Low- To Middle-income Countries Research Articles

SARS-CoV-2 Detection and COVID-19 Diagnosis: A Bird's Eye View.

The battle against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) is continued worldwide by administering firsttime emergency authorized novel mRNA-based and conventional vector-antigen-based antiCOVID-19 vaccines to prevent further transmission of the virus as well as to reduce the severe respiratory complications of the infection in infected individuals. However; the emergence of numerous SARS-CoV-2 variants is of concern, and the identification of certain breakthrough and reinfection cases in vaccinated individuals as well as new cases soaring in some low-to-middle income countries (LMICs) and even in some resource-replete nations have raised concerns that only vaccine jabs would not be sufficient to control and vanquishing the pandemic. Lack of screening for asymptomatic COVID-19-infected subjects and inefficient management of diagnosed COVID-19 infections also pose some concerns and the need to fill the gaps among policies and strategies to reduce the pandemic in hospitals, healthcare services, and the general community. For this purpose, the development and deployment of rapid screening and diagnostic procedures are prerequisites in premises with high infection rates as well as to screen mass unaffected COVID-19 populations. Novel methods of variant identification and genome surveillance studies would be an asset to minimize virus transmission and infection severity. The proposition of this pragmatic review explores current paradigms for the screening of SARS-CoV-2 variants, identification, and diagnosis of COVID-19 infection, and insights into the late-stage development of new methods to better understand virus super spread variants and genome surveillance studies to predict pandemic trajectories.

Neuromuscular disease genetics in under-represented populations: increasing data diversity.

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.

Challenges and opportunities of molecular epidemiology: using omics to address complex One Health issues in tropical settings

The molecular biology tools available since the early 1970s have been crucial to the development of molecular epidemiology as an important branch of public health, and are used for the identification of host genetic and environmental factors associated with both communicable (CDs) and non-communicable diseases (NCDs) across human and animal populations. Molecular epidemiology has significantly contributed to the understanding of etiological agents, disease distribution, and how to track outbreaks, as well as to prevention and control measures against tropical infectious diseases. However, there have been significant limitations compromising the successful application of molecular epidemiology in low-to-middle income countries (LMICs) to address complex issues at the animal–human–environment interface. Recent advances in our capacity to generate information by means of high-throughput DNA genomic sequencing, transcriptomics, and metabolomics have allowed these tools to become accessible at ever-lower costs. Furthermore, recently emerged omics fields such as lipidomics are improving our insights into molecular epidemiology by measuring lipid phenotypes that gauge environmental and genetic factors in large epidemiological studies. In parallel, the development of bioinformatic tools has revolutionized the utility of omics, providing novel perspectives to better characterize pools of biological molecules and translate them into the structure, function, and dynamics of organisms. Unfortunately, the use of such powerful tools has not been optimal for a One Health approach to both CDs and NCDs, particularly in low-resource tropical settings. The aim of this review is to present the fundamentals of omics tools and their potential use in molecular epidemiology, and to critically discuss the impact of omics on the evolving One Health dimension applied to tropical diseases. We use Ethiopia and Brazil as model systems to illustrate existing gaps and opportunities, while also addressing global applications. Moreover, we also discuss perspectives on exploring omics based molecular epidemiology in the context of One Health as a crucial approach to preventing and mitigating the burden of CDs and NCDs at the interface of human health, animal health, and the environment. This review shows that building capacity in the tropical regions is crucial to establishing equitable global health.

An absence of evidence breeds contempt: A qualitative study of health system stakeholder perceptions of the quality of medicines available in Senegal.

