Ethical dilemmas in prioritizing patients for scarce radiotherapy resources.

BACKGROUND: Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve all patients who would benefit from it. Allocation systems are needed to guide patient prioritization for radiotherapy in resource-limited contexts. These systems should be informed by allocation principles deemed relevant to stakeholders. This study explores the ethical dilemmas and views of decision-makers engaged in real-world prioritization of scarce radiotherapy resources at a cancer center in Rwanda in order to identify relevant principles. METHODS: Semi-structured interviews were conducted with a purposive sample of 22 oncology clinicians, program leaders, and clinical advisors. Interviews explored the factors considered by decision-makers when prioritizing patients for radiotherapy. The framework method of thematic analysis was used to characterize these factors. Bioethical analysis was then applied to determine their underlying normative principles. RESULTS: Participants considered both clinical and non-clinical factors relevant to patient prioritization for radiotherapy. They widely agreed that disease curability should be the primary overarching driver of prioritization, with the goal of saving the most lives. However, they described tension between curability and competing factors including age, palliative benefit, and waiting time. They were divided about the role that non-clinical factors such as social value should play, and agreed that poverty should not be a barrier. CONCLUSIONS: Multiple competing principles create tension with the agreed upon overarching goal of maximizing lives saved, including another utilitarian approach of maximizing life-years saved as well as non-utilitarian principles, such as egalitarianism, prioritarianism, and deontology. Clinical guidelines for patient prioritization for radiotherapy can combine multiple principles into a single allocation system to a significant extent. However, conflicting views about the role that social factors should play, and the dynamic nature of resource availability, highlight the need for ongoing work to evaluate and refine priority setting systems based on stakeholder views.

Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report.

BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS: Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons). CONCLUSIONS: A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

Procedural fairness for radiotherapy priority setting in a low resource context.

Radiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve their populations. This mismatch between demand and supply creates the need for priority setting. There is no widely accepted system to guide patient prioritization for radiotherapy in a low resource context. In the absence of consensus on allocation principles, fair procedures for priority setting should be established. Research is needed to understand what elements of procedural fairness are important to decision makers in diverse settings, assess the feasibility of implementing fair procedures for priority setting in low resource contexts, and improve these processes. This study presents the views of decision makers engaged in everyday radiotherapy priority setting at a cancer center in Rwanda. Semi-structured interviews with 22 oncology physicians, nurses, program leaders, and advisors were conducted. Participants evaluated actual radiotherapy priority setting procedures at the program (meso) and patient (micro) levels, reporting facilitators, barriers, and recommendations. We discuss our findings in relation to the leading Accountability for Reasonableness (AFR) framework. Participants emphasized procedural elements that facilitate adherence to normative principles, such as objective criteria that maximize lives saved. They ascribed fairness to AFR's substantive requirement of relevance more than transparency, appeals, and enforcement. They identified several challenges unresolved by AFR, such as conflicting relevant rationales and unintended consequences of publicity and appeals. Implementing fair procedure itself is resource intensive, a paradox that calls for innovative, context-appropriate solutions. Finally, socioeconomic and structural barriers to care that undermine procedural fairness must be addressed.

Minimally Invasive Postmortem Intestinal Tissue Sampling in Malnourished and Acutely Ill Children Is Feasible and Informative.

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. RESULTS: Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02-0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. CONCLUSIONS: Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors.

Moral Distress and Resilience Associated with Cancer Care Priority Setting in a Resource-Limited Context.

