Outcomes following heart or bilateral-lung transplantation from donors who died of drug toxicity in British Columbia, Canada.

INTRODUCTION: The illicit drug toxicity (overdose) crisis has worsened across Canada; between 2016 and 2021, more than 28,000 individuals have died of drug toxicity. Organ donation from persons who experience drug toxicity death (DTD) has increased in recent years. This study examines whether survival after heart or bilateral-lung transplantation differed by donor cause of death. METHODS: We studied transplant recipients in British Columbia who received heart (N = 110) or bilateral-lung (N = 223) transplantation from deceased donors aged 12-70 years between 2013 and 2019. Transplant recipient survival was compared by donor cause of death from drug toxicity or other. Five-year Kaplan-Meier estimates of survival and 3-year inverse probability treatment weighted Cox proportional hazards models were conducted. RESULTS: DTD donors made up 36% (40/110) of heart and 24% (54/223) of bilateral-lung transplantations. DTD donors were more likely to be young, white, and male. Unadjusted 5-year recipient survival was similar by donor cause of death (heart: 87% for DTD and 86% for non-DTD, p = .75; bilateral- lung: 80% for DTD and 76% for non-DTD, p = .65). Adjusted risk of mortality at 3-years post-transplant was similar between recipients of DTD and non-DTD donor heart (hazard ratio [HR]: .94, 95% confidence interval (CI): .22-4.07, p = .938) and bilateral-lung (HR: 1.06, 95% CI: .41-2.70, p = .908). CONCLUSION: Recipient survival after heart or bilateral-lung transplantation from DTD donors and non-DTD donors was similar. Donation from DTD donors is safe and should be considered more broadly to increase organ donation.

Association between antibiotic usage during infancy and asthma incidence among children: a population-level ecological study in British Columbia, Canada.

Background: This study follows published associations in BC to 2014 (updated in 2019) to model the predicted incidence of asthma in BC children attributable to antibiotic use within the context of reduced antibiotic use and increased breastfeeding in BC infants from 2000 to 2019. Methods: A population-based ecological study was conducted in BC from 2000 to 2019, using outpatient antibiotic prescription data from BC PharmaNet and asthma diagnoses from the Chronic Disease Registry. Breastfeeding estimates were calculated using the Canadian Community Health Survey (CCHS). Population attributable risk (PAR) was calculated using a blended relative risk (RR) of asthma in antibiotic-exposed children who were and were not breastfed. PAR was used to calculate predicted vs. actual asthma incidence in 2019. Negative binomial regression was used to estimate the association between the average antibiotic prescription rate in infants under 1 and asthma incidence in 1-4 year olds, stratified by periods between 2000-2014 and 2015-2019. Results: In BC, antibiotic prescribing decreased by 77% in infants under 1 and asthma incidence decreased by 41% in children 1-4 years from 2000 to 2019. BC breastfeeding rates increased from 46% in the 2005 CCHS to 71% in the 2017/18 CCHS. After calculating the PAR using a blended RR, the predicted asthma incidence in 2019 was 18.8/1,000 population. This was comparable to the observed asthma incidence in children 1-4 years of 16.6/1,000 population in 2019. During 2000-2014, adjusted incidence risk ratio (aIRR) for children under Quintile 5 of average antibiotic prescribing was 1.75 (95% CI: 1.63-1.88, P < 0.0001) times higher than that for Quintile 1. However, between 2015 and 2019, this association weakened (as expected because of increasing prevalence of breastfeeding), with the expected asthma incidence for Quintile 5 only 11% (aIRR 1.11, 95% CI: 0.78-1.57) higher than for Quintile 1. Conclusion: We identified that over the past 20 years, antibiotic exposure in infants under 1 and asthma incidence in children 1-4 years has decreased significantly. Decreasing antibiotic exposure and increasing breastfeeding (which further mitigates risk associated with antibiotics) are of sufficient scale to explain much of this population trend. Changes in environmental, social and other exposures remain relevant to this complicated etiological pathway.

Observational Study Examining Kidney Transplantation Outcomes Following Donation From Individuals That Died of Drug Toxicity in British Columbia, Canada.

