Treatment outcomes of esophageal cancer in Eastern Africa: protocol of a multi-center, prospective, observational, open cohort study.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined. METHODS: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach. DISCUSSION: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research. TRIAL REGISTRATION: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 .

Correction: [On Becoming a Global Citizen: Transformative Learning Through Global Health Experiences].

[This corrects the article DOI: 10.1016/j.aogh.2017.07.005.].

Developing Ethical and Sustainable Global Health Educational Exchanges for Clinical Trainees: Implementation and Lessons Learned from the 30-Year Academic Model Providing Access to Healthcare (AMPATH) Partnership.

Background: There is strong interest among healthcare trainees and academic institutions in global health rotations. There are a number of guidelines detailing the ethical principles for equitable and ethical global health rotations and bilateral exchanges, but it is often challenging to know to implement those principles and develop longstanding partnerships. Objectives: The Academic Model Providing Access to Healthcare (AMPATH) is a 30-year continuous partnership between a consortium of 12 universities in North America and Moi University in Kenya. The AMPATH bilateral educational exchange has had 1,871 North American and over 400 Kenyan clinical trainees participate to date. The article describes the bilateral exchange of trainees including curriculum, housing, and costs and discusses how each is an application of the principles of ethical global engagement. Findings: The article takes the experiences of the AMPATH partnership and offers practical strategies for implementing similar partnerships based on previously published ethical principles. Conclusions: AMPATH provides a model for developing an institutional partnership for a bilateral educational exchange grounded in cultural humility, bidirectional relationships, and longitudinal, sustainable engagement.

Traditional and commercial alcohols and esophageal cancer risk in Kenya.

Squamous cell esophageal cancer is common throughout East Africa, but its etiology is poorly understood. We investigated the contribution of alcohol consumption to esophageal cancer in Kenya, based on a hospital-based case-control study conducted from 08/2013 to 03/2018 in Eldoret, western Kenya. Cases had an endoscopy-confirmed esophageal tumor whose histology did not rule out squamous cell carcinoma. Age and gender frequency-matched controls were recruited from hospital visitors/patients without digestive diseases. Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CI) adjusting for tobacco (type, intensity) and 6 other potential confounders. A total of 422 cases (65% male, mean at diagnosis 60 (SD 14) years) and 414 controls were included. ORs for ever-drinking were stronger in ever-tobacco users (9.0, 95% CI: 3.4, 23.8, with few tobacco users who were never drinkers) than in never-tobacco users (2.6, 95% CI: 1.6, 4.1). Risk increased linearly with number of drinks: OR for >6 compared to >0 to ≤2 drinks/day were 5.2 (2.4, 11.4) in ever-tobacco users and 2.1 (0.7, 4.4) in never-tobacco users. Although most ethanol came from low ethanol alcohols (busaa or beer), for the same ethanol intake, if a greater proportion came from the moonshine chang'aa, it was associated with a specific additional risk. The population attributable fraction for >2 drinks per day was 48% overall and highest in male tobacco users. Alcohol consumption, particularly of busaa and chang'aa, contributes to half of the esophageal cancer burden in western Kenya.

Hot beverages and oesophageal cancer risk in western Kenya: Findings from the ESCCAPE case-control study.

Oesophageal squamous cell carcinoma (ESCC) has markedly high incidence rates in Kenya and much of East Africa, with a dire prognosis and poorly understood aetiology. Consumption of hot beverages-a probable carcinogen to humans-is associated with increased ESCC risk in other settings and is habitually practiced in Kenya. We conducted a case-control study in Eldoret, western Kenya between August 2013 and March 2018. Cases were patients with endoscopically confirmed oesophageal cancer whose histology did not rule out ESCC. Age and sex-matched controls were hospital visitors and hospital out and in-patients excluding those with digestive diseases. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for self-reported drinking temperatures; consumption frequency; mouth burning frequency and hot porridge consumption using logistic regression models adjusted for potential confounders. Drinking temperature association with tumour sub-location was also investigated. The study included 430 cases and 440 controls. Drinkers of 'very hot' and 'hot' beverages (>95% tea) had a 3.7 (95% CI: 2.1-6.5) and 1.4-fold (1.0-2.0) ESCC risk, respectively compared to 'warm' drinkers. This trend was consistent in males, females, never and ever alcohol/tobacco and was stronger over than under age 50 years. The tumour sub-location distribution (upper/middle/lower oesophagus) did not differ by reported drinking temperature. Our study is the first comprehensive investigation in this setting to-date to observe a link between hot beverage consumption and ESCC in East Africa. These findings provide further evidence for the role of this potentially modifiable risk factor in ESCC aetiology.

