Advancing access to care: An assessment of the prehospital system in Senegal.

BACKGROUND: Most low- and middle-income countries do not have a mature prehospital system limiting access to definitive care. This study sought to describe the current state of the prehospital system in Senegal and offer recommendations aimed at improving system capacity and population access to definitive care. METHODS: Structured interviews were conducted with key informants in various regions throughout the country using qualitative and quantitative techniques. A standardized questionnaire was generated using needs assessment forms and system frameworks. Descriptive statistics were performed for quantitative data analysis, and qualitative data was consolidated and presented using ATLAS.ti. RESULTS: Two (20%) of the studied regions, Dakar and Saint-Louis, had a mature prehospital system in place, including dispatch centers and teams of trained personnel utilizing equipped ambulances. 80% of the studied regions lacked an established prehospital system. The vast majority of the population relied on the fire department for transport to a healthcare facility. The ambulances in rural regions were not part of a formal prehospital system, were not equipped with life-support supplies, and were limited to inter-facility transfers. CONCLUSIONS: While Dakar and Saint-Louis have mature prehospital systems, the rest of the country is served by the fire department. There are significant opportunities to further strengthen the prehospital system in rural Senegal by training the fire department in basic life support and first aid, maintaining cost efficiency, and building on existing national resources. This has the potential to significantly improve access to definitive care and outcomes of emergent illness in the Senegalese community.

MS-HRM protocol: a simple and low-cost approach for technical validation of next-generation methylation sequencing data.

DNA methylation is a fundamental epigenetic process and have a critical role in many biological processes. The study of DNA methylation at a large scale of genomic levels is widely conducted by several techniques that are next-generation sequencing (NGS)-based methods. Methylome data revealed by DNA methylation next-generation sequencing (mNGS), should be always verified by another technique which they usually have a high cost. In this study, we offered a low-cost approach to corroborate the mNGS data. In this regard, mNGS was performed on 6 colorectal cancer (case group) and 6 healthy individual colon tissue (control group) samples. An R-script detected differentially methylated regions (DMRs), was further validated by high resolution melting (MS-HRM) analysis. After analyzing the data, the algorithm found 194 DMRs. Two locations with the highest level of methylation difference were verified by MS-HRM, which their results were in accordance with the mNGS. Therefore, in the present study, we suggested MS-HRM as a simple, accurate and low-cost method, useful for confirming methylation sequencing results.

Biochemical analysis of patients with mutations in MTHFD1 and a diagnosis of methylenetetrahydrofolate dehydrogenase 1 deficiency.

MTHFD1 is a trifunctional protein containing 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase and 5,10-methylenetetrahydrofolate dehydrogenase activities. It is encoded by MTHFD1 and functions in the cytoplasmic folate cycle where it is involved in de novo purine synthesis, synthesis of thymidylate and remethylation of homocysteine to methionine. Since the first reported case of severe combined immunodeficiency resulting from MTHFD1 mutations, seven additional patients ascertained through molecular analysis have been reported with variable phenotypes, including megaloblastic anemia, atypical hemolytic uremic syndrome, hyperhomocysteinemia, microangiopathy, infections and autoimmune diseases. We determined the level of MTHFD1 expression and dehydrogenase specific activity in cell extracts from cultured fibroblasts of three previously reported patients, as well as a patient with megaloblastic anemia and recurrent infections with compound heterozygous MTHFD1 variants that were predicted to be deleterious. MTHFD1 protein expression determined by Western blotting in fibroblast extracts from three of the patients was markedly decreased compared to expression in wild type cells (between 4.8 and 14.3% of mean control values). MTHFD1 expression in the fourth patient was approximately 44% of mean control values. There was no detectable methylenetetrahydrofolate dehydrogenase specific activity in extracts from any of the four patients. This is the first measurement of MTHFD1 function in MTHFD1 deficient patients and confirms the previous molecular diagnoses.

Obesity, diabetes and the risk of colorectal adenoma and cancer.

