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BackgroundPatients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. ObjectiveThe aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. MethodsThe PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. ResultsAmong 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI –277 to –213; P

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.

Abstract Background Germline genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) for individuals including, but not limited to, those with a personal history of ovarian cancer, young-onset (

Abstract Background Increased breast density augments breast cancer risk and reduces mammography sensitivity. Supplemental breast MRI screening can significantly increase cancer detection among women with dense breasts. However, few women undergo this exam, and screening is consistently lower among racially minoritized populations. Implementation strategies informed by behavioral economics (“nudges”) can promote evidence-based practices by improving clinician decision-making under conditions of uncertainty. Nudges directed toward clinicians and patients may facilitate the implementation of supplemental breast MRI. Methods Approximately 1600 patients identified as having extremely dense breasts after non-actionable mammograms, along with about 1100 clinicians involved with their care at 32 primary care or OB/GYN clinics across a racially diverse academically based health system, will be enrolled. A 2 × 2 randomized pragmatic trial will test nudges to patients, clinicians, both, or neither to promote supplemental breast MRI screening. Before implementation, rapid cycle approaches informed by clinician and patient experiences and behavioral economics and health equity frameworks guided nudge design. Clinicians will be clustered into clinic groups based on existing administrative departments and care patterns, and these clinic groups will be randomized to have the nudge activated at different times per a stepped wedge design. Clinicians will receive nudges integrated into the routine mammographic report or sent through electronic health record (EHR) in-basket messaging once their clinic group (i.e., wedge) is randomized to receive the intervention. Independently, patients will be randomized to receive text message nudges or not. The primary outcome will be defined as ordering or scheduling supplemental breast MRI. Secondary outcomes include MRI completion, cancer detection rates, and false-positive rates. Patient sociodemographic information and clinic-level variables will be examined as moderators of nudge effectiveness. Qualitative interviews conducted at the trial’s conclusion will examine barriers and facilitators to implementation. Discussion This study will add to the growing literature on the effectiveness of behavioral economics-informed implementation strategies to promote evidence-based interventions. The design will facilitate testing the relative effects of nudges to patients and clinicians and the effects of moderators of nudge effectiveness, including key indicators of health disparities. The results may inform the introduction of low-cost, scalable implementation strategies to promote early breast cancer detection. Trial registration ClinicalTrials.gov NCT05787249. Registered on March 28, 2023.

Recognizing the rising incidence, prevalence, and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has committed to expanding its engagement at a global level. In 2017, the ASCO Academic Global Oncology Task Force sought to define the potential role for ASCO in supporting global oncology as an academic field. A set of recommendations to advance the status of global oncology as an academic discipline were created through a consensus-based process involving participation by a diverse group of global oncology and global health practitioners; these recommendations were then published. The recommendations included developing a set of global oncology competencies for trainees and faculty interested in a career in academic global oncology. Here, we describe the global oncology competencies developed by this task force. These competencies consist of knowledge and skills needed in general global health as well as cancer-specific care and research, including understanding global cancer health disparities, defining unique resources and needs in low- and middle-resource settings, and promoting international collaboration. Although the competencies were originally developed for US training programs, they are intended to be widely applicable globally. By formalizing the training of oncologists and supporting career pathways in the field of global oncology, we can make progress in achieving global equity in cancer care and control.

Abstract Despite its involvement in various cancers, the function of the deubiquitinase USP1 (ubiquitin-specific protease 1) is unexplored in cholangiocarcinoma (CCA). In this study, we provide evidence that USP1 promotes CCA progression through the stabilization of Poly (ADP-ribose) polymerase 1 (PARP1), consistent with the observation that both USP1 and PARP1 are upregulated in human CCA. Proteomics and ubiquitylome analysis of USP1-overexpressing CCA cells nominated PARP1 as a top USP1 substrate. Indeed, their direct interaction was validated by a series of immunofluorescence, co-immunoprecipitation (CO-IP), and GST pull-down assays, and their interaction regions were identified using deletion mutants. Mechanistically, USP1 removes the ubiquitin chain at K197 of PARP1 to prevent its proteasomal degradation, with the consequent PARP1 stabilization being necessary and sufficient to promote the growth and metastasis of CCA in vitro and in vivo. Additionally, we identified the acetyltransferase GCN5 as acetylating USP1 at K130, enhancing the affinity between USP1 and PARP1 and further increasing PARP1 protein stabilization. Finally, both USP1 and PARP1 are significantly associated with poor survival in CCA patients. These findings describe PARP1 as a novel deubiquitination target of USP1 and a potential therapeutic target for CCA.

Abstract Background In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission. Methods As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics. Results From 4563 households included in the survey, 4856 children aged 5–48 months were enrolled. Out of 4732 children with documented gender, 52.2% were female and 47.8% male. Among the 4856 children, 33.8% reported fever in the two weeks prior to the survey. Fever prevalence was high in communities with low socio-economic status (SES) (38.3% [95% CI: 33.7–43.5%]) and low in areas with high SES (29.8% [95% CI: 25.6–34.2%]). Among children with fever, 648 (39.5%) sought treatment promptly i.e., within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education (aOR:1.37, 95% CI: 1.11–3.03); in communities with high compared to low SES [aOR: 2.78, 95% CI: 1.27–6.07]. Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km [aOR: 0.44, 95% CI: 0.21–0.92]. Conclusion The high heterogeneity in prevalence of fever and levels of prompt treatment-seeking behaviour underscore the need to promote community-level malaria control interventions (such as use of long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent preventive therapy (IPT), presumptive treatment and education). Programmes aimed at improving treatment-seeking behaviour should consider targeting communities with low SES and those far from health facility.

A challenge with studying cancer transcriptomes is in distilling the wealth of information down into manageable portions of information. In this resource, we develop an approach that creates and assembles cancer type-specific gene expression modules into flexible barcodes, allowing for adaptation to a wide variety of uses. Specifically, we propose that modules derived organically from high-quality gold standards such as The Cancer Genome Atlas (TCGA) can accurately capture and describe functionally related genes that are relevant to specific cancer types. We show that such modules can: (1) uncover novel gene relationships and nominate new functional memberships, (2) improve and speed up analysis of smaller or lower-resolution datasets, (3) re-create and expand known cancer subtyping schemes, (4) act as a “decoder” to bridge seemingly disparate established gene signatures, and (5) efficiently apply single-cell RNA sequencing information to other datasets. Moreover, such modules can be used in conjunction with native spreadsheet program commands to create a powerful and rapid approach to hypothesis generation and testing that is readily accessible to non-bioinformaticians. Finally, we provide tools for users to create and interpret their own modules. Overall, the flexible modular nature of the proposed barcoding provides a user-friendly approach to rapidly decoding transcriptome-wide data for research or, potentially, clinical uses.