Dental fluorosis and oral health in the African Esophageal Cancer Corridor: Findings from the Kenya ESCCAPE case-control study and a pan-African perspective.

There are no studies of oral health in relation to esophageal cancer in Africa, or of Eastern Africa's endemic dental fluorosis, an irreversible enamel hypo-mineralization due to early-life excessive fluoride intake. During 2014-18, we conducted a case-control study of squamous cell esophageal cancer in Eldoret, western Kenya. Odds ratios (AORs (95% confidence intervals)) were adjusted for design factors, tobacco, alcohol, ethnicity, education, oral hygiene and missing/decayed teeth. Esophageal cancer cases (N = 430) had poorer oral health and hygiene than controls (N = 440). Compared to no dental fluorosis, moderate/severe fluorosis, which affected 44% of cases, had a crude OR of 20.8 (11.6, 37.4) and on full adjustment was associated with 9.4-fold (4.6, 19.1) increased risk, whilst mild fluorosis (43% of cases) had an AOR of 2.3 (1.3, 4.0). The prevalence of oral leukoplakia and tooth loss/decay increased with fluorosis severity, and increased cancer risks associated with moderate/severe fluorosis were particularly strong in individuals with more tooth loss/decay. Using a mswaki stick (AOR = 1.7 (1.0, 2.9)) rather than a commercial tooth brush and infrequent tooth brushing also independently increased risk. Geographic variations showed that areas of high esophageal cancer incidence and those of high groundwater fluoride levels have remarkably similar locations across Eastern Africa. In conclusion, poor oral health in combination with, or as a result of, high-altitude susceptibility to hydro-geologically influenced dental fluorosis may underlie the striking co-location of Africa's esophageal cancer corridor with the Rift Valley. The findings call for heightened research into primary prevention opportunities of this highly fatal but common cancer.

On Becoming a Global Citizen: Transformative Learning Through Global Health Experiences.

BACKGROUND: Globalization has increased the demand for international experiences in medical education. International experiences improve medical knowledge, clinical skills, and self-development; influence career objectives; and provide insights on ethical and societal issues. However, global health rotations can end up being no more than tourism if not structured to foster personal transformation and global citizenship. OBJECTIVE: We conducted a qualitative assessment of trainee-reported critical incidents to more deeply understand the impact of our global health experience on trainees. METHODS: A cross-sectional survey was administered to trainees who had participated in a 2-month elective in Kenya from January 1989 to May 2013. We report the results of a qualitative assessment of the critical incident reflections participants (n = 137) entered in response to the prompt, "Write about one of your most memorable experiences and explain why you chose to describe this particular one." Qualitative analyses were conducted using thematic analysis and crystallization immersion analytic methods based on the principles of grounded theory, employing a constructivists' research paradigm. FINDINGS: Four major themes emerged. These themes were Opening Oneself to a Broader World View; Impact of Suffering and Death; Life-Changing Experiences; and Commitment to Care for the Medically Underserved. CONCLUSIONS: Circumstances that learners encounter in the resource-scarce environment in Kenya are eye-opening and life-changing. When exposed to these frame-shifting circumstances, students elaborate on or transform existing points of view. These emotionally disruptive experiences in an international health setting allowed students to enter a transformational learning process with a global mind. Students can see the world as an interdependent society and develop the capacity to advance both their enlightened self-interest and the interest of people elsewhere in the world as they mature as global citizens. Medical schools are encouraged to foster these experiences by finding ways to integrate them into curriculum.

Career choices and global health engagement: 24-year follow-up of U.S. participants in the Indiana University-Moi University elective.

