Low-cost transcriptional diagnostic to accurately categorize lymphomas in low- and middle-income countries

Abstract Inadequate diagnostics compromise cancer care across lower- and middle-income countries (LMICs). We hypothesized that an inexpensive gene expression assay using paraffin-embedded biopsy specimens from LMICs could distinguish lymphoma subtypes without pathologist input. We reviewed all biopsy specimens obtained at the Instituto de Cancerología y Hospital Dr. Bernardo Del Valle in Guatemala City between 2006 and 2018 for suspicion of lymphoma. Diagnoses were established based on the World Health Organization classification and then binned into 9 categories: nonmalignant, aggressive B-cell, diffuse large B-cell, follicular, Hodgkin, mantle cell, marginal zone, natural killer/T-cell, or mature T-cell lymphoma. We established a chemical ligation probe-based assay (CLPA) that quantifies expression of 37 genes by capillary electrophoresis with reagent/consumable cost of approximately $10/sample. To assign bins based on gene expression, 13 models were evaluated as candidate base learners, and class probabilities from each model were then used as predictors in an extreme gradient boosting super learner. Cases with call probabilities < 60% were classified as indeterminate. Four (2%) of 194 biopsy specimens in storage <3 years experienced assay failure. Diagnostic samples were divided into 70% (n = 397) training and 30% (n = 163) validation cohorts. Overall accuracy for the validation cohort was 86% (95% confidence interval [CI]: 80%-91%). After excluding 28 (17%) indeterminate calls, accuracy increased to 94% (95% CI: 89%-97%). Concordance was 97% for a set of high-probability calls (n = 37) assayed by CLPA in both the United States and Guatemala. Accuracy for a cohort of relapsed/refractory biopsy specimens (n = 39) was 79% and 88%, respectively, after excluding indeterminate cases. Machine-learning analysis of gene expression accurately classifies paraffin-embedded lymphoma biopsy specimens and could transform diagnosis in LMICs.

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COVID-19 therapeutics for low- and middle-income countries: a review of re-purposed candidate agents with potential for near-term use and impact

10.1101/2021.03.22.21253621 ◽

2021 ◽

Author(s):

Daniel Maxwell ◽

Kelly C. Sanders ◽

Oliver Sabot ◽

Ahmad Hachem ◽

Alejandro Llanos-Cuentas ◽

...

Keyword(s):

The United States ◽

World Health ◽

Middle Income ◽

Middle Income Countries ◽

Clinical Trial Registries ◽

Oral Agents ◽

The Us ◽

Near Term ◽

Health Organization ◽

Low And Middle Income

Low- and middle-income countries (LMICs) face significant challenges in the control of COVID-19, given limited resources, especially for inpatient care. In a parallel effort to that for vaccines, the identification of therapeutics that have near-term potential to be available and easily administered is critical. Using the United States, European Union, and World Health Organization clinical trial registries, we reviewed COVID-19 therapeutic agents currently under investigation. The search was limited to oral or potentially oral agents, with at least a putative anti-SARS-CoV-2 virus mechanism, and with at least 3 registered trials. We describe the available evidence regarding agents that met these criteria and additionally discuss the need for additional investment by the global scientific community in large well-coordinated trials of accessible agents and their combinations in LMICs. The search yielded 636, 175, and 930 trials, in the US, EU, and WHO trial registers, respectively. These trials covered 17 oral or potentially oral repurposed agents that are currently used as antimicrobials and immunomodulatory therapeutics and therefore have established safety. The available evidence regarding proposed mechanism of actions, clinical efficacy, and potential limitations is summarized. We also identified the need for large well-coordinated trials of accessible agents and their combinations in LMICs. Several repurposed agents have potential to be safe, available, and easily administrable to treat COVID-19. To prevent COVID-19 from becoming a neglected tropical disease, there is critical need for rapid and coordinated effort in their evaluation and the deployment of those found to be efficacious.