Objectives Narrative communication has demonstrated effectiveness in promoting positive health behaviours, delivering support and coping with complex decision-making. Formal research evaluating this intervention for cancer treatment in Africa is lacking. We aimed to develop, and assess acceptability and usability of survivor video narrative interventions for breast cancer treatment in Botswana.Design A pilot study design.Setting Single-centre, tertiary hospital, sub-Saharan Africa.Participants Eight women, ≥18 years old, with stages I–III breast cancer were enrolled for the video intervention. 106 women, ≥18 years old, with stages I–IV breast cancer viewed the narrative videos and 98 completed the acceptability and usability surveys.Intervention Survivor narrative videos were developed using the theory of planned behaviour and using a purposive sample of Batswana, Setswana-speaking, breast cancer survivors, who had completed systemic treatment and surgery with high rates of adherence to the prescribed treatment plan.Primary outcomes We assessed acceptability and usability among prospectively enrolled patients presenting for routine breast cancer care at Princess Marina Hospital in Botswana, using a 13-item survey.Results Participants expressed high acceptability and usability of the videos, including 99% (97/98) who strongly agreed/agreed that the video presentations were easy to understand, 92% (90/98) who would recommend to other survivors and 94% (92/98) who wished there were more videos. Additionally, 89% (87/98) agreed or strongly agreed that the one-on-one instruction on how to use the tablet was helpful and 87% (85/98) that the video player was easy to use.Conclusion Culturally appropriate survivor video narratives have high acceptability and usability among patients with breast cancer in Botswana. There is an opportunity to leverage this intervention in routine breast cancer care for treatment support. Future studies will test the implementation and effectiveness of narrative videos on a wider scale, including for patients being treated for other cancers.

IntroductionLength of hospital stay (LOS), defined as the time from inpatient admission to discharge, death, referral, or abscondment, is one of the key indicators of quality in patient care. Reduced LOS lowers health care expenditure and minimizes the chance of in-hospital acquired infections. Conventional methods for estimating LOS such as the Kaplan-Meier survival curve and the Cox proportional hazards regression for time to discharge cannot account for competing risks such as death, referral, and abscondment. This study applied competing risk methods to investigate factors important for risk-stratifying patients based on LOS in order to enhance patient care.MethodsThis study analyzed data from ongoing safety surveillance of the malaria vaccine implementation program in Malawi's four district hospitals of Balaka, Machinga, Mchinji, and Ntchisi. Children aged 1–59 months who were hospitalized (spending at least one night in hospital) with a medical illness were consecutively enrolled between 1 November 2019 and 31 July 2021. Sub-distribution-hazard (SDH) ratios for the cumulative incidence of discharge were estimated using the Fine-Gray competing risk model.ResultsAmong the 15,463 children hospitalized, 8,607 (55.7%) were male and 6,856 (44.3%) were female. The median age was 22 months [interquartile range (IQR): 12–33 months]. The cumulative incidence of discharge was 40% lower among HIV-positive children compared to HIV-negative (sub-distribution-hazard ratio [SDHR]: 0.60; [95% CI: 0.46–0.76]; P

Abstract Background Land-use is a major driver of changes in biodiversity worldwide, but studies have overwhelmingly focused on above-ground taxa: the effects on soil biodiversity are less well known, despite the importance of soil organisms in ecosystem functioning. We modelled data from a global biodiversity database to compare how the abundance of soil-dwelling and above-ground organisms responded to land use and soil properties. Results We found that land use affects overall abundance differently in soil and above-ground assemblages. The abundance of soil organisms was markedly lower in cropland and plantation habitats than in primary vegetation and pasture. Soil properties influenced the abundance of soil biota in ways that differed among land uses, suggesting they shape both abundance and its response to land use. Conclusions Our results caution against assuming models or indicators derived from above-ground data can apply to soil assemblages and highlight the potential value of incorporating soil properties into biodiversity models.

PURPOSETo evaluate the scope and types of cancer research projects in sub-Saharan Africa (SSA) to identify research gaps and inform future efforts.METHODSThis retrospective observational study summarized information on cancer research projects in SSA from the International Cancer Research Partnership (ICRP) between 2015 and 2020, alongside 2020 cancer incidence and mortality data from the Global Cancer Observatory. SSA cancer research projects were identified as led by investigators in SSA countries, or by investigators in non-SSA countries with collaborators in SSA, or in database keyword searches. Projects from the Coalition for Implementation Research in Global Oncology (CIRGO) were also summarized.RESULTSA total of 1,846 projects were identified from the ICRP database, funded by 34 organizations in seven countries (only one, Cancer Association of South Africa, based in SSA); only 156 (8%) were led by SSA-based investigators. Most projects focused on virally induced cancers (57%). Across all cancer types, projects were most frequently related to cervical cancer (24%), Kaposi sarcoma (15%), breast cancer (10%), or non-Hodgkin lymphoma (10%). Gaps were observed for several cancers with higher incidence/mortality burden in SSA; for example, prostate cancer accounted for only 4% of projects but 8% of cancer-related deaths and 10% of new cases. Approximately 26% were dedicated to etiology. Treatment-related research declined over the study period (14%-7% of all projects), while projects related to prevention (15%-20%) and diagnosis/prognosis (15%-29%) increased. Fifteen CIRGO projects were identified; seven were relevant across multiple cancer types, and 12 focused either wholly or partially on cancer control (representing 50% of the total research effort).CONCLUSIONThis analysis shows notable discrepancies between cancer burden and research projects and identifies opportunities for future strategic investments in cancer care in SSA.

No abstract available.

The regulation of the distinct intrinsic phenotypic states in melanoma remain poorly characterised. Here, multi-omics analysis for a panel of 68 early passage melanoma cell lines reveals that cancer cell intrinsic transcriptomic programs are associated with distinct immune features.

Despite the significant advances made in our understanding of cancer and how to treat it over the last hundred years, there are wide global disparities in access to cancer care and in who gets to benefit from cutting-edge cancer research.

PURPOSEAt the 12th meeting of AORTIC (African Organization for Research and Training in Cancer) in Maputo, Mozambique, held between November 5 and November 8, 2019, a special workshop was organized to focus on the need for collaboration and coordination between governments and health systems in Africa with academic, industry, association, and other nongovernmental organizations to effect sustainable positive change for the care of patients with cancer.METHODSRepresentatives from seven different projects in Africa presented implementation science and demonstration projects of their to date efforts in cancer system improvement including patient access, South-South partnerships, in-country specialized training, palliative care consortium, treatment outcomes, and focused pathology and diagnostic capacity building. Key partners of the various projects served as moderators and commentators during the session.RESULTSFrom across all the presentations, lessons learned and exemplary evidence of the value of partnerships were gathered and summarized.CONCLUSIONThe concluding synthesis of the presentations determined that with the broad needs across cancer requiring in-depth expertise at each point on a patient’s journey, no single organization can effect change alone. Multipartner collaborations not only should be the norm but should also be coordinated so that efforts are not duplicated and maximum patient access to cancer diagnosis and care is achieved.

