, cancer type, registry, country, and human development index (HDI). 1-year and 3-year survival data were available for all registries and all cancer sites, whereas availability of 5-year survival data was slightly more variable; thus to provide medium-term survival prospects, we have focused on 3-year survival in the Results section.
    RESULTS: 10 500 individuals from 13 population-based cancer registries in 11 countries were included in the survival analyses. 9177 (87·4%) of 10 500 cases were morphologically verified. Survival from cancers with a high burden and amenable to prevention was poor: the 3-year age-standardised net survival was 52·3% (95% CI 49·4-55·0) for cervical cancer, 18·1% (11·5-25·9) for liver cancer, and 32·4% (27·5-37·3) for lung cancer. Less than half of the included patients were alive 3 years after a cancer diagnosis for eight cancer types (oral cavity, oesophagus, stomach, larynx, lung, liver, non-Hodgkin lymphoma, and leukaemia). There were differences in survival for some cancers by sex: survival was longer for females with stomach or lung cancer than males with stomach or lung cancer, and longer for males with non-Hodgkin lymphomas than females with non-Hodgkin lymphomas. Survival did not differ by country-level HDI for cancers of the oral cavity, oesophagus, liver, thyroid, and for Hodgkin lymphoma.
    CONCLUSIONS: For cancers for which population-level prevention strategies exist, and with relatively poor prognosis, these estimates highlight the urgent need to upscale population-level prevention activities in sub-Saharan Africa. These data are vital for providing the knowledge base for advocacy to improve access to prevention, diagnosis, and care for patients with cancers in sub-Saharan Africa.
    BACKGROUND: Vital Strategies, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer.
    UNASSIGNED: For the French and Portuguese translations of the abstract see Supplementary Materials section.
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  • 文章类型: Journal Article
    背景:为感染艾滋病毒的儿童和青少年提供差异化服务(DSD)可以改善有针对性的资源使用。我们得出了死亡率预测评分,以指导HIV感染儿童和青少年的临床决策。
    方法:这项回顾性观察性队列研究的数据被评估为所有感染艾滋病毒并开始抗逆转录病毒治疗(ART)的儿童和青少年;年龄0-19岁;并在埃斯瓦蒂尼的贝勒诊所注册,马拉维,莱索托,坦桑尼亚,和乌干达在2005年至2020年之间。临床预测数据,包括人体测量值,体检,ART,世卫组织阶段,和实验室检查在ART开始时进行。进行反向逐步变量选择和逻辑回归,以建立ART开始后1年内死亡率的预测模型。产生了死亡的可能性,与真实结果相比,内部验证,并根据世卫组织高级艾滋病毒标准进行评估。
    结果:研究人群包括2005年5月18日至2020年12月18日期间接受ART的16958名感染艾滋病毒的儿童和青少年。最准确模型的预测变量包括:年龄,CD4百分比,白细胞计数,血红蛋白浓度,血小板计数,和BMIZ评分作为连续变量,和WHO临床分期和水肿,异常肌张力和呼吸窘迫检查为分类变量。预测模型的曲线下面积(AUC)在训练集中为0·851(95%CI0·839-0·863),在测试集中为0·822(0·800-0·845),与WHOHIV高级标准的0·606(0·595-0·617)相比(p<0·0001)。
    结论:这项研究评估了一个大的,多国人口为感染艾滋病毒的儿童和青少年得出死亡率预测工具。该模型比WHO先进的HIV标准更准确地预测临床结果,并且有可能改善高负担环境中HIV感染儿童和青少年的DSD。
    背景:国家卫生研究所福格蒂国际中心。
    BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.
    METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria.
    RESULTS: The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001).
    CONCLUSIONS: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings.
    BACKGROUND: National Institute of Health Fogarty International Center.
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  • 文章类型: Journal Article
    背景:恶性疟原虫dhfr基因的突变赋予对乙胺嘧啶的抗性,在非洲广泛用于疟疾化学预防。我们旨在评估非洲卵形疟原虫dhfr突变的频率和进化及其功能后果,不完全表征。
    方法:我们分析了2004年2月1日至2023年8月31日从法国国家疟疾参考中心收集和贝宁实地研究中收集的卵卵卵圆菌分离株中的dhfr突变及其频率,加蓬,肯尼亚。研究了阳性选择的遗传模式。在细菌中表达了来自卵圆刀和卵圆刀的全长重组野生型和突变型DHFR酶,以测试最常见的突变是否降低了乙胺嘧啶的敏感性。
    结果:我们包括了518个卵圆类样本(314个卵圆类和204个卵圆类)。在POvaleCurtisi,Ala15Ser-Ser58Arg是最常见的dhfr突变(39%;314个样品中的124个)。在POvaleWallikeri,dhfr突变频率较低,Phe57Leu-Ser58Arg达到17%(204个样品中的34个)。这两个突变体在中非和东非最普遍,并固定在肯尼亚的分离株中。我们检测到六个和四个其他非同义突变,代表8%(24个分离株)和2%(5个分离株)的卵卵圆虫和卵圆虫的分离株,分别。全基因组测序和微卫星分析显示,突变pocdhfr和powdhfr基因周围的遗传多样性降低。突变型DHFR蛋白在计算机上的乙胺嘧啶结合位点显示出结构变化,在Phe57Leu-Ser58Arg突变体的大肠杆菌生长测定中,乙胺嘧啶半最大抑制浓度增加了4倍,而Ala15Ser-Ser58Arg突变体增加了50倍,与野生型同行相比。
    结论:磺胺多辛-乙胺嘧啶在疟疾化学预防中的广泛使用可能对卵圆虫中的dhfr突变产生了偶然的选择压力。这要求更密切地监测卵卵圆中的dhfr和dhps突变。
    背景:法国卫生部,国家机构,和武装部队健康监测司全球新兴感染监测科。
    BACKGROUND: Mutations in the Plasmodium falciparum dhfr gene confer resistance to pyrimethamine, which is widely used for malaria chemoprevention in Africa. We aimed to evaluate the frequency and evolution of dhfr mutations in Plasmodium ovale spp in Africa and their functional consequences, which are incompletely characterised.