BACKGROUND: Global health experiences evoke a profound awareness of cultural differences, inspire learners to prioritize professional values, and provide a lens for addressing global health care challenges. This study compares the long-term career and practice choices of participants in a 2-month Indiana University-Moi University, Kenya elective from 1989-2013 with those of a control group. METHODS: Global health elective (GHE) participants and a random sample of alumni without GHE experience were surveyed on their clinical practice, public health and global health activities. RESULTS: Responses from 176 former participants were compared with a control group of 177 alumni. GHE participants were more likely than similar controls to provide care to underserved U.S. populations (p=0.037), spend time in global health, public health, and public policy activities (p=0.005) and be involved in global health advocacy (p=0.001). Using multivariable analysis, GHE participants were more likely to be generalists (p<0.05), report that healthcare costs influenced medical decision-making (p<0.05), and provide healthcare outside the U.S. for ≥1 week/year (p<0.001). CONCLUSIONS: Many years out of training, GHE participants were more likely to be generalists working with underserved populations, to be cost-conscious in their healthcare decision-making, and to be involved in global health, public health or public policy. IMPLICATIONS: With the primary care provider shortage and need for greater awareness among providers of healthcare costs, our study shows that that global health experiences may yield broader benefits to the U.S. medical system.

Building Comprehensive and Sustainable Health Informatics Institutions in Developing Countries: Moi University Experience.

Current approaches for capacity building in Health Informatics (HI) in developing countries mostly focus on training, and often rely on support from foreign entities. In this paper, we describe a comprehensive and multidimensional capacity-building framework by Lansang & Dennis, and its application for HI capacity building as implemented in a higher-education institution in Kenya. This framework incorporates training, learning-by-doing, partnerships, and centers of excellence. At Moi University (Kenya), the training dimensions include an accredited Masters in HI Program, PhD in HI, and HI short courses. Learning-by-doing occurs through work within MOH facilities at the AMPATH care and treatment program serving 3 million people. Moi University has formed strategic HI partnerships with Regenstrief Institute, Inc. (USA), University of Bergen (Norway), and Makerere University (Uganda), among others. The University has also created an Institute of Biomedical Informatics to serve as an HI Center of Excellence in the region. This Institute has divisions in Training, Research, Service and Administration. The HI capacity-building approach by Moi provides a model for adoption by other institutions in resource-limited settings.

Implementation and operational research: evaluating outcomes of patients lost to follow-up in a large comprehensive care treatment program in western Kenya.

BACKGROUND: Academic Model Providing Access To Healthcare (AMPATH) program provides comprehensive HIV care and treatment services. Approximately, 30% of patients have become lost to follow-up (LTFU). We sought to actively trace and identify outcomes for a sample of these patients. METHODS: LTFU was defined as missing a scheduled visit by ≥3 months. A randomly selected sample of 17% of patients identified as LTFU between January 2009 and June 2011 was generated, with sample stratification on age, antiretroviral therapy (ART) status at last visit, and facility. Chart reviews were conducted followed by active tracing. Tracing was completed by trained HIV-positive outreach workers July 2011 to February 2012. Outcomes were compared between adults and children and by ART status. RESULTS: Of 14,811 LTFU patients, 2540 were randomly selected for tracing (2179 adults, 1071 on ART). The chart reviews indicated that 326 (12.8%) patients were not actually LTFU. Outcomes for 71% of sampled patients were determined including 85% of those physically traced. Of those with known outcomes, 21% had died, whereas 29% had disengaged from care for various reasons. The remaining patients had moved away (n = 458, 25%) or were still receiving HIV care (n = 443 total, 25%). CONCLUSIONS: Our findings demonstrate the feasibility of a large-scale sampling-based approach. A significant proportion of patients were found not to be LTFU, and further, high numbers of patients who were LTFU could not be located. Over a quarter of patients disengaged from care for various reasons including access challenges and familial influences.

"Not too far to walk": the influence of distance on place of delivery in a western Kenya health demographic surveillance system.