BACKGROUND: Colorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide. In the current case-control study, an association between diagnosis of CRC, obesity and diabetes was investigated. METHODS: Demographic characteristics, colonoscopy reports, history of drug, smoking, and medical history were collected from patients referred to a colonoscopy unit. The location, size and number of the polyps were recorded during the colonoscopy. Statistically, t-test was conducted for mean comparison for the groups. Pearson's chi-squared test (χ2) was applied to categorize variables. Five classification methods based on the important clinicopathological characteristics such as age, BMI, diabetes, family history of colon cancer was performed to predict the results of colonoscopy. RESULTS: Overall, 693 patients participated in this study. In the present study, 115 and 515 patients were evaluated for adenoma/adenocarcinoma and normal colonoscopy, respectively. The mean age of patients positive for adenoma or adenocarcinoma were significantly higher than the negative groups (p value < 0.001). Incidence of overweight and/or obesity (BMI > 25 kg/m2) were significantly higher in adenoma positive patients as compared to controls (49.9 and 0.9% respectively, p value = 0.04). The results also demonstrated a significant association between suffering from diabetes and having colon adenoma (OR = 1.831, 95%CI = 1.058-3.169, p value = 0.023). The experimental results of 5 classification methods on higher risk factors between colon adenoma and normal colonoscopy data were more than 82% and less than 0.42 for the percentage of classification accuracy and root mean squared error, respectively. CONCLUSIONS: In the current study, the occurrence of obesity measured based on BMI and diabetes in the adenoma positive patient group was significantly higher than the control group although there was no notable association between obesity, diabetes and adenocarcinoma.

Research Letter-Outcomes of Outpatient Native Kidney Biopsies at the McGill University Health Center: A Quality Assurance Audit.

Background: Percutaneous kidney biopsies are essential for diagnosis and management of kidney diseases. However, post-procedural bleeding is a significant risk associated with biopsies. At the McGill University Health Center, the 2 main hospitals, the Royal Victoria Hospital and the Montreal General Hospital, have different observation protocols for outpatient native kidney biopsies. Currently, patients are admitted for a 24-hour inpatient observation at the Montreal General Hospital, whereas patients biopsied at the Royal Victoria Hospital are discharged after 6 to 8 hours of observation at the end of the day. Most Canadian centers do not admit patients for an overnight observation, and it was unclear why this practice continued at the Montreal General Hospital. Objective: Our objective was to determine the incidence of complications post-renal biopsy over the past 5 years at both hospital sites, and compare them to each other, as well as to established rates in the available literature. Design: This assessment was designed as a quality assurance audit. Setting: This audit was conducted from a local registry of renal biopsies performed at the McGill University Health Center between January 2015 to January 2020. Patients: We included all adult patients (between the ages 18 and 80) with outpatient native kidney biopsies performed at the McGill University Health Center between 2015 and 2020. Measurements: We collected the included patients' baseline demographics and risk factors at the time of biopsy, including age, BMI, creatinine, estimated glomerular filtration rate, pre- and post-biopsy hemoglobin, platelet, urea, coagulation profile, blood pressure, kidney side/size as well as needle size, and number of passes made. Methods: We compared the incidence of both minor and major bleeding complications at the Montreal General and the Royal Victoria Hospital. Variables that were measured included hemoglobin before and after biopsy, incidence of minor bleeding complications (defined by hematomas and gross hematuria), and incidence of major complications (defined by post-biopsy bleeding requiring either transfusions or another procedure to stop the bleeding), as well as the incidence of admissions post-biopsy. Results: The incidence of major complications was 2.87% over 5 years (5/174 patients), which is comparable with that reported in the literature. Our transfusion incidence was 1.72% (3/174 patients) and our embolization incidence was 2.3% (4/174 patients) over the 5 study years. Our total number of major events was low and the patients who had major events had significant risk factors for bleeding. All events occurred within 6 hours of observation. Limitations: This was a retrospective study with a low event number. Additionally, since the events included only those recorded at the McGill University Health Center, it is possible that the events of interest may have occurred at other hospital sites without the author's knowledge. Conclusions: Based on the results of this audit, all major bleeding events occurred within 6 hours of a percutaneous kidney biopsy, suggesting that patients should be monitored for 6 to 8 hours following biopsy. The next step after this quality assurance audit is a quality improvement project and a cost-effectiveness analysis to assess whether post-biopsy practices should be amended at the McGill University Health Center.

Contexte: Les biopsies rénales percutanées sont essentielles pour diagnostiquer et prendre en charge l'insuffisance rénale, mais elles exposent le patient à un risque significatif de saignements post-procéduraux. Les deux principaux hôpitaux du Center universitaire de santé McGill, soit l'Hôpital Royal Victoria et l'Hôpital général de Montréal, suivent un protocole d'observation différent à la suite d'une biopsie rénale en consultation externe. À l'Hôpital général de Montréal, les patients sont admis 24 heures pour observation, alors qu'à l'Hôpital Royal Victoria, les patients sont libérés en fin de journée, après 6-8 heures d'observation. La plupart des centers hospitaliers canadiens n'admettent pas les patients pour la nuit; on ignore pourquoi cette pratique a toujours cours à l'Hôpital général de Montréal. Objectifs: L'objectif était de mesurer l'incidence des complications post-biopsie rénale dans chacun des deux centers hospitaliers au cours des cinq dernières années, puis de les comparer d'un hôpital à l'autre ainsi qu'aux taux établis dans la littérature. Conception: Cette étude a été conçue comme un examen de qualité de l'acte. Cadre: L'étude a été réalisée à partir d'un registre local des biopsies rénales effectuées au Center universitaire de santé McGill entre janvier 2015 et janvier 2020. Sujets: Nous avons inclus tous les patients adultes (18 à 80 ans) ayant subi une biopsie rénale en ambulatoire au Center universitaire de santé McGill entre 2015 et 2020. Mesures: Les données démographiques de base et les facteurs de risque des patients inclus ont été recueillis au moment de la biopsie, notamment l'âge, l'IMC, le taux de créatinine, le débit de filtration glomérulaire estimé, le taux d'hémoglobine avant et après la biopsie, le décompte plaquettaire, l'urée, le profil de coagulation, la pression artérielle, le côté/taille des reins, la taille de l'aiguille et le nombre de ponctions. Méthodologie: Nous avons comparé l'incidence des complications hémorragiques mineures et majeures à l'Hôpital général de Montréal et à l'Hôpital Royal Victoria. Les variables mesurées comprenaient: le taux d'hémoglobine avant et après la biopsie, l'incidence de complications hémorragiques mineures (définies par des hématomes et de l'hématurie macroscopique) et majeures (définies par des saignements post-biopsie nécessitant une transfusion ou une procédure pour arrêter le saignement), ainsi que l'incidence des admissions après la biopsie. Résultats: Pour les cinq années à l'étude, l'incidence des complications majeures était de 2.87% (5/174 patients), ce qui est comparable au taux rapporté dans la littérature. Au cours de cette même période, l'incidence des transfusions s'est établie à 1.72% (3/174 patients) et celle des embolisations à 2.3% (4/174 patients). Le nombre total d'événements majeurs était faible et les patients qui les avaient subis présentaient d'importants facteurs de risque de saignement. Tous les événements sont survenus dans les six premières heures d'observation. Limites: Il s'agit d'une étude rétrospective avec un faible nombre d'événements. En outre, seuls les événements enregistrés au Center universitaire de santé McGill ont été pris en compte; il est possible que des événements intéressants se soient produits à l'insu de l'auteur dans d'autres hôpitaux. Conclusion: Selon les résultats de cet examen, tous les événements hémorragiques majeurs se sont produits dans les 6 heures suivant une biopsie rénale percutanée, ce qui plaide en faveur d'une surveillance des patients pendant 6 à 8 heures après la biopsie. Après cet examen de qualité de l'acte, les prochaines étapes sont un projet d'amélioration de la qualité et une analyze coût-efficacité, lesquels permettront de déterminer si les pratiques post-biopsies devraient être modifiées au Center universitaire de santé McGill.

Long interspersed nucleotide element-1 (LINE-1) methylation in colorectal cancer.

Colorectal cancer (CRC) represents a group of molecularly heterogeneous diseases characterized by genetic and epigenetic alterations. Long interspersed nuclear elements (LINEs) are a form of retrotransposable element found in many eukaryotic genomes. These LINEs, when active, can mobilize in the cell and steadily cause genomic rearrangement. Active LINE reorganization is a source of endogenous mutagenesis and polymorphism in the cell that brings about individual genomic variation. In normal somatic cells, these elements are heavily methylated and thus mostly suppressed, in turn, preventing their potential for bringing about genomic instability. When LINEs are inadequately controlled, they can play a role in the pathogenesis of several genetic diseases, such as cancer. In tumor cells, LINE hypomethylation can reactivate the mobilization of these elements and is associated with both an advanced stage and a poor prognosis. In this article, we summarize the current knowledge surrounding LINE methylation, its correlation to CRC and its application as a diagnostic, prognostic and predictive biomarker in colon cancer.