Ventricular restoration in adults with huge congenital left ventricular aneurysm: report of two cases.

Congenital ventricular aneurysms (CVA) are rare cardiac anomalies that have been predominantly described in the Black population. They are characterized by an akinetic ventricular protrusion that is commonly located at the basal and apical segments. Although the diagnosis is often incidental and the majority of patients are asymptomatic, life-threatening events such as persistent ventricular arrhythmias, CVA rupture, and heart failure are not uncommon. However, no standardized therapy is currently available and good outcomes have been reported with both conservative and surgical management. We report the cases of two young Black African patients with huge symptomatic CVA lesions who underwent successful surgical repair with a ventricular restoration technique. Both cases were consulted for chest pain and dyspnea. Chest X-ray and transthoracic Doppler echocardiography suggested the diagnosis. Thoracic angioscanner and thoracic magnetic resonance imaging confirmed the diagnosis. Both patients underwent successful surgery. This case report aims to revisit the diagnostic and therapeutic approach to this rare pathology, in our professional environment.

Human papillomavirus vaccination coverage among young women in the three sub-Saharan African countries using Demographic and Health Surveys data.

Cervical cancer is the fourth most common cancer, with 99% of cases linked to human papillomavirus (HPV) infection. It reflects global inequity as its burden is highest in low- and middle-income countries. The aim of this study was to determine the HPV vaccination coverage and its determinant factors among young women in the three sub-Saharan African countries. Data from the Demographic and Health Surveys among three sub-Saharan African countries were used for analysis. A total of 4,952 women were included in the study. Stata 14 was used to analyze the data. The determinants of the outcome variable were identified using a multilevel mixed-effects logistic regression model. Factors with p-values < 0.05 at 95% confidence interval were declared statistically significant. About 7.5% young women were vaccinated for HPV vaccine against cervical cancer in the current study. Younger age, use of internet, rich economic class, and individual-level media exposure were found to be favorable conditions, whereas being employed was negatively associated with HPV vaccination. Only few segments of young women in these three countries got HPV vaccination. The authors recommend that increasing internet use, media exposure, and economic level of young women will increase the HPV vaccination rates. Furthermore, creating awareness among employed women will also increase the possibility of HPV vaccination.

Mapping evidence on the distribution of uterine fibroids in sub-Saharan Africa: A scoping review protocol.

BACKGROUND: Uterine fibroids are the most common pelvic benign tumours found in reproductive-aged women and may affect up to 70% of all women by menopause. Uterine fibroids place a heavy burden on women and society resulting in poor quality of life, impaired self-image, and impaired social, sexual, emotional, and physical well-being of affected individuals. AIM: This study aims to map the evidence on the burden of uterine fibroids in Sub-Saharan Africa; uterine fibroids' burden by age, uterine fibroids' geographic burden, uterine fibroids' cost estimation and reported experiences among women diagnosed with uterine fibroids. SETTING: Articles will be selected from countries within Sub-Saharan Africa. METHODS AND ANALYSIS: This scoping review will be guided by the Arksey & O'Malley framework, enhanced by Levac et al (2010). The following electronic databases will be searched; PubMed, EBSCOhost (Cumulated Index to Nursing and Allied Health Literature and Health Source), Medical Literature Analysis and Retrieval System Online, Cochrane Library, Scopus, Web of Science, Africa Journal Online, and Google Scholar. The Population Concept and Context (PCC) framework will be used and the PRISMA flow diagram will also be used to show the literature search and selection of studies. Descriptive data analysis will be used; results will be presented in themes, narrative summaries, tables, and charts. DISCUSSION: The study anticipates finding relevant literature on the distribution of uterine fibroids, the burden of uterine fibroids in terms of geographic distribution, age distribution, and cost approximation related to the disease. This will assist in identifying research gaps to guide future research contribute to the body of scientific knowledge and develop preventative strategies for the disease.

Multinational, Multicenter Evaluation of Prostate Cancer Tissue in Sub-Saharan Africa: Challenges and Opportunities.

