Young Women with Breast Cancer in Resource-Limited Settings: What We Know and What We Need to Do Better.

Young women with breast cancer (YWBC) account for a variable proportion of patients diagnosed with breast cancer around the globe, with a higher prevalence in resource-limited settings than in high-income countries. This group represents a unique population that warrants special attention due to specific biological considerations and age-specific supportive care issues. This review aims to explore existing knowledge regarding YWBC's needs, particularly in resource-restricted settings. To date, scarce information regarding the care of YWBC in resource-constrained countries is available, with most reports describing suboptimal care in terms of survivorship needs. Health care providers should implement actions to improve endocrine treatment adherence, referrals for fertility counseling and preservation, contraceptive use compliance, timely body image and sexual function interventions, comprehensive genetic risk assessments, and early quality of life and psychosocial health interventions. While high costs act as a barrier for optimal care in resource-limited settings, improving patient education represents a promising and cost-effective solution to improve patient care. Future research on developing tailored educational resources for YWBC in resource-limited settings should be considered a priority.

A Multiplex and Colorimetric Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Sensitive and Rapid Detection of Novel SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major threat to public health. Rapid molecular testing for convenient and timely diagnosis of SARS-CoV-2 infections represents a challenge that could help to control the current pandemic and prevent future outbreaks. We aimed to develop and validate a multiplex and colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using lyophilized LAMP reagents for sensitive and rapid detection of SARS-CoV-2. LAMP primers were designed for a set of gene targets identified by a genome-wide comparison of viruses. Primer sets that showed optimal features were combined into a multiplex RT-LAMP assay. Analytical validation included assessment of the limit of detection (LoD), intra- and inter-assay precision, and cross-reaction with other respiratory pathogens. Clinical performance compared to that of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was assessed using 278 clinical RNA samples isolated from swabs collected from individuals tested for COVID-19. The RT-LAMP assay targeting the RNA-dependent RNA polymerase (RdRp), membrane (M), and ORF1ab genes achieved a comparable LoD (0.65 PFU/mL, CT=34.12) to RT-qPCR and was 10-fold more sensitive than RT-qPCR at detecting viral RNA in clinical samples. Cross-reactivity to other respiratory pathogens was not observed. The multiplex RT-LAMP assay demonstrated a strong robustness and acceptable intra- and inter-assay precision (mean coefficient of variation, 4.75% and 8.30%). Diagnostic sensitivity and specificity values were 100.0% (95% CI: 97.4-100.0%) and 98.6% (95% CI: 94.9-99.8%), respectively, showing high consistency (Cohen's kappa, 0.986; 95% CI: 0.966-1.000; p<0.0001) compared to RT-qPCR. The novel one-step multiplex RT-LAMP assay is storable at room temperature and showed similar diagnostic accuracy to conventional RT-qPCR, while being faster (<45 min), simpler, and cheaper. The new assay could allow reliable and early diagnosis of SARS-CoV-2 infections in primary health care. It may aid large-scale testing in resource-limited settings, especially if it is integrated into a point-of-care diagnostic device.

Standardized Extubation and High Flow Nasal Cannula Training Program for Pediatric Critical Care Providers in Lima, Peru.

Introduction: Acute lower respiratory tract infections are the top cause of nonneonatal mortality in children under 5 years of age. Since many resource-limited settings lack basic pediatric respiratory support modalities, introducing respiratory technology in these settings may improve survival. Unfortunately, data suggest that many interventions in these settings are not sustainable and that after several months, local staff are no longer comfortable using newly implemented technology. Methods: We aimed to create training modules for implementation of a standardized extubation process and high flow nasal cannula for physician and nurse providers at a tertiary care center in Lima, Peru. This training curriculum combined a didactic lecture with hands-on practicum and clinical case discussion over multiple sessions spanning a year. We created all materials in English and translated to Spanish for use. Participants completed evaluations after the training program to determine whether objectives were met. This training was intended for critical care providers but could be modified for other audiences. Results: A total of 76 providers (12 attending/fellow critical care physicians, 40 bedside nurses, eight pediatric residents, and 14 medical technicians) participated in this multiday training. Almost all (75, 99%) participants felt the objectives were clearly stated, and 70 (92%) felt objectives were met. Discussion: We have provided materials to help instructors set up and implement a standardized training curriculum with recommended timing and improvements based on feedback. The tools provided allow for adaptation depending on the instructors' primary objectives, language of audience (English or Spanish), and learners' level of training.

Drug resistance in HIV-infected children living in rural South Africa: Implications of an antiretroviral therapy initiated during the first year of life.

INTRODUCTION: Management of antiretroviral-drug resistance in HIV-infected children is a global health concern. We compared the long-term virological outcomes of two cohorts of children living in a rural setting of South Africa. The first cohort initiated treatment before one year and the second after two years of age. The aim of this study was to describe the long-term consequences of early treatment initiation in terms of viral load and drug-resistance. METHODS: This retrospective study was conducted at the Edendale Hospital located in a peri-urban area of KwaZulu-Natal. Children were included during their planned appointment. Drug resistance was assessed genotypically on proviral DNA. RESULTS: From the 161 children included in this study, 93 samples were successfully genotyped. Both cohorts had comparable viral loads, but children treated early more often presented NRTI or NNRTI mutations, while there was no difference for PI mutations rates. CONCLUSIONS: Treatment was highly effective when comparing virological outcomes in both early- and late-treated cohorts. The persistence of NNRTI mutations could lead to treatment failures in children older than 3 years initiating their therapy with a NNRTI, or for those switching from a PI to NNRTI based regimen. The accumulation of NRTI mutations may lead to a functional PI monotherapy and consequently to viral escape. To promote access to HIV genotyping in resource-limited settings is challenging but essential to avoid inappropriate therapy switches in case of virological failure, and to adapt national treatment guidelines in line with the epidemiology of resistance.