Poor-quality medicines pose a significant challenge for health systems in low- to middle-income countries (LMICs),with recent deaths in multiple countries following ingestion of substandard cough syrups emphasising the need for quality-assurance of medicines in our increasingly interconnected global markets. Research also suggests that the source (country of manufacture) and type of medicine (generic/brand) are perceived to be associated with medicine quality. This study explores perceptions of medicines quality among national stakeholders of a medicines quality assurance system (MQAS) in sub-Saharan Africa. Through semi-structured interviews (n = 29) with managers from organisations responsible for the MQAS, public-sector doctors and nurses, and regulated private-sector pharmacists in three urban centres in Senegal in 2013. A thematic approach to analysis was undertaken with themes organised under three main categories, the source of drugs, the type of medicine, and medicines storage. A key emerging theme was the perception of the inferior quality of generic medicines, especially those produced in Asia and Africa, as they were lower in cost and thus believed to be less effective in alleviating symptoms than their brand versions. Medicines in Senegal's less regulated (informal) street markets were also thought to be of poor-quality as they were not subjected to national regulatory processes or stored appropriately, resulting in exposure to direct sunlight and high temperatures. In contrast, the interviewees expressed confidence in medicines quality within the regulated sectors (public and private retail pharmacies) attributed to stringent national medicines regulation, secure medicines supply chains and adequate technical capacity to survey and analyse for medicines quality. Also, the views expressed typically described a medicine's quality in terms of its effectiveness in alleviating the symptoms of ill health (efficacy of a medicine).These perceptions may have implications for developing national medicines policy, the procurement and supply of affordable medicines and consumers' decision-making when purchasing medicines. Indeed, a proclivity for supplying and purchasing more expensive brand medicines may act as a barrier to accessing essential medicines.

An international, prospective observational study on traumatic brain injury epidemiology study protocol: GEO-TBI: Incidence.

The epidemiology of traumatic brain injury (TBI) is unclear - it is estimated to affect 27-69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment. The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research. Multi-centre, international, registry-based, prospective cohort study. Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence. All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol. Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

Large-Scale Remote Training for Medical Physicists to improve Intensity-Modulated Radiation Therapy/Volumetric Modulated Arc Therapy in Low and Middle-Income Countries

Background High-quality intensity-modulated radiation therapy (IMRT) / volumetric modulated arc therapy (VMAT) is necessary to drive positive patient outcomes, yet gaps in staff training hinder its implementation in low-to-middle-income countries (LMICs). We aimed to evaluate a large-scale remote training curriculum for medical physicists and clinicians with existing IMRT capabilities in LMICs. Methods We conducted a virtual course on "Mastering IMRT/VMAT for Medical Physicists." The program comprised 15 weekly 1-hour live video conferencing sessions with interactive didactics and case-based learning taught by expert volunteer medical physicists. Enrollment was free and open to LMICs globally for 1 month on a first-come basis with a limit of 500, plus few exceptions. We distributed an electronic survey before and after the course to assess participants' confidence (on a 1-5 Likert scale) in 7 domains of IMRT/VMAT and knowledge through 11 multiple choice questions. We tracked attendance hours for course credit. We also gave participants the option to develop an IMRT or VMAT plan for identical, standardized bilateral Head & Neck cancer cases before and after the course, earning additional credit hours upon submission. After the program, 8 medical physics volunteers independently graded treatment plans using a rubric for qualitative domains. Furthermore, we gave plans a quantitative score using an automated scorecard with dose-volume histogram metrics. We utilized the ProKnow DS platform for file-sharing and grading. Two-tailed paired t-test analyses compared pre- vs. post-course survey and treatment planning scores for medical physicists, medical physics residents, and dosimetrists. Results A total of 514 participants from 63 countries and 342 unique centers enrolled, including 448 (87.1%) medical physicists, 49 (9.5%) medical physics residents, 5 (1%) dosimetrists, and 12 (2.4%) other clinicians. Of these, 240 medical physicists, medical physics residents, and dosimetrists responded to both the pre- and post-course surveys. Mean confidence scores increased from 3.00/5 (SD: 1.04) to 3.80/5 (0.87) (p < 0.001). Knowledge scores improved from 4.16/11 (SD: 1.77) to 5.98/11 (SD: 2.11) (p < 0.001). Additionally, 33 participants completed both the pre-course and post-course treatment planning assignments. Automated scorecard performance significantly improved from 12.64/25 (SD: 7.50) to 17.74/25 (SD: 6.74) (p = 0.0068). Grading rubric scores did not significantly change, from 9.15/14 (SD: 3.33) to 9.76/14 (SD: 2.65) (p = 0.4). Discussion A virtual curriculum on IMRT/VMAT improved participant's treatment planning performance, knowledge, and confidence. A distributed team of volunteers enabled this to be a low-cost, scalable intervention to help clinics in LMICs. High-quality intensity-modulated radiation therapy (IMRT) / volumetric modulated arc therapy (VMAT) is necessary to drive positive patient outcomes, yet gaps in staff training hinder its implementation in low-to-middle-income countries (LMICs). We aimed to evaluate a large-scale remote training curriculum for medical physicists and clinicians with existing IMRT capabilities in LMICs. We conducted a virtual course on "Mastering IMRT/VMAT for Medical Physicists." The program comprised 15 weekly 1-hour live video conferencing sessions with interactive didactics and case-based learning taught by expert volunteer medical physicists. Enrollment was free and open to LMICs globally for 1 month on a first-come basis with a limit of 500, plus few exceptions. We distributed an electronic survey before and after the course to assess participants' confidence (on a 1-5 Likert scale) in 7 domains of IMRT/VMAT and knowledge through 11 multiple choice questions. We tracked attendance hours for course credit. We also gave participants the option to develop an IMRT or VMAT plan for identical, standardized bilateral Head & Neck cancer cases before and after the course, earning additional credit hours upon submission. After the program, 8 medical physics volunteers independently graded treatment plans using a rubric for qualitative domains. Furthermore, we gave plans a quantitative score using an automated scorecard with dose-volume histogram metrics. We utilized the ProKnow DS platform for file-sharing and grading. Two-tailed paired t-test analyses compared pre- vs. post-course survey and treatment planning scores for medical physicists, medical physics residents, and dosimetrists. A total of 514 participants from 63 countries and 342 unique centers enrolled, including 448 (87.1%) medical physicists, 49 (9.5%) medical physics residents, 5 (1%) dosimetrists, and 12 (2.4%) other clinicians. Of these, 240 medical physicists, medical physics residents, and dosimetrists responded to both the pre- and post-course surveys. Mean confidence scores increased from 3.00/5 (SD: 1.04) to 3.80/5 (0.87) (p < 0.001). Knowledge scores improved from 4.16/11 (SD: 1.77) to 5.98/11 (SD: 2.11) (p < 0.001). Additionally, 33 participants completed both the pre-course and post-course treatment planning assignments. Automated scorecard performance significantly improved from 12.64/25 (SD: 7.50) to 17.74/25 (SD: 6.74) (p = 0.0068). Grading rubric scores did not significantly change, from 9.15/14 (SD: 3.33) to 9.76/14 (SD: 2.65) (p = 0.4). A virtual curriculum on IMRT/VMAT improved participant's treatment planning performance, knowledge, and confidence. A distributed team of volunteers enabled this to be a low-cost, scalable intervention to help clinics in LMICs.