PURPOSE: Prostate cancer disproportionately affects men of African descent, yet their representation in tissue-based studies is limited. This multinational, multicenter pilot study aims to establish the groundwork for collaborative research on prostate cancer in sub-Saharan Africa. METHODS: The Men of African Descent and Carcinoma of the Prostate network formed a pathologist working group representing eight institutions in five African countries. Formalin-fixed paraffin-embedded prostate tissue specimens were collected from Senegal, Nigeria, and Ghana. Histology slides were produced and digitally scanned. A central genitourinary pathologist (P.L.) and eight African general pathologists reviewed anonymized digital whole-slide images for International Society of Urological Pathology grade groups and other pathologic parameters. Discrepancies were re-evaluated, and consensus grading was assigned. A virtual training seminar on prostate cancer grading was followed by a second assessment on a subcohort of the same tissue set. RESULTS: Of 134 tissue blocks, 133 had evaluable tissue; 13 lacked cancer evidence, and four were of insufficient quality. Post-training, interobserver agreement for grade groups improved to 56%, with a median Cohen's quadratic weighted kappa of 0.83 (mean, 0.74), compared with an initial 46% agreement and a quadratic weighted kappa of 0.77. Interobserver agreement between African pathologist groups was 40%, with a quadratic weighted kappa of 0.66 (95% CI, 0.51 to 0.76). African pathologists tended to overgrade (36%) more frequently than undergrade (18%) compared with the reference genitourinary pathologist. Interobserver variability tended to worsen with a decrease in tissue quality. CONCLUSION: Tissue-based studies on prostate cancer in men of African descent are essential for a better understanding of this common disease. Standardized tissue handling protocols are crucial to ensure good tissue quality and data. The use of digital slide imaging can enhance collaboration among pathologists in multinational, multicenter studies.

Mapping the evidence on integrated service delivery for non-communicable and infectious disease comorbidity in sub-Saharan Africa: protocol for a scoping review.

INTRODUCTION: The concurrent occurrence of infectious diseases (IDs) and non-communicable diseases (NCDs) presents complex healthcare challenges in sub-Saharan Africa (SSA), where healthcare systems often grapple with limited resources. While an integrated care approach has been advocated to address these complex challenges, there is a recognised gap in comprehensive evidence regarding the various models of integrated care, their components and the feasibility of their implementation. This scoping review aims to bridge this gap by examining the breadth and nature of evidence on integrated care models for NCDs and IDs within SSA, thereby updating the current evidence base in the domain. METHODS AND ANALYSIS: Based on the Joanna Briggs Institute (JBI) framework for scoping reviews, this study will include peer-reviewed and grey literature reporting on integrated care models for NCD-ID comorbidities in SSA. A comprehensive search of published sources in electronic databases (PubMed, Scopus, Embase, the Cochrane Library, Health System Evidence and Research4Life) and grey literature (Google Scholar, EBSCO Open Dissertations and relevant organisational websites) will be conducted to identify sources of information reported in English from 2018 onwards. The review will consider sources of evidence reporting on integrated care model for NCDs such as diabetes; chronic cardiovascular, respiratory and kidney diseases; cancers; epilepsy; and mental illness, and comorbid IDs such as HIV, tuberculosis and malaria. All sources of evidence will be considered irrespective of the study designs or methods used. The review will exclude sources that solely focus on the differentiated or patient-centred care delivery approach, and that focus on other conditions, populations or settings. The reviewers will independently screen the sources for eligibility and extract data using a JBI-adapted data tool on the Parsifal review platform. Data will be analysed using descriptive and thematic analyses and results will be presented in tables, figures, diagrams and a narrative summary. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as it will synthesise published data and does not involve human participants. The final report will be submitted for publication in a peer-reviewed journal. The findings will be used to inform future research. STUDY REGISTRATION: OSF: https://doi.org/10.17605/OSF.IO/KFVEY.

Challenges and opportunities in neonatal sepsis management: insights from a survey among clinicians in 25 Sub-Saharan African countries.

