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Objectives: Visual inspection with acetic acid (VIA) is a low‐cost approach for cervical cancer screening used in most low‐ and middle‐income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial‐intelligence‐based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone‐captured images of the cervix and identify precancerous lesions, helping augment VIA performance. Design: Prospective study. Setting: Eight public health facilities in Zambia. Participants: A total of 8204 women aged 25–55. Interventions: Cervical images captured on commonly used low‐cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. Main Outcome Measures: Area under the receiver operating curve (AUC); sensitivity; specificity. Results: As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89–0.93), which translates to a sensitivity of 85% (95% CI = 81%–90%) and specificity of 86% (95% CI = 84%–88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta‐analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88–0.93), and among those testing positive for high‐risk HPV types, the AUC was 0.87 (95% CI = 0.83–0.91). Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto‐white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study). [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) vaccine is effective in cervical cancer prevention. However, many barriers to uptake exist and strategies to overcome them are needed. Therefore, this study aimed to select and tailor implementation strategies to barriers identified by multiple stakeholders in Zambia. The study was conducted in Lusaka district between January and February 2023. Participants were purposively sampled from three stakeholder groups namely, adolescent girls, parents, and teachers and healthcare workers. With each of the stakeholders' groups (10–13 participants per group), we used the nominal group technique to gain consensus to tailor feasible and acceptable implementation strategies for mitigating the identified contextual barriers. The identified barriers included low levels of knowledge and awareness about the HPV vaccine, being out of school, poor community sensitisation, lack of parental consent to vaccinate daughters, and myths and misinformation about the HPV vaccine. The lack of knowledge and awareness of the HPV vaccine was a common barrier across the three groups. Tailored strategies included conducting educational meetings and consensus-building meetings, using mass media, changing service sites, re-examining implementation, and involving patients/consumers and their relatives. Our study contributes to the available evidence on the process of selecting and tailoring implementation strategies to overcome contextual barriers. Policymakers should consider these tailored strategies to mitigate barriers and improve HPV vaccine uptake. [ABSTRACT FROM AUTHOR]

Cervical cancer can be prevented, primarily by the administration of the human papillomavirus (HPV) vaccine. Healthcare workers (HCWs) and teachers play important roles when schools are used for vaccine delivery; however, challenges exist. This study aimed to understand the barriers and facilitators to HPV vaccination that are perceived by HCWs and teachers. Guided by the consolidated framework for implementation research (CFIR), key informant interviews were conducted in Lusaka district between June 2021 and November 2021 using a semi-structured questionnaire. Recorded interviews were transcribed verbatim and imported into NVIVO 12 for data management and analysis. We coded transcripts inductively and deductively based on the adapted CFIR codebook. We reached saturation with 23 participants. We identified barriers and facilitators across the five CFIR domains. Facilitators included offering the HPV vaccine free of charge, HPV vaccine effectiveness, stakeholder engagement, and timely planning of the HPV vaccination. Barriers included vaccine mistrust due to its perceived novelty, low levels of parental knowledge, myths and misinformation about the vaccine, lack of parental consent to vaccinate daughters, lack of transport for vaccination outreach, lack of staff incentives, and inadequate sensitisation. Using the CFIR as a guiding framework, we have identified implementation barriers and facilitators to HPV vaccination among HCWs and teachers. Most of the identified barriers are modifiable, hence it is prudent that these are addressed for a high HPV vaccine uptake. [ABSTRACT FROM AUTHOR]

