Accuracy of surgical death information: comparison of data held by Victorian Audit of Surgical Mortality and Victorian Agency for Health Information.

BACKGROUND: The Victorian Audit of Surgical Mortality (VASM) investigates all surgically related deaths in Victoria. The Victorian Admitted Episodes Database (VAED) is an administrative dataset maintained by the Health Department's Victorian Agency of Health Information (VAHI). We have reviewed clinical records to assess the correlation between deaths reported to the databases. METHODS: Data July 2019 to June 2020 were compared. All hospitals that had surgical deaths not reported to VASM were asked to provide clinical summaries which were analysed to assess the deaths should have been reported. Case note review of 280 deaths only reported to VAHI through VAED was undertaken to establish whether these should have been reported to VASM. RESULTS: VASM received 1763 reported surgical deaths with VAHI recording 1907. Using individual patient identifiers, 517 (29.3%) of the VASM deaths were not reported to VAHI but subsequent data analysis revealed they were correctly identified as reportable deaths in 385 (74.5%). There were 914 (47.9%) VAED recorded deaths that were not reported to VASM. 280/914 (30.6%) were reviewed from 21 hospitals. Only 24 (8.6%) of these had a surgical procedure in the patient's final admission and should have been reported. This suggests that the current method of VASM capture of surgical mortality only missed 4% cases for the 2019/20 year. CONCLUSION: There were major differences between surgical deaths reported to VASM and those reported by health services and recorded in VAED. Less than 5% of cases are not reported to VASM and thus not subjected to peer review.

TRNT-1 Deficiency Is Associated with Loss of tRNA Integrity and Imbalance of Distinct Proteins.

Mitochondrial diseases are a group of heterogeneous disorders caused by dysfunctional mitochondria. Interestingly, a large proportion of mitochondrial diseases are caused by defects in genes associated with tRNA metabolism. We recently discovered that partial loss-of-function mutations in tRNA Nucleotidyl Transferase 1 (TRNT1), the nuclear gene encoding the CCA-adding enzyme essential for modifying both nuclear and mitochondrial tRNAs, causes a multisystemic and clinically heterogenous disease termed SIFD (sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay; SIFD). However, it is not clear how mutations in a general and essential protein like TRNT1 cause disease with such clinically broad but unique symptomatology and tissue involvement. Using biochemical, cell, and mass spectrometry approaches, we demonstrate that TRNT1 deficiency is associated with sensitivity to oxidative stress, which is due to exacerbated, angiogenin-dependent cleavage of tRNAs. Furthermore, reduced levels of TRNT1 lead to phosphorylation of Eukaryotic Translation Initiation Factor 2 Subunit Alpha (eIF2α), increased reactive oxygen species (ROS) production, and changes in the abundance of distinct proteins. Our data suggest that the observed variable SIFD phenotypes are likely due to dysregulation of tRNA maturation and abundance, which in turn negatively affects the translation of distinct proteins.

Systematic review of the use of metformin compared to insulin for the management of gestational diabetes: Implications for low-resource settings.

Introduction: This systematic review examines the effectiveness of metformin treatment compared to insulin treatment for gestational diabetes within the context of a low-resource environment. Methods: Electronic data searches of Medline, EMBASE, Scopus and Google scholar databases from 1 January, 2005 to 30 June, 2021 were performed using medical subject headings: 'gestational diabetes or pregnancy diabetes mellitus' AND 'Pregnancy or pregnancy outcomes' AND 'Insulin' AND 'Metformin Hydrochloride Drug Combination/or Metformin/or Hypoglycemic Agents' AND 'Glycemic control or blood glucose'. Randomized controlled trials were included if: participants were pregnant women with gestational diabetes mellitus (GDM); the interventions were metformin and/or insulin. Studies among women with pre-gestational diabetes, non-randomised control trials or studies with a limited description of the methodology were excluded. Outcomes included adverse maternal outcomes: weight gain, C-section, pre-eclampsia and glycaemic control and adverse neonatal outcomes: birth weight, macrosomia, pre-term birth and neonatal hypoglycaemia. The revised Cochrane Risk of Bias Assessment for randomised trials was used for the evaluation of bias. Results: We screened 164 abstracts and 36 full-text articles. Fourteen studies met the inclusion criteria. The studies provide moderate to high-quality evidence demonstrating the effectiveness of metformin as an alternative therapy to insulin. Risk of bias was low; multiple countries and robust sample sizes improved external validity. All studies were from urban centres with no rural data. Conclusion: These recent high quality studies comparing metformin to insulin for the treatment of GDM generally found either improved or equivalent pregnancy outcome and good glycaemic control for most patients, although many required insulin supplementation. Its ease of use, safety and efficacy suggest metformin may simplify the management of gestational diabetes, particularly in rural and other low-resource environments.