BACKGROUND: Moral distress and burnout are highly prevalent among oncology clinicians. Research is needed to better understand how resource constraints and systemic inequalities contribute to moral distress in order to develop effective mitigation strategies. Oncology providers in low- and middle-income countries are well positioned to provide insight into the moral experience of cancer care priority setting and expertise to guide solutions. METHODS: Semistructured interviews were conducted with a purposive sample of 22 oncology physicians, nurses, program leaders, and clinical advisors at a cancer center in Rwanda. Interviews were recorded, transcribed verbatim, and analyzed using the framework method. RESULTS: Participants identified sources of moral distress at three levels of engagement with resource prioritization: witnessing program-level resource constraints drive cancer disparities, implementing priority setting decisions into care of individual patients, and communicating with patients directly about resource prioritization implications. They recommended individual and organizational-level interventions to foster resilience, such as communication skills training and mental health support for clinicians, interdisciplinary team building, fair procedures for priority setting, and collective advocacy for resource expansion and equity. CONCLUSION: This study adds to the current literature an in-depth examination of the impact of resource constraints and inequities on clinicians in a low-resource setting. Effective interventions are urgently needed to address moral distress, reduce clinician burnout, and promote well-being among a critical but strained oncology workforce. Collective advocacy is concomitantly needed to address the structural forces that constrain resources unevenly and perpetuate disparities in cancer care and outcomes. IMPLICATIONS FOR PRACTICE: For many oncology clinicians worldwide, resource limitations constrain routine clinical practice and necessitate decisions about prioritizing cancer care. To the authors' knowledge, this study is the first in-depth analysis of how resource constraints and priority setting lead to moral distress among oncology clinicians in a low-resource setting. Effective individual and organizational interventions and collective advocacy for equity in cancer care are urgently needed to address moral distress and reduce clinician burnout among a strained global oncology workforce. Lessons from low-resource settings can be gleaned as high-income countries face growing needs to prioritize oncology resources.

Improved quality of life following direct-acting antiviral treatment for chronic hepatitis C infection in Rwanda: Results from a clinical trial in sub-Saharan Africa (the SHARED study).

Around 71 million people are living with chronic hepatitis C virus (HCV) infection, with approximately 14% residing in sub-Saharan Africa. Direct-acting antiviral (DAA) therapies offer clear benefits for liver-related morbidity and mortality, and data from high-income settings suggest that DAA treatments also provide significant benefits in terms of health-related quality of life (HRQL). In this study, we assessed the effect of DAA treatment on HRQL for individuals treated for HCV in a clinical trial in Rwanda. We assessed the HRQL of participants using an 83-question composite survey at Day 0 ('baseline') and Week 24 ('endpoint'). Data were analysed in R. A total of 296 participants were included in this analysis. Their ages ranged from 19 to 90, and 184 (62.2%) were female. There were significant improvements from baseline to endpoint median scores for all physical and mental quality of life sub-scales. Additionally, a reduction-before and after treatment-in the proportion of those classified as depressed and needing social support was statistically significant (both P < .001). Economic productivity increased after treatment (P < .001), and households classified as food secure increased from baseline to endpoint (P < .001). These results demonstrate that Rwandans with chronic HCV infection experience both clinical and HRQL benefits, including household-level benefits like substantial gains in workforce stability, economic productivity, and poverty alleviation, from DAA treatment. A stronger demonstration of accurate and broader household-level benefits achieved through treatment of HCV with DAAs will help financing and investment for HCV in resource-constrained settings become an urgent priority.

Factors influencing mothers' decisions regarding obstetrical care in Western Kenya: a mixed-methods study.

BACKGROUND: Siaya County in Western Kenya has one of the highest maternal mortality rates in Kenya. We sought to elucidate factors that influence mothers' decisions regarding where to seek obstetrical care, to inform interventions that seek to promote effective use of obstetric services and reduce maternal mortalities. To guide our research, we used the "Three Delays Model", focusing on the first delay-seeking care. While interventions to reduce maternal mortalities have focused on addressing delays in accessing and receiving care, context-specific data on drivers of the first delay are scarce. METHODS: We used a mixed-method study to assess how maternal decision-making of birth location is influenced by personal, contextual, and cultural factors. We conducted structured interviews with women aged 14 years or older living in Siaya, Bondo, and Yala, rural districts in Western Kenya. We then conducted focus group interviews with a subset of women to elucidate this question: How do drivers of the first delay (i.e., seeking care) affect the decision to seek home versus hospital delivery, potentially negatively influencing maternal mortality. RESULTS: Three hundred and seven women responded to the surveys, and 67 women (22%) from this group participated in focus group interviews. Although we focused on type 1 delays, we discovered that several factors that impact type 2 and type 3 delays directly contribute to type 1 delays. Our findings highlighted that factors influencing women's decisions to seek care are not simply medical or cultural but rather contextual, involving many elements of life, particularly in rural communities. CONCLUSIONS: It is imperative to address multiple-level factors that influence women's decisions to seek care and have in-hospital deliveries. To curtail maternal mortality in rural Western Kenya and comparable settings, targeted interventions must take into consideration these important influencers.

