Effect of Donor Sex on Recipient Mortality in Transfusion.

BACKGROUND: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS: A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS: This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

Serological markers and long COVID-A rapid systematic review.

BACKGROUND: Long COVID is highly heterogeneous, often debilitating, and may last for years after infection. The aetiology of long COVID remains uncertain. Examination of potential serological markers of long COVID, accounting for clinical covariates, may yield emergent pathophysiological insights. METHODS: In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and long COVID status and investigated sources of inter-study variability, such as severity of acute illness, long COVID symptoms assessed and target antigen(s). RESULTS: Of 8018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of long COVID varied. In studies that reported anti-nucleocapsid (N) IgG (n = 10 studies; n = 989 participants in aggregate), full or partial anti-Spike IgG (i.e. the whole trimer, S1 or S2 subgroups, or receptor binding domain, n = 19 studies; n = 2606 participants), or neutralizing response (n = 7 studies; n = 1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders. CONCLUSIONS: Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency and comprehension of study findings.

Inherited thrombophilia gene mutations and risk of venous thromboembolism in patients with cancer: A systematic review and meta-analysis.

In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.

The Transformative Potential of AI in Obstetrics and Gynaecology.

The transformative power of artificial intelligence (AI) is reshaping diverse domains of medicine. Recent progress, catalyzed by computing advancements, has seen commensurate adoption of AI technologies within obstetrics and gynaecology. We explore the use and potential of AI in three focus areas: predictive modelling for pregnancy complications, Deep learning-based image interpretation for precise diagnoses, and large language models enabling intelligent health care assistants. We also provide recommendations for the ethical implementation, governance of AI, and promote research into AI explainability, which are crucial for responsible AI integration and deployment. AI promises a revolutionary era of personalized health care in obstetrics and gynaecology.

Relationship Between Gestational Weight Gain and Health Service Utilization in Early Childhood: A Retrospective Cohort Study.

OBJECTIVE: Gestational weight gain (GWG) outside recommended ranges can negatively impact both the woman and child. The long-term effects of below-recommended or above-recommended GWG on the child are unclear. METHODS: This retrospective cohort study used a population-based birth registry of 258,005 live births to evaluate the relationship between maternal GWG and paediatric health service use. RESULTS: The results suggest below recommended GWG in underweight women in particular is associated with an increased rate of hospitalizations and specialist visits for the child in the first 24 months. CONCLUSION: Findings indicate that GWG may impact paediatric outcomes in ways that depend on pre-pregnancy body mass index, as derived from maternal height and weight measures.

Gestational weight loss and fetal growth in uncomplicated pregnancies among women with obesity: a population-based retrospective cohort study.

OBJECTIVE: The impact of gestational weight loss (GWL) on fetal growth among women with obesity remains unclear. This study aimed to examine the association between weight loss during pregnancy among women with body mass index (BMI) ≥ 30 kg/m2 and the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) neonates. METHODS: We conducted a retrospective, population-based cohort study of women with pre-pregnancy obesity that resulted in a singleton live birth in 2012-2017, using birth registry data in Ontario, Canada. Women with pregnancy complications or health conditions which could cause weight loss were excluded. GWL is defined as negative gestational weight change (≤0 kg). The association between GWL and fetal growth was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class (I:30-34.9 kg/m2, II:35-39.9 kg/m2, and III + : ≥40 kg/m2). RESULTS: Of the 52,153 eligible women who entered pregnancy with a BMI ≥ 30 kg/m2, 5.3% had GWL. Compared to adequate gestational weight gain, GWL was associated with an increased risk of SGA neonates (aRR:1.45, 95% CI: 1.30-1.60) and a decreased risk of LGA neonates (aRR: 0.81, 95% CI:0.73-0.93). Non-linear L-shaped associations were observed between gestational weight change and SGA neonates, with an increased risk of SGA observed with increased GWL. On the contrary, non-linear S-shaped associations were observed between gestational weight change and LGA neonates, with a decreased risk of LGA observed with increased GWL. Similar findings were observed from the stratified analysis by obesity class. CONCLUSION: These findings highlight that GWL in women with obesity may increase the risk of SGA neonates but reduce the risk of LGA neonates. Recommendations of GWL for women with obesity should be interpreted with caution.

Maternal weight and paediatric health use: mediating role of adverse birth outcomes: a retrospective cohort study.

BACKGROUND: Maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) above or below recommendations have been associated with increased paediatric health service utilization as well as increased risk of adverse birth outcomes, including small for gestational age (SGA) and preterm birth (PTB). SGA and PTB are associated with numerous adverse health outcomes in the child, including delayed growth, motor and cognitive impairment. Previous research has identified birth weight and gestational age on the causal pathway in the association between maternal pre-pregnancy BMI and child hospital admissions, there are no studies to date to quantify this relationship across other areas of health service utilization, nor the impact of gestational weight gain. This study aimed to assess if SGA or PTB partially explain the association between maternal weight and paediatric health service utilization. METHODS: The study population consisted of all women who delivered a singleton, live infant in Ontario between 2012 and 2014, and was assembled from data contained in the provincial birth registry. Health service utilization over the first 24 months following birth was examined by linking data from the registry with other provincial health administrative databases housed at ICES. The mediating roles of PTB and SGA were assessed using the Baron-Kenny method and causal mediation analysis. RESULTS: A total of 204,162 infants were included in the analysis of maternal pre-pregnancy BMI and 171,127 infants were included in the GWG analysis. The small magnitude of association between maternal BMI and paediatric health service utilization impacted our ability to estimate the indirect effect of maternal BMI through adverse birth outcomes (adjusted indirect effect = 0.00). 56.7% of the association between below recommended GWG and increased hospitalizations was attributed to PTB, while 6.8% of the association was attributed to SGA. CONCLUSION: Paediatric hospitalizations may be partially attributable to PTB and SGA in children born to mothers with below-recommended GWG. However, maternal weight also appears to be related to increased paediatric health service utilization independent of PTB and SGA.

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.

BACKGROUND: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. METHODS: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type. RESULTS: During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy. CONCLUSIONS: In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. METHODS: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. RESULTS: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. CONCLUSIONS: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Patterns of cesarean birth among women living with HIV in Ontario: A cross-sectional, population-level study.

BACKGROUND: In Canada, as is found globally, women of reproductive age are a growing demographic of persons living with HIV. Combination antiretroviral therapy (cART) treatment enables women living with HIV (WLWH) to become pregnant without perinatal transmission, and they are increasingly planning to become pregnant. Since 2014, Canadian guidelines no longer recommend routine elective cesarean birth (CB) for women who are virally suppressed and receiving cART. It is unknown whether their obstetric care has changed since this update. Our objective was to describe trends in cesarean births among WLWH in Ontario, Canada, over a 12-year period. METHODS: Our research is co-led and codesigned with WLWH. We conducted a retrospective population-