PURPOSEThere is limited evidence to guide incorporation of breast cancer early detection into resource-constrained health systems where mammography screening is not yet available. To inform such strategies, we sought to understand health care workers' perspectives on a breast cancer early detection initiative integrated into community, primary, and secondary levels of care in Rwanda.METHODSWe conducted a qualitative study using semistructured interviews with 33 community health workers, clinicians, and administrators at health facilities participating in the Women's Cancer Early Detection Program (WCEDP), through which women received clinical breast examination if they were receiving cervical cancer screening, or had breast concerns. Through thematic analysis, we identified dynamics and patterns associated with successes and challenges of the program's breast health services.RESULTSSuccesses and challenges identified by participants corresponded with the community- and primary care–based steps of cancer early diagnosis identified by the WHO. Regarding step 1 (community awareness/access), participants noted increases in awareness and care-seeking. Challenges included difficulty overcoming stigma and engaging older women. Regarding step 2 (clinical evaluation), all participants described increased breast health knowledge, skills, and confidence. Integrating the WCEDP with other services was challenging because of inadequate staffing; offering WCEDP services on a designated day/week had advantages and disadvantages. Although participants appreciated WCEDP referral mechanisms, they desired more communication from referral facilities. Patients' poverty was the most consistently identified impediment to referral completion.CONCLUSIONRwandan health care workers identified real-world successes and challenges of implementing principles of early cancer diagnosis for breast cancer early detection. Future interventions should focus on engagement of older women, community awareness, patient socioeconomic support, and optimizing integration into primary care.

Abstract Background To ensure safe delivery of oncologic care during the COVID-19 pandemic, telemedicine has been rapidly adopted. However, little data exist on the impact of telemedicine on quality and accessibility of oncologic care. This study assessed whether conducting an office visit for thoracic oncology patients via telemedicine affected time to treatment initiation and accessibility. Methods This was a retrospective cohort study of patients with thoracic malignancies seen by a multidisciplinary team during the first surge of COVID-19 cases in Philadelphia (March 1 to June 30, 2020). Patients with an index visit for a new phase of care, defined as a new diagnosis, local recurrence, or newly discovered metastatic disease, were included. Results 240 distinct patients with thoracic malignancies were seen: 132 patients (55.0%) were seen initially in-person vs 108 (45.0%) via telemedicine. The majority of visits were for a diagnosis of a new thoracic cancer (87.5%). Among newly diagnosed patients referred to the thoracic oncology team, the median time from referral to initial visit was significantly shorter amongst the patients seen via telemedicine vs. in-person (median 5.0 vs. 6.5 days, p

Abstract Background Serious illness conversations (SICs) are an evidence-based approach to eliciting patients’ values, goals, and care preferences that improve patient outcomes. However, most patients with cancer die without a documented SIC. Clinician-directed implementation strategies informed by behavioral economics (“nudges”) that identify high-risk patients have shown promise in increasing SIC documentation among clinicians. It is unknown whether patient-directed nudges that normalize and prime patients towards SIC completion—either alone or in combination with clinician nudges that additionally compare performance relative to peers—may improve on this approach. Our objective is to test the effect of clinician- and patient-directed nudges as implementation strategies for increasing SIC completion among patients with cancer. Methods We will conduct a 2 × 2 factorial, cluster randomized pragmatic trial to test the effect of nudges to clinicians, patients, or both, compared to usual care, on SIC completion. Participants will include 166 medical and gynecologic oncology clinicians practicing at ten sites within a large academic health system and their approximately 5500 patients at high risk of predicted 6-month mortality based on a validated machine-learning prognostic algorithm. Data will be obtained via the electronic medical record, clinician survey, and semi-structured interviews with clinicians and patients. The primary outcome will be time to SIC documentation among high-risk patients. Secondary outcomes will include time to SIC documentation among all patients (assessing spillover effects), palliative care referral among high-risk patients, and aggressive end-of-life care utilization (composite of chemotherapy within 14 days before death, hospitalization within 30 days before death, or admission to hospice within 3 days before death) among high-risk decedents. We will assess moderators of the effect of implementation strategies and conduct semi-structured interviews with a subset of clinicians and patients to assess contextual factors that shape the effectiveness of nudges with an eye towards health equity. Discussion This will be the first pragmatic trial to evaluate clinician- and patient-directed nudges to promote SIC completion for patients with cancer. We expect the study to yield insights into the effectiveness of clinician and patient nudges as implementation strategies to improve SIC rates, and to uncover multilevel contextual factors that drive response to these strategies. Trial registration ClinicalTrials.gov , NCT04867850 . Registered on April 30, 2021. Funding National Cancer Institute P50CA244690

Abstract Background Routine evidence-based tobacco use treatment minimizes cancer-specific and all-cause mortality, reduces treatment-related toxicity, and improves quality of life among patients receiving cancer care. Few cancer centers employ mechanisms to systematically refer patients to evidence-based tobacco cessation services. Implementation strategies informed by behavioral economics can increase tobacco use treatment engagement within oncology care. Methods A four-arm cluster-randomized pragmatic trial will be conducted across nine clinical sites within the Implementation Science Center in Cancer Control Implementation Lab to compare the effect of behavioral economic implementation strategies delivered through embedded messages (or “nudges”) promoting patient engagement with the Tobacco Use Treatment Service (TUTS). Nudges are electronic medical record (EMR)-based messages delivered to patients, clinicians, or both, designed to counteract known patient and clinician biases that reduce treatment engagement. We used rapid cycle approaches (RCA) informed by relevant stakeholder experiences to refine and optimize our implementation strategies and methods prior to trial initiation. Data will be obtained via the EMR, clinician survey, and semi-structured interviews with a subset of clinicians and patients. The primary measure of implementation is penetration, defined as the TUTS referral rate. Secondary outcome measures of implementation include patient treatment engagement (defined as the number of patients who receive FDA-approved medication or behavioral counseling), quit attempts, and abstinence rates. The semi-structured interviews, guided by the Consolidated Framework for Implementation Research, will assess contextual factors and patient and clinician experiences with the nudges. Discussion This study will be the first in the oncology setting to compare the effectiveness of nudges to clinicians and patients, both head-to-head and in combination, as implementation strategies to improve TUTS referral and engagement. We expect the study to (1) yield insights into the effectiveness of nudges as an implementation strategy to improve uptake of evidence-based tobacco use treatment within cancer care, and (2) advance our understanding of the multilevel contextual factors that drive response to these strategies. These results will lay the foundation for how patients with cancer who smoke are best engaged in tobacco use treatment and may lead to future research focused on scaling this approach across diverse centers. Trial registration Clinicaltrials.gov, NCT04737031 . Registered 3 February 2021.