Barriers and coping mechanisms to accessing healthcare during the COVID-19 lockdown: a cross-sectional survey among patients with chronic diseases in rural Rwanda.

BACKGROUND: Large scale physical distancing measures and movement restrictions imposed to contain COVID-19, often referred to as 'lockdowns', abruptly and ubiquitously restricted access to routine healthcare services. This study describes reported barriers and coping mechanisms to accessing healthcare among chronic care patients during the nationwide COVID-19 lockdown in Rwanda. METHODS: This cross-sectional study was conducted among chronic care patients enrolled in pediatric development, HIV/AIDS, non-communicable diseases, mental health, and oncology programs at 3 rural Rwandan districts. Active patients with an appointment scheduled between March-June 2020 and a phone number recorded in the electronic medical record system were eligible. Data were collected by telephone interviews between 23rd April and 11th May 2020, with proxy reporting by caregivers for children and critically ill-patients. Fisher's exact tests were used to measure associations. Logistic regression analysis was also used to assess factors associated with reporting at least one barrier to accessing healthcare during the lockdown. RESULTS: Of 220 patient respondents, 44% reported at least one barrier to accessing healthcare. Barriers included lack of access to emergency care (n = 50; 22.7%), lack of access to medication (n = 44; 20.0%) and skipping clinical appointments (n = 37; 16.8%). Experiencing barriers was associated with the clinical program (p < 0.001), with oncology patients being highly affected (64.5%), and with increasing distance from home to the health facility (p = 0.031). In the adjusted logistic regression model, reporting at least one barrier to accessing healthcare was associated with the patient's clinical program and district of residence. Forty (18.2%) patients identified positive coping mechanisms to ensure continuation of care, such as walking long distances during suspension of public transport (n = 21; 9.6%), contacting clinicians via telephone for guidance or rescheduling appointments (n = 15; 6.8%), and delegating someone else for medication pick-up (n = 6; 2.7%). Of 124 patients who reported no barriers to accessing healthcare, 9% used positive coping mechanisms. CONCLUSION: A large proportion of chronic care patients experienced barriers to accessing healthcare during the COVID-19 lockdown. However, many patients also independently identified positive coping mechanisms to ensure continuation of care - strategies that could be formally adopted by healthcare systems in Rwanda and similar settings to mitigate effects of future lockdowns on patients.

Safe Anesthesia Care in Western Kenya: A Preliminary Assessment of the Impact of Nurse Anesthetists at Multiple Levels of Government Hospitals.

BACKGROUND: Only 20% of the surgical burden in eastern sub-Saharan Africa is currently met, leaving >17 million surgical cases annually in need of safe surgery and anesthesia. Similarly, there is an extreme shortage of anesthesia providers in East Africa, with just 0.44 anesthesiologists per 100,000 people in Kenya compared to 20.82 per 100,000 in the United States. Additionally, surgical access is not equally distributed within countries, with rural settings often having the greatest unmet need. We developed and tested a set of tools to assess if graduates of the Kenya registered nurse anesthetist (KRNA) training program, who were placed in rural hospitals in Kenya, would have any impact on surgical numbers, referral patterns, and economics of these hospitals. METHODS: Cross-sectional data were collected from facility assessments in 9 referral hospitals to evaluate the possible impact of the KRNAs on anesthesia care. The hospitals were grouped based on both the number of beds and the assigned national hospital level. At each level, a hospital that had KRNA graduates (intervention) was matched with comparison hospitals in the same category with no KRNA graduates (control). The facility assessment survey included questions capturing data on personnel, infrastructure, supplies, medications, procedures, and outcomes. At the intervention sites, the medical directors of the hospitals and the KRNAs were interviewed. Descriptive statistics were used to present the findings. RESULTS: Intervention sites had a density of anesthesia providers that was 43% higher compared to the control sites. Intervention sites performed at least twice as many surgical cases compared to the control sites. Most KRNAs stated that the anesthesia training program had given them sufficient training and leadership skills to perform safe anesthesia in their clinical practice setting. Medical directors at the intervention sites reported increased surgical volumes and fewer referrals to larger hospitals due to the anesthesia gaps that had been addressed. CONCLUSIONS: Our findings from this study suggest that KRNAs may be associated with an increased volume of surgical cases completed in these rural Kenyan hospitals and may therefore be filling a known anesthetic void. The presence of skilled anesthesia providers is a first step toward providing safe surgery and anesthesia care for all; however, significant gaps still remain. Future analysis will focus on surgical outcomes, the appropriate anesthesia delivery model for a rural population, and how the availability of anesthesia infrastructure impacts referral patterns and safe surgery capacity.