Résumé Introduction: Cette revue systématique examine l'efficacité du traitement par metformine par rapport au traitement par insuline pour le diabète gestationnel dans le contexte d'un environnement à faibles ressources. Méthodes: Des recherches de données électroniques ont été effectuées dans les bases de données Medline, Embase, Scopus et Google scholar du 1er janvier 2005 au 30 juin 2021 en utilisant les termes MeSH: 'gestational diabetes or pregnancy diabetes mellitus' AND 'Pregnancy or pregnancy outcomes' AND 'Insulin' AND 'Metformin Hydrochloride Drug Combination/or Metformin/or Hypoglycemic Agents' AND 'Glycemic control or blood glucose'. Les essais contrôlés randomisés ont été inclus si: les participantes étaient des femmes enceintes atteintes de diabète gestationnel (DG); les interventions étaient la metformine et/ou l'insuline. Les études portant sur des femmes atteintes de diabète prégestationnel, les essais contrôlés non randomisés ou les études dont la description de la méthodologie était limitée ont été exclus. Les résultats comprenaient des résultats maternels défavorables: prise de poids, césarienne, prééclampsie, contrôle glycémique et des résultats néonatals défavorables: poids de naissance, macrosomie, naissance prématurée et hypoglycémie néonatale. La version révisée de l'évaluation du risque de biais de Cochrane pour les essais randomisés a été utilisée pour l'évaluation du biais. Résultats: Nous avons examiné 164 résumés et 36 articles complets. Quatorze études répondaient aux critères d'inclusion. Les études fournissent des preuves modérées à de haute qualité démontrant l'efficacité de la metformine comme thérapie alternative à l'insuline. Le risque de biais était faible; la multiplicité des pays et la taille robuste des échantillons ont amélioré la validité externe. Toutes les études provenaient de centres urbains, sans données rurales. Conclusion: Ces études récentes de haute qualité comparant la metformine à l'insuline pour le traitement du DG ont généralement constaté une amélioration ou une équivalence de l'issue de la grossesse et un bon contrôle glycémique pour la plupart des patientes, bien que beaucoup d'entre elles aient eu besoin d'un supplément d'insuline. Sa facilité d'utilisation, son innocuité et son efficacité suggèrent que la metformine pourrait simplifier la prise en charge du diabète gestationnel, notamment en milieu rural et dans d'autres environnements à faibles ressources. Mots clés: Diabète gestationnel, traitement, metformine, rural.

Traditional Medicine and Type 2 Diabetes in First Nations Patients.

BACKGROUND: Diabetes may be a cultural experience for many First Nations patients. In this study, we explore the potential role for traditional medicine in the treatment of diabetes. METHODS: A responsive interviewing qualitative methodology was used for 10 First Nations key informant interviews. The first objective was to accurately "re-tell" participants' stories. The second was to develop an overview of traditional medicine and its role in health and diabetes management by synthesizing academic literature, pre-existing local knowledge and perspectives, and stories shared by elders and traditional healers. The traditional medicine healers gave specific permission for this study and its publication. RESULTS: There is a strong cultural and historic context for the experience of diabetes in First Nations. Political and cultural suppression, lifestyle change and ongoing social determinants of health place diabetes in a unique context and generate a sense of fatalism. Traditional medicine can facilitate individual empowerment by connecting a patient with the lessons of previous generations and traditional beliefs and practices. CONCLUSIONS: Traditional medicine can be a valuable resource for First Nations patients living with diabetes and should be considered as a therapeutic modality.

