Finding significant pathogens in blood cultures in children: Should we set the timer to 36 hours?

Background: Knowledge of time to positivity (TTP) for blood cultures is useful to assess timing of discontinuation of empiric antimicrobials for suspected bacteremia with no focus. Methods: An audit of positive blood cultures from the Children's Hospital of Eastern Ontario (CHEO) from November 1, 2019, to October 31, 2020, was performed to determine TTP, defined as the start of incubation to a positive signal from automated incubators. Results: Three hundred seventy-six positive blood cultures were identified from 248 patients (average age: 6.27 [SD 6.24] years). Of these, 247 isolates were speciated; 90 (36.4%) were definitive/probable (DP) pathogens (median TTP 12.75 hours) and 157 (63.6%) possible/probable (PP) contaminants (median TTP 24.08 hours). At each time point, the adjusted rate of positive blood culture was significantly higher for DP pathogens compared to PP contaminants (hazard ratio [HR] 1.80 [95% CI 1.37, 2.36]) and for children ≤27 days old compared to the oldest age group (HR 1.94 [95% CI 1.19, 3.17]). By 36 hours, the proportion of positive cultures was significantly higher in the youngest age group (≤27 days) compared with the 3-11 years old age group (91.7% [95% CI 68.6%, 97.8%] versus 58.2% [95% CI 46.91%, 68.06%]). Conclusion: Across all ages, the TTP was significantly shorter for blood cultures with DP pathogens compared to those with PP contaminants (HR 1.80 [95% CI 1.37, 2.36]). In newborns, 90% of blood cultures were positive by 36 hours supporting this re-assessment time for empiric antimicrobials. TTP was longer in children ≥12 months, possibly related to other factors such as blood culture volume.

Historique: Il est utile de connaître le délai de positivité (DdP) des hémocultures pour évaluer le moment de mettre un terme aux antimicrobiens empiriques en cas de présomption de bactériémie sans source apparente. Méthodologie: Les chercheurs ont procédé à un audit des hémocultures positives du Centre hospitalier pour enfants de l'est de l'Ontario (CHEO) entre le 1er novembre 2019 et le 31 octobre 2020 pour déterminer le DdP, défini comme la période entre le début de l'incubation et le signal positif d'incubateurs automatisés. Résultats: Les chercheurs ont extrait 376 hémocultures positives provenant de 248 patients (d'un âge moyen de 6,27 ± 6,24 ans). De ce nombre, ils ont différencié 247 isolats, dont 90 (36,4 %) étaient des agents pathogènes confirmés ou probables (CP) (DdP médian de 12,75 heures) et 157 (63,6 %), des contaminants possibles ou probables (PP) (DdP médian de 24,08 heures). À chaque point temporel, le taux corrigé d'hémocultures positives était sensiblement plus élevé à l'égard des agents pathogènes CP que des contaminants PP (rapport de risque instantanés [RRI] : 1,80 [IC à 95 % 1,37,2,36]) et des nouveau-nés de 27 jours de vie ou moins que des enfants plus âgés (RRI 1,94 [IC à 95 % 1,19,3,17]). Au bout de 36 heures, la proportion de cultures positives était sensiblement plus élevée dans le groupe le plus jeune (27 jours de vie ou moins) que dans celui des enfants de trois à 11 ans, soit de 91,7 % (IC à 95 % 68,6 %, 97,8 %) par rapport à 58,2 % (IC à 95 % 46,91 %, 68,06 %). Conclusion: À tout âge, le DdP était sensiblement plus court, à l'égard des hémocultures contenant des agents pathogènes CP que des contaminants PP (RRI 1,80 [IC à 95 % 1,37,2,36]). Chez les nouveau-nés, 90 % des hémocultures sont positives au bout de 36 heures, ce qui appuie ce moment pour réévaluer la prise d'antimicrobiens empiriques. Le DdP était plus long chez les enfants âgés de plus de 12 mois, peut-être à cause d'autres facteurs comme le volume de l'hémoculture.

Ascertaining the Francophone population in Ontario: validating the language variable in health data.

BACKGROUND: Language barriers can impact health care and outcomes. Valid and reliable language data is central to studying health inequalities in linguistic minorities. In Canada, language variables are available in administrative health databases; however, the validity of these variables has not been studied. This study assessed concordance between language variables from administrative health databases and language variables from the Canadian Community Health Survey (CCHS) to identify Francophones in Ontario. METHODS: An Ontario combined sample of CCHS cycles from 2000 to 2012 (from participants who consented to link their data) was individually linked to three administrative databases (home care, long-term care [LTC], and mental health admissions). In total, 27,111 respondents had at least one encounter in one of the three databases. Language spoken at home (LOSH) and first official language spoken (FOLS) from CCHS were used as reference standards to assess their concordance with the language variables in administrative health databases, using the Cohen kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV). RESULTS: Language variables from home care and LTC databases had the highest agreement with LOSH (kappa = 0.76 [95%CI, 0.735-0.793] and 0.75 [95%CI, 0.70-0.80], respectively) and FOLS (kappa = 0.66 for both). Sensitivity was higher with LOSH as the reference standard (75.5% [95%CI, 71.6-79.0] and 74.2% [95%CI, 67.3-80.1] for home care and LTC, respectively). With FOLS as the reference standard, the language variables in both data sources had modest sensitivity (53.1% [95%CI, 49.8-56.4] and 54.1% [95%CI, 48.3-59.7] in home care and LTC, respectively) but very high specificity (99.8% [95%CI, 99.7-99.9] and 99.6% [95%CI, 99.4-99.8]) and predictive values. The language variable from mental health admissions had poor agreement with all language variables in the CCHS. CONCLUSIONS: Language variables in home care and LTC health databases were most consistent with the language often spoken at home. Studies using language variables from administrative data can use the sensitivity and specificity reported from this study to gauge the level of mis-ascertainment error and the resulting bias.