HPV vaccination in Kenya: a study protocol to assess stakeholders' perspectives on implementation drivers of HPV vaccination and the acceptability of the reduced dose strategy among providers.

Background: Cervical cancer is the leading cause of cancer-related deaths among Kenyan women. Persistent infection with high-risk oncogenic Human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. HPV vaccines are safe, durable, and efficacious in preventing incident HPV infections. In Kenya, despite efforts to increase HPV vaccination, coverage remains low. We sought to assess: (1) barriers and facilitators of HPV vaccination from the perspective of adolescent girls and young women (AGYW), their guardians as well as stakeholders involved in HPV vaccine delivery, and (2) the acceptability of the single dose of the HPV vaccination among healthcare providers (HCPs). Methods: Our study is nested within the KENya Single-dose HPV-vaccine Efficacy study (KEN SHE) that sought to test the efficacy of single-dose bivalent (HPV 16/18) and single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination. We are conducting this study in Kiambu, Nairobi, and Kisumu counties. In these counties, we are interviewing stakeholders (n = ∼25), selected based on their role in HPV vaccination at the county and national levels. Interviews are audio recorded and conducted in English or Swahili. The semi-structured interview guides were designed based on: (1) the Theoretical Domains Framework (TDF) for AGYW and guardians and (2) the Consolidated Framework for Implementation Research (CFIR) for other stakeholders. The Theoretical Framework of Acceptability (TFA) was leveraged to design the survey administered to HCPs (n = ∼309) involved in HPV vaccination. We will develop a codebook based on emerging codes from the transcripts and constructs from the TDF and CFIR. Emerging themes will be summarized highlighting similarities and differences between and within the different stakeholder groups and counties. Descriptive statistics and a χ2 test will be used to assess the distribution of responses between the different sites and regression analysis will be used to assess factors associated with high acceptability of the single-dose strategy while controlling for confounding variables. Discussion: Our study will describe key barriers and facilitators that affect HPV vaccination from the perspective of multiple stakeholders as well as insights on the perspective of HCPs towards the single-dose strategy to inform the designing of strategies to increase HPV vaccination uptake in Kenya and comparable settings.

Evaluation of acute flaccid paralysis surveillance performance before and during the 2014-2015 Ebola virus disease outbreak in Guinea and Liberia.

Introduction: the number of wild poliomyelitis cases, worldwide, dropped from 350,000 cases in 1988 to 33 in 2018. Acute flaccid paralysis (AFP) surveillance is a key strategy toward achieving global polio eradication. The 2014 Ebola virus disease (EVD) epidemic in West Africa infected over 28,000 people and had devastating effects on health systems in Guinea, Liberia, and Sierra Leone. We sought to assess the effects of the 2014 Ebola outbreak on AFP surveillance in Guinea and Liberia. Methods: a retrospective cross-sectional analysis was performed for Guinea and Liberia to evaluate EVD´s impact on World Health Organization (WHO) AFP surveillance performance indicators during 2012-2015. Results: both Guinea and Liberia met the WHO target non-polio AFP incidence rate nationally, and generally sub-nationally, prior to the EVD outbreak; rates decreased substantially during the outbreak in seven of eight regions in Guinea and 11 of 15 counties in Liberia. Throughout the study period, both Guinea and Liberia attained appropriate overall targets nationally for "notification" and "stool adequacy" indicators, but each country experienced periods of poor regional/county-specific indicator performance. Conclusion: these findings mirrored the negative effect of the Ebola outbreak on polio elimination activities in both countries and highlights the need to reinforce this surveillance system during times of crisis.