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Caste, religion, and mental health in India

10.31235/osf.io/f3zxb ◽

2019 ◽

Author(s):

Aashish Gupta ◽

Diane Coffey

Keyword(s):

Mental Health ◽

Health Disparities ◽

Population Level ◽

The United States ◽

World Health ◽

Adult Health ◽

Mental Health Disparities ◽

Middle Income ◽

Middle Income Countries ◽

Scheduled Castes

The relationship between mental health and social disadvantage in low and middle income countries is poorly understood. Our study contributes the first population-level analysis of mental health disparities in India, where the two marginalized groups that we study constitute a population larger than that of the United States. Applying two complementary empirical strategies to data on 10,125 adults interviewed by the World Health Organisation's Survey of Global Ageing and Adult Health (WHO-SAGE), we document and standardize gaps in self-reported mental health between the dominant social group (higher caste Hindus) and two marginalized social groups (Scheduled Castes and Muslims). We find that differences in socioeconomic status cannot fully explain the large disparities in mental health that we document, especially for Muslims. Our results highlight the need for research to understand the causes and consequences of mental health disparities in India, and for policies to move beyond redistribution and address discrimination against Scheduled Castes and Muslims.

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Defining Preterm Birth and Stillbirth in the Western Pacific: A Systematic Review

Asia Pacific Journal of Public Health ◽

10.1177/10105395211026099 ◽

2021 ◽

pp. 101053952110260

Author(s):

Mairead Connolly ◽

Laura Phung ◽

Elise Farrington ◽

Michelle J. L. Scoullar ◽

Alyce N. Wilson ◽

...

Keyword(s):

Preterm Birth ◽

National Level ◽

Health Indicators ◽

Western Pacific ◽

World Health ◽

Middle Income ◽

Middle Income Countries ◽

Definition Of ◽

Health Organization ◽

The Impact

Preterm birth and stillbirth are important global perinatal health indicators. Definitions of these indicators can differ between countries, affecting comparability of preterm birth and stillbirth rates across countries. This study aimed to document national-level adherence to World Health Organization (WHO) definitions of preterm birth and stillbirth in the WHO Western Pacific region. A systematic search of government health websites and 4 electronic databases was conducted. Any official report or published study describing the national definition of preterm birth or stillbirth published between 2000 and 2020 was eligible for inclusion. A total of 58 data sources from 21 countries were identified. There was considerable variation in how preterm birth and stillbirth was defined across the region. The most frequently used lower gestational age threshold for viability of preterm birth was 28 weeks gestation (range 20-28 weeks), and stillbirth was most frequently classified from 20 weeks gestation (range 12-28 weeks). High-income countries more frequently used earlier gestational ages for preterm birth and stillbirth compared with low- to middle-income countries. The findings highlight the importance of clear, standardized, internationally comparable definitions for perinatal indicators. Further research is needed to determine the impact on regional preterm birth and stillbirth rates.

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Tuberculosis and Non-Communicable Disease Multimorbidity: An Analysis of the World Health Survey in 48 Low- and Middle-Income Countries

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18052439 ◽

2021 ◽

Vol 18 (5) ◽

pp. 2439

Author(s):

Brendon Stubbs ◽

Kamran Siddiqi ◽

Helen Elsey ◽

Najma Siddiqi ◽

Ruimin Ma ◽

...

Keyword(s):