Intravenous iron therapy in a rural hospital: A retrospective chart review.

INTRODUCTION: Intravenous iron infusion therapy is commonly delivered in rural hospitals, but there are no common guidelines for dosing or choice of agent. The objective of the study was to understand present practice and alternate therapies and develop practical recommendations for small hospital use. METHODS: This was a retrospective chart review of all non-dialysis patients aged 15 years or older who received iron replacement therapy at Sioux Lookout Meno Ya Win Health Centre from May 2013 to May 2019 and a literature review of available iron preparations. RESULTS: Of the 147 patients who received intravenous iron replacement, 75 were administered a single dose of 200 mg or 500 mg iron sucrose. Commonly used in pregnant patients, an increase in haemoglobin by an average of 9.2 g/L followed a 200 mg dose and 12.5 g/L after 500 mg. The 3-h infusion time for the 500 mg dose consumed considerably more nursing resources. Non-pregnant patients can be transfused more effectively with iron maltoside which can efficiently deliver larger doses of iron. CONCLUSION: We recommend iron maltoside for efficient intravenous iron replacement in non-pregnant patients and single or multiple doses of 200 mg iron sucrose during pregnancy.

Résumé Introduction: La perfusion intraveineuse de fer est fréquente dans les hôpitaux ruraux, mais il n'existe pas de lignes directrices courantes sur la posologie ou le choix de l'agent. Cette étude visait à comprendre la pratique actuelle, et les autres options thérapeutiques et d'émettre des recommandations pratiques à l'intention des petits hôpitaux. Méthodologie: Revue rétrospective des dossiers de tous les patients de 15 ans et plus non sous dialyse qui avaient reçu une supplémentation en fer à l'Hôpital SLMHC entre les mois de mai 2013 et mai 2019 et revue de la littérature sur les préparations de fer commercialisées. Résultats: Sur les 147 patients ayant reçu une perfusion de supplémentation en fer, 75 ont reçu une dose unique de 200 mg ou de 500 mg de fer-saccharose. Fréquemment utilisées chez les femmes enceintes, les doses de 200 et de 500 mg ont augmenté le taux d'Hb d'en moyenne 9,2 g/L et de 12.5 g/L, respectivement. La perfusion de 3 heures nécessaire à la dose de 500 mg a utilisé considérablement plus de ressources infirmières. Le fer-isomaltoside, qui administre efficacement des doses supérieures de fer, est perfusé plus efficacement chez les patients, à l'exclusion des femmes enceintes. Conclusion: Nous recommandons le fer-isomaltoside pour la supplémentation en fer efficace chez les patients, à l'exclusion des femmes enceintes et une dose unique ou multiple de 200 mg de fer-saccharose durant la grossesse. Mots-clés: Fer-isomaltoside, médecine rurale, perfusion intraveineuse de fer.

Fluoroquinolone use in a rural practice.

INTRODUCTION: Fluoroquinolones (FQs) are a commonly prescribed class of antibiotics in Canada. Evidence of a constellation of possible adverse events is developing. Central and peripheral nervous system abnormalities and collagen-related events (including aortic aneurysm/dissection, tendinopathy/rupture and retinal detachment) are associated with FQ exposure in large population-based aftermarket studies. In 2017, Health Canada warned about rare FQ-related persistent or disabling side effects. This study explores FQ use in a rural community. METHODS: Antibiotic prescriptions (including FQs) in the over 18 adult population (5416) were measured in the town of Sioux Lookout for 5 years, January 2013 to 31 December 2017. RESULTS: FQ prescriptions accounted for 16.0% of adult antibiotics, superseded by penicillins (21.1%) and macrolides (18.2%). Ciprofloxacin accounted for one half of FQ use (51.2%), followed by levofloxacin (36.7%) and norfloxacin (13.3%). FQs were commonly used for respiratory (33%) and urinary tract infections (18%). CONCLUSION: Aftermarket evidence reports increased risk of 'disabling and persistent serious adverse events'(Health Canada) in patients using FQs. Appropriate clinical caution should be exercised in the prescribing of FQs. Common overuse seems to occur in the treatment of uncomplicated community-acquired pneumonia and cystitis, despite recommendations to use other antimicrobial agents as first-line treatments.