Introduction: Cancellations of elective surgery in low-and middle-income countries (LMIC) are common and a major hindrance for patients who are in need of surgical therapeutic modalities. This is especially important in the context of scaling up needed surgical interventions for gynaecological cancer care. There is a knowledge gap in the literature related to cancellation of gynaecologic oncology surgeries in LMIC, where there is enormous need for this specific cancer surgical capacity. We report in an observational descriptive fashion, our experience at the UTH/CDH in Lusaka, Zambia, on the causes of surgical cancellations in gynaecologic oncology. Methods: From January 1, 2021 through June 31, 2023, we retrospectively evaluated the surgical registry for gynaecologic oncology at the UTH/CDH in Lusaka, Zambia to assess the number and causes of surgical cancellations. Results: There were a total of 66 (16.96%) surgical cancellations out of 389 scheduled gynaecologic oncology cases. Lack of available blood and/or low haemoglobin was the most frequent cause of surgical cancellations, 27 cases (40.90%). Conclusion: We highlight in our series that the lack of blood, leading to surgical cancellations was the most frequent impediment related to performing scheduled gynaecologic oncology surgical procedures. As gynaecologic oncology services scale up in LMIC, given the radical nature of surgery and its association with blood loss, it is incumbent on the entire clinical ecosystem to address this issue and to develop mitigating strategies, specific to their respective resource setting. [ABSTRACT FROM AUTHOR]

Background: WHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE). Methods: In this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements (which did not influence clinical care) including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output (HPV16, HPV18/45, HPV31/33/52/58, HPV35/39/51/56/59/66/68, human DNA control), and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer. Results: HPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well. Conclusions: These results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women. [ABSTRACT FROM AUTHOR]

Parental consent for adolescent human papillomavirus (HPV) vaccine uptake is important; however, refusal is prevalent. Therefore, this study aimed to understand factors associated with parental consent for their adolescent daughter's HPV vaccination. A cross-sectional study was conducted in Lusaka, Zambia, between September and October 2021. We recruited parents from different social settings. The means and standard deviations or median and interquartile ranges were used as appropriate to summarise continuous variables. Simple and multiple logistic regression models were fitted with robust estimation of standard errors. The odds ratios are presented with 95% CI. Mediation analysis was conducted using a generalised structural equation model. The study enrolled 400 parents, mean age 45.7 years [95% CI, 44.3–47.1]. Two hundred and fifteen (53.8%) parents reported consenting to their daughters' HPV vaccination, and their daughters received it. None of the health belief model (HBM) construct scores showed an independent association with parental consent. Higher, compared to lower wealth index (AOR; 2.32, 95% CI: 1.29–4.16), knowing someone with genital warts (AOR = 2.23, 95 CI: 1.04–4.76), cervical cancer screening uptake (AOR = 1.93, 95% CI: 1.03–3.62) were associated with increased odds of parental consent. This study highlights factors influencing parental consent for their daughters' HPV vaccination. Ongoing sensitisation programs are important to improve their decision-making. [ABSTRACT FROM AUTHOR]

Objective: Thermal ablation (TA) was implemented in public sector cervical cancer prevention services in Zambia in 2012. Initially introduced as a treatment modality in primary healthcare clinics, it was later included in mobile outreach campaigns and clinical research trials. We report the feasibility, acceptability, safety, and provider uptake of TA in diverse clinical contexts. Methods: Screening services based on visual inspection with acetic acid were offered by trained nurses to non-pregnant women aged 25–59 years. Women with a type 1 transformation zone (TZ) were treated with same-visit TA. Those with a type 2 or 3 TZ, or suspicious for cancer, were managed with same-visit electrosurgical excision or punch biopsy, respectively. A provider survey was conducted. Results: Between 2012 and 2020, 2123 women were treated with TA: primary healthcare clinics, n = 746; mobile outreach clinics, n = 1127; research clinics, n = 250. Of the 996 women treated in primary healthcare and research clinics, 359 (48%) were HIV positive. Mild cramping during treatment was the most common adverse effect. No treatment interruptions occurred. No major complications were reported in the early (6 weeks) follow-up period. Providers expressed an overwhelming preference for TA over cryotherapy. Conclusion: TA was feasible, safe, and acceptable in diverse clinical contexts. It was the preferred ablation method of providers when compared with cryotherapy. [ABSTRACT FROM AUTHOR]