Health Survey ◽

Low Income ◽

World Health ◽

Low Income Countries ◽

Multivariable Logistic Regression Analysis ◽

World Health Survey ◽

Middle Income ◽

Middle Income Countries ◽

The World ◽

Low And Middle Income

Tuberculosis (TB) is a leading cause of mortality in low- and middle-income countries (LMICs). TB multimorbidity [TB and ≥1 non-communicable diseases (NCDs)] is common, but studies are sparse. Cross-sectional, community-based data including adults from 21 low-income countries and 27 middle-income countries were utilized from the World Health Survey. Associations between 9 NCDs and TB were assessed with multivariable logistic regression analysis. Years lived with disability (YLDs) were calculated using disability weights provided by the 2017 Global Burden of Disease Study. Eight out of 9 NCDs (all except visual impairment) were associated with TB (odds ratio (OR) ranging from 1.38–4.0). Prevalence of self-reported TB increased linearly with increasing numbers of NCDs. Compared to those with no NCDs, those who had 1, 2, 3, 4, and ≥5 NCDs had 2.61 (95% confidence interval (CI) = 2.14–3.22), 4.71 (95%CI = 3.67–6.11), 6.96 (95%CI = 4.95–9.87), 10.59 (95%CI = 7.10–15.80), and 19.89 (95%CI = 11.13–35.52) times higher odds for TB. Among those with TB, the most prevalent combinations of NCDs were angina and depression, followed by angina and arthritis. For people with TB, the YLDs were three times higher than in people without multimorbidity or TB, and a third of the YLDs were attributable to NCDs. Urgent research to understand, prevent and manage NCDs in people with TB in LMICs is needed.

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Effectiveness of Breastfeeding Support Packages in Low- and Middle-Income Countries for Infants under Six Months: A Systematic Review

Nutrients ◽

10.3390/nu13020681 ◽

2021 ◽

Vol 13 (2) ◽

pp. 681

Author(s):

Ritu Rana ◽

Marie McGrath ◽

Ekta Sharma ◽

Paridhi Gupta ◽

Marko Kerac

Keyword(s):

At Risk ◽

Severe Acute Malnutrition ◽

Acute Malnutrition ◽

World Health ◽

Cochrane Library ◽

Breastfeeding Support ◽

Middle Income ◽

Middle Income Countries ◽

Breastfeeding Practices ◽

Low And Middle Income

Small and nutritionally at-risk infants under six months, defined as those with wasting, underweight, or other forms of growth failure, are at high-risk of mortality and morbidity. The World Health Organisation 2013 guidelines on severe acute malnutrition highlight the need to effectively manage this vulnerable group, but programmatic challenges are widely reported. This review aims to inform future management strategies for small and nutritionally at-risk infants under six months in low- and middle-income countries (LMICs) by synthesising evidence on existing breastfeeding support packages for all infants under six months. We searched PubMed, CINAHL, Cochrane Library, EMBASE, and Global Health databases from inception to 18 July 2018. Intervention of interest were breastfeeding support packages. Studies reporting breastfeeding practices and/or caregivers’/healthcare staffs’ knowledge/skills/practices for infants under six months from LMICs were included. Study quality was assessed using NICE quality appraisal checklist for intervention studies. A narrative data synthesis using the Synthesis Without Meta-analysis (SWiM) reporting guideline was conducted and key features of successful programmes identified. Of 15,256 studies initially identified, 41 were eligible for inclusion. They were geographically diverse, representing 22 LMICs. Interventions were mainly targeted at mother–infant pairs and only 7% (n = 3) studies included at-risk infants. Studies were rated to be of good or adequate quality. Twenty studies focused on hospital-based interventions, another 20 on community-based and one study compared both. Among all interventions, breastfeeding counselling (n = 6) and education (n = 6) support packages showed the most positive effect on breastfeeding practices followed by breastfeeding training (n = 4), promotion (n = 4) and peer support (n = 3). Breastfeeding education support (n = 3) also improved caregivers’ knowledge/skills/practices. Identified breastfeeding support packages can serve as "primary prevention" interventions for all infants under six months in LMICs. For at-risk infants, these packages need to be adapted and formally tested in future studies. Future work should also examine impacts of breastfeeding support on anthropometry and morbidity outcomes. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018102795).

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The impact of COVID-19 on the care of people living with noncommunicable diseases in low- and middle-income countries: an online survey of physicians and pharmacists in nine countries

Primary Health Care Research & Development ◽

10.1017/s146342362100030x ◽

2021 ◽

Vol 22 ◽

Author(s):

Chris Bullen ◽

Jessica McCormack ◽

Amanda Calder ◽

Varsha Parag ◽

Kannan Subramaniam ◽

...