Résumé Introduction: Les fluoroquinolones sont une classe d'antibiotiques souvent prescrite au Canada. Mais les données étayant une gamme d'événements indésirables possibles s'accumulent. Des anomalies du système nerveux central et périphérique, et des événements liés au collagène (dont anévrisme ou dissection de l'aorte, tendinopathie/rupture et décollement de la rétine) sont associés à l'exposition aux fluoroquinolones dans des études de pharmacovigilance d'envergure basées sur la population. En 2017, Santé Canada a émis une mise en garde au sujet des effets indésirables rares, persistants ou incapacitants liés aux fluoroquinolones. Cette étude se penche sur l'emploi de fluoroquinolones dans une communauté rurale. Méthodologie: La prescription d'antibiotiques (y compris de fluoroquinolones) a été mesurée dans la ville de Sioux Lookout pendant 5 ans, soit de janvier 2013 au 31 décembre 2017 auprès de la population de 18 ans et plus (5416 personnes). Résultats: Les fluoroquinolones comptaient pour 16,0 % des antibiotiques prescrits aux adultes, elles étaient précédées des pénicillines (21,1 %) et des macrolides (18,2 %). La ciprofloxacine représentait la moitié de l'emploi de fluoroquinolones (51,2 %), suivie de la lévofloxacine (36,7 %) et de la norfloxacine (13,3 %). Les fluoroquinolones étaient fréquemment utilisées contre les infections respiratoires (33 %) et urinaires (18 %). Conclusion: Les données de pharmacovigilance rapportent un risque accru "d'événements indésirables graves persistants et incapacitants" (Santé Canada) chez les patients sous fluoroquinolones. La prudence clinique appropriée est de mise lors de la prescription de fluoroquinolones. La pneumonie extra-hospitalière non compliquée et la cystite semblent être à l'origine de la surutilisation, malgré les recommandations d'utiliser d'autres antimicrobiens en première intention. Mots-clés: Fluoroquinolones; antibiotiques; effets indésirables; rural.

Demographics, prevalence and outcomes of diabetes in pregnancy in NW Ontario.

INTRODUCTION: Diabetes in pregnancy confers increased risk. This study examines the prevalence and birth outcomes of diabetes in pregnancy at the Sioux Lookout Meno Ya Win Health Centre (SLMHC) and other small Ontario hospitals. METHODS: This was a retrospective study of maternal profile: age, parity, comorbidities, mode of delivery, neonatal birth weight, APGARS and complications. Data were compared to other Ontario hospitals offering an equivalent level of obstetrical services. RESULTS: Type 2 diabetes mellitus in pregnancy is far more prevalent in mothers who deliver at SLMHC (relative risk [RR]: 20.9, 95% confidence interval [CI]: 16.0-27.2); the rates of gestational diabetes (GDM) are double (RR: 2.0, 95% CI: 1.7-2.3). SLMHC mothers with diabetes were on average 5 years younger and of greater parity with increased substance use. Neonates largely had equivalent outcomes except for increased macrosomia, neonatal hypoglycaemia and hyperbilirubinaemia in GDM pregnancies. CONCLUSION: Patients with diabetes in pregnancy at SLMHC differ substantially from mothers delivering at Ontario hospitals with a comparable level of service. Programming and resources must meet the service needs of these patients.