BACKGROUND: Neonatal sepsis (NS) is a global health issue, particularly in Sub-Saharan Africa, where it accounts for a substantial portion of neonatal morbimortality. This multicountry survey aimed to elucidate current practices, challenges and case definitions in managing NS among clinicians in Sub-Saharan Africa. METHODS: The survey targeted physicians and medical practitioners working in neonatal care who participated in a Self-Administered Web Questionnaire. The main objective was to understand NS and infection case definitions and management from the clinician's point of view and to identify challenges and opportunities in sepsis management. Participants were queried on demographics, definitions and diagnostic criteria, treatment approaches, and infection prevention and control (IPC) measures. A total of 136 participants from 93 healthcare structures responded, providing valuable insights into NS management practices. RESULTS: From May to July 2022 across 21 Sub-Saharan African countries, 136 neonatal clinicians with an average from 93 structures with on average 10-year experience took the survey. NS ranked highest among prevalent neonatal conditions. Diagnostic case definitions between sepsis and infection were attributed to clinical signs, anamnesis, C reactive protein, white blood cll count and blood cultures with no statistically significant differences. Early-onset sepsis was defined within 72 hours by 48%, while late-onset varied. Antibiotics were likely on admission (86.4%) and during the stay (82.2%). Treatment abandonment was reported unlikely. The preferred antibiotic regimen for early-onset sepsis was intravenous amoxicillin (or ampicillin), gentamycin and cefotaxime. Blood culture availability and IPC protocols were reported as limited, particularly concerning patient environment, pharmacy protocols and clean-dirty circuits. CONCLUSIONS: This NS survey emphasises clinicians' challenges due to limited access to diagnostic tools and raises concerns about antimicrobial overexposure. IPC also seem limited, according to participants. Addressing these challenges can enhance diagnostic practices, antibiotic stewardship and infection control in the region.

Outcomes of jaundice in advanced hepatocellular carcinoma - a sub-Saharan perspective.

BACKGROUND: Jaundice is a marker of advanced disease and poor outcomes in hepatocellular carcinoma (HCC). The aim of this study was to describe and analyse the management and outcomes of jaundiced HCC patients at a large academic referral centre in sub-Saharan Africa (SSA). METHODS: Treatment-naïve adult HCC patients who presented with jaundice between 1990 and 2023 were analysed. RESULTS: During the inclusion period, 676 HCC patients were treated at Groote Schuur Hospital. The mean age of the 126 (18.6%) who were jaundiced was 48.8 (± 13.2) years. Eighty-nine (70.6%) were male. Ninety-four (74.6%) patients with jaundice secondary to diffuse tumour infiltration had best supportive care (BSC) only. Thirty-two had obstructive jaundice (OJ); four were excluded because of missing hospital records. In 28 of these patients, 16 underwent biliary drainage (BD) and 12 received BSC only. The mean overall survival (OS) of the 126 patients was 100.5 (± 242.3) days. The patients with diffuse tumour infiltration had an OS of 105.9 (± 273.3) days. The patients with OJ survived 86.5 (± 135.0) days. There was no significant difference in OS between the three patient groups (p = 0.941). In the OJ group, patients who underwent BD survived longer than the BSC group (117.9 ± 166.4 vs. 29.2 ± 34.7 days, p = 0.015).

An analytical framework for breast cancer public policies in Sub-Saharan Africa: results from a comprehensive literature review and an adapted policy Delphi.