    METHODS: We analysed dhfr mutations and their frequencies in P ovale spp isolates collected between Feb 1, 2004, and Aug 31, 2023, from the French National Malaria Reference Centre collection and from field studies in Benin, Gabon, and Kenya. Genetic patterns of positive selection were investigated. Full-length recombinant wild-type and mutant DHFR enzymes from both P ovale curtisi and P ovale wallikeri were expressed in bacteria to test whether the most common mutations reduced pyrimethamine susceptibility.
    RESULTS: We included 518 P ovale spp samples (314 P ovale curtisi and 204 P ovale wallikeri). In P ovale curtisi, Ala15Ser-Ser58Arg was the most common dhfr mutation (39%; 124 of 314 samples). In P ovale wallikeri, dhfr mutations were less frequent, with Phe57Leu-Ser58Arg reaching 17% (34 of 204 samples). These two mutants were the most prevalent in central and east Africa and were fixed in Kenyan isolates. We detected six and four other non-synonymous mutations, representing 8% (24 isolates) and 2% (five isolates) of the P ovale curtisi and P ovale wallikeri isolates, respectively. Whole-genome sequencing and microsatellite analyses revealed reduced genetic diversity around the mutant pocdhfr and powdhfr genes. The mutant DHFR proteins showed structural changes at the pyrimethamine binding site in-silico, confirmed by a 4-times increase in pyrimethamine half-maximal inhibitory concentration in an Escherichia coli growth assay for the Phe57Leu-Ser58Arg mutant and 50-times increase for the Ala15Ser-Ser58Arg mutant, compared with the wild-type counterparts.
    CONCLUSIONS: The widespread use of sulfadoxine-pyrimethamine for malaria chemoprevention might have exerted fortuitous selection pressure for dhfr mutations in P ovale spp. This calls for closer monitoring of dhfr and dhps mutations in P ovale spp.
    BACKGROUND: French Ministry of Health, Agence Nationale de la Recherche, and Global Emerging Infections Surveillance branch of the Armed Forces Health Surveillance Division.
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  • 文章类型: Journal Article
    背景:对于生活在撒哈拉以南非洲的人们来说,获得麻醉和手术护理是一个主要问题。在这个地区,氯胺酮对于提供麻醉护理至关重要。然而,在国际上控制氯胺酮作为受控物质的努力可能会极大地影响其可得性。因此,这项研究旨在评估氯胺酮在撒哈拉以南非洲的麻醉和手术护理中的重要性,并评估如果计划使用氯胺酮对获得氯胺酮的潜在影响。
    方法:这项研究是一项混合方法研究,包括卢旺达医院层面的横断面调查,以及与撒哈拉以南非洲麻醉护理专家的关键线人访谈。从卢旺达的医院(n=54)收集了四种麻醉剂的可用性数据。对10名主要举报人进行了半结构化访谈,收集有关氯胺酮重要性的信息,在国际上安排氯胺酮的潜在影响,以及关于滥用氯胺酮的意见。访谈被逐字转录,并使用专题分析方法进行分析。
    结果:在卢旺达进行的调查发现,氯胺酮和异丙酚的可利用性约为80%,而硫喷妥钠和吸入剂只有大约一半的医院可用。确定了阻碍获得麻醉护理的重大障碍,包括政府普遍缺乏对专业的关注,麻醉师的短缺和训练有素的麻醉师的迁移,以及药品和设备的匮乏。由于这些障碍,氯胺酮被描述为对提供麻醉护理至关重要。线人认为滥用氯胺酮不是问题。
    结论:氯胺酮对于在撒哈拉以南非洲提供麻醉护理至关重要,并且其时间安排将对其用于麻醉护理的可用性产生重大负面影响。
    BACKGROUND: Access to anaesthesia and surgical care is a major problem for people living in Sub-Saharan Africa. In this region, ketamine is critical for the provision of anaesthesia care. However, efforts to control ketamine internationally as a controlled substance may significantly impact its accessibility. This research therefore aims to estimate the importance of ketamine for anaesthesia and surgical care in Sub-Saharan Africa and assess the potential impact on access to ketamine if it were to be scheduled.