Résumé Introduction: Le diabète durant la grossesse élève le risque. Cette étude s'est penchée sur la prévalence des issues liées à l'accouchement causées par le diabète durant la grossesse au centre de santé SLMHC (Sioux Lookout Meno Ya Win Health Centre) et dans d'autres petits hôpitaux ontariens. Méthodologie: Il s'agissait d'une étude rétrospective du profil de la mère: âge, parité, comorbidités, méthode d'accouchement, poids du bébé à la naissance, score APGAR et complications. Les données ont été comparées à celles d'autres hôpitaux ontariens qui offrent un niveau équivalent de services obstétriques. Résultats: Le diabète de type 2 durant la grossesse est beaucoup plus répandu chez les femmes qui accouchent au SLMHC (risque relatif [RR]: 20,9; intervalle de confiance [CI] à 95 %: 16,0­27,2); le taux de diabète gestationnel est deux fois plus élevé (RR: 2,0; IC à 95 %: 1,7­2,3). Les femmes diabétiques ayant accouché au SLMHC étaient en moyenne 5 ans plus jeunes, avaient eu plus de naissances et elles consommaient des drogues en plus grand nombre. L'état des nouveau-nés était grandement équivalent, à l'exception d'un plus grand nombre de macrosomies, d'hypoglycémies néonatales et d'hyperbilirubinémies dans les cas de diabète gestationnel. Conclusion: Les patientes diabétiques durant la grossesse vues au SLMHC diffèrent substantiellement des femmes qui accouchent dans les hôpitaux ontariens offrant un niveau comparable de services. La programmation et les ressources doivent répondre aux besoins en matière de services de ces patientes. Mots-clés: Diabete, Premieres Nations, grossesse.

Diseases Associated with Defects in tRNA CCA Addition.

tRNA nucleotidyl transferase 1 (TRNT1) is an essential enzyme catalyzing the addition of terminal cytosine-cytosine-adenosine (CCA) trinucleotides to all mature tRNAs, which is necessary for aminoacylation. It was recently discovered that partial loss-of-function mutations in TRNT1 are associated with various, seemingly unrelated human diseases including sideroblastic anemia with B-cell immunodeficiency, periodic fevers and developmental delay (SIFD), retinitis pigmentosa with erythrocyte microcytosis, and progressive B-cell immunodeficiency. In addition, even within the same disease, the severity and range of the symptoms vary greatly, suggesting a broad, pleiotropic impact of imparting TRNT1 function on diverse cellular systems. Here, we describe the current state of knowledge of the TRNT1 function and the phenotypes associated with mutations in TRNT1.

Screening for gestational diabetes in pregnancy in Northwestern Ontario.

INTRODUCTION: We estimate the screening and prevalence of gestational diabetes mellitus (GDM) in a primarily first nations obstetrical population in Northwestern Ontario. METHODS: The study is an 8-year retrospective analysis of all gestational glucose challenge and tolerance tests performed at the Sioux Lookout Meno Ya Win Health Centre (SLMHC) laboratory from 1 January, 2010 to 31 December, 2017. Test, gestational timing and completion rate of screening were recorded, and GDM prevalence was calculated on the tested population. Screening completion rates were recorded for the subset of women who delivered at SLMHC from 2014 to 2017. RESULTS: The average annual GDM prevalence was 12%, double the Ontario rate. Over the 8-year period, 513 patients were diagnosed with GDM among the 4298 patients screened. Patients were screened with the 2-step (90%) or the 1-step (10%) protocol. Screening occurred <20 weeks in 3%; 54% occurred in <28 weeks and 40% >28 weeks. Seventy percent of the tests were from remote nursing stations. The screening completion rate for women delivering at SLMHC in 2017 was 80.8%. CONCLUSION: The prevalence of GDM in Northwestern Ontario is twice the provincial rate. Most screening used the 2-step protocol; early screening was underused. Improvements in screening programming are underway and future research may match surveillance rates and results to GDM outcomes.