Resilience among organ donation coordinators: a Canadian mixed-methods study.

Background: Organ and Tissue Donation Coordinators (OTDCs) are key to the success of deceased organ donation processes. However, reduced resilience can leave them susceptible to the incidence of work-related issues and decrease the quality of the care provided. Therefore, this study aimed to examine the extent of resilience and influencing aspects among OTDCs in Canada. Methods: Mixed-method (QUAN-qual) explanatory sequential design. Quantitative data was collected using an online cross-sectional survey approach with demographic data and the validated scales and analyzed using descriptive and inferential statistics. Qualitative data was collected using a descriptive approach with a semi-structured interview guide and analyzed using content analysis. Results: One hundred twenty participants responded to the survey, and 39 participants were interviewed. Most participants from the survey were female (82%), registered nurses (97%) and on average 42 years old. The quantitative data revealed that OTDCs had a high level of perceived compassion satisfaction (ProQOL-CS = 36.3) but a resilience score (CD-RISC = 28.5) lower than other groups of healthcare professionals. OTDCs with over a year of experience in the role were more likely to have higher levels of resilience. The qualitative data identified that participants saw resilience as crucial for their work-related well-being. Although coping strategies were identified as a key factor that enhance resilience, many OTDCs reported difficulty in developing healthy coping strategies, and that the use of unhealthy mechanisms (e.g., alcohol and smoking) can result in negative physical consequences (e.g., weight gain) and reduced resilience levels. Conclusion: Participants reported using a series of coping and protective strategies to help build resilience, but also difficulty in developing healthy mechanisms. The lack of healthy coping strategies were seen as contributing to negative work-related issues (e.g., burnout). Our findings are being used to develop tailored interventions to improve resilience and healthy coping strategies among organ donor coordinators in Canada.

Rates of pediatric emergency department visits vary according to neighborhood marginalization in Ottawa, Canada.

OBJECTIVES: To determine the association between neighborhood marginalization and rates of pediatric ED visits in Ottawa, Ontario. Secondary objectives investigated if the association between neighborhood marginalization and rates varied by year, acuity, and distance to hospital. METHODS: We calculated rates of pediatric ED visits per 1000 person-years for census dissemination areas within 100 km of the Children's Hospital of Eastern Ontario for patients < 18 years old from January 2018 through December 2020. The 2016 Ontario Marginalization Index categorized neighborhoods along quintiles of residential instability, material deprivation, ethnic concentration, and dependency. Generalized mixed-effects models determined the incidence rate ratios of pediatric ED visits for each quintile of marginalization; multivariate models were used to control for year of presentation and distance to hospital. Analysis was repeated for low versus high acuity ED visits. RESULTS: There were 154,146 ED visits from patients in 2055 census dissemination areas within 100 km of CHEO from 2018 to 2020. After controlling for year and distance from hospital in multivariate analyses, there were higher rates of pediatric ED visits for dissemination areas with high residential instability, high material deprivation, and low ethnic concentration. These findings did not change according to visit acuity. CONCLUSIONS: Neighborhood residential instability and material deprivation should be considered when locating alternatives to emergency care.

RéSUMé: OBJECTIFS: Déterminer l'association entre la marginalisation du quartier et les taux de visites aux urgences pédiatriques à Ottawa, en Ontario. Les objectifs secondaires visaient à déterminer si l'association entre la marginalisation du quartier et les taux variait selon l'année, l'acuité et la distance à l'hôpital. MéTHODES: Nous avons calculé les taux de visites aux urgences pédiatriques par tranche de 1000 années-personnes dans les aires de diffusion du recensement à moins de 100 km du Centre hospitalier pour enfants de l'est de l'Ontario pour les patients de moins de 18 ans de janvier 2018 à décembre 2020. L'Indice de marginalisation de l'Ontario de 2016 classait les quartiers selon des quintiles d'instabilité résidentielle, de privation matérielle, de concentration ethnique et de dépendance. Les modèles à effets mixtes généralisés ont déterminé les ratios des taux d'incidence des visites aux urgences pédiatriques pour chaque quintile de marginalisation; des modèles multivariés ont été utilisés pour contrôler l'année de présentation et la distance à l'hôpital. L'analyse a été répétée pour les visites à l'urgence de faible acuité par rapport à haute acuité. RéSULTATS: Il y a eu 154 146 visites aux urgences de patients dans 2 055 aires de diffusion du recensement à moins de 100 km du CHEO de 2018 à 2020. Après avoir tenu compte de l'année et de la distance par rapport à l'hôpital dans les analyses multivariées, on a constaté des taux plus élevés de visites aux urgences pédiatriques dans les zones de diffusion présentant une instabilité résidentielle élevée, une privation matérielle élevée et une faible concentration ethnique. Ces résultats n'ont pas changé selon l'acuité de la visite. CONCLUSIONS: L'instabilité résidentielle du quartier et la privation matérielle doivent être prises en compte lors de la recherche de solutions de rechange aux soins d'urgence.

Prevalence and patterns of multimorbidity among linguistic groups of patients receiving home care in Ontario: a retrospective cohort study.