Background: Globally, women living with HIV have a higher risk of vulvar neoplasia than HIV-negative women. Vulvar neoplasia among women living with HIV has not previously been characterised in Zambia. Objective: This study determined the clinical and pathologic features of vulvar neoplasia among women living with HIV at the University Teaching Hospital, Lusaka, Zambia. Methods: We conducted a cross-sectional study of vulvar lesions among 53 women living with HIV who presented with vulvar lesions between July 2017 and February 2018. The study assessed clinical and histological characteristics and prevalence of high-risk human papillomavirus (HRHPV). Results: Twenty-one patients were diagnosed with vulvar squamous cell carcinoma (VSCC), 20 with usual vulvar intraepithelial neoplasm (uVIN), and the rest with either benign lesions or non-neoplastic lesions (NNL). Participants' mean age was 40 years. Patients with VSCC were significantly older than those with NNL (mean (s.d.): 43 (21) vs 33 (10), p = 0.004). The prevalence of HRHPV was 88.9% in VSCC patients and 100.0% in high-grade squamous intraepithelial lesion patients. HPV16 was the most common (52.6%) genotype. The clinical features of neoplasia were similar to those of NNL. Conclusion: VSCC was significantly more common among women aged ≥ 40 years. HRHPV in VSCC and high-grade squamous intraepithelial lesions was high. Women with vulvar lesions, especially those aged > 40 years, should be evaluated for vulvar cancer. Young girls should be vaccinated to prevent vulvar cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: Worldwide, more than 80% of people diagnosed with cancer will require surgery during their disease course, but only 5% to 20% of low- and middle-income countries have access to safe, affordable, and timely surgery. Developing surgical oncology skills requires significant time and mentoring. Virtual reality (VR) simulators can reduce the time required to master surgical procedures but are prohibitively expensive. We sought to determine whether a VR simulator using low-cost computer gaming equipment could train novice surgeons in Africa to perform a virtual radical abdominal (open) hysterectomy (RAH). METHODS: Our RAH VR simulator used the Oculus Rift (Oculus VR, Menlo Park, CA), a VR headset with hand controllers that costs less than $1,500. Surgical novices learned to perform five key steps of a virtual RAH. We measured and identified predictors of movement and time efficiency for the simulation. RESULTS: Ten novice surgeons in Lusaka, Zambia, enrolled in the study. Movement and time efficiency greatly improved over time. Independent predictors of movement efficiency were number of simulations, surgical experience, and time since college graduation. Independent predictors of time efficiency were number of simulations, surgical experience, days between simulation sessions, age, sex, and an interaction between number of simulations and surgical experience. CONCLUSION: Low-cost VR may be an effective tool to help surgical novices learn complex surgical oncology procedures. If learning to perform VR surgical procedures with low-cost hardware leads to faster mastery of surgical procedures in the operating room, low-cost VR may represent one of the solutions to increasing access to surgical cancer care globally. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how the influence of traditional Chiefs can be leveraged to promote access to cervical cancer prevention services in rural Zambia.Methods: A retrospective review of outcome data was conducted for all screening outreach events that occurred in Zambian Chiefdoms between October 4, 2015, and October 3, 2016. Members of the health promotion team of the Cervical Cancer Prevention Program in Zambia visited local Chiefs to inform them of the importance of cervical cancer prevention. The local Chiefs then summoned adults living within their Chiefdoms to assemble for cervical cancer prevention health talks. Screen-and-treat services were implemented within each of the Chiefdoms over a 1-week period.Results: VIA-enhanced digital imaging of the cervix (digital cervicography) was offered to 8399 women in ten Chiefdoms as part of a village-based screening (VBS) program. In all, 419 (4.9%) women had positive screening test results. Of these women, 276 (65.8%) were treated immediately with thermocoagulation and 143 (34.1%) were referred to provincial government hospitals to undergo either the loop electrosurgical excision procedure/large loop excision of the transformation zone (n=109, 26.0%) or punch biopsy (n=34, 8.1%).Conclusion: The influence of traditional Chiefs was leveraged to facilitate access to cervical cancer prevention services in rural Zambia. [ABSTRACT FROM AUTHOR]