Objective: Bioprosthetic heart valves (BHVs) are commonly used in surgical and percutaneous valve replacement. The durability of percutaneous valve replacement is unknown, but surgical valves have been shown to require reintervention after 10 to 15 years. Further, smaller-diameter surgical BHVs generally experience higher rates of prosthesis–patient mismatch, which leads to higher rates of failure. Bioprosthetic aortic valves can flutter in systole, and fluttering is associated with fatigue and failure in flexible structures. The determinants of flutter in BHVs have not been well characterized, despite their potential to influence durability. Methods: We use an experimental pulse duplicator and a computational fluid-structure interaction model of this system to study the role of device geometry on BHV dynamics. The experimental system mimics physiological conditions, and the computational model enables precise control of leaflet biomechanics and flow conditions to isolate the effects of variations in BHV geometry on leaflet dynamics. Results: Both experimental and computational models demonstrate that smaller-diameter BHVs yield markedly higher leaflet fluttering frequencies across a range of conditions. The computational model also predicts that fluttering frequency is directly related to leaflet thickness. A scaling model is introduced that rationalizes these findings. Conclusions: We systematically characterize the influence of BHV diameter and leaflet thickness on fluttering dynamics. Although this study does not determine how flutter influences device durability, increased flutter in smaller-diameter BHVs may explain how prosthesis–patient mismatch could induce BHV leaflet fatigue and failure. Ultimately, understanding the effects of device geometry on leaflet kinematics may lead to more durable valve replacements.

PURPOSENephroblastoma is a highly curable pediatric cancer that requires multidisciplinary care. Few reports have assessed long-term treatment outcomes in low-resource settings using a task-shifting model of care. We report outcomes of a large cohort and factors associated with survival.METHODSWe performed a retrospective chart review of all patients with nephroblastoma presenting to the Butaro Cancer Center of Excellence in Rwanda between July 2012 and June 2018.RESULTSIn total, 136 patients were identified and treated according to International Society of Pediatric Oncology guidelines for low-income settings. Median age at diagnosis was 39.7 months (interquartile range, 25.3-61.8 months); 56.6% were female. Sixty-one (44.9%) patients presented with stage I-III disease, 35 (25.7%) with stage IV disease, and 6 (4.4%) with stage V disease; the remainder were unstaged (n = 34; 25.0%). Most patients completed surgery (n = 97; 71.3%) and postoperative chemotherapy (n = 82; 60.2%); 17 patients received radiotherapy. With a median follow-up time of 18.1 months, 44.9% of patients were alive, 41.9% had died, 8.8% were lost to follow-up, and 4.4% were referred for palliative care or declined further care at the end of the study. Three-year overall survival was 57.5% (95% CI, 48.1 to 65.8) for the entire cohort, and 80.1% (95% CI, 66.8 to 88.5) and 44.0% (95% CI, 26.8 to 60.0) for stages I-III and IV-V, respectively.CONCLUSIONWe demonstrate that patients with nephroblastoma can be successfully treated in a low-resource setting. Survival remains lower than in high-income countries, in part due to early deaths, contributing to approximately 30% of patients not being medically able to receive surgical intervention. Next steps include the development of strategies that focus on earlier diagnosis, supportive care during the early phases of therapy, and efficient and timely transitions between specialties for multimodal care.

PURPOSEIn describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development.METHODSWe retrospectively reviewed all patients with BCR-ABL–positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test.RESULTSOne hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days (P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis (P = .056) and imatinib initiation (P = .170) was not significantly different.CONCLUSIONCoupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

This study investigated the effect of extraction parameters such as particle size, temperature, and time on yield alongside the kinetic and thermodynamics variables for Chrysophyllum albidum. For the extraction, the oil yield increased as the extraction temperature and time increased, but the reverse was observed as the particle size increased. At the temperature of 55 °C, particle size of 0.55 mm, and extraction time of 150 min, the maximum oil yield of 14.98% was obtained. The extracted oil was analyzed and was found to have a saponification value of 134.64 mgKOH/kg, Iodine value of 82.53 mg I/g, peroxide value of 5mEq/kg, and acid value of 14.47 mg KOH/mg. In addition, the oil viscosity and specific gravity were 54.54 mm2 s−1 and 0.941, respectively. Hyperbolic, second-order, and Elovich's kinetic models were used to fit the data gotten from experimental findings. The three models fitted the experimental data suitably, with hyperbolic kinetic model giving the best fit (R2=0.93288, RMS=0.12133, and SD=0.02715) followed by Elovich's model kinetic model (R2=0.92172, RMS=0.205329, and SD=0.039349) and (R2=0.92968, RMS=0.66867, and SD=0.542885) in that order. Thermodynamic parameters ∆H and ∆S for ASA seed oil extraction were evaluated at temperature of 318 K. The enthalpy values for the five particle sizes used were 19.35, 22.24, 26.08, 29.57 and 49.98 KJ/mol and the Entropy 0.08, 0.09 0.10 0.11 and 0.17 KJ/mol respectively. These positives values for the enthalpy and entropy change shows that the extraction is endothermic and irreversible in nature. The Gibbs free energy change (∆G) for the extraction was found to be below zero showing that the extraction was a spontaneous process. Using ANOVA and Tukey's post hoc HSD analyses, extraction time variation was found to significantly affect oil yield. Particle size and extraction temperature variations were statistically insignificant.

PURPOSEGeographic access to care is an important measure of health equity. In this study, we describe geographic access to cancer care centers (CCCs) in Rwanda with the current facilities providing care and examine how access could change with expanded care infrastructure.METHODSHealth facilities included are public hospitals administered by the Rwanda Ministry of Health. The WorldPop Project was used to estimate population distribution, and OpenStreetMap was used to determine travel routes. On the basis of geolocations of the facilities, AccessMod 5 was used to estimate the percentage of the population that live within 1 hour, 2 hours, and 4 hours of CCCs under the current (two facilities) and expanded care (seven facilities) scenarios. Variations in access by region, poverty, and level of urbanization were described.RESULTSCurrently, 13%, 41%, and 85% of Rwandans can access CCCs within one, two, and 4 hours of travel, respectively. With expansion of CCCs to seven facilities, access increases to 37%, 84%, and 99%, respectively. There is a substantial variation in current geographic access by province, with 1-hour access in Kigali at 98%, whereas access in the Western Province is 0%; care expansion could increase 2-hour access in the Western Province from 1% to 71%. Variation in access is also seen across the level of urbanization, with current 1-hour access in urban versus rural areas of 45% and 8%, respectively. Expanded care results in improvement of 1-hour access to 67% and 33%, respectively. Similar trends were also noted across poverty levels.CONCLUSIONGeographical access to CCCs varies substantially by province, level of urbanization, and poverty. These disparities can be alleviated by strategic care expansion to other tertiary care facilities across Rwanda.