BACKGROUND: Prior studies have demonstrated the negative impact of language barriers on access, quality, and safety of healthcare, which can lead to health disparities in linguistic minorities. As the population ages, those with multiple chronic diseases will require increasing levels of home care and long-term services. This study described the levels of multimorbidity among recipients of home care in Ontario, Canada by linguistic group. METHODS: Population-based retrospective cohort of 510,685 adults receiving home care between April 1, 2010, to March 31, 2018, in Ontario, Canada. We estimated and compared prevalence and characteristics of multimorbidity (2 or more chronic diseases) across linguistic groups (Francophones, Anglophones, Allophones). The most common combinations and clustering of chronic diseases were examined. Logistic regression models were used to explore the main predictors of 'severe' multimorbidity (defined as the presence of five or more chronic diseases). RESULTS: The proportion of home care recipients with multimorbidity and severe multimorbidity was 92% and 44%, respectively. The prevalence of multimorbidity was slightly higher among Allophones (93.6%) than among Anglophones (91.8%) and Francophones (92.4%). However, Francophones had higher rates of cardiovascular and respiratory disease (64.9%) when compared to Anglophones (60.2%) and Allophones (61.5%), while Anglophones had higher rates of cancer (34.2%) when compared to Francophones (25.2%) and Allophones (24.3%). Relative to Anglophones, Allophones were more likely to have severe multimorbidity (adjusted OR = 1.04, [95% CI: 1.02-1.06]). CONCLUSIONS: The prevalence of multimorbidity among Ontarians receiving home care services is high; especially for whose primary language is a language other than English or French (i.e., Allophones). Understanding differences in the prevalence and characteristics of multimorbidity across linguistic groups will help tailor healthcare services to the unique needs of patients living in minority linguistic situations.

Variability in criteria for death determination in the intensive care unit.

PURPOSE: Variability in practice exists in death determination by circulatory criteria in the context of organ donation. We sought to describe the practices of intensive care health care professionals for death determination by circulatory criteria with and without organ donation. METHODS: This study is a retrospective analysis of prospectively collected data. We included patients with death determination by circulatory criteria in intensive care units at 16 hospitals in Canada, three in the Czech Republic, and one in the Netherlands. Results were recorded using a checklist for the determination of death questionnaire. RESULTS: A total of 583 patients had their death determination checklist reviewed for statistical analysis. The mean (standard deviation) age in years was 64 (15). Three hundred and fourteen (54.0%) patients were from Canada, 230 (39.5%) were from the Czech Republic, and 38 (6.5%) were from the Netherlands. Fifty-two (8.9%) patients proceeded with donation after death determination by circulatory criteria (DCD). The most common diagnostic tests reported for the whole group were absent heart sounds by auscultation (81.8%), flat continuous arterial blood pressure (ABP) tracing (77.0%), and flat electrocardiogram tracing (73.2%). In patients who successfully underwent DCD (N = 52), death was determined most frequently using a flat continuous ABP tracing (94%), absent pulse oximetry (85%), and absent palpable pulse (77%). CONCLUSION: In this study, we have described practices for death determination by circulatory criteria both within and between countries. Though some variability exists, we are reassured that appropriate criteria are almost always used in the context of organ donation. In particular, the use of continuous ABP monitoring in DCD was consistent. It highlights the need for standardization of practice and up to date guidelines, especially within the context of DCD where there is both an ethical and a legal requirement to adhere to the dead donor rule, while minimizing time between death determination and organ procurement.

RéSUMé: OBJECTIF: Il existe de la variabilité dans la pratique en matière de détermination du décès selon des critères circulatoires dans le contexte d'un don d'organes. Nous avons cherché à décrire les pratiques des professionnels de la santé en soins intensifs en ce qui touche à la détermination du décès selon des critères circulatoires avec et sans don d'organes. MéTHODE: Cette étude est une analyse rétrospective de données recueillies prospectivement. Nous avons inclus des patients dont le décès avait été déterminé par des critères circulatoires dans les unités de soins intensifs de 16 hôpitaux au Canada, trois en République tchèque et un aux Pays-Bas. Les résultats ont été consignés à l'aide de la liste de contrôle d'un questionnaire sur la détermination du décès. RéSULTATS: Au total, les listes de contrôle pour la détermination du décès de 583 patients ont été examinées à des fins d'analyse statistique. L'âge moyen (écart type) en années était de 64 ans (15). Trois cent quatorze (54,0 %) patients provenaient du Canada, 230 (39,5 %) de la République tchèque et 38 (6,5 %) des Pays-Bas. Cinquante-deux (8,9 %) patients ont procédé au don après la détermination du décès selon des critères circulatoires (DCC). Les tests diagnostiques les plus fréquemment rapportés pour l'ensemble du groupe étaient l'absence de bruits cardiaques à l'auscultation (81,8 %), le tracé plat continu de la tension artérielle (TA) (77,0 %) et le tracé plat à l'électrocardiogramme (73,2 %). Chez les patients ayant été soumis avec succès à un DCD (N = 52), le décès a été déterminé le plus souvent à l'aide d'un tracé continu plat de la TA (94 %), d'une oxymétrie de pouls absente (85 %) et d'un pouls palpable absent (77 %). CONCLUSION: Dans cette étude, nous avons décrit les pratiques de détermination du décès selon des critères circulatoires à la fois à l'intérieur et entre les pays. Bien qu'il existe une certaine variabilité, nous sommes rassurés par le fait que des critères appropriés sont presque toujours utilisés dans le contexte du don d'organes. En particulier, l'utilisation du monitorage continu de la TA était constant en cas de DCC. Cela souligne la nécessité de normaliser la pratique et de disposer de lignes directrices mises à jour, en particulier dans le contexte de DCC où il existe une exigence à la fois éthique et légale de respecter la règle du donneur décédé, tout en minimisant le temps entre la détermination du décès et la collecte d'organes.