BACKGROUND: Breast cancer is the leading cause of death from cancer in women and is a major public health problem worldwide. Despite the lower incidence rates of breast cancer in resource-limited settings, especially sub-Saharan Africa, there is a higher mortality rate compared to high-resource countries where the disease has a higher incidence. This makes breast cancer the second deadliest cancer in African women. These poor results reflect the weakness in public health policies. The aim of this paper is to contribute to the effective control of breast cancer by designing a framework for a comprehensive and systemic analysis of these policies in Sub-Saharan Africa. METHODS: This research is based on a literature review that adopted a systematic approach followed by a modified policy Delphi involving breast cancer experts in Sub-Saharan Africa. We included narrative reviews and systematic reviews/meta-analyses published between 2015 and 2022 as well as official documents in the analysis. We integrated the World Health Organization's health system building blocks with Walt and Gilson's policy analysis triangle to analyse the information collected and develop our analytical framework. RESULTS: A total of 22 reviews and documents were included in the study. Sixteen breast cancer experts from Sub-Saharan Africa participated in the first Delphi round, and nine participated in the second round. The different components identified for a comprehensive and systemic analysis of effective breast cancer policies can be classified into policy content divided according to the health system building blocks and related policy processes; individual, organized national and international policy stakeholders; and policy contexts. CONCLUSION: This study enabled the design of a framework suitable for the comprehensive and systemic analysis of breast cancer control policies in Sub-Saharan Africa. This framework can be used as a checklist for stakeholders to guide the planning, implementation and evaluation of policies and specific breast cancer control programmes at the national and facility levels.

Climate change-induced shifts in the food systems and diet-related non-communicable diseases in sub-Saharan Africa: a scoping review and a conceptual framework.

OBJECTIVES: To determine the relationship between climate change, food systems and diet-related non-communicable diseases (DR-NCDs) in sub-Saharan Africa (SSA) and propose a conceptual framework for food systems in SSA. DESIGN: A scoping review. ELIGIBILITY CRITERIA: Studies included investigated the relationship between climate change and related systemic risks, food systems, DR-NCDs and its risk factors in SSA. Studies focusing on the association between climate change and DR-NCDs unrelated to food systems, such as social inequalities, were excluded. SOURCES OF EVIDENCE: A comprehensive search was conducted in ProQuest (nine databases), Google Scholar and PubMed in December 2022. CHARTING METHODS: Data extracted from studies included author, study type, country of study, climate change component, DR-NCD outcomes and risk factors, and impacts of climate change on DR-NCDs. A narrative approach was used to analyse the data. Based on the evidence gathered from SSA, we modified an existing food system conceptual framework. RESULTS: The search retrieved 19 125 studies, 10 of which were included in the review. Most studies used a cross-sectional design (n=8). Four explored the influence of temperature on liver cancer through food storage while four explored the influence of temperature and rainfall on diabetes and obesity through food production. Cross-sectional evidence suggested that temperature is associated with liver cancer and rainfall with diabetes. CONCLUSION: The review highlights the vulnerability of SSA's food systems to climate change-induced fluctuations, which in turn affect dietary patterns and DR-NCD outcomes. The evidence is scarce and concentrates mostly on the health effects of temperature through food storage. It proposes a conceptual framework to guide future research addressing climate change and DR-NCDs in SSA.

Weekly iron-folic acid supplementation and its impact on children and adolescents iron status, mental health and school performance: a systematic review and meta-analysis in sub-Saharan Africa.

OBJECTIVE: This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and educational outcomes of children and adolescents in sub-Saharan Africa. DESIGN: A systematic review and meta-analysis was used. DATA SOURCES: Five databases, namely, MEDLINE, Scopus, Web of Science, Cochrane Library and Google Scholar, were systematically searched for relevant articles up to 23 August 2023. ELIGIBILITY CRITERIA: It was focused on randomised controlled trials involving children and adolescents in sub-Saharan Africa, exploring the effects of iron supplementation on various outcomes, such as serum ferritin and haemoglobin levels, anaemia, mental health and school performance. DATA EXTRACTION AND SYNTHESIS: The Joanna Briggs Institute Critical Appraisal tools were used for quality assessment, with two independent reviewers thoroughly evaluating each paper. Using the Cochrane risk of bias tool, we evaluated the certainty of evidence such as the risk of bias, inconsistency, indirectness, imprecision and publication bias. RESULTS: A systematic review of 10 articles revealed that WIFAS significantly increased serum ferritin levels in adolescent girls (Hedge's g=0.53, 95% CI 0.28 to 0.78; heterogeneity I2=41.21%, p<0.001) and haemoglobin levels in school-aged children (Hedge's g=0.37, 95% CI 0.01 to 0.73; heterogeneity I2=91.62%, p<0.001). The analysis further demonstrated a substantial reduction in the risk of anaemia by 20% (risk ratio=0.8, 95% CI 0.69 to 0.93; heterogeneity I2=28.12%, p<0.001). CONCLUSION: WIFAS proved effective in enhancing serum ferritin and haemoglobin concentrations and lowering the risk of anaemia in school-aged children and adolescents compared with a placebo. Similarly, there are not enough studies to examine the effects of WIFAS on school performance. However, information regarding mental health problems, mortality and potential side effects remains insufficient. PROSPERO REGISTRATION NUMBER: CRD42023397898.