Key considerations prior to nasal high flow deployment in a Peruvian PICU from providers' perspectives.

AIM: Implementation of healthcare interventions in resource-limited settings remains challenging. This exploratory qualitative study describes social and institutional factors to consider prior to nasal high flow deployment in a middle-income country. METHODS: Researchers conducted eight nursing focus groups and four semi-structured physician interviews at Instituto Nacional de Salud del Niño in Lima, Peru. Participants were identified via purposive sampling. Data were transcribed, translated and coded using a rigorous and iterative process. Pertinent themes were identified using thematic analysis with Dedoose software. RESULTS: Thirty-nine nurses and four physicians participated in focus groups and interviews, respectively. Participants identified five major factors: (i) Adequate training, (ii) Clinician buy-in, (iii) Resource-limited setting, (iv) Local social context and (v) Organizational change management. To create buy-in, physicians and nurses emphasised the need to recognise benefit of the intervention and agree with clinical practice standardization. Physicians and nurses described barriers specific to resource-limited settings, including unreliable supply chain, whereas nurses shared concerns about increasing workload and physician-nurse social hierarchy. Participants recognised the importance of team commitment and ongoing interdisciplinary communication for sustainability. CONCLUSION: While some factors to consider prior to deployment of healthcare technology are universal, resource-limited settings have unique implementation barriers.

Collaborative Implementation Strategy for Newborn Resuscitation and Essential Care Training in the Dominican Republic.

BACKGROUND: Neonatal mortality accounts for 45% of under-5 mortality worldwide, with 98% of newborn deaths occurring in developing countries. The Dominican Republic (DR) demonstrates one of the highest neonatal mortality rates in Latin America despite broad access to care. Strategies to support professional capacity building and strengthen the local health care system are needed to improve neonatal outcomes in the DR. RATIONALE: Helping babies breathe (HBB) and essential care for every baby (ECEB) are evidence-based newborn resuscitation and essential care training programs that have been shown to improve providers' confidence, knowledge, and clinical skills. Lack of professional support and infrequent resuscitation skills practice are commonly cited as barriers to skill retention after HBB training, while establishment of program mentoring and regular skills refreshers are associated with retention of clinical knowledge and skills and improved clinical performance and outcomes. Global partnerships to facilitate implementation of a comprehensive newborn resuscitation and essential care training program with ongoing clinical and program mentorship in the DR should have a lasting impact on workforce capacity, quality of care, and clinical outcomes. METHODS: A multidisciplinary, international group of clinicians partnered with the Ministry of Health to design and implement a comprehensive newborn health initiative in the DR. A train-the-trainer model structured the regional rollout of a combined HBB/ECEB program with integrated quality improvement (QI) initiatives and systems for ongoing program monitoring, reinforcement, and mentorship. Cognitive, affective, behavioral, and clinical outcomes are being measured. RESULTS: Seventeen local champions representing six hospitals participated in the HBB/ECEB master trainer course and design of a QI tool for site-specific clinical performance monitoring. One hundred seventy-eight and 171 providers participated in HBB and ECEB courses, respectively, at pilot sites during the following year. Participants completed prior training need assessment, pre-/post-knowledge assessments and course evaluations. Program mentorship and monitoring of continuing education and clinical performance are ongoing. The Ministry of Health has assumed responsibility for program sustainability and current scale-up, including integration of maternal resuscitation training. CONCLUSION: International partnerships facilitated the collaborative implementation of scalable, locally sustainable newborn resuscitation and essential care training in the DR, mobilizing local resources and empowering the workforce to capably pursue improved care of an exceedingly vulnerable community.

Performance of a mathematical model to forecast lives saved from HIV treatment expansion in resource-limited settings.

BACKGROUND: International guidelines recommend HIV treatment expansion in resource-limited settings, but funding availability is uncertain. We evaluated the performance of a model that forecasts lives saved through continued HIV treatment expansion in Haiti. METHODS: We developed a computer-based, mathematical model of HIV disease and used incidence density analysis of patient-level Haitian data to derive model parameters for HIV disease progression. We assessed the internal validity of model predictions and internally calibrated model inputs when model predictions did not fit the patient-level data. We then derived uncertain model inputs related to diagnosis and linkage to care, pretreatment retention, and enrollment on HIV treatment through an external calibration process that selected input values by comparing model predictions to Haitian population-level data. Model performance was measured by fit to event-free survival (patient level) and number receiving HIV treatment over time (population level). RESULTS: For a cohort of newly HIV-infected individuals with no access to HIV treatment, the model predicts median AIDS-free survival of 9.0 years precalibration and 6.6 years postcalibration v. 5.8 years (95% confidence interval, 5.1-7.0) from the patient-level data. After internal validation and calibration, 16 of 17 event-free survival measures (94%) had a mean percentage deviation between model predictions and the empiric data of <6%. After external calibration, the percentage deviation between model predictions and population-level data on the number on HIV treatment was <1% over time. CONCLUSIONS: Validation and calibration resulted in a good-fitting model appropriate for health policy decision making. Using local data in a policy model-building process is feasible in resource-limited settings.