A population-based study of factors associated with systemic treatment in advanced prostate cancer decedents.

INTRODUCTION: Life-prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real-world uptake are not well characterized. METHODS: In this cohort of prostate-cancer decedents, we analyzed factors associated with LPT access. Population-level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death. RESULTS: Of 3575 patients who died of prostate cancer, 40.4% (n = 1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium-223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p < 0.0001), driven by uptake of all agents except docetaxel. Adjusted odds of use were higher for patients seen at Regional Cancer Centers (OR: 1.8, 95% CI: 1.5-2.1) and who received prior prostate-directed therapy (OR: 1.3, 95% CI: 1.0-1.5), but lower with advanced age (≥85: OR: 0.54, 95% CI:0.39-0.75), increased chronic conditions (≥6: OR: 0.62, 95% CI: 0.43-0.92), and long-term care residency (OR: 0.38, 95% CI: 0.17-0.89). Income, stage at presentation, and distance to the cancer center were not associated with LPT uptake. CONCLUSION: In this cohort of prostate cancer-decedents, real-world uptake of novel prostate cancer therapies occurred at substantially higher rates for patients receiving care at Regional Cancer Centers, reinforcing the potential benefits for treatment access for patients referred to specialist centers.

Association of distinct features of villitis of unknown etiology histopathology and fetal growth restriction diagnosis in a retrospective cohort from Eastern Ontario.

INTRODUCTION: Villitis of unknown etiology (VUE) is associated with fetal growth restriction (FGR) and adverse short-term neonatal outcomes. No investigation to date has found which VUE features are driving the association with FGR diagnosis. METHODS: A retrospective cohort study of placenta pathology specimens (2013-2017) was conducted. Independent variables of interest were: VUE distribution (focal vs diffuse), location (basal vs non-basal), and grade (high vs low). The primary outcome was FGR, and secondary outcomes were neonatal intensive care unit (NICU) admission, NICU length of stay, Apgar scores <7 at 1, 5, and 10-min, and recurrence rate of villitis in subsequent pregnancies. Association between VUE characteristics and our primary outcome were investigated using logistic regression. Secondary outcomes were explored with regression analyses and recurrence rate of VUE for members of the cohort with a recorded subsequent pregnancy was calculated. RESULTS: One hundred and twenty seven placentas were included. Adjusted models showed no difference in the odds of FGR between high-grade versus low-grade VUE [aOR 1.25 95% CI (0.50, 3.26), p = 0.6], focal/multi-focal vs diffuse cases [aOR 1.03 95% CI (0.28, 4.34), p = >0.9], and basal vs non-basal VUE [aOR 0.06 95% CI (0.00, 1.10), p = 0.058]. After adjusting for prematurity <37 weeks, there were lower odds of NICU admission in basal vs non-basal cases [aOR 0.25, 95% CI (0.06, 0.90), p = 0.048). There was no difference in the odds of neonates presenting with Apgar <7 for the distinct VUE histopathology features. Three cases had recurrent VUE, resulting in a 6.8% [95% CI (3.02%, 10.61%)] recurrence rate. All recurrent cases were high-grade and identified with basal localization. DISCUSSION: There are no statistical associations between distinct VUE features and FGR diagnosis, however location of villitis may be associated with worse neonatal outcomes. Villitis of any type (severity, degree, location) could potentially drive insufficient placental function and poor fetal growth.

Factors associated with hypothermia within the first 6 hours of life in infants born at ≥340 weeks' gestation: a multivariable analysis.

BACKGROUND: Lack of appropriate temperature management has been associated with significant adverse outcomes in preterm and low birthweight neonates. There is a lack of similar investigations in the late preterm (340-366) and term (≥370) neonate population. Our aim was to identify key risk factors as well as clinical outcomes associated with hypothermia in this population. METHODS: A retrospective chart review was conducted at the Ottawa Hospital including all eligible infants ≥340 weeks' gestation over a one-month period in November 2020. Infant, maternal, and delivery room variables were collected, including prematurity, maternal temperature, delivery mode, birthweight, and premature rupture of membranes, as well as clinical outcomes such as NICU/SCN admission and length of stay. Regression models were generated, adjusted for covariates, and stepwise regression was performed. RESULTS: Four hundred forty infants were included in the analysis; 26.8% (118/440) were hypothermic within 6 hours of delivery. In the multivariable analysis, prematurity, low 5 minute Apgar score (< 7) or need for resuscitation, maternal hypertension, and absence of premature rupture of membranes > 18 hours or suspected maternal infection were significantly associated with hypothermia within 6 hours of delivery (p < 0.05). Multivariable analysis of clinical outcomes demonstrated a significant association between hypothermia within 6 hours of delivery and NICU/SCN admission (OR = 2.87; 95% CI 1.36, 6.04), need for respiratory support or diagnosis of respiratory distress syndrome (OR = 3.94; 95% CI 1.55, 10.50), and length of stay (exp(ß) = 1.20; 95% bootstrap CI 1.04, 1.37). CONCLUSIONS: Our results suggest there are similar factors associated with hypothermia in our study population of infants born at ≥340 weeks' gestation compared to prior studies in preterm and low-birthweight infants. Furthermore, hypothermia is associated with higher risk of adverse outcomes, which highlights the need to prevent hypothermia in all newborns.