Purpose: In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ) was implemented and has since provided cervical cancer screen-and-treat services to more than 500,000 women. By leveraging the successes and experiences of the CCPPZ, we intended to build capacity for the early detection and surgical treatment of breast cancer. Methods: Our initiative sought to build capacity for breast cancer care through the (1) formation of a breast cancer advocacy alliance to raise awareness, (2) creation of resource-appropriate breast cancer care training curricula for mid- and high-level providers, and (3) implementation of early detection and treatment capacity within two major health care facilities. Results: Six months after the completion of the initiative, the following outcomes were documented: Breast health education and clinical breast examination (CBE) services were successfully integrated into the service platforms of four CCPPZ clinics. Two new breast diagnostic centers were opened, which provided access to breast ultrasound, ultrasound-guided core needle biopsy, and needle aspiration. Breast health education and CBE were provided to 1,955 clients, 167 of whom were evaluated at the two diagnostic centers; 55 of those evaluated underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer. Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel lymph node dissections, and 10 breast conservation surgeries (lumpectomies). Conclusion: This initiative successfully established clinical services in Zambia that are critical for the early detection and surgical management of breast cancer. [ABSTRACT FROM AUTHOR]

Background: HIV infection is associated with a higher incidence of precancerous cervical lesions and their progression to invasive cervical cancer (ICC). Zambia is a global epicenter of HIV and ICC, yet the overall burden of cervical pre-cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV positive adult female population is unknown. The objective of this study was to determine the burden of cervical disease among HIV positive women in Zambia by estimating the number with CIN3 and ICC. Methods: We conducted a cross-sectional study among 309 HIV positive women attending screening in Lusaka (Zambia's most populated province) to measure the cervical disease burden by visual inspection with acetic acid enhanced by digital cervicography (DC), cytology, and histology. We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional study and Spectrum model-based estimates for HIV infection among Zambian women to estimate the burden of CIN3 and ICC among HIV positive women nationally. Results: Over half (52 %) of the study participants screened positive by DC, while 45 % had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or worse. Histopathologic evaluation revealed that 20 % of women had evidence of CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model, we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and 7,297 have ICC. Conclusions: The DC, cytology, and histology results revealed a large cervical disease burden in this previously unscreened HIV positive population. This very large burden indicates that continued scale-up of cervical cancer screening and treatment is urgently needed. [ABSTRACT FROM AUTHOR]

Background: Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries. Methods: In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts. Findings: Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25–49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women. Interpretation: We creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps. [ABSTRACT FROM AUTHOR]

Background The most common human papillomavirus (HPV) genotypes isolated from cervical cancer in select African countries are HPV-16, HPV-18, HPV-35, and HPV-45, but the most common genotypes in Zambia are unknown. The overall objective of this study was to assess the potential impact of current HPV vaccines in preventing cervical cancer in Zambia, by determining the combined prevalence of HPV-16 and/or HPV-18 in invasive cervical cancer (ICC) and high-grade pre-cancer [cervical intraepithelial neoplasia 2 or 3 (CIN2/3)] cases. Findings We compared DNA extraction techniques to determine which assay performs well in the Zambian context, where unbuffered formalin is used to fix specimens. We then tested specimens with the Abbott RealTime High-Risk HPV test to estimate the prevalence of HPV-16/18 in formalin-fixed, paraffin-embedded ICC and CIN2/3 specimens. DNA extraction using heat (without xylene) was more successful than xylene-based extraction. Over 80% of specimens tested using heat extraction and the Abbott RealTime HPV test were positive for HPV. HPV-16 and/or HPV-18 were identified in 65/93 (69.9%) ICC specimens positive for HPV and in 43/65 (58.5%) CIN2/3 specimens positive for HPV. Conclusions To our knowledge this is the first report to identify HPV genotypes in cervical cancers in Zambia. A combined HPV-16/18 prevalence of 69.9% in ICC specimens suggests that current vaccines will be highly protective against cervical cancer in Zambia. [ABSTRACT FROM AUTHOR]