Keyword(s):

Public Health ◽

Healthcare Workers ◽

Online Survey ◽

World Health ◽

Noncommunicable Diseases ◽

Middle Income ◽

Middle Income Countries ◽

Health Measures ◽

The Impact ◽

Low And Middle Income

Abstract Background: The global COVID-19 pandemic has disrupted healthcare worldwide. In low- and middle-income countries (LMICs), where people may have limited access to affordable quality care, the COVID-19 pandemic has the potential to have a particularly adverse impact on the health and healthcare of individuals with noncommunicable diseases (NCDs). A World Health Organization survey found that disruption of delivery of healthcare for NCDs was more significant in LMICs than in high-income countries. However, the study did not elicit insights into the day-to-day impacts of COVID-19 on healthcare by front-line healthcare workers (FLHCWs). Aim: To gain insights directly from FLHCWs working in countries with a high NCD burden, and thereby identify opportunities to improve the provision of healthcare during the current pandemic and in future healthcare emergencies. Methods: We recruited selected frontline healthcare workers (general practitioners, pharmacists, and other medical specialists) from nine countries to complete an online survey (n = 1347). Survey questions focused on the impact of COVID-19 pandemic on clinical practice and NCDs; barriers to clinical care during the pandemic; and innovative responses to the many challenges presented by the pandemic. Findings: The majority of FLHCWs responding to our survey reported that their care of patients had been impacted both adversely and positively by the public health measures imposed. Most FLHCs (95%) reported a deterioration in the mental health of their patients. Conclusions: Continuity of care for NCDs as part of pandemic preparedness is needed so that chronic conditions are not exacerbated by public health measures and the direct impacts of the pandemic.

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Spatial Externalities of Income Inequality on Security in Latin America

Mathematics ◽

10.3390/math9030245 ◽

2021 ◽

Vol 9 (3) ◽

pp. 245

Author(s):

Pablo Ponce ◽

José Álvarez-García ◽

Mary Cumbicus ◽

María de la Cruz del Río-Rama

Keyword(s):

Income Inequality ◽

Latin American ◽

Spatial Dependence ◽

Generalized Least Squares ◽

Homicide Rate ◽

World Health ◽

Control Variables ◽

Spatial Error ◽

Middle Income ◽

Middle Income Countries

The aim of this research is to analyse the effect of income inequality on the homicide rate. The study is carried out in 18 Latin American countries for the period 2005–2018. The methodology used is the Generalized Least Squares (GLS) model and the data were obtained from World Development Indicators, the World Health Organization and the Inter-American Development Bank. Thus, the dependent variable is the homicide rate and the independent variable is income inequality. In addition, some control variables are included, such as: poverty, urban population rate, unemployment, schooling rate, spending on security and GDP per capita, which improve the consistency of the model. The results obtained through GLS model determine that inequality has a negative and significant effect on the homicide rate for high-income countries (HIC) and lower-middle-income countries (LMIC), whereas it is positive and significant for upper-middle-income countries (UMIC). On the other hand, the control variables show different results by group of countries. In the case of unemployment, it is not significant in any group of countries. Negative spatial dependence was found regarding spatial models such as: the spatial lag (SAR) and spatial error (SEM) method. In the spatial Durbin model (SDM), positive spatial dependence between the variables was corroborated. However, spatial auto-regressive moving average (SARMA) identified no spatial dependence. Under these results it is proposed: to improve productivity, education and improve the efficiency of security-oriented resources.

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Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain

Pathogens ◽

10.3390/pathogens10040471 ◽

2021 ◽

Vol 10 (4) ◽

pp. 471

Author(s):

Camila Pimentel ◽

Casin Le ◽

Marisel R. Tuttobene ◽

Tomas Subils ◽

Jasmine Martinez ◽

...

Keyword(s):

Gene Expression ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Acinetobacter Baumannii ◽

Pleural Fluid ◽

Gene Expression Profile ◽

Expression Profile ◽

The United States ◽

World Health

Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and a priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug-susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug-resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems, and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and demonstrated a distinctive role of HSA as the molecule involved in A. baumannii’s response.