Background: The illicit drug toxicity (overdose) crisis has worsened across Canada, between 2016 and 2021 more than 28 000 individuals have died of drug toxicity. Organ donation from persons who experience drug toxicity death has increased in recent years. Objective: This study examines whether graft loss after kidney transplantation differed by donor cause of death. Design: Retrospective cohort. Setting: Provincial transplant program of British Columbia, Canada. Patients: Transplant recipients who received kidney transplantation from deceased donors aged 12 to 70 years between 2013 and 2019 (N = 1012). Measurements: Transplant recipient all cause graft loss (graft loss due to any cause including death) was compared by donor cause of death from drug toxicity or other. Methods: Five-year Kaplan-Meier estimates of all-cause graft survival, and 3-year complete as well as stratified inverse probability of treatment weighted Cox proportional hazards models were conducted. Results: Drug toxicity death donors donated to 25% (252/1012) of kidney transplantations. Drug toxicity death donors were more likely to be young, white, males, with fewer comorbidities such as diabetes or hypertension but were more likely to have a terminal serum creatinine ≥1.5 mg/dL or be hepatitis C virus (HCV) positive. Unadjusted 5-year estimate of all-cause graft survival was 97% for recipients of drug toxicity donor kidneys and 83% for recipients of non-drug toxicity donor kidneys (P < .001). Recipients of drug toxicity death donor kidneys had decreased risk of all cause graft loss compared to recipients of non-drug toxicity death donor kidneys (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.12-0.77, P = .012). This is primarily due to the reduced risk of all-cause graft loss for recipients of younger (≤35 years) drug toxicity death donor kidneys (HR: 0.05, 95% CI: 0.00-0.55, P = .015). Limitations: Potential selection bias, potential unmeasured confounding. Conclusions: Donation after drug toxicity death is safe and should be considered more broadly to increase deceased donor kidney donation.

Contexte: La crise liée à la toxicité des drogues illicites (surdose) s'est aggravée partout au Canada. Entre 2016 et 2021, plus de 28 000 personnes sont mortes en raison de la toxicité des drogues. Les dons d'organes provenant de personnes décédées d'une surdose ont augmenté dans les dernières années. Objectif: Déterminer si la cause de décès du donneur influe sur la survie du greffon après une transplantation rénale. Conception: Étude de cohorte rétrospective. Cadre: Program provincial de transplantation de la Colombie-Britannique (Canada). Sujets: Des receveurs (N=1012) d'une greffe de rein entre 2013 et 2019 dont l'organe provenait de donneurs décédés âgés de 12 à 70 ans. Mesures: La perte du greffon toutes causes confondues (y compris le décès du receveur) a été comparée selon la cause de décès du donneur, que celle-ci soit attribuable à une surdose ou à une autre cause. Méthodologie: Des estimations de Kaplan-Meier de la survie de la greffe toutes causes confondues à 5 ans et à 3 ans ont été réalisées, ainsi que des modèles de risques proportionnels de Cox à probabilité inverse de traitements pondérés. Résultats: Les donneurs décédés par surdose comptaient pour 25 % (252/1012) des organes reçus pour les transplantations rénales. Les donneurs dont le décès était attribuable à une surdose étaient plus susceptibles d'être de jeunes hommes blancs présentant moins de comorbidités comme le diabète ou l'hypertension, mais plus susceptibles d'avoir un taux de créatinine sérique terminal d'au moins 1,5 mg/dl ou d'être positifs pour l'hépatite C. L'estimation non corrigée de la survie du greffon toutes causes confondues après 5 ans était de 97 % pour les reins provenant de donneurs décédés d'une surdose et de 83 % pour les reins provenant de donneurs décédés d'une autre cause (p < 0,001). Les receveurs d'un rein provenant d'un donneur décédé par surdose présentaient un plus faible risque de perte du greffon toutes causes confondues comparativement aux receveurs d'un rein de donneur décédé d'une autre cause (risque relatif [RR]: 0,30; intervalle de confiance à 95 % [IC 95 %]: 0,12-0,77; p=0,012). Ces résultats sont principalement attribuables à un plus faible risque de perte du greffon toutes causes confondues lorsque le rein provient d'un donneur plus jeune (≤ 35 ans) même si ce dernier est décédé de surdose (RR: 0,05; IC 95 %: 0,00-0,55; p=0,015). Limites: Possible biais de sélection; possibles facteurs de confusion non mesurés. Conclusion: Le don d'organes à la suite d'un décès par surdose est sans danger et devrait être envisagé plus largement afin d'augmenter les dons de reins par des donneurs décédés.