A Bibliometric Analysis of Publication Patterns in Pediatric Neurology.

Purpose: To examine the publication patterns of pediatric neurology articles in general pediatric, general neurology, and neurology subspecialty journals using a bibliometric approach. Methods: The top 5 journals in general pediatrics, general neurology and neurology subspecialties were identified using the 2017 Journal Citations Report (JCR). For general pediatric journals, we selected 4 pediatric subspecialties for comparison of publication patterns with neurology: immunology, endocrinology, gastroenterology, and respirology. For general neurology and neurology subspecialty journals, we searched both the top 5 neurology and neurology subspecialty journals for pediatric articles. Using Ovid Medline, we identified articles published between 2009-2017. Results: With regards to child neurology-based articles, 1501 were published in general pediatrics journals, 643 in general neurology journals and 685 in neurology subspecialty journals. Examination of the top pediatric journals revealed that Pediatrics published the most neurology-based articles. Neurology-based studies were published more frequently than other pediatric subspecialty studies. Of the top general neurology Neurology published the most child neurology-based articles, while Epilepsia published the most child neurology-based articles out of neurology subspecialty journals. Cohort studies were the most frequent study type across all journals. Conclusion: Our study revealed that child neurology articles are published more often in pediatric journals as opposed to general neurology and neurology subspecialty journals. We also found that in general pediatric journals, neurology-based articles are published more frequently compared to other specialties. Our results provide guidance to authors when considering submission of their pediatric neurology research.

Therapeutic Hypothermia on Transport: The Quest for Efficiency: Results of a Quality Improvement Project.

Introduction: Therapeutic hypothermia (TH) within 6 hours after birth is known to improve both survival and neurodevelopmental outcomes in neonates with hypoxic ischemic encephalopathy (HIE). Meeting this recommended target temperature for neonates who require transport for TH treatment can be complex for various reasons. This study aimed to reduce the time from birth to the initiation of TH and target temperature, thereby increasing the proportion of transported neonates reaching target temperature within 6 hours to >50%. Methods: We evaluated the effect of three quality improvement interventions, including revised transport team processes, outreach education/resources, and the use of a servo-controlled cooling device on land transports. We compared key outcome TH metrics for cohorts before and after implementation. Results: The study team compared baseline data for 77 to 102 neonates born between 2009 and April 2015 (preintervention) and September 2015 and September 2020 (postintervention(s)). We observed reductions in both the time from birth to the initiation of passive cooling (38%) and time to reach target TH temperature (23%), with an increase in the proportion of neonates reaching target temperature by 6 hours of age from 50% to 71%. Conclusions: We used quality improvement methodology to identify key areas for intervention(s) and improvement. Targeted interventions have successfully and consistently improved the timing and delivery of TH to neonates with hypoxic ischemic encephalopathy within the transport environment, with a 20% increase in neonates reaching target temperature by 6 hours of age.

Amiodarone, Verapamil, or Diltiazem Use With Direct Oral Anticoagulants and the Risk of Hemorrhage in Older Adults.

Background: Routinely used cardiac medications, based on pharmacokinetics, are hypothesized to increase drug levels of direct oral anticoagulants (DOACs), with the potential to increase the risk of hemorrhage. We set out to compare the risk for hemorrhage following initiation of amiodarone, verapamil, or diltiazem (moderate cytochrome P450 3A4 and/or P-glycoprotein activity) vs metoprolol or amlodipine (weak or no activity), among older adults prescribed DOACs. Methods: We conducted a population-based, retrospective cohort study of all adults (aged ≥ 66 years) on a DOAC (dabigatran, apixaban, rivaroxaban; n = 295,038) who were newly prescribed amiodarone (n = 4872), verapamil (n = 1284), or diltiazem (n = 14,638), compared with metoprolol or amlodipine, from Ontario, Canada (2009-2016). The outcome was hospital admission or emergency room visit with a major hemorrhage (upper or lower gastrointestinal tract, intracranial), examined using weighted models. Results: A total of 1737 hemorrhage events occurred (amiodarone, 80 [1.6%] vs metoprolol 503 [2.3%]; verapamil, 32 [2.5%] vs amlodipine, 406 [1.6%]; diltiazem, 312 [2.1%] vs amlodipine, 404 [1.5%]). The weighted risk of major hemorrhage was not elevated with amiodarone, verapamil, or diltiazem initiation in DOAC users, compared to metoprolol or amlodipine, during the full follow-up period (hazard ratio [HR; 95% confidence interval]: amiodarone HR 0.77 [0.61-0.97]; verapamil HR 1.32 [0.88-1.98]; diltiazem HR 0.99 [0.85-1.15]). This finding was consistent with a broader definition of bleeding, adjusting for kidney function, by DOAC type or dosage. Conclusions: Hemorrhage risk with amiodarone, verapamil, and diltiazem was similar to that with comparators, among DOAC users aged > 66 years.