PURPOSEKey to achieving better population-based outcomes for patients with lung cancer is the improvement of medical imaging and nuclear medicine infrastructure globally. This paper aims to outline why and spark relevant health systems strengthening.METHODSThe paper synthesizes the global lung cancer landscape, imaging referral guidelines (including resource-stratified ones), the reliance of TNM staging upon imaging, relevant multinational health technology assessments, and precisely how treatment selection and in turn patient outcomes hinge upon imaging findings. The final discussion presents data on current global gaps in both diagnostics (including imaging) and therapies and how, informed by such data, improved population-based outcomes are tangible through strategic planning.RESULTSImaging findings are central to appropriate lung cancer patient management and can variably lead to life-prolonging interventions and/or to life-enhancing palliative measures. Early-stage lung cancer can be treated with curative intent but, unfortunately, most patients with lung cancer still present at advanced stages and many patients lack access to both diagnostics and therapies. Furthermore, half of lung cancer cases occur in low- and middle-income countries. The role of medical imaging and nuclear medicine in lung cancer management, as outlined herein, may help inform strategic planning.CONCLUSIONLung cancer is the number one cancer killer worldwide. The essential role that medical imaging and nuclear medicine play in early diagnosis and disease staging cannot be overstated, pivotal in selecting the many patients for whom measurably improved outcomes are attainable. Prevention synergized with patient-centered, compassionate, high-quality lung cancer management provision mandate that strategic population-based planning, including universal health coverage strategies, should extend well beyond the scope of disease prevention to include both curative and noncurative treatment options for the millions afflicted with lung cancer.

PURPOSEPatients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT).METHODSThis was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding.RESULTSIn total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy.CONCLUSIONPatients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes.

Abstract Mutations in the BRAF gene at or near the p. V600 locus are informative for therapy selection, but current methods for analyzing FFPE tissue DNA generally have a limit of detection of 5% variant allele frequency (VAF), or are limited to the single variant (V600E). These can result in false negatives for samples with low VAFs due to low tumor content or subclonal heterogeneity, or harbor non-V600 mutations. Here, we show that Sanger sequencing using the NuProbe VarTrace BRAF assay, based on the Blocker Displacement Amplification (BDA) technology, is capable of detecting BRAF V600 mutations down to 0.20% VAF from FFPE lymph node tissue samples. Comparison experiments on adjacent tissue sections using BDA Sanger, immunohistochemistry (IHC), digital droplet PCR (ddPCR), and NGS showed 100% concordance among all 4 methods for samples with BRAF mutations at ≥ 1% VAF, though ddPCR did not distinguish the V600K mutation from the V600E mutation. BDA Sanger, ddPCR, and NGS (with orthogonal confirmation) were also pairwise concordant for lower VAF mutations down to 0.26% VAF, but IHC produced a false negative. Thus, we have shown that Sanger sequencing can be effective for rapid detection and quantitation of multiple low VAF BRAF mutations from FFPE samples. BDA Sanger method also enabled detection and quantitation of less frequent, potentially actionable non-V600 mutations as demonstrated by synthetic samples.

Due to the heterogeneity among households across locations, predicting the impacts of stay-at-home mitigation and lockdown strategies for COVID-19 control is crucial. In this study, we quantitatively assessed the effects of the Namibia government’s lockdown control measures on food insecurity in urban informal settlements with a focus on Windhoek, Namibia. We developed three types of conditional regression models to predict food insecurity prevalence (FIP) scenarios incorporating household frequency of food purchase (FFP) as the impacting factor, based on the Hungry Cities Food Matrix. Empirical data were derived from the 2017 African Food Security Urban Network (AFSUN) Windhoek study and applied univariate probit and bivariate partial observability models to postulate the relation between food insecurity and FFP within the context of stay-at-home disease mitigation strategy. The findings showed that FFP was positively correlated with the prevalence of food insecurity (r = 0.057, 95% CI: 0.0394, 0.085). Daily purchases portrayed a survivalist behaviour and were associated with increased food insecurity (coeff = 0.076, p = 0.05). Only those who were purchasing food twice monthly were significantly associated with reduced food insecurity (coeff = −0.201, p = 0.001). Those households in informal settlements were severely impacted by food insecurity (coeff = 0.909, p-value = 0.007). We conclude that public health compliance should precede with cash or food support to poor households in balance with the need for long-term placement of control measures to fully contain COVID-19 or related infectious diseases.

Abstract DNA repair gene aberrations (GAs) occur in several cancers, may be prognostic and are actionable. We investigated the frequency of DNA repair GAs in gallbladder cancer (GBC), association with tumor mutational burden (TMB), microsatellite instability (MSI), programmed cell death protein 1 (PD-1), and its ligand (PD-L1) expression. Comprehensive genomic profiling (CGP) of 760 GBC was performed. We investigated GAs in 19 DNA repair genes including direct DNA repair genes (ATM, ATR, BRCA1, BRCA2, FANCA, FANCD2, MLH1, MSH2, MSH6, PALB2, POLD1, POLE, PRKDC, and RAD50) and caretaker genes (BAP1, CDK12, MLL3, TP53, and BLM) and classified patients into 3 groups based on TMB level: low (

PURPOSE Brain drain is the migration of educated and skilled individuals from a less developed region or country to a more economically established one. The Trump administration proposed a merit-based immigration plan. This article addresses its potential impact on health care delivery in low- and middle-income countries (LMICs) and their preparedness to deal with it. MATERIALS AND METHODS Data on immigration policies, numbers of international medical graduates practicing in high-income countries (HICs), various scientific exchange methods, and efforts for capacity building in LMICs. RESULTS Talented individuals seek to advance their knowledge and skills, and may stay in HICs because of greater rewards and opportunities. HICs also rely on immigrant international medical graduates to supplement their physician workforces. CONCLUSION Ambitious individuals from LMICs need and should have opportunities to advance their education and training in more advanced countries. LMICs should increase their educational efforts, research capabilities, infrastructures, and living conditions to better serve their own populations and reduce their brain drain phenomenon.

In recognition of the rising incidence and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has prioritized efforts to enhance its engagement at a global level. Among the recommendations included in the 2016 Global Oncology Leadership Task Force report to the ASCO Board of Directors was that ASCO should promote the recognition of global oncology as an academic field. The report suggested that ASCO could serve a role in transitioning global oncology from an informal field of largely voluntary activities to a more formal discipline with strong research and well-defined training components. As a result of this recommendation, in 2017, ASCO formed the Academic Global Oncology Task Force (AGOTF) to guide ASCO’s contributions toward formalizing the field of global oncology. The AGOTF was asked to collect and analyze key issues and barriers toward the recognition of global oncology as an academic discipline, with an emphasis on training, research, and career pathways, and produce a set of recommendations for ASCO action. The outcome of the AGOTF was the development of recommendations designed to advance the status of global oncology as an academic discipline.