Investigating the effect of early life antibiotic use on asthma and allergy risk in over 600 000 Canadian children: a protocol for a retrospective cohort study in British Columbia and Manitoba.

INTRODUCTION: Allergic conditions, such as asthma, hay fever and eczema, are some of the most common conditions impacting children globally. There is a strong incentive to study their determinants to improve their prevention. Asthma, hay fever and eczema are influenced through the same immunological pathway and often copresent in children ('the atopic march'). Increasing evidence shows a link between infant antibiotic use and the risk of childhood atopic conditions, mediated through gut microbial dysbiosis during immune system maturation, however, the potential for confounding remains. This study will investigate the relationship between infant antibiotic use and risk of allergic conditions in British Columbian and Manitoban children born over 10 years, adjusting for relevant confounders. METHODS AND ANALYSIS: Provincial administrative datasets will be linked to perform comparable retrospective cohort analyses, using Population Data BC and the Manitoba Population Research Data Repository. All infants born between 2001 and 2011 in BC and Manitoba will be included (approximately 460 000 and 162 500 infants, respectively), following up to age 7. Multivariable logistic regression will determine the outcome risk by the fifth birthday among children who did and did not receive antibiotics before their first birthday. Clinical, demographic and environmental covariates will be explored, and sensitivity analyses performed to reduce confounding by indication. ETHICS AND DISSEMINATION: The University of British Columbia Research Ethics Board (H19-03255) and University of Manitoba Ethics Board (HS25156 (H2021:328)) have approved this study. Data stewardship committees for all administrative datasets have granted permissions, facilitated by Population Data BC and the Manitoba Centre for Health Policy. Permissions from the Canadian Health Infant Longitudinal Development Study are being sought for breastfeeding data (CP185). Findings will be published in scientific journals and presented at infectious disease and respiratory health conferences. A stakeholder committee will guide and enhance sensitive and impactful communication of the findings to new parents.

Community Antibiotic Use at the Population Level During the SARS-CoV-2 Pandemic in British Columbia, Canada.

BACKGROUND: The objective of this study was to examine the aggregate rates of antibiotic use at the population level and compare these rates over time against historical averages to identify the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting control measures on community prescribing. METHODS: We collected antibiotic prescriptions and physician office visits from January 1, 2016, to July 21, 2020. We calculated monthly prescription rates stratified by sex, age group, profession, diagnosis type, and antibiotic class. We looked at monthly prescription rate as a moving average over time. Using the interrupted time series analysis method, we estimated the changes in prescription rates after March 2020. RESULTS: The moving average of overall monthly prescription rates during January-June 2020 was below the minimum of the historical years' moving averages (2016-2019). We observed a >30% reduction in overall monthly prescription rates in April, May, and July of 2020 compared with the same months of 2019. We observed that overall monthly prescription rates experienced a significant level change of -12.79 (P < .001) during the coronavirus disease 2019 pandemic after March 2020, with the greatest level change being -18.02 among children 1-4 years of age (P < .001). We estimated an average -5.94 (P < .001) change in respiratory tract infection (RTI)-associated monthly prescription rates after March 2020. Overall prescription rates comparing January-July 2019 and their 2020 counterparts showed a decrease in monthly prescribing ranging from -1 to -5 for amoxicillin, amoxicillin and enzyme inhibitors, azithromycin, clarithromycin, and sulfamethoxazole. CONCLUSIONS: In British Columbia, Canada, overall and RTI-specific monthly antibiotic prescription rates declined significantly during April-July 2020 compared with the same months in prepandemic years.