Contexte: Les médicaments cardiaques couramment utilisés, selon la pharmacocinétique, devraient théoriquement augmenter les taux d'anticoagulants oraux directs (AOD), ce qui s'accompagne d'un risque accru d'hémorragie. Nous avons entrepris de comparer le risque d'hémorragie après l'instauration de l'amiodarone, du vérapamil ou du diltiazem (activité modérée du cytochrome P450 3A4 ou de la P-glycoprotéine) par rapport au métoprolol ou à l'amlodipine (activité faible ou nulle), chez des personnes âgées à qui l'on avait prescrit des AOD. Méthodologie: Nous avons mené une étude de cohortes rétrospective en population auprès de tous les adultes (âgés de 66 ans et plus) prenant un AOD (dabigatran, apixaban, rivaroxaban; n = 295 038) à qui l'on venait de prescrire de l'amiodarone (n = 4872), du vérapamil (n = 1284) ou du diltiazem (n = 14 638), comparativement au métoprolol ou à l'amlodipine, en Ontario, au Canada (2009-2016). Le critère d'évaluation était une admission à l'hôpital ou une consultation à l'urgence pour une hémorragie grave (voie gastro-intestinale supérieure ou inférieure, intracrânienne), examiné à l'aide de mo-dèles pondérés. Résultats: Au total, 1 737 événements hémorragiques sont survenus (amiodarone, 80 [1,6 %] contre métoprolol, 503 [2,3 %]; vérapamil, 32 [2,5 %] contre amlodipine, 406 [1,6 %]; diltiazem, 312 [2,1 %] contre amlodipine, 404 [1,5 %]). Le risque pondéré d'hémorragie grave ne s'est pas accru avec l'instauration de l'amiodarone, du vérapamil ou du diltiazem chez les utilisateurs d'AOD, comparativement au métoprolol ou à l'amlodipine, pendant toute la période de suivi (rapport des risques instantanés [RRI; intervalle de confiance à 95 %] : amiodarone : RRI 0,77 [0,61-0,97]; vérapamil : RRI 1,32 [0,88-1,98]; diltiazem : RRI 0,99 [0,85-1,15]). Ce résultat concorde avec une définition plus large du saignement, après ajustement pour la fonction rénale, par type ou posologie d'AOD. Conclusions: Le risque d'hémorragie associé à l'amiodarone, au vérapamil et au diltiazem était semblable à celui des médicaments de comparaison chez les utilisateurs d'AOD âgés de plus de 66 ans.

Hyperkalemia-Related Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Renin-angiotensin-aldosterone system (RAAS) inhibitors are evidence-based therapies that slow the progression of chronic kidney disease (CKD) but can cause hyperkalemia. We aimed to evaluate the association of discontinuing RAAS inhibitors after an episode of hyperkalemia and clinical outcomes in patients with CKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults in Manitoba (7,200) and Ontario (n = 71,290), Canada, with an episode of de novo RAAS inhibitor-related hyperkalemia (serum potassium ≥ 5.5 mmol/L) and CKD. EXPOSURE: RAAS inhibitor prescription. OUTCOME: The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, fatal and nonfatal CV events, dialysis initiation, and a negative control outcome (cataract surgery). ANALYTICAL APPROACH: Cox proportional hazards models examined the association of RAAS inhibitor continuation (vs discontinuation) and outcomes using intention to treat approach. Sensitivity analyses included time-dependent, dose-dependent, and propensity-matched analyses. RESULTS: The mean potassium and mean estimated glomerular filtration rate were 5.8 mEq/L and 41 mL/min/1.73 m2, respectively, in Manitoba; and 5.7 mEq/L and 41 mL/min/1.73 m2, respectively, in Ontario. RAAS inhibitor discontinuation was associated with a higher risk of all-cause mortality (Manitoba: HR, 1.32 [95% CI, 1.22-1.41]; Ontario: HR, 1.47 [95% CI, 1.41-1.52]) and CV mortality (Manitoba: HR, 1.28 [95% CI, 1.13-1.44]; and Ontario: HR, 1.32 [95% CI, 1.25-1.39]). RAAS inhibitor discontinuation was associated with an increased risk of dialysis initiation in both cohorts (Manitoba: HR, 1.65 [95% CI, 1.41-1.85]; Ontario: HR, 1.11 [95% CI, 1.08-1.16]). LIMITATIONS: Retrospective study and residual confounding. CONCLUSIONS: RAAS inhibitor discontinuation is associated with higher mortality and CV events compared with continuation among patients with hyperkalemia and CKD. Strategies to maintain RAAS inhibitor treatment after an episode of hyperkalemia may improve clinical outcomes in the CKD population.

Primary care bonus payments and patient-reported access in urban Ontario: a cross-sectional study.

BACKGROUND: Rurality strongly correlates with higher pay-for-performance access bonuses, despite higher emergency department use and fewer primary care services than in urban settings. We sought to evaluate the relation between patient-reported access to primary care and access bonus payments in urban settings. METHODS: We conducted a cross-sectional, secondary data analysis using Ontario survey and health administrative data from 2013 to 2017. We used administrative data to calculate annual access bonuses for eligible urban family physicians. We linked this payment data to adult (≥ 16 yr) patient data from the Health Care Experiences Survey to examine the relation between access bonus achievement (in quintiles of the proportion of bonus achieved, from lowest [Q1, reference category] to highest [Q5]) and 4 patient-reported access outcomes. The average survey response rate to the patient survey during the study period was 51%. We stratified urban geography into large, medium and small settings. In a multilevel regression model, we adjusted for patient-, physician- and practice-level covariates. We tested linear trends, adjusted for clustering, for each outcome. RESULTS: We linked 18 893 respondents to 3940 physicians in 414 bonus-eligible practices. Physicians in small urban settings earned the highest proportion of their maximum potential access bonuses. Access bonus achievement was positively associated with telephone access (Q2 odds ratio [OR] 1.18, 95% confidence interval [CI] 0.98-1.42; Q3 OR 1.34, 95% CI 1.10-1.63; Q4 OR 1.46, 95% CI 1.19-1.79; Q5 OR 1.87, 95% CI 1.50-2.33), after hours access (Q2 OR 1.26, 95% CI 1.09-1.47; Q3 OR 1.46, 95% CI 1.23-1.74; Q4 OR 1.77, 95% CI 1.46-2.15; Q5 OR 1.88, 95% CI 1.52-2.32), wait time for care (Q2 OR 1.01, 95% CI 0.85-1.20; Q3 OR 1.17, 95% CI 0.97-1.41; Q4 OR 1.27, 95% CI 1.05-1.55; Q5 OR 1.63, 95% CI 1.32-2.00) and timeliness (Q2 OR 1.29, 95% CI 0.98-1.69; Q3 OR 1.29, 95% CI 0.94-1.77; Q4 OR 1.58, 95% CI 1.16-2.13; Q5 OR 1.98, 95% CI 1.38-2.82). When stratified by geography, we observed several of these associations in large urban settings, but not in small urban settings. Trend tests were statistically significant for all 4 outcomes. INTERPRETATION: Although the access bonus correlated with access in larger urban settings, it did not in smaller settings, aligning with previous research questioning its utility in smaller geographies. The access bonus may benefit from a redesign that considers geography and patient experience.