Scoping review protocol on the perception and attitude of women on methods for collecting cervicovaginal samples for human papillomavirus testing in sub-Saharan Africa.

INTRODUCTION: Sub-Saharan Africa (SSA) regions have the highest burden of cervical cancer (CC), accounting for nearly a quarter of global mortality. Many women in SSA are reluctant to access CC screening because they are uncomfortable exposing their private parts to healthcare providers. The perception of women who have experienced self-sampling in SSA is yet to be reviewed. This scoping review will explore the literature on the perception and attitude of women towards methods of collecting cervicovaginal samples for human papillomavirus (HPV) testing in SSA. METHODS AND ANALYSIS: An extensive search using the Arksey and O'Malley framework will be conducted. The search criteria will be limited to original research conducted in community or clinical settings in SSA within the last 10 years. Four databases, namely, PUBMED, Cochrane, African Journals Online and Google Scholar, will be searched. Two independent persons (UIAB and DOO) will screen the titles and abstracts and later full texts using population, intervention, comparison and outcome criteria. IOMB will serve as a tiebreaker whenever there is no agreement on the choice of eligibility criteria. The screening process will be presented using Preferred Reporting Items for Systematic Reviews and Meta-Analyses for the scoping review flow format. The descriptive analysis of eligible studies for scoping reviews will be summarised. We will describe themes of attitude and perception covering pain, embarrassment, privacy and comfortability, willingness to self-sample, anxiety and confidence. ETHICS AND DISSEMINATION: This is a scoping review protocol and does not require ethical approval. Findings from this review will be disseminated through peer-reviewed publications, the production of policy briefs, and presentations at local and international conferences.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Perspectives on the state of cleft lip and cleft palate patient care in Africa.

PURPOSE OF REVIEW: Patients with cleft lip -palate (CLP) experience morbidity and social stigma, particularly in low-income and middle-income countries (LMICs) such as those of sub-Saharan Africa (SSA). Delays in treatment secondary either to lack of awareness, skills, equipment and consumables; poor health infrastructure, limited resources or a combination of them, has led to SSA having the highest rates of death and second highest rates of disability-adjusted life years in patients with CLP globally. Here we review current perspectives on the state of comprehensive cleft lip and palate repair in Africa. RECENT FINDINGS: To bridge gaps in government health services, nongovernmental organizations (NGOs) have emerged to provide care through short-term surgical interventions (STSIs). These groups can effect change through direct provision of care, whereas others strengthen internal system. However, sustainability is lacking as there continue to be barriers to achieving comprehensive and longitudinal cleft care in SSA, including a lack of awareness of CLP as a treatable condition, prohibitive costs, poor follow-up, and insufficient surgical infrastructure. With dedicated local champions, a comprehensive approach, and reliable partners, establishing sustainable CLP services is possible in countries with limited resources. SUMMARY: The replacement of CLP 'missions' with locally initiated, internationally supported capacity building initiatives, integrated into local healthcare systems will prove sustainable in the long-term.

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Cancer survival in sub-Saharan Africa (SURVCAN-3): a population-based study.

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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Vital Strategies, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial.

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 Sß 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation.