Genomic medicine without borders: which strategies should developing countries employ to invest in precision medicine? A new "fast-second winner" strategy

Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a “one-size-fits-all-countries” development strategy, in the same way that drug treatments should be customized. This begs a timely, difficult but crucial question: How should developing countries, and the resource-limited regions of developed countries, invest in genomic medicine? Although a full-scale investment in infrastructure from discovery to the translational implementation of genomic science is ideal, this may not always be feasible in all countries at all times. A simple “transplantation of genomics” from developed to developing countries is unlikely to be feasible. Nor should developing countries be seen as simple recipients and beneficiaries of genomic medicine developed elsewhere because important advances in genomic medicine have materialized in developing countries as well. There are several noteworthy examples of genomic medicine success stories involving resource-limited settings that are contextualized and described in this global genomic medicine innovation analysis. In addition, we outline here a new long-term development strategy for global genomic medicine in a way that recognizes the individual country's pressing public health priorities and disease burdens. We term this approach the “Fast-Second Winner” model of innovation that supports innovation commencing not only “upstream” of discovery science but also “mid-stream,” building on emerging highly promising biomarker and diagnostic candidates from the global science discovery pipeline, based on the unique needs of each country. A mid-stream entry into innovation can enhance collective learning from other innovators' mistakes upstream in discovery science and boost the probability of success for translation and implementation when resources are limited. This à la carte model of global innovation and development strategy offers multiple entry points into the global genomics innovation ecosystem for developing countries, whether or not extensive and expensive discovery infrastructures are already in place. Ultimately, broadening our thinking beyond the linear model of innovation will help us to enable the vision and practice of genomics without borders in both developed and resource-limited settings

Success stories in genomic medicine from resource-limited countries

In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments

Equity, diversity, and inclusion at the Global Alliance for Genomics and Health

A lack of diversity in genomics for health continues to hinder equitable leadership and access to precision medicine approaches for underrepresented populations. To avoid perpetuating biases within the genomics workforce and genomic data collection practices, equity, diversity, and inclusion (EDI) must be addressed. This paper documents the journey taken by the Global Alliance for Genomics and Health (a genomics-based standard-setting and policy-framing organization) to create a more equitable, diverse, and inclusive environment for its standards and members. Initial steps include the creation of two groups: the Equity, Diversity, and Inclusion Advisory Group and the Regulatory and Ethics Diversity Group. Following a framework that we call "Reflected in our Teams, Reflected in our Standards," both groups address EDI at different stages in their policy development process. [Abstract copyright: © 2023 The Author(s).

Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013–2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

MEDTalks : The Genomics Revolution

The sequencing of the human genome has been hailed as a scientific breakthrough in that it has opened the human genetic blueprint to investigations of all questions ranging from human origins to the understanding of health and complex diseases. As a result of this revolutionary sequencing of human genomes, our knowledge about how and why we differ from each other as well as how interactions between genes and culture have shaped our community is now more clearly understood. How can this knowledge be used to improve human health through disease prevention, diagnosis and personalized treatment approaches? What does the Genomics Revolution mean for you and your health? What is the potential for future generations? Join UBC’s Faculties of Medicine, Dentistry and Pharmaceutical Sciences, in partnership with alumni UBC, to hear from five top UBC researchers and learn about the work they are doing to accelerate the genomics revolution which is advancing their fields.Dentistry, Faculty ofMedicine, Faculty ofPharmaceutical Sciences, Faculty ofAlumniFamily Practice, Department ofMedical Oncology, Division ofMedicine, Department ofUnreviewedFacultyResearche

Implementation of a soft tissue infection management protocol perianal in pediatric patients with oncological pathology from the Department of Pediatric Surgery of the Central Military Hospital in the period covered between June 2017 and December 2019