A pilot curriculum to transition from 2D to 3D image-guided brachytherapy: A preliminary needs assessment.

11039 Background: Gynecologic cancers are one of the leading causes of death globally with a disproportionate burden of disease found in low to middle income countries (LMIC). Brachytherapy is often a necessary component in treatment management as it can deliver a high dose of radiation to the tumor while employing a steep dose fall off that spares the adjacent organs at risk. With 3D image guided brachytherapy (3D-IGBT), treatment planning utilizes volumetric images with the target volume and organs at risk contoured, reducing toxicity and improving outcomes when compared to 2D planar imaging. Despite this advantage, only a limited number of LMIC centers perform 3D-IGBT. Transitioning to 3D-IGBT requires considerable planning, resources, and training. The development of a multidisciplinary, computer-based training program to facilitate the transition to 3D-IGBT was identified as a priority of multiple Radiation Oncology departments in Nigeria. The aim of this preliminary needs assessment was to identify the necessary resources and anticipated barriers to development of a pilot training curriculum for the transition to 3D-IGBT. Methods: An anonymous, 16-question online survey was distributed to clinicians, physicists, radiation therapists, and staff within a Radiation Oncology department of a teaching hospital in Lagos, Nigeria. Results: In January 2023, 53 respondents completed the survey. Of the respondents, 36.5% were female and 63.5% were male. The average age was 37.5 (SD = 7.8). Clinical experience ranged from &lt; 5 years (52.6%), 6-10 years (9.4%), to &gt; 10 years (30.2%). Respondents included radiation therapists (28.8%), clinicians (27%), nurses (23.1%), and physicists (15.4%). Multiple barriers to implementation of 3D-IGBT were identified including lack of training (79.2%) or experience (58.5%), lack of financial investment (50.9%), and anticipated repair/replacement of equipment (41.5%). A majority of respondents identified staff training/education (66%) as critical to delivering 3D-IGBT. When asked about the curriculum components needed, most respondents believed that it should include plan review (96.2%), contour review (94.3%), and peer review of clinical cases (92.5%). Conclusions: Various areas of potential need were identified through this preliminary needs assessment, most notably, staff training. These findings suggest that there is an unmet need to further develop and implement a structured didactic and skills-based curriculum to transition from 2D to 3D-IGBT at these institutions. Identified focus areas including contour, peer, and plan review will help guide the refinement of this curriculum. These findings are an important first step in delivery of safe and efficacious 3D-IGBT in an LMIC.