A randomized control trial of a battery-operated thermocoagulator for the treatment of precancerous cervical lesions is ongoing in Lusaka, Zambia. We describe preliminary results of treatment efficacy in HIV-positive women. Visual inspection with acetic acid (VIA) screen-positive women eligible for ablative treatment are randomized to receive thermal ablation (TA), cryotherapy or large loop excision of the transformation zone (LLETZ). Demographic information is collected, including human immunodeficiency virus (HIV) status and antiretroviral therapy (ART) use. Human papillomavirus (HPV) DNA sampling for known or suspected oncogenic HPV types is performed at baseline and follow-up. Treatment efficacy is based on VIA and HPV status at 6- and/or 12-month follow-up. Side-effects, pain and client satisfaction are scored and recorded, however, these data are not included in this analysis. Of the 1,683 women who have been randomized to treatment, 994 (59%) are HIV-positive with the vast majority (97%) on anti-retroviral therapy (ART). HIV-positive women were equally distributed between treatment arms (p=0.28). Among the 1328 (79%) eligible for follow-up, follow-up data are available on 722 women (54%), of which 383 are HIV-positive. Based on VIA results alone for cure, HIV positive women had lower overall cure rates than HIV-negative women (77% vs 88%, respectively, p<0.001), regardless of treatment type. HIV-positive women, who were also positive for HPV 16 at baseline, had significantly lower cure rates (HPV 16 clearance and VIA negative) across all study arms, compared to HIV-negative women (73% vs 88%, respectively, p<0.001). When all HPV types are considered, overall cure rates (clearance of baseline type-specific HPV and VIA negative) in HIV positive women decreased to 49% and did not differ based on duration of HIV infection (<2 years, 43%; >2yrs, 55%; p=0.072). [Display omitted] In May 2020, the 173rd World Health Assembly adopted the Global Strategy to Eliminate Cervical Cancer. This sub-analysis of data from a randomized control trial of locally ablative methods for cervical precancer highlights the challenges in eradicating this disease in women living with HIV. Investigations are underway to determine the underlying causes of these findings. (NCI Grant No. 4UH3CA202721-03) [ABSTRACT FROM AUTHOR]

Worldwide, more than 80% of people with cancer will require surgery during their disease course, but less than 25% have access to safe, affordable and timely surgery. Among the barriers to increasing surgical capacity are the time and costs required to train novices. Virtual reality (VR) surgical simulations can reduce the time required for novices to reach surgical proficiency, though their costs may exceed USD $100,000. The goal of this study was to determine if a low-cost system, using commercially available technology designed for in-home computer gaming, could be used to create a realistic VR surgical oncology simulation. Standard commercially available VR software and Oculus Rift hardware have been used to provide high-quality visuals and believable surgeon hand interactions. Near identical VR reproduction of an operating room using 1:1 scale matching of real-world elements, including equipment, instruments, supplies and sounds, maintaining frame rate greater than 60 fps to maintain visual fidelity has been created. Internal anatomy was designed as VR replica of human female pelvic anatomy, including organs, veins and other vessels, peritoneum and connective tissue. Internal anatomy was designed to run at 120 fps and to allow for a realistic abdominal radical hysterectomy simulation. Surgical hands were modelled to scale for those with large and small hands. Multiple hand positions were simulated using Oculus touch hardware. Reconstructing the virtual environment to simulate reality as accurately as possible was done to immerse users in the simulator so that they focus on learning and practise without distractions. Training modules were co-designed by experts in learning sciences, human behaviour, VR and gynaecologic oncology. We have successfully created a low-cost VR simulation to help prepare novice surgeons to perform a radical abdominal hysterectomy surgery procedure. The simulation can be used with commercially available computer gaming hardware that currently costs less than USD $1,500. Low-cost VR simulation has the potential to reduce the time and cost to train surgeons to perform surgical oncology procedures, as well as both improve and audit quality. If effective in real-world clinical trials, such simulations have relevance to multiple surgical procedures and applicability in both resource-limited and high-income settings. [ABSTRACT FROM AUTHOR]