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

BACKGROUND AND OBJECTIVES: Maternal immunization with tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is routinely recommended in many countries as a strategy to protect young infants against severe pertussis infection; few studies have assessed whether prenatal exposure to the vaccine is associated with any longer-term adverse health effects in children. We evaluated the long-term safety of exposure to Tdap vaccination during pregnancy. METHODS: Population-based retrospective cohort study conducted in Ontario, Canada using multiple linked province-wide health administrative databases. All live births between April 2012 and March 2017 were included, and children were followed for up to 6 years to ascertain study outcomes. Children exposed to prenatal Tdap were propensity score matched to unexposed children at a 1:5 ratio. Tdap vaccination during pregnancy was ascertained by using vaccine-specific fee codes. Immune-related (infectious diseases, asthma) and nonimmune-related (neoplasm, sensory disorders) outcomes and a nonspecific morbidity outcome (urgent or inpatient health service use) were evaluated from birth to end of follow-up. RESULTS: Of 625 643 live births, 12 045 (1.9%) were exposed to Tdap in utero. There were no significant increased risks of adverse childhood outcomes and prenatal Tdap exposure; however, we observed inverse associations (adjusted incidence rate ratio [95% confidence interval]) with upper respiratory infections (0.94 [0.90-0.99]), gastrointestinal infections (0.85 [0.79-0.91]), and urgent and inpatient health service use (0.93 [0.91-0.96]). CONCLUSIONS: Exposure to Tdap vaccination in pregnancy was not associated with any increased risk of adverse health outcomes in early childhood, supporting the long-term safety of Tdap administration in pregnancy.

Obstetric and perinatal health outcomes after pertussis vaccination during pregnancy in Ontario, Canada: a retrospective cohort study.

BACKGROUND: In February 2018, Canada's National Advisory Committee on Immunization recommended maternal vaccination with tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy to prevent severe pertussis infection in young infants. This study assessed the relation between maternal Tdap vaccination and obstetric and perinatal outcomes in Ontario. METHODS: We performed a population-based cohort study of all births from April 2012 to March 2017 using multiple linked health administrative databases. We used Cox regression with a time-dependent exposure variable to estimate adjusted hazard ratios (HRs) for preterm birth (< 37 wk), very preterm birth (< 32 wk) and stillbirth. We assessed remaining outcomes (gestational hypertension, chorioamnionitis, postpartum hemorrhage, severe postpartum hemorrhage, being small for gestational age, neonatal intensive care unit stay > 24 h, composite neonatal morbidity) using log-binomial regression to generate adjusted risk ratios (RRs). We adjusted estimates for potential confounding using propensity score weighting. RESULTS: Of 615 213 infants (live births and stillbirths), 11 519 were exposed to Tdap vaccination in utero. There was no increased risk for preterm birth (adjusted HR 0.98, 95% confidence interval [CI] 0.91-1.06), very preterm birth (adjusted HR 1.10, 95% CI 0.86-1.41), stillbirth (adjusted HR 1.15, 95% CI 0.82-1.60) or being small for gestational age (adjusted RR 0.96, 95% CI 0.90-1.02). The risks of a neonatal intensive care unit stay exceeding 24 hours (adjusted RR 0.82, 95% CI 0.76-0.88) and neonatal morbidity (adjusted RR 0.81, 95% CI 0.75-0.87) were decreased. There was no association with chorioamnionitis (adjusted RR 1.17, 95% CI 0.99-1.39), postpartum hemorrhage (adjusted RR 1.01, 95% CI 0.91-1.13) or severe postpartum hemorrhage (adjusted RR 0.79, 95% CI 0.55-1.13), but we observed a reduced risk of gestational hypertension (adjusted RR 0.87, 95% CI 0.78-0.96). INTERPRETATION: Our results complement evidence that maternal Tdap vaccination is not associated with adverse outcomes in mothers or infants. Ongoing evaluation in Canada is needed as maternal Tdap vaccination coverage increases in coming years.

Does Housing Improve Health Care Utilization and Costs? A Longitudinal Analysis of Health Administrative Data Linked to a Cohort of Individuals With a History of Homelessness.