BACKGROUND: Maternal health service coverage in Kenya remains low, especially in rural areas where 63% of women deliver at home, mainly because health facilities are too far away and/or they lack transport. The objectives of the present study were to (1) determine the association between the place of delivery and the distance of a household from the nearest health facility and (2) study the demographic characteristics of households with a delivery within a demographic surveillance system (DSS). METHODS: Census sampling was conducted for 13,333 households in the Webuye health and demographic surveillance system area in 2008-2009. Information was collected on deliveries that had occurred during the previous 12 months. Digital coordinates of households and sentinel locations such as health facilities were collected. Data were analyzed using STATA version 11. The Euclidean distance from households to health facilities was calculated using WinGRASS version 6.4. Hotspot analysis was conducted in ArcGIS to detect clustering of delivery facilities. Unadjusted and adjusted odds ratios were estimated using logistic regression models. P-values less than 0.05 were considered significant. RESULTS: Of the 13,333 households in the study area, 3255 (24%) reported a birth, with 77% of deliveries being at home. The percentage of home deliveries increased from 30% to 80% of women living within 2 km from a health facility. Beyond 2 km, distance had no effect on place of delivery (OR 1.29, CI 1.06-1.57, p = 0.011). Heads of households where women delivered at home were less likely to be employed (OR 0.598, CI 0.43-0.82, p = 0.002), and were less likely to have secondary education (OR 0.50, CI 0.41-0.61, p < 0.0001). Hotspot analysis showed households having facility deliveries were clustered around facilities offering comprehensive emergency obstetric care services. CONCLUSION: Households where the nearest facility was offering emergency obstetric care were more likely to have a facility delivery, but only if the facility was within 2 km of the home. Beyond the 2-km threshold, households were equally as likely to have home and facility deliveries. There is need for further research on other factors that affect the choice of place of delivery, and their relationships with maternal mortality.

HIV testing uptake and prevalence among adolescents and adults in a large home-based HIV testing program in Western Kenya.

OBJECTIVE: To describe HIV testing uptake and prevalence among adolescents and adults in a home-based HIV counseling and testing program in western Kenya. METHODS: Since 2007, the Academic Model Providing Access to Healthcare program has implemented home-based HIV counseling and testing on a large scale. All individuals aged ≥13 years were eligible for testing. Data from 5 of 8 catchments were included in this analysis. We used descriptive statistics and multivariate logistic regression to examine testing uptake and HIV prevalence among adolescents (13-18 years), younger adults (19-24 years), and older adults (≥25 years). RESULTS: There were 154,463 individuals eligible for analyses as follows: 22% adolescents, 19% younger adults, and 59% older adults. Overall mean age was 32.8 years and 56% were female. HIV testing was high (96%) across the following 3 groups: 99% in adolescents, 98% in younger adults, and 94% in older adults (P < 0.001). HIV prevalence was higher (11.0%) among older adults compared with younger adults (4.8%) and adolescents (0.8%) (P < 0.001). Those who had ever previously tested for HIV were less likely to accept HIV testing (adjusted odds ratio: 0.06, 95% confidence interval: 0.05 to 0.07) but more likely to newly test HIV positive (adjusted odds ratio: 1.30, 95% confidence interval: 1.21 to 1.40). Age group differences were evident in the sociodemographic and socioeconomic factors associated with testing uptake and HIV prevalence, particularly, gender, relationship status, and HIV testing history. CONCLUSIONS: Sociodemographic and socioeconomic factors were independently associated with HIV testing and prevalence among the age groups. Community-based treatment and prevention strategies will need to consider these factors.

Multiple cardiovascular risk factors in Kenya: evidence from a health and demographic surveillance system using the WHO STEPwise approach to chronic disease risk factor surveillance.

OBJECTIVE: To describe the distribution of cardiovascular risk factors in western Kenya using a Health and Demographic Surveillance System (HDSS). DESIGN: Population based survey of residents in an HDSS. SETTING: Webuye Division in Bungoma East District, Western Province of Kenya. PATIENTS: 4037 adults ≥ 18 years of age. INTERVENTIONS: Home based survey using the WHO STEPwise approach to chronic disease risk factor surveillance. MAIN OUTCOME MEASURES: Self-report of high blood pressure, high blood sugar, tobacco use, alcohol use, physical activity, and fruit/vegetable intake. RESULTS: The median age of the population was 35 years (IQR 26-50). Less than 6% of the population reported high blood pressure or blood sugar. Tobacco and alcohol use were reported in 7% and 16% of the population, respectively. The majority of the population (93%) was physically active. The average number of days per week that participants reported intake of fruits (3.1 ± 0.1) or vegetables (1.6 ± 0.1) was low. In multiple logistic regression analyses, women were more likely to report a history of high blood pressure (OR 2.72, 95% CI 1.9 to 3.9), less likely to report using tobacco (OR 0.08, 95% CI 0.06 to 0.11), less likely to report alcohol use (OR 0.18, 95% CI 0.15 to 0.21) or eat ≥ 5 servings per day of fruits or vegetables (OR 0.87, 95% CI 0.76 to 0.99) compared to men. CONCLUSIONS: The most common cardiovascular risk factors in peri-urban western Kenya are tobacco use, alcohol use, and inadequate intake of fruits and vegetables. Our data reveal locally relevant subgroup differences that could inform future prevention efforts.