A South African central hospital's experience with malignant colorectal obstruction.

The spectrum and outcome of colorectal cancer (CRC) presenting with obstruction is not well studied in low- to middle-income countries (LMIC) and could have implications for health policy. This study aimed to address this deficit in an LMIC setting. A retrospective analysis was conducted of patients with large bowel obstruction, during the period 2000-2019 from the prospective Inkosi Albert Luthuli Central Hospital (IALCH) CRC registry data. Data analysed included the site of CRC, tumour differentiation, management of patients with obstructive CRC, resection margins post resection, oncological management and reasons for failure to receive oncological therapy. Patient follow-up and recurrence were recorded. Malignant obstruction from CRC occurred in 510 patients (20% of the CRC registry). Median age at presentation was 57 years (IQR 48-67). One hundred and seventy-six (34.5%) and 135 (26.5%) had stage III and IV disease respectively. Moderately differentiated cancer was seen in 335 (65.6%). Management was resection (370; 72.5%), diverting colostomy (123; 24.1%) and stent insertion (55; 10.8%). Twenty-one patients (5.7%) had positive resection margins. Recurrence occurred in 34 patients (6.7%), all of whom had initially undergone resection, giving a recurrence rate of 9.8% in those receiving surgery. Median disease-free interval for patients developing recurrence was 21 months (IQR 12-32). One in five patients with CRC presented with obstruction. These patients were younger than in high incomecountry (HIC) series. Over 70% underwent resection. Stomas were used twice as frequently as stents to relieve the obstruction, a finding that is the reverse of that in HICs.

Capturing deprived areas using unsupervised machine learning and open data: a case study in São Paulo, Brazil

ABSTRACT Managing the rapid growth of deprived areas (commonly known as slums, informal settlements, etc.) in cities of Low- to Middle-Income Countries (LMICs) demands detailed and consistent information that is often unavailable. Recent Earth Observation (EO) mapping approaches with supervised classification models overlook the diversity of deprived areas and require resource-intensive training sets. In this study, we analyse the potential of unsupervised machine learning (ML) models to capture intra-urban diversity of deprived areas in São Paulo, using solely open geodata. We provide a workflow of characterising deprivation at a city scale with a disaggregated approach, offering scalability and transferability potential. First, we extract a pool of spatial features from open geospatial datasets to characterise the morphological and environmental conditions of the study area. After input preparation, we train and optimise a k-means model, including a coupled feature importance tool. Four cluster types emerged with different deprivation aspects such as higher and lower accessibility to services and infrastructure, sparser and denser occupation; regular and complex morphology; flat and steep terrain. This alternative methodology to capture diversity of deprived areas with open EO-based features can inform locally targeted, thus more efficient, urban policies and interventions.

Understanding Filipino Jail Detainees’ Self-Harming Behavior: A Grounded Theory Explortion

This grounded theory exploration aims to advance a theory that explains the development of self harming behavior (SHB) among a select group of Filipino jail detainees. Using the Classical Glaserian Grounded Theory procedure, a novel process that describes Filipino Detainees’ Phases of Self Harming Behavior (gravitational, transformational, interventional and dispositional) emerged. Findings from this inquiry may serve as bases for policy-making and intervention programs that inform the triggers and preventative factors associated with SHB in the penal setting. These may further raise awareness of forensic mental health and human rights violations among detainees in flawed justice systems in low-to-middle income countries (LMICs).