BACKGROUND: Individuals who are homeless have complex health care needs, which contribute to the frequent use of health services. In this study, we investigated the relationship between housing and health care utilization among adults with a history of homelessness in Ontario. METHODS: Survey data from a 4-year prospective cohort study were linked with administrative health records in Ontario. Annual rates of health encounters and mean costs were compared across housing categories (homeless, inconsistently housed, housed), which were based on the percentage of time an individual was housed. Generalized estimating equations were applied to estimate the average annual effect of housing status on health care utilization and costs. RESULTS: Over the study period, the proportion of individuals who were housed increased from 37% to 69%. The unadjusted rates of ambulatory care visits, prescription medications, and laboratory tests were highest during person-years spent housed or inconsistently housed and the rate of emergency department visits was lowest during person-years spent housed. Following adjustment, the rate of prescription claims remained higher during person-years spent housed or inconsistently housed compared with the homeless. Rate ratios for other health care encounters were not significant (P>0.05). An interaction between time and housing status was observed for total health care costs; as the percentage of days housed increased, the average costs increased in year 1 and decreased in years 2-4. CONCLUSIONS: These findings highlight the effects of housing on health care encounters and costs over a 4-year study period. The rate of prescription medications was higher during person-years spent housed or inconsistently housed compared with the homeless. The cost analysis suggests that housing may reduce health care costs over time; however, future work is needed to confirm the reason for the reduction in total costs observed in later years.

Association of frailty with days alive at home after cardiac surgery: a population-based cohort study.

BACKGROUND: Frailty is a geriatric syndrome that leaves people vulnerable to adverse outcomes. In cardiac surgery, minimal data describe associations between frailty and patient-centred outcomes. Our objective was to estimate the association between frailty and days alive at home after cardiac surgery. METHODS: We conducted a population-based cohort study using linked health administrative data in the Canadian province of Ontario. All individuals >65 yr at the time of cardiac surgery were assigned a frailty score using a validated frailty index. Days alive and at home in the 30 and 365 days after surgery were calculated. The unadjusted and adjusted associations between frailty and days alive at home were calculated. RESULTS: We identified 61 389 patients from 2009 to 2015. Frailty was associated with reduced days at home within 30 days (adjusted ratio of means for every 10% increase in frailty=0.79; 95% confidence interval [CI], 0.78-0.81; P<0.0001) and 365 days (adjusted ratio of means for every 10% increase in frailty=0.92; 95% CI, 0.91-0.93; P<0.0001) of surgery. Results were consistent in sensitivity analyses (5.0 fewer days alive at home [95% CI, 4.8-5.2] within 30 days and 9.0 fewer days alive at home [95% CI, 8.7-9.2] within 365 days after surgery). CONCLUSION: Frailty is associated with a reduction in days alive at home after major cardiac surgery. This information should be considered in prognostic discussions before surgery and in care planning for vulnerable older patient groups. Days alive at home may be a useful outcome for routine measurement in quality, reporting, and studies using routinely collected data.

Maternal cannabis use in pregnancy and child neurodevelopmental outcomes.

Cannabis use in pregnancy has increased1,2, and many women continue to use it throughout pregnancy3. With the legalization of recreational cannabis in many jurisdictions, there is concern about potentially adverse childhood outcomes related to prenatal exposure4. Using the provincial birth registry containing information on cannabis use during pregnancy, we perform a retrospective analysis of all live births in Ontario, Canada, between 1 April 2007 and 31 March 2012. We link pregnancy and birth data to provincial health administrative databases to ascertain child neurodevelopmental outcomes. We use matching techniques to control for confounding and Cox proportional hazards regression models to examine associations between prenatal cannabis use and child neurodevelopment. We find an association between maternal cannabis use in pregnancy and the incidence of autism spectrum disorder in the offspring. The incidence of autism spectrum disorder diagnosis was 4.00 per 1,000 person-years among children with exposure compared to 2.42 among unexposed children, and the fully adjusted hazard ratio was 1.51 (95% confidence interval: 1.17-1.96) in the matched cohort. The incidence of intellectual disability and learning disorders was higher among offspring of mothers who use cannabis in pregnancy, although less statistically robust. We emphasize a cautious interpretation of these findings given the likelihood of residual confounding.

Pathways from parenting practices to adolescent suicidality: Evidence on the role of emotional and behavioral symptoms from a prospective cohort of Canadian children.

OBJECTIVE: To investigate longitudinal relationships between parenting practices in childhood and adolescent suicidality, and assess the mediating role of emotional and behavioral symptoms. METHODS: Data were drawn from the National Longitudinal Survey of Children and Youth, a Canadian population-based longitudinal cohort study. The sample included 9,490 children aged 10-11 who were followed up biennially to ages 14-15. Parents reported their positive and punitive parenting practices when children were 10-11. Adolescents self-reported symptoms of depression/anxiety, hyperactivity, conduct disorder, and social aggression at 12-13, and past-year suicidal ideation and suicide attempts at 14-15. RESULTS: The inverse associations between positive parenting at 10-11 and suicidal behaviors at 14-15 were significantly mediated by symptoms of hyperactivity, conduct disorder, and social aggression at 12-13. Direct relationships between punitive parenting and suicidal behaviors were observed. These associations were significantly mediated by hyperactivity and, among boys only, by conduct disorder and social aggression. The association between punitive parenting and suicide attempt was additionally mediated by depression/anxiety. CONCLUSIONS: Parenting in childhood may be associated with adolescent suicidality both directly and indirectly through emotional and behavioral symptoms. Interventions aimed at reducing the use of harsh disciplinary strategies and promoting positive parent-child interactions may reduce the burden of adolescent suicidality.