La infección de tejidos blandos perianales en pacientes pediátricos con patología oncológica es una de las complicaciones infecciosas más frecuentes con altas tasas de morbimortalidad. La asociación con el manejo quimioterapéutico y la inmunosupresión de dichos pacientes hacen del enfoque diagnóstico y terapéutico un reto, por lo que, en el Servicio de Cirugía Pediátrica del Hospital Militar Central, se estableció un Protocolo de Manejo para la Infección Perianal de Tejidos Blandos en la población entre los 0 – 15 años desde el año 2017. Se realizó un estudio de serie de casos, de los pacientes entre 0-15 años con patología oncológica quienes requirieron valoración y manejo de infección perianal de tejidos blandos por el Servicio de Cirugía Pediátrica del Hospital Militar Central. Pacientes en quienes se realizó valoración y manejo en el periodo de junio 2017 a diciembre 2019. Se describió y caracterizó la evolución de los pacientes oncológicos en quienes se implementó el protocolo instaurado reportando tiempo de evolución, medicamentos utilizados, necesidad de manejo quirúrgico y unidad de cuidado intensivo pediátrico, demostrando la ausencia de mortalidad.Portada 1 Índice de Contenido 2 Resumen 3 Introducción 5 Identificación y formulación del problema 8 Objetivos 10 Metodología 11 Plan de análisis 13 Aspectos éticos 14 Resultados 15 Discusión 19 Conclusión 21 Referencias Bibliográficas 22The Perianal soft tissue infection in pediatric patients with oncological pathology is one of the most frequent infectious complications with high rates of morbidity and mortality. The association with chemotherapeutic management and immunosuppression of these patients make the diagnostic and therapeutic approach a challenge, for which reason, in the Pediatric Surgery Service of the Central Military Hospital, a Management Protocol for Perianal Soft Tissue Infection was established in the population between 0 - 15 years of age since 2017. A case series study was carried out of patients between 0-15 years of age with oncological pathology who required evaluation and management of perianal soft tissue infection by the Pediatric Surgery Service of the Central Military Hospital. Patients in whom assessment and management were performed in the period from June 2017 to December 2019. The evolution of cancer patients in whom the established protocol was implemented was described and characterized, reporting evolution time, medications used, need for surgical management and pediatric intensive care unit, demonstrating the absence of mortality.Especializació

Fractales: ayuda diagnóstica para células preneoplásicas y cancerígenas del epitelio escamoso cervical confirmación de aplicabilidad clínica

Antecedentes: Se desarrolló un método diagnóstico fractal para evaluar células del cuello uterino utilizando el concepto de Armonía Matemática Intrínseca (AMI) y variabilidad celular, el cual diferencia matemáticamente células normales de células L-SIL y H-SIL, haciendo innecesario el diagnóstico de células ASCUS.Objetivo: confirmar la capacidad diagnóstica de la metodología desarrollada mediante un estudio ciego de comparación con el Gold StandardMétodos: se tomaron fotografías digitales de 50 preparaciones citológicas de mujeres entre 20 y 55 años: 5 con diagnóstico de citología normal y 45 con diferentes grados de lesión hasta carcinoma, incluyendo 5 ASCUS. Se calculó la dimensión fractal de tres objetos matemáticos: núcleo, citoplasma y totalidad, a partir de la superposición de cinco rejillas. Además se evaluó su dimensión fractal mediante el concepto de AMI y variabilidad celular. Los resultados obtenidos se compararon con el diagnóstico citopatológico convencional determinando su sensibilidad, especificidad y coeficiente kappa.Resultados: La sensibilidad y especificidad fue del 100%, y el coeficiente Kappa de 1.Conclusiones: Los resultados en una población diferente a la inicial son una evidencia de la capacidad de esta metodología para diagnosticar objetiva y cuantitativamente células normales, L-SIL y H-SIL, así como aclarar el diagnóstico de las células ASCUS con base en la dimensión fractal y el concepto de AMI y variabilidad.

Evaluación probabilista de la dinámica cardiaca arrítmica con y sin metoprolol

. AbstractIntroduction: Based on the theory of dynamic systems and probability theory, highly sensitive clinical methodologies have been developed to differentiate normality, disease and evolution towards cardiac disease.Methods: Holter recordings, 7 normal and 73 with arrhythmia diagnosis with and without therapeutic treatment of Metoprolol, were selected. Probability measures, established in a previous work, were applied for assessing maximum, minimal and average heart rate and beats per hour.Results: it was found that almost a half of the cases with arrhythmias without beta-blocker therapy exhibited mathematical measures of illness and evolution towards disease, whereas in the treatment group with Metoprolol, three quarters accomplished these features.Conclusions: More objective mathematical distinctions were achieved between cardiac dynamics treated with and without metoprolol, which is very useful for individual follow-up.Introducción: a partir de la teoría de los sistemas dinámicos y la teoría de la probabilidad se han desarrollado metodologías altamente sensibles de aplicación clínica que permiten diferenciar normalidad, enfermedad y evolución hacia la enfermedad cardiacaMétodos: se seleccionaron los registros Holter de 7 casos normales y 73 con diagnóstico de arritmia con y sin tratamiento terapéutico de Metoprolol. Se aplicaron medidas de probabilidad establecidas en un trabajo previo para evaluar la frecuencia cardiaca máxima, mínima y promedio, y el número de latidos por hora.Resultados: se encontró que casi la mitad de los casos con arritmias sin tratamiento betabloqueante exhibieron medidas matemáticas de enfermedad y evolución hacia la enfermedad, mientras que del grupo con tratamiento con Metoprolol, tres cuartas partes cumplieron con estas características.Conclusiones: la comparación entre los subgrupos de Metoprolol evidenció que menos casos en el subgrupo de tratamiento exclusivo con Metoprolol tuvieron diagnóstico de enfermedad que el subgrupo de consumo variado de medicamentos junto con el Metoprolo