Community health worker-led household screening and management of neonatal hyperbilirubinemia in rural Bangladesh: a cluster randomized control trial protocol

Background: Extreme hyperbilirubinemia leading to neurologic disability and death is disproportionately high in low to middle income countries (LMIC) such as Bangladesh, and is largely preventable through timely treatment. Of the estimated 50% of newborns born in LMICs born at home, few receive screening or treatment for hyperbilirubinemia, leading to 6 million newborns per year who need phototherapy treatment for hyperbilirubinemia but are untreated. Household screening and treatment for neonatal hyperbilirubinemia with phototherapy administered by a trained community health worker (CHW) may increase indicated treatment for neonatal hyperbilirubinemia in comparison to the existing care system in Bangladesh. Methods: 530 Bangladeshi women in their 2nd or 3rd trimester of pregnancy from the rural community of Sakhipur, Bangladesh will be recruited for a cluster randomized trial and randomized to the intervention arm — home screening and treatment for neonatal hyperbilirubinemia — or the comparison arm to receive usual care. In the intervention arm, CHWs will provide mothers with two prenatal visits, visit newborns by 2 days of age and then daily for 3 days to measure transcutaneous bilirubin (TcB) and monitor clinical danger signs. Newborns without danger signs but with a TcB above the treatment threshold &lt;15 mg/dL will be treated with light-emitting diode (LED) phototherapy at home. Newborns with danger signs or TcB &gt;15 mg/dL will be referred to a hospital for treatment. Treatment rates for neonatal hyperbilirubinemia in each arm will be compared. Conclusion: This study will evaluate the effectiveness of CHW-led home phototherapy to increase neonatal hyperbilirubinemia treatment rates in rural Bangladesh. LMICs are expanding access to postnatal care by using CHWs, and our work will give CHWs a curative treatment option for neonatal hyperbilirubinemia. Similar projects in other LMICs can be pursued to dramatically extend healthcare access to vulnerable newborns with hyperbilirubinemia.

Exploring resistomes and microbiomes in pilot-scale microalgae-bacteria wastewater treatment systems for use in low-resource settings

Antibiotic resistance genes (ARGs) released into the environment are an emerging human and environmental health concern, including ARGs spread in wastewater treatment effluents. In low-to-middle income countries (LMICs), an alternate wastewater treatment option instead of conventional systems are low-energy, high-rate algal ponds (HRAP) that use microalgae-bacteria aggregates (MABA) for waste degradation. Here we studied the robustness of ARG removal in MABA-based pilot-scale outdoor systems for 140 days of continuous operation. The HRAP system successfully removed 73 to 88 % chemical oxygen demand and up to 97.4 % ammonia, with aggregate size increasing over operating time. Fourteen ARG classes were identified in the HRAP influent, MABA, and effluent using metagenomics, with the HRAP process reducing total ARG abundances by up to 5-fold from influent to effluent. Parallel qPCR analyses showed the HRAP system significantly reduced exemplar ARGs (p < 0.05), with 1.2 to 4.9, 2.7 to 6.3, 0 to 1.5, and 1.2 to 4.8 log-removals for sul1, tetQ, blaKPC, and intl1 genes, respectively. Sequencing of influent, effluent and MABAs samples showed associated microbial communities differed significantly, with influent communities by Enterobacteriales (clinically relevant ARGs carrying bacteria), which were less evident in MABA and effluent. In this sense, such bacteria might be excluded from MABA due to their good settling properties and the presence of antimicrobial peptides. Microalgae-bacteria treatment systems steadily reduced ARGs from wastewater during operation time, using sunlight as the energetic driver, making them ideal for use in LMIC wastewater treatment applications.

Social Isolation, Loneliness, and Cognitive Performance in Older Adults: Evidence From the ELSI-Brazil Study