PURPOSEFew studies have explored the relationship between body habitus and breast cancer outcomes in Caribbean women of African ancestry. This study evaluates the association between body mass index (BMI) and disease-free survival (DFS) in a retrospective cohort of 224 female Haitian patients with nonmetastatic breast cancer.PATIENTS AND METHODSBMI was obtained from the medical records and categorized as normal weight (< 25 kg/m2), overweight (25-29.9 kg/m2), and obese (≥ 30 kg/m2). DFS was defined as time from surgical resection to disease recurrence, death, or censoring. Kaplan-Meier survival curves were generated, and the association between BMI and DFS was evaluated using Cox proportional hazard models to control for multiple confounders. Exploratory analyses were conducted on weight changes during adjuvant chemotherapy.RESULTSEighty-three patients (37.1%) were normal weight, 66 (29.5%) were overweight, and 75 (33.5%) were obese. There were no statistical differences in baseline characteristics or treatments received by BMI group. Twenty-six patients died and 73 had disease recurrence. Median DFS was 41.1 months. Kaplan-Meier estimates showed no significant DFS differences by BMI categories. After controlling for confounders, normal weight patients, when compared with overweight and obese patients, had adjusted hazard ratios of 0.85 (95% CI, 0.49 to 1.49) and 0.90 (95% CI, 0.52 to 1.55), respectively. Overall, mean weight loss of 2% of body weight was noted over the course of adjuvant chemotherapy. Patients who were postmenopausal (P = .007) and obese (P = .05) lost more weight than other groups. However, chemotherapy-related weight changes did not have an impact on DFS.CONCLUSIONBaseline BMI and weight changes during adjuvant chemotherapy did not have an impact on DFS in this cohort. Future prospective studies in similar Caribbean breast cancer cohorts are needed to verify study findings.

PURPOSE Hodgkin lymphoma (HL) is highly curable in high-income countries (HICs), yet many patients around the world do not have access to therapy. In 2012, cancer care was established at a rural district hospital in Rwanda through international collaboration, and a treatment protocol using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiotherapy was implemented. METHODS We conducted a retrospective cohort study of all patients with confirmed HL seen at Butaro Hospital from 2012 to 2018 to evaluate quality indicators and clinical outcomes. RESULTS Eighty-five patients were included (median age, 16.8 years; interquartile range, 11.0-30.5 years). Ten (12%) were HIV positive. Most had B symptoms (70%) and advanced stage (56%) on examination and limited imaging. Of 21 specimens evaluated for Epstein-Barr virus, 14 (67%) were positive. Median time from biopsy to treatment was 6.0 weeks. Of 73 patients who started ABVD, 54 (74%) completed 6 cycles; the leading reasons for discontinuation were treatment abandonment and death. Median dose intensity of ABVD was 92%. Of 77 evaluable patients, 33 (43%) are in clinical remission, 27 (36%) are deceased, and 17 (22%) were lost to follow-up; 3-year survival estimate is 63% (95% CI, 50% to 74%). Poorer performance status, advanced stage, B symptoms, anemia, dose intensity < 85%, and treatment discontinuation were associated with worse survival. CONCLUSION Treating HL with standard chemotherapy in a low-resource setting is feasible. Most patients who completed treatment experienced a clinically significant remission with this approach. Late presentation, treatment abandonment, and loss to follow-up contribute to the discrepancy in survival compared with HICs. A strikingly younger age distribution in our cohort compared with HICs suggests biologic differences and warrants further investigation.

Rwanda is a densely populated low-income country in East Africa. Previously considered a failed state after the genocide against the Tutsi in 1994, Rwanda has seen remarkable growth over the past 2 decades. Health care in Rwanda is predominantly delivered through public hospitals and is emerging in the private sector. More than 80% of patients are covered by community-based health insurance (Mutuelle de Santé). The cancer unit at the Rwanda Biomedical Center (a branch of the Ministry of Health) is responsible for setting and implementing cancer care policy. Rwanda has made progress with human papillomavirus (HPV) and hepatitis B vaccination. Recently, the cancer unit at the Rwanda Biomedical Center launched the country’s 5-year National Cancer Control Plan. Over the past decade, patients with cancer have been able to receive chemotherapy at Butaro Cancer Center, and recently, the Rwanda Cancer Center was launched with 2 linear accelerator radiotherapy machines, which greatly reduced the number of referrals for treatment abroad. Palliative care services are increasing in Rwanda. A cancer registry has now been strengthened, and more clinicians are becoming active in cancer research. Despite these advances, there is still substantial work to be done and there are many outstanding challenges, including the need to build capacity in cancer awareness among the general population (and shift toward earlier diagnosis), cancer care workforce (more in-country training programs are needed), and research.

PURPOSEThe burden of cancer is growing in low- and middle-income countries (LMICs), including sub-Saharan Africa. Ensuring the delivery of high-quality cancer care in such regions is a pressing concern. There is a need for strategies to identify meaningful and relevant quality measures that are applicable to and usable for quality measurement and improvement in resource-constrained settings.METHODSTo identify quality measures for breast cancer care at Butaro Cancer Center of Excellence (BCCOE) in Rwanda, we used a modified Delphi process engaging two panels of experts, one with expertise in breast cancer evidence and measures used in high-income countries and one with expertise in cancer care delivery in Rwanda.RESULTSOur systematic review of the literature yielded no publications describing breast cancer quality measures developed in a low-income country, but it did provide 40 quality measures, which we adapted for relevance to our setting. After two surveys, one conference call, and one in-person meeting, 17 measures were identified as relevant to pathology, staging and treatment planning, surgery, chemotherapy, endocrine therapy, palliative care, and retention in care. Successes of the process included participation by a diverse set of global experts and engagement of the BCCOE community in quality measurement and improvement. Anticipated challenges include the need to continually refine these measures as resources, protocols, and measurement capacity rapidly evolve in Rwanda.CONCLUSIONA modified Delphi process engaging both global and local expertise was a promising strategy to identify quality measures for breast cancer in Rwanda. The process and resulting measures may also be relevant for other LMIC cancer facilities. Next steps include validation of these measures in a retrospective cohort of patients with breast cancer.

Arsenic is a carcinogenic groundwater contaminant that is toxic even at the parts-per-billion (ppb) level and its on-site determination remains challenging. Colorimetric test strips, though cheap and widely used, often fail to give reliable quantitative data. On the other hand, electrochemical detection is sensitive and accurate but considerably more expensive at the onset. Here, we present a study on arsenic detection in groundwater using a low-cost, open-source potentiostat based on Arduino technology. We tested different types of gold electrodes (screen-printed and microwire) with anodic stripping voltammetry (ASV), achieving low detection limits (0.7 μg L-1). In a study of arsenic contaminated groundwaters in Mexico, the microwire technique provides greater accuracy than test strips (reducing the median error from -50% to +2.9%) and greater precision (reducing uncertainties from ±25% to ±4.9%). Most importantly, the rate of false negatives versus the World Health Organisation’s 10 μg L-1 limit was reduced from 50% to 0% (N = 13 samples). Arsenic determination using open-source potentiostats may offer a low-cost option for research groups and NGOs wishing to perform arsenic analysis in-house, yielding superior quantitative data than the more widely used colorimetric test strips.