    METHODS: This research is a mixed-methods study, comprising of a cross-sectional survey at the hospital level in Rwanda, and key informant interviews with experts on anaesthesia care in Sub-Saharan Africa. Data on availability of four anaesthetic agents were collected from hospitals (n = 54) in Rwanda. Semi-structured interviews with 10 key informants were conducted, collecting information on the importance of ketamine, the potential impact of scheduling ketamine internationally, and opinions on misuse of ketamine. Interviews were transcribed verbatim and analysed using a thematic analysis approach.
    RESULTS: The survey conducted in Rwanda found that availability of ketamine and propofol was comparable at around 80%, while thiopental and inhalational agents were available at only about half of the hospitals. Significant barriers impeding access to anaesthesia care were identified, including a general lack of attention given to the specialty by governments, a shortage of anaesthesiologists and migration of trained anaesthesiologists, and a scarcity of medicines and equipment. Ketamine was described as critical for the provision of anaesthesia care as a consequence of these barriers. Misuse of ketamine was not believed to be an issue by the informants.
    CONCLUSIONS: Ketamine is critical for the provision of anaesthesia care in Sub-Saharan Africa, and its scheduling would have a significantly negative impact on its availability for anaesthesia care.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    背景:使用羟基脲(REACH)实现跨大洲的有效性是一项针对撒哈拉以南非洲地区镰状细胞贫血儿童的羟基脲(羟基脲)的开放标签非随机试验。REACH对安全性的短期结果,可行性,和羟基脲的有效性以前发表过。在本文中,我们报告了REACH队列中延长羟基脲治疗长达8年的结果。
    方法:在此开放标签中,非随机化,1/2期试验,参与者从基利菲的四个临床地点招募,肯尼亚;姆贝尔,乌干达;罗安达,安哥拉;和金沙萨,刚果民主共和国。符合条件的儿童为1-10岁,有记录的血红蛋白SS或血红蛋白Sβ零地中海贫血,体重至少10公斤。参与者接受固定剂量的羟基脲,每天17.5(±2.5)mg/kg,持续6个月(固定剂量阶段),随后6个月的剂量递增(每8周增加2·5-5·0mg/kg)作为耐受,每天20-35mg/kg(最大耐受剂量;MTD),定义为轻度骨髓抑制。达到MTD后,根据体重和实验室值随时间的变化(具有优化阶段的MTD),为每个参与者优化了羟基脲给药。完成前12个月后,毒性特征可接受且反应良好的儿童有机会继续使用羟基脲,直至18岁.3年后的安全性和可行性结果已有报道。这里,血液学反应,临床事件,和毒性率在给药阶段(固定剂量羟基脲vsMTD,优化阶段)作为方案指定的结局进行比较.REACH已在ClinicalTrials.gov(NCT01966731)上注册,并且正在进行中。
    结果:我们在2014年7月4日至2016年11月11日之间招募了635名儿童。606名儿童接受了羟基脲治疗,522名(86%;266[51%]男孩和256[49%]女孩)接受了中位93个月的治疗(IQR84-97),4340患者-年的治疗。当前(2023年10月5日)平均剂量为每天28·2(SD5·2)mg/kg,平均血红蛋白浓度增加(基线时7·3[SD1·1]g/dL至8·5[1·5]g/dL)和平均胎儿血红蛋白水平(10·9%[SD6·8]至23·3%[9·5]/L细胞×8·109/L细胞计数0·109MTD与固定剂量羟基脲的发生率比(IRR)表明血管闭塞发作减少(0·60;95%CI0·52-0·70;p<0·0001),急性胸部综合征事件(0·21;0·13-0·33;p<0·0001),复发性卒中事件(0·27;0·07-1·06;p=0·061),疟疾感染(0·58;0·46-0·72;p<0·0001),非疟疾感染(0·52;0·46-0·58;p<0·0001),严重不良事件(0·42;0·27-0·67;p<0·0001),和死亡(0·70;0·25-1·97;p=0·50)。固定剂量(每100例患者年24·1)和MTD阶段(每100例患者年23·2;0·97;0·70-1·35;p=0·86)之间的剂量限制性毒性率相似。3级和4级不良事件很少发生(每100名患者年18·5),包括疟疾感染,非疟疾感染,血管闭塞性疼痛,和急性胸部综合症。严重不良事件并不常见(3·6/100患者-年),包括疟疾感染,细小病毒相关性贫血,脓毒症,和中风,没有治疗相关的死亡。
    结论:在剂量优化的情况下,羟基脲剂量递增至MTD显著改善了临床反应和治疗结果,在撒哈拉以南非洲,不会增加镰状细胞贫血儿童的毒性。
    背景:美国国家心脏,肺,血液研究所和辛辛那提儿童研究基金会。
    BACKGROUND: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years.
    METHODS: In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sβ zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing.
    RESULTS: We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 109 cells per L to 3·6 [2·2] × 109 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths.
    CONCLUSIONS: Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa.
    BACKGROUND: US National Heart, Lung, and Blood Institute and Cincinnati Children\'s Research Foundation.
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