The association between social isolation and cognitive performance has been less investigated in low-to-middle-income countries (LMIC) and the presence of depression as a moderator on this association has not been examined. The authors examined the associations of social isolation and perceived loneliness with cognitive performance in the Brazilian Longitudinal Study of Aging. In this cross-sectional analysis, social isolation was evaluated by a composite score including marital status, social contact, and social support. The dependent variable was global cognitive performance, which considered memory, verbal fluency, and temporal orientation tests. Linear and logistic regressions were adjusted for sociodemographic and clinical variables. The authors added interaction terms of depressive symptoms with social isolation and loneliness to examine whether depression, measured through the Center for Epidemiologic Studies-Depression Scale, modified these associations. Among 6,986 participants (mean age=62.1 ± 9.2 years), higher levels of social connections were associated with better global cognitive performance (B=0.02, 95%CI: 0.02; 0.04). Perceived loneliness was associated with worse cognition (B=-0.26, 95%CI=-0.34; -0.18). Interactions of depressive symptoms with social connections scores were found on memory z-score and with loneliness on global and memory z-scores, suggesting a weaker association between social isolation or loneliness and cognition among those with depressive symptoms. In a large sample from an LMIC, social isolation and loneliness were associated with worse cognitive performance. Surprisingly, depressive symptoms decrease the strength of these associations. Future longitudinal studies are important to assess the direction of the association between social isolation and cognitive performance.

Ethical Challenges in Ventilator Allocation during COVID-19 Crisis Level Care in a Low-Resource Setting, Subtitle: Who gets the last ventilator?

Health crisis-level situations, such as the COVID-19 pandemic, has brought the challenge of ethical allocation of scarce life-saving resources (e.g. mechanical ventilator) in the face of sudden demand by critically ill patients. The problem is heightened in low-resource countries with limited number of ventilators. This article analyzes the ethical challenges in mechanical ventilator allocation during the COVID-19 pandemic in low to middle-income countries (LMIC), such as the Philippines. Among the three rationing principles of substantive justice, maximizing the benefit of the limited and vital resource for the most in society is acknowledged by majority of public health experts to be the prevailing principle to guide resource allocation. In low-resource settings, such as low to middleincome countries, with pre-existing health inequities in health care resources and absence of legal framework supporting advance directives, the principle of maximizing benefit is tempered with proportionate need focused on the vulnerable population sectors that may have suffered from inequities even before the COVID-19 crisis. The procedural aspect of the allocation decision formulation and implementation should ensure community engagement with solidarity, openness, veracity, transparency and accountability as values to be consistently manifested. Painful decisions will still be made at the frontline on who will receive the life-saving ventilator or not, but, as long as there is transparency and community participation in these decisions, then the decision-makers will be able to live with these decisions without undue burden on their conscience.

Characterization of drug‐related problems and evaluation of pharmacist interventions in the cardiovascular intensive care settings in Thailand

AbstractIntroductionData regarding drug‐related problems (DRPs) and pharmacist's role in the cardiovascular intensive care units (CICU) from low‐ to middle‐income countries (LMIC) are limited.ObjectiveThe study aimed to characterize the DRP and interventions provided by clinical pharmacists in the CICU settings.MethodA retrospective, cross‐sectional study was conducted in patients admitted to CICU of a tertiary‐care hospital in Thailand during January 2021 to March 2022 was performed. Data were collected from patient's medical records and pharmacy service records. DRPs were categorized according to the Pharmaceutical Care Network Europe classification. Two board‐certified pharmacotherapy specialists, pharmacy residents, and trained clinical pharmacists staffed the units 5 days a week. The pharmacist team conducted a medication review and provided interventions to the cardiology team either verbally during the ward round or in writing, as appropriate. Pharmacist interventions were categorized into two groups including retrospective intervention (interventions made to resolve DRPs after an order was made) and prospective interventions (interventions made prior to ordering process). Outcome measures were (1) number of DRPs identified; (2) category of DRPs; (3) number interventions; and (4) acceptance rate of interventions by the medical team.ResultsAmong 576 patients admitted to the CICU, 345 DRPs were identified in 203 patients. The pharmacist team provided a total of 790 interventions including 345 retrospective interventions to resolve DRPs and 445 prospective interventions to guide medication use prior to the ordering process. The most frequent intervention was related to dosage adjustment, drug administration, adding drugs for existing conditions, and suggesting laboratory monitoring. The acceptance rate of the pharmacist intervention was 97.4%, most of which led to changes in drug therapy.ConclusionDRPs in CICU settings are common. Trained clinical pharmacists can effectively resolve DRPs and provide recommendations to improve quality of care through both clinical and distribution functions.

Killer to cure: Expression and production costs calculation of tobacco plant-made cancer-immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have achieved huge clinical success. However, many still have limited response rates, and are prohibitively costly. There is a need for effective and affordable ICIs, as well as local manufacturing capacity to improve accessibility, especially to low-to-middle income countries (LMICs). Here, we have successfully expressed three key ICIs (anti-PD-1 Nivolumab, anti-NKG2A Monalizumab, and anti-LAG-3 Relatimab) transiently in Nicotiana benthamiana and Nicotiana tabacum plants. The ICIs were expressed with a combination of different Fc regions and glycosylation profiles. They were characterized in terms of protein accumulation levels, target cell binding, binding to human neonatal Fc receptors (hFcRn), human complement component C1q (hC1q) and various Fcγ receptors, as well as protein recovery during purification at 100 mg- and kg-scale. It was found that all ICIs bound to the expected target cells. Furthermore, the recovery during purification, as well as Fcγ receptor binding, can be altered depending on the Fc region used and the glycosylation profiles. This opens the possibility of using these two parameters to fine-tune the ICIs for desired effector functions. A scenario-based production cost model was also generated based on two production scenarios in hypothetical high- and low-income countries. We have shown that the product accumulation and recovery of plant production platforms were as competitive as mammalian cell-based platforms. This highlights the potential of plants to deliver ICIs that are more affordable and accessible to a widespread market, including LMICs.

International Health Electives: defining learning outcomes for a unique experience

BackgroundAn International Health Elective (IHE) can be a unique learning experience for students. However, it has proven difficult to clearly define learning outcomes that capture the complexity of an IHE and are aligned with future professional performance. This study aimed to further define learning outcomes for IHEs in low- to middle-income countries (LMIC) from a student perspective.MethodsWe conducted a deductive analysis of pre-departure and post-elective reflective reports of fifth-year medical students who participated in an IHE as part of their program. This provided possible learning objectives that were further explored in semi-structured individual interviews with medical students who had recently returned from an IHE.ResultsWe analyzed 33 reports of students participating in an IHE from 2017–2019 and held 19 interviews. Thematic analysis revealed 9 themes: developing intercultural competence, developing appreciation for differences in health care delivery systems, understanding international health, understanding the global burden of disease, developing a career perspective, developing clinical skills in resource low settings, becoming cost conscious, developing social responsibility and self-actualization.ConclusionsWe identified 9 learning outcomes that are directly and indirectly related to clinical practice. They add to the on-going discourse on the benefits of IHEs. These outcomes can be further developed by investigating the perspectives of home and host supervisors and educationalists, while taking the local context into account. Follow-up studies can evaluate to what extend these outcomes are achieve during an IHE.

Predicting indirect effects of rotavirus vaccination programs on rotavirus mortality among children in 112 countries

Rotavirus is a leading cause of diarrhea deaths in children, particularly in low-to-middle income countries (LMICs). Licensed rotavirus vaccines provide strong direct protection, but their indirect effect—the protection due to reduced transmission—is not fully understood. We aimed to quantify the population-level effects of rotavirus vaccination and identify factors that drive indirect protection. We used an SIR-like transmission model to estimate the indirect effects of vaccination on rotavirus deaths in 112 LMICs. We performed a regression analysis to identify predictors of indirect effect magnitude (linear regression) and the occurrence of negative indirect effects (logistic regression). Indirect effects contributed to vaccine impacts in all regions, with effect sizes 8-years post-vaccine introduction ranging from 16.9% in the WHO European region to 1.0% in the Western Pacific region. Indirect effect estimates were higher in countries with higher under-5 mortality, higher vaccine coverage, and lower birth rates. Of the 112 countries analyzed, 18 (16%) had at least 1 year with a predicted negative indirect effect. Negative indirect effects were more common in countries with higher birth rate, lower under-5 mortality and lower vaccine coverage. Rotavirus vaccination may have a larger impact than would be expected from direct effects alone, but the impact of these indirect effects is expected to vary by country.