Abstract Background and Aim This study quantifies how changes in healthcare utilization and delivery during the first months of the COVID‐19 pandemic have altered the presentation, treatment, and management of patients with gastrointestinal (GI) malignancies within an academic health system. Methods and results Patients diagnosed with a GI malignancy (ICD10: C15‐C26) who received medical care within the health system during the observation period (first 44 weeks of 2019 and 2020) were identified for a retrospective cohort study. Deidentified patient encounter parameters were collected for this observation period and separated into pre‐pandemic (weeks 1–10) and early pandemic (weeks 11–20) study periods. Difference‐in‐difference analyses adjusted for week‐specific and year‐specific effects quantified the impact of the COVID‐19 pandemic on care delivery between pre‐pandemic and early pandemic study periods in 2020. Across all GI malignancies, the COVID‐19 pandemic has been associated with a significant decline in the number of patients with new patient visits (NPVs) (p = 1.2 × 10−4), Radiology encounters (p = 1.9 × 10−7), Surgery encounters (p = 1.6 × 10−3), Radiation Oncology encounters (p = 4.1 × 10−3), and infusion visits (6.1 × 10−5). Subgroup analyses revealed cancer‐specific variations in changes to delivery. Patients with colorectal cancer (CRC) had the most significant decrease in NPVs (p = 7.1 × 10−5), which was significantly associated with a concomitant decrease in colonoscopies performed during the early pandemic period (r2 = 0.722, p = 2.1 × 10−10). Conclusions The COVID‐19 pandemic has been associated with significant disruptions to care delivery. While these effects were appreciated broadly across GI malignancies, CRC, diagnosed and managed by periodic screening, has been affected most acutely.

BackgroundWhile health systems have implemented multifaceted interventions to improve physician and patient communication in serious illnesses such as cancer, clinicians vary in their response to these initiatives. In this secondary analysis of a randomized trial, we identified phenotypes of oncology clinicians based on practice pattern and demographic data, then evaluated associations between such phenotypes and response to a machine learning (ML)-based intervention to prompt earlier advance care planning (ACP) for patients with cancer.Methods and findingsBetween June and November 2019, we conducted a pragmatic randomized controlled trial testing the impact of text message prompts to 78 oncology clinicians at 9 oncology practices to perform ACP conversations among patients with cancer at high risk of 180-day mortality, identified using a ML prognostic algorithm. All practices began in the pre-intervention group, which received weekly emails about ACP performance only; practices were sequentially randomized to receive the intervention at 4-week intervals in a stepped-wedge design. We used latent profile analysis (LPA) to identify oncologist phenotypes based on 11 baseline demographic and practice pattern variables identified using EHR and internal administrative sources. Difference-in-differences analyses assessed associations between oncologist phenotype and the outcome of change in ACP conversation rate, before and during the intervention period. Primary analyses were adjusted for patients' sex, age, race, insurance status, marital status, and Charlson comorbidity index. The sample consisted of 2695 patients with a mean age of 64.9 years, of whom 72% were White, 20% were Black, and 52% were male. 78 oncology clinicians (42 oncologists, 36 advanced practice providers) were included. Three oncologist phenotypes were identified: Class 1 (n = 9) composed primarily of high-volume generalist oncologists, Class 2 (n = 5) comprised primarily of low-volume specialist oncologists; and 3) Class 3 (n = 28), composed primarily of high-volume specialist oncologists. Compared with class 1 and class 3, class 2 had lower mean clinic days per week (1.6 vs 2.5 [class 3] vs 4.4 [class 1]) a higher percentage of new patients per week (35% vs 21% vs 18%), higher baseline ACP rates (3.9% vs 1.6% vs 0.8%), and lower baseline rates of chemotherapy within 14 days of death (1.4% vs 6.5% vs 7.1%). Overall, ACP rates were 3.6% in the pre-intervention wedges and 15.2% in intervention wedges (11.6 percentage-point difference). Compared to class 3, oncologists in class 1 (adjusted percentage-point difference-in-differences 3.6, 95% CI 1.0 to 6.1, p = 0.006) and class 2 (adjusted percentage-point difference-in-differences 12.3, 95% confidence interval [CI] 4.3 to 20.3, p = 0.003) had greater response to the intervention.ConclusionsPatient volume and time availability may be associated with oncologists' response to interventions to increase ACP. Future interventions to prompt ACP should prioritize making time available for such conversations between oncologists and their patients.

PURPOSE: Feasible and effective strategies are needed to facilitate earlier diagnosis of breast cancer in low-income countries. The goal of this study was to examine the impact of health worker breast health training on health care utilization, patient diagnoses, and cancer stage in a rural Rwandan district. METHODS: We conducted a cluster randomized trial of a training intervention at 12 of the 19 health centers (HCs) in Burera District, Rwanda, in 2 phases. We evaluated the trainings’ impact on the volume of patient visits for breast concerns using difference-in-difference models. We used generalized estimating equations to evaluate incidence of HC and hospital visits for breast concerns, biopsies, benign breast diagnoses, breast cancer, and early-stage disease in catchment areas served by intervention versus control HCs. RESULTS: From April 2015 to April 2017, 1,484 patients visited intervention HCs, and 308 visited control HCs for breast concerns. The intervention led to an increase of 4.7 visits/month for phase 1 HCs (P = .001) and 7.9 visits/month for phase 2 HCs (P = .007) compared with control HCs. The population served by intervention HCs had more hospital visits (115.1 v 20.5/100,000 person-years, P < .001) and biopsies (36.6 v 8.9/100,000 person-years, P < .001) and higher breast cancer incidence (6.9 v 3.3/100,000 person-years; P = .28). The incidence of early-stage breast cancer was 3.3 per 100,000 in intervention areas and 0.7 per 100,000 in control areas (P = .048). CONCLUSION: In this cluster randomized trial in rural Rwanda, the training of health workers and establishment of regular breast clinics were associated with increased numbers of patients who presented with breast concerns at health facilities, more breast biopsies, and a higher incidence of benign breast diagnoses and early-stage breast cancers.

Religious and existential concerns interweave in many books of the Bible to give attention to human’s existential anguish, the sense of guilt, the horror of death, the atrocious experience of the absurd. While many contemporary existentialist philosophers prefer to do without God in the attempt to deal with human’s existential contradictions, the search takes the authors of the Bible through intense spiritual struggles as they attempt to confront the belief in the goodness of God with the human experience of futility in all its facets. We want to seek a meeting point between the existentialist concerns of the book of Qoholeth with the profound theology of meaningfulness as elaborated in Genesis 1:1–2:4a. Our article therefore, has a decidedly pastoral orientation. We will attempt to move, through an analysis of select texts, to a re-affirmation of one of the spiritual truths that many mystics have tried to teach: that reason alone is not enough to guide the human person to the mysteries of life, the believer has to learn to unite with God or to the realities themselves to discover the fundamental goodness in many of the experiences that, in human perspectives, seem to be absurd. Intradisciplinary and/or interdisciplinary implications: We believe such union is needed in a world where racism, violence to minorities, gender inequalities, homophobic attitudes are thickening the clouds of discrimination and threatening some to doubt the fundamental goodness of creation as made by God.