Frequency and factors associated with adherence to and completion of combination antiretroviral therapy for prevention of mother to child transmission in western Kenya.

INTRODUCTION: The objective of this analysis was to identify points of disruption within the prevention of mother-to-child transmission (PMTCT) continuum from combination antiretroviral therapy (CART) initiation until delivery. METHODS: To address this objective, the electronic medical records of all antiretroviral-naïve adult pregnant women who were initiating CART for PMTCT between January 2006 and February 2009 within the Academic Model Providing Access To Healthcare (AMPATH), western Kenya, were reviewed. Outcomes of interest were clinician-initiated change or stop in regimen, disengagement from programme (any, early, late) and self-reported medication adherence. Disengagement was categorized as early disengagement (any interval of greater than 30 days between visits but returning to care prior to delivery) or late disengagement (no visit within 30 days prior to the date of delivery). The association between covariates and the outcomes of interest were assessed using bivariate (Kruskal-Wallis test for continuous variables and the Chi-square test for categorical variables) and multivariate logistic regression analysis. RESULTS: A total of 4284 antiretroviral-naïve pregnant women initiated CART between January 2006 and February 2009. The majority of women (89%) reported taking all of their medication at every visit. There were 18 (0.4%) deaths reported. Clinicians discontinued CART in 10 patients (0.7%) while 1367 (31.9%) women disengaged from care. Of those disengaging, 404 (29.6%) disengaged early and 963 (70.4%) late. In the multivariate model, the odds of disengagement decreased with increasing age (odds ratio [OR] 0.982; confidence interval [CI] 0.966-0.998) and increasing gestational age at CART initiation (OR 0.925; CI 0.909-0.941). Women receiving care at a district hospital (OR 0.794; CI 0.644-0.980) or tuberculosis medication (OR 0.457; CI 0.202-0.935) were less likely to disengage. The odds of disengagement were higher in married women (OR 1.277; CI 1.034-1.584). The odds of early disengagement decreased with increasing age at CART initiation (OR 0.902; CI 0.881-0.924). The odds of late disengagement decreased with increasing age at CART initiation (OR 0.936; CI 0.917-0.956). While they increased with higher CD4 counts at CART-initiation (OR 1.001; CI 1.000-1001) and in married women (OR 1.297; CI 1.000-1.695). CONCLUSIONS: In a PMTCT programme embedded in an antiretroviral treatment programme with an active outreach department, the majority (67.4%) of women remained engaged and received uninterrupted prenatal CART.

Sustainability of first-line antiretroviral regimens: findings from a large HIV treatment program in western Kenya.

OBJECTIVE: To describe first change or discontinuation in combination antiretroviral treatment (cART) among previously treatment naive, HIV-infected adults in a resource-constrained setting. METHODS: The United States Agency for International Development-Academic Model Providing Access to Healthcare Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout western Kenya. Patients in this analysis were aged > or =18 years, previously antiretroviral treatment naive, and initiated to cART between January 2006 and November 2007, with at least 1 follow-up visit. A treatment change or discontinuation was defined as change of regimen including single drug substitutions or a complete halting of cART. RESULTS: There were 14,162 patients eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed or stopped their cART. Among these, 859 (62%) changed their regimen (including 514 patients who had a single drug substitution) and 517 (38%) completely discontinued cART. The overall incidence rate (IR) of cART changes or stops per 100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The incidence was much higher in the first year of post-cART initiation (IR: 25.0, 95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The most commonly cited reason was toxicity (46%). In multivariate regression, individuals were more likely to discontinue cART if they were World Health Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69] or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88). Individuals were more likely to change their regimen if they were aged > or =38 years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3 (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those receiving stavudine-containing regimens were less likely to experience either a discontinuation or a change of their cART. CONCLUSIONS: These data suggest a moderate incidence of cART changes and discontinuations among this large population of adults in western Kenya. Mostly occurring within 12 months of cART initiation, and primarily due to toxicity, older individuals, those with more advanced disease, and those using zidovudine are at higher risk of experiencing a change or a discontinuation in their cART.