Résumé Introduction: Nous estimons le dépistage et la prévalence du diabète gestationnel au sein d'une population obstétrique composée principalement de femmes des Premières Nations du Nord-Ouest de l'Ontario. Méthodologie: Il s'agissait d'une analyse rétrospective de 8 ans de toutes les épreuves d'hyperglycémie gestationnelle provoquée et de tous les tests de tolérance au glucose effectués au laboratoire Sioux Lookout Meno Ya Win Health Centre (SLMHC) entre le 1er janvier 2010 et le 31 décembre 2017. Le nombre de tests, le moment de la grossesse et le taux d'achèvement des tests de dépistage ont été consignés, et la prévalence du diabète gestationnel a été calculée dans la population testée. Le taux d'achèvement des tests de dépistage du sous-groupe de femmes ayant accouché au SLMHC entre 2014 et 2017 a aussi été consigné. Résultats: La prévalence annuelle moyenne de diabète gestationnel était de 12 %, soit le double de celle de l'Ontario. Durant les 8 ans qu'a duré l'étude, 513 patientes ont reçu un diagnostic de diabète gestationnel parmi les 4298 patientes soumises au dépistage. Le protocole à 2 étapes ou à 1 étape a servi au dépistage chez les patientes, à raison de respectivement 90 et 10 %. Le dépistage a eu lieu à < 20 semaines chez 3 %; à < 28 semaines chez 54 % et à > 28 semaines chez 40 % des patientes. Soixante-dix pour cent des tests ont été effectués dans des postes éloignés de soins infirmiers. Le taux d'achèvement du dépistage chez les femmes ayant accouché au SLMHC en 2017 était de 80,8 %. Conclusion: La prévalence de diabète gestationnel dans le Nord-Ouest de l'Ontario est le double du taux provincial. La plupart des tests effectués ont eu recours au protocole à 2 étapes; le dépistage précoce était sous-utilisé. L'on tente actuellement d'améliorer les programmes de dépistage, et de plus amples recherches pourraient documenter le taux de surveillance et approfondir notre compréhension des issues liées au diabète gestationnel.

Early Gestational Diabetes Mellitus Screening With Glycated Hemoglobin: A Systematic Review.

OBJECTIVE: This review sought to examine the association of HbA1c levels <6.5% in early pregnancy with the subsequent development of gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. METHODS: A search of Medline and EMBASE was conducted for the period of January 1, 2000 to July 9, 2019 and the terms: "gestational diabetes or pregnancy diabetes mellitus" and "glycosylated hemoglobin or glycated hemoglobin A" and "pregnancy trimester, first, or first-trimester pregnancy," "screening or prenatal screening," "prenatal diagnosis or early diagnosis or prediction," "retrospective studies or prospective studies." Quality of evidence was assessed using the Newcastle-Ottawa scale. Inclusion criteria were: measurement of HbA1c <20 weeks gestation, the absence of pre-gestational diabetes mellitus, and analysis of HbA1c levels below 6.5%. The primary outcome evaluated was the development of GDM. Secondary outcomes were adverse pregnancy outcomes, including large-for-gestational-age birth weight, macrosomia, preterm birth, neonatal and perinatal death, congenital anomaly, preeclampsia, shoulder dystocia, and cesarean section. RESULTS: We screened 121 relevant abstracts. Thirty-two studies qualified for a full review, of which 11 met the eligibility criteria. All studies were assessed as high quality and found an increased risk of GDM with HbA1c levels >5.7. Levels >6.0 identified all patients who developed GDM. Adverse pregnancy outcomes were associated with elevated HbA1c levels in 4 of 6 studies and included preeclampsia, induced labour, shoulder dystocia, cesarean section, large-for-gestational-age birth weight, macrosomia, congenital anomalies, and perinatal death. Two studies found no association with adverse events. CONCLUSION: HbA1c levels between 5.7% and 6.4% in early pregnancy consistently identified patients who went on to develop GMD. The evidence that particular levels are associated with adverse outcomes is less robust.

Outcomes of Pregnancies Affected by Gestational Diabetes and Type 2 Diabetes in a Rural First Nations Obstetrical Program in Northwest Ontario.

OBJECTIVES: In this work, we describe diabetes prevalence and birth outcomes in a primarily First Nations obstetrical population in northwest Ontario. METHODS: This retrospective, observational study of maternal and neonatal characteristics and birth outcomes was performed at the Sioux Lookout Meno Ya Win Health Centre between April 1, 2012 and March 31, 2017. RESULTS: The prevalence of pre-existing type 2 diabetes mellitus was 3.7% and gestational diabetes mellitus was 7.9%. Mothers with diabetes, compared to those without diabetes, were, on average, 5 years older and were of greater parity. Average prepregnancy weight was higher, with an increased incidence of hypertension, inductions and caesarean sections. Neonates had increased incidence of macrosomia, hypoglycemia and hyperbilirubinemia. All maternal cohorts had high rates of alcohol, tobacco and illicit opioid use. CONCLUSIONS: We have identified a high prevalence of diabetes in this First Nations obstetrical population, with associated adverse maternal and neonatal outcomes.