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Tobacco Control in Low- and Middle-Income Countries: Changing the Present to Help the Future

The Journal of Smoking Cessation ◽

10.1017/jsc.2018.4 ◽

2018 ◽

Vol 13 (4) ◽

pp. 187-188 ◽

Cited By ~ 4

Author(s):

Bethany Hipple Walters ◽

Ionela Petrea ◽

Harry Lando

Keyword(s):

World Health Organization ◽

World Health ◽

Second Hand Smoke ◽

Vulnerable Children ◽

Middle Income ◽

Middle Income Countries ◽

The Past ◽

Second Hand Smoke Exposure ◽

Health Organization ◽

Low And Middle Income

While the global smoking rate has dropped in the past 30 years (from 41.2% of men in 1980 to 31.1% in 2012 and from 10.6% of women in 1980 to 6.2% in 2012), the number of tobacco smokers has increased due to population growth (Ng et al., 2014). This tobacco use and second-hand smoke exposure continue to harm people worldwide. Those harmed are often vulnerable: children, those living in low- and middle-income countries (LMICs), those with existing diseases, etc. As noted by the World Health Organization (WHO), nearly 80% of those who smoke live in a LMIC (World Health Organization, 2017). Furthermore, it is often those who are more socio-economically disadvantaged or less educated in LMICs that are exposed to second-hand smoke at home and work (Nazar, Lee, Arora, & Millett, 2015).

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Resolving driver events in MLL-r negative high-risk infant ALL.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10030 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10030-10030

Author(s):

Jennifer Seelisch ◽

Matthew Zatzman ◽

Federico Comitani ◽

Fabio Fuligni ◽

Ledia Brunga ◽

...

Keyword(s):

Gene Expression ◽

T Cell ◽

High Risk ◽

B Cell ◽

Gene Expression Profiling ◽

Rna Sequencing ◽

Clinical Features ◽

Expression Profiling ◽

High Risk Infant ◽

Childhood All

10030 Background: Infant acute lymphoblastic leukemia (ALL) is the only subtype of childhood ALL whose outcome has not improved over the past two decades. The most important prognosticator is the presence of rearrangements in the Mixed Lineage Leukemia gene (MLL-r), however, many patients present with high-risk clinical features but without MLL-r. We recently identified two cases of infant ALL with high-risk clinical features resembling MLL-r, but were negative for MLL-r by conventional diagnostics. RNA sequencing revealed a partial tandem duplication in MLL (MLL-PTD). We thus aimed to determine if MLL-PTD, other MLL abnormalities, or other genetic or transcriptomic features were driving this subset of high-risk infant ALL without MLL-r. Methods: We obtained 19 banked patient samples from the Children’s Oncology Group (COG) infant ALL trial (AALL0631) from MLL wildtype patients as determined by FISH and cytogenetics. Utilizing deep RNA-sequencing, we manually inspected the MLL gene for MLL-PTD, while also performing automated fusion detection and gene expression profiling in search of defining features of these tumors. Results: 3 additional MLL-PTDs were identified, all in patients with infant T-cell ALL, whereas both index cases were in patients with infant B-cell ALL. Gene expression profiling analysis revealed that all five MLL-PTD infants clustered together. Eight infants (7 with B-cell ALL) were found to have Ph-like expression. Five of these 8 infants were also found to have an IKZF1/JAK2 expression profile; one of these five had a PAX5-JAK2 fusion detected. Two infants (including the one noted above) had novel PAX5 fusions, known drivers of B-cell leukemia. Additional detected fusions included TCF3-PBX1 and TCF4-ZNF384. Conclusions: MLL-PTDs were found in both B- and T-cell infant ALL. Though Ph-like ALL has been described in adolescents and young adults, we found a substantial frequency of Ph-like expression among MLL-WT infants. Further characterization of these infants is ongoing. If replicated in other infant cohorts, these two findings may help explain the poor prognosis of MLL-WT ALL when compared to children with standard risk ALL, and offer the possibility of targeted therapy for select infants.

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