Surgical Site Infections and Antimicrobial Resistance After Cesarean Section Delivery in Rural Rwanda.

Background: As the volume of surgical cases in low- and middle-income countries (LMICs) increases, surgical-site infections (SSIs) are becoming more prevalent with anecdotal evidence of antimicrobial resistance (AMR), despite a paucity of data on resistance patterns. Objectives: As a primary objective, this prospective study aimed to describe the epidemiology of SSIs and the associated AMR among women who delivered by cesarean at a rural Rwandan hospital. As secondary objectives, this study also assessed patient demographics, pre- and post-operative antibiotic use, and SSI treatment. Methods: Women who underwent cesarean deliveries at Kirehe District Hospital between September 23rd, 2019, and March 16th, 2020, were enrolled prospectively. On postoperative day (POD) 11 (+/- 3 days), their wounds were examined. When an SSI was diagnosed, a wound swab was collected and sent to the Rwandan National Reference Laboratory for culturing and antibiotic susceptibility testing. Findings: Nine hundred thirty women were enrolled, of whom 795 (85.5%) returned for the POD 11 clinic visit. 45 (5.7%) of the 795 were diagnosed with SSI and swabs were collected from 44 of these 45 women. From these 44 swabs, 57 potential pathogens were isolated. The most prevalent bacteria were coagulase-negative staphylococci (n = 12/57, 20.3% of all isolates), and Acinetobacter baumannii complex (n = 9/57, 15.2%). 68.4% (n = 39) of isolates were gram negative; 86.7% if excluding coagulase-negative staphylococci. No gram-negative pathogens isolated were susceptible to ampicillin, and the vast majority demonstrated intermediate susceptibility or resistance to ceftriaxone (92.1%) and cefepime (84.6%). Conclusions: Bacterial isolates from SSI swab cultures in rural Rwanda predominantly consisted of gram-negative pathogens and were largely resistant to commonly used antibiotics. This raises concerns about the effectiveness of antibiotics currently used for surgical prophylaxis and treatment and may guide the appropriate selection of treatment of SSIs in rural Rwanda and comparable settings.

Strengthening Antimicrobial Resistance Diagnostic Capacity in Rural Rwanda: A Feasibility Assessment.

Introduction: Antimicrobial resistance (AMR) is a global public health threat. Worse still, there is a paucity of data from low- and middle-income countries to inform rational antibiotic use. Objective: Assess the feasibility of setting up microbiology capacity for AMR testing and estimate the cost of setting up microbiology testing capacity at rural district hospitals in Rwanda. Methods: Laboratory needs assessments were conducted, and based on identified equipment gaps, appropriate requisitions were processed. Laboratory technicians were trained on microbiology testing processes and open wound samples were collected and cultured at the district hospital (DH) laboratories before being transported to the National Reference Laboratory (NRL) for bacterial identification and antibiotic susceptibility testing. Quality control (QC) assessments were performed at the DHs and NRL. We then estimated the cost of three scenarios for implementing a decentralized microbiology diagnostic testing system. Results: There was an eight-month delay from the completion of the laboratory needs assessments to the initiation of sample collection due to the regional unavailability of appropriate supplies and equipment. When comparing study samples processed by study laboratory technicians and QC samples processed by other laboratory staff, there was 85.0% test result concordance for samples testing at the DHs and 90.0% concordance at the NRL. The cost for essential equipment and supplies for the three DHs was $245,871. The estimated costs for processing 600 samples ranged from $29,500 to $92,590. Conclusion: There are major gaps in equipment and supply availability needed to conduct basic microbiology assays at rural DHs. Despite these challenges, we demonstrated that it is feasible to establish microbiological testing capacity in Rwandan DHs. Building microbiological testing capacity is essential for improving clinical care, informing rational antibiotics use, and ultimately, contributing to the establishment of robust national antimicrobial stewardship programs in rural Rwanda and comparable settings.