Abstract Number ‐ 109: Mechanical Thrombectomy Hands‐on Skill Workshop for MT2020+ in the Caribbean

Introduction While mechanical thrombectomy (MT) is proven to be lifesaving and disability‐sparing, there remains disparities in access in low‐ to middle‐income countries (LTMICs), including the Caribbean. We hypothesized that team‐oriented MT workshops would improve MT skills and change practice patterns for MT services in this region. Methods We designed a 22‐hour MT workshop which was conducted as two identical events: in English (Jamaica, January 2022), and in Spanish (Dominican Republic, May 2022). The workshops included neurointerventional teams (practicing neurointerventionalists, neuroIR nurses and technicians), focused on patient selection, acutetreatment and post‐MT care of patients with stroke due to large vessel occlusion. MT skills, procedure duration and potential harmful techniques were recorded before and after by independent evaluators utilizing flow models under fluoroscopy. Overall course evaluation was performed. Press conferences were included to raise stroke awareness and emphasize the importance of early stroke presentation. Results Twenty‐two physicians and their teams from eight countries across the Caribbean completed the didactic and hands‐on training. Eighteen groups completed both pre‐ and post‐MT hands‐on testing and were included in the final analysis. Pre‐ and post‐course hands‐on assessment showed that the course effectively reduced the total time to complete a simulated MT procedure from 36.5 to 21.1 min (Figure 1; p&lt; 1.0×10‐7). All groups showed an improvement in measures of good MT techniques, which resulted in a 39% improvement in complete reperfusion (8/18 groups achieved a TICI 3 score on pre‐course vs. 15/18 groups on post‐course). There was a significant reduction in total potentially dangerous maneuvers by 82% (p&lt; 0.002), with 12/18 groups performing an average 2 dangerous maneuvers on pre‐course simulation vs. only 4/18 groups performing an average 1 dangerous maneuver after completing the course. Participants also demonstrated increased knowledge of stroke treatment and stroke system of care. Utilizing a basic stroke knowledge questionnaire, we found 28% respondents did not have a baseline passing grade vs 100% passed after the workshop. The average post‐workshop knowledge score was 80%. Universally the workshop was rated as very satisfactory and likely to change practice in 93% of the Dominican Republic participants and 75% among Jamaican participants. Conclusions A team‐based approach to MT training is novel, effective in reducing time to reperfusion and harmful techniques, and improves competencies. Team members independently demonstrated advanced stroke learning post‐training. To our knowledge, this is the first workshop of its kind; it is feasible, practice‐changing and creates a pathway for increasing access to MT in LTMICs.

Predictors of Survival in Patients with Metastatic Brain Tumors: Experience from a Low-to-Middle-Income Country.

Objective The interplay of static factors and their effect on metastatic brain tumor survival, especially in low-to-middle-income countries (LMICs), has been rarely studied. To audit our experience, and explore novel survival predictors, we performed a retrospective analysis of brain metastases (BM) patients at Shaukat Khanum Memorial Cancer Hospital (SKMCH), Pakistan. Materials and Methods A retrospective review was conducted of consecutive patients who presented with BM between September 2014 and September 2019 at SKMCH. Patients with incomplete records were excluded. Statistical Analysis SPSS (v.25 IBM, Armonk, New York, United States) was used to collect and analyze data via Cox-Regression and Kaplan-Meier curves. Results One-hundred patients (mean age 45.89 years) with confirmed BM were studied. Breast cancer was the commonest primary tumor. Median overall survival (OS) was 6.7 months, while the median progression-free survival (PFS) was 6 months. Age ( p = 0.001), gender ( p = 0.002), Eastern Cooperative Oncology Group ( p < 0.05), anatomical site ( p = 0.002), herniation ( p < 0.05), midline shift ( p = 0.002), treatment strategies ( p < 0.05), and postoperative complications (p < 0.05) significantly impacted OS, with significantly poor prognosis seen with extremes of age, male gender (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.3-3.1; p = 0.003), leptomeningeal lesions (HR: 5.7; 95% CI: 1.1-29.7; p = 0.037), and patients presenting with uncal herniation (HR: 3.5; 95% CI: 1.9-6.3; p < 0.05). Frontal lobe lesions had a significantly better OS (HR: 0.5; 95% CI: 0.2-1.0; p = 0.049) and PFS (HR: 0.08; 95% CI: 0.02-0.42; p = 0.003). Conclusion BM has grim prognoses, with comparable survival indices between developed countries and LMICs. Early identification of both primary malignancy and metastatic lesions, followed by judicious management, is likely to significantly improve survival.