Objectives Patients with morbid obesity have impaired responses to resuscitation following severe injury, which may contribute to adverse outcomes. Obesity is associated with microvascular dysfunction and metabolic changes associated with altered hemorheological profiles. These include decreased red blood cell (RBC) deformity associated with increased aggregation and adhesion. These RBC changes may be impacted by the glycocalyx layer of the endothelial cell (EC) and RBC. Degradation of either or both glycocalyx layers may impair microvascular perfusion. This was studied from blood obtained from patients with obesity and in an in vitro microfluidic device to mimic the microvascular environment.Methods RBCs were obtained from fresh whole blood from normal controls and patients with obesity (body mass index 37.6–60.0). RBC glycocalyx was indexed by fluorescent intensity and shedding of EC glycocalyx components into the serum was determined by measurement of syndecan-1 and hyaluronic acid. In a second set of experiments, human umbilical vein endothelial cell monolayers (HUVEC) were perfused with RBC suspensions from control and patients with obesity using a microfluidic device and RBC adherence under normoxic or shock conditions (hypoxia+epinephrine) was determined using confocal microscopy. HUVEC glycocalyx thickness and shedding were also measured.Results Microfluidic studies demonstrated that RBC obtained from subjects with obesity had increased adhesion to the endothelial layer, which was more profound under shock conditions versus normal subjects. This appeared to be related to increased shedding of the endothelial glycocalyx following shock as well as a diminished RBC glycocalyx layer in the obese population.Conclusion Blood from patients with obesity have decreased RBC glycocalyx thickness accompanied by evidence of increased EC glycocalyx shedding. In vitro adhesion to the endothelium was more pronounced with RBC from patients with obesity and was significantly greater under ‘shock conditions’. Hemorheological properties of RBC from patients with obesity may account for failure of standard resuscitation procedures in the trauma patient.Level of evidence

Objective Cancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply.Design A retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016.Setting Princess Marina Hospital in Gaborone, Botswana.Participants Patients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy.Primary and secondary outcome measures Frequency of delays and patterns of prescription changes for specific regimens and cancer types.Results 167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p

Abstract Background Modelling risk of malaria in longitudinal studies is common, because individuals are at risk for repeated infections over time. Malaria infections result in acquired immunity to clinical malaria disease. Prospective cohorts are an ideal design to relate the historical exposure to infection and development of clinical malaria over time, and analysis methods should consider the longitudinal nature of the data. Models must take into account the acquisition of immunity to disease that increases with each infection and the heterogeneous exposure to bites from infected Anopheles mosquitoes. Methods that fail to capture these important factors in malaria risk will not accurately model risk of malaria infection or disease. Methods Statistical methods applied to prospective cohort studies of clinical malaria or Plasmodium falciparum infection and disease were reviewed to assess trends in usage of the appropriate statistical methods. The study was designed to test the hypothesis that studies often fail to use appropriate statistical methods but that this would improve with the recent increase in accessibility to and expertise in longitudinal data analysis. Results Of 197 articles reviewed, the most commonly reported methods included contingency tables which comprised Pearson Chi-square, Fisher exact and McNemar’s tests (n = 102, 51.8%), Student’s t-tests (n = 82, 41.6%), followed by Cox models (n = 62, 31.5%) and Kaplan–Meier estimators (n = 59, 30.0%). The longitudinal analysis methods generalized estimating equations and mixed-effects models were reported in 41 (20.8%) and 24 (12.2%) articles, respectively, and increased in use over time. A positive trend in choice of more appropriate analytical methods was identified over time. Conclusions Despite similar study designs across the reports, the statistical methods varied substantially and often represented overly simplistic models of risk. The results underscore the need for more effort to be channelled towards adopting standardized longitudinal methods to analyse prospective cohort studies of malaria infection and disease.

PURPOSE: Essential cancer medicine stock outs are occurring at an increasing frequency worldwide and represent a potential barrier to delivery of standard therapy in patients with cancer in low- and middle-income countries. The objective of this study was to measure the impact of cancer medicine stock outs on delivery of optimal therapy in Botswana. METHODS: We conducted a retrospective analysis of patients with common solid tumor malignancies who received systemic cancer therapy in 2016 at Princess Marina Hospital, Gaborone, Botswana. Primary exposure was the duration of cancer medicine stock out during a treatment cycle interval, when the cancer therapy was intended to be administered. Mixed-effects univariable and multivariable logistic regression analyses were used to calculate the association of the primary exposure, with the primary outcome, suboptimal therapy delivery, defined as any dose reduction, dose delay, missed cycle, or switch in intended therapy. RESULTS: A total of 378 patients met diagnostic criteria and received systemic chemotherapy in 2016. Of these, 76% received standard regimens consisting of 1,452 cycle intervals and were included in this analysis. Paclitaxel stock out affected the highest proportion of patients. In multivariable mixed-effects logistic regression, each week of any medicine stock out (odds ratio, 1.9; 95% CI, 1.7 to 2.13; P < .001) was independently associated with an increased risk of a suboptimal therapy delivery event. CONCLUSION: Each week of cancer therapy stock out poses a substantial barrier to receipt of high-quality cancer therapy in low- and middle-income countries. A concerted effort between policymakers and cancer specialists is needed to design implementation strategies to build sustainable systems promoting a reliable supply of cancer medicines.

Cotton is one of the most valuable materials in the world, popularly used in the clothing industry and other products. However, its production is limited by the high infestation of insect pests. A study was conducted to evaluate the effects of different biopesticides on the control of the African bollworm (Helicoverpa armigera) under cotton field conditions. Four biopesticides—namely, Eco-Bb® (Beauveria bassiana), Bb endophyte (Beauveria bassiana), Bolldex® (Nucleopolyhedrovirus), and Delfin® (Bacillus thuringiensis)—were evaluated and compared with the pyrethroid Karate® (lambda-cyhalothrin) and an untreated control against H. armigera. Field trials were conducted at the Agriculture Research Council, Rustenburg, in the North West Province of South Africa during the 2017 and 2018 cotton seasons. The results revealed that in plots sprayed with Karate® and Bolldex®, the numbers of H. armigera were significantly reduced compared to the untreated controls. Plots treated with Bolldex® had the lowest number of damaged bolls in 2017, while those treated with Karate® had the lowest number of damaged bolls in 2018. All treated plots had significantly fewer damaged bolls when compared to the controls. A seed cotton yield of 5987 kg/ha was recorded in the plots that were treated with Bolldex®—significantly higher than the yields from plots treated with Eco-Bb®, Delfin®, and Bb endophyte—in 2017. However, the yield in treatments with Eco-Bb®, Delfin®, and Bb endophyte was lower than that from the untreated controls during this season. In 2018, plots treated with Bolldex® had the highest yield, at 6818 kg/ha, which was not different from the other treatments. The highest average seed cotton yield of 6400 kg/ha was recorded in the plots treated with Bolldex®, followed by Karate®. In summary, the efficacy of different biopesticides against H. armigera varied significantly, while the synthetic pesticide (Karate®) and Bolldex® resulted in more consistent control of this pest. The results suggest that biopesticides may, however, have the potential for use in the sustainable control of cotton bollworms as part of integrated pest management programmes, although further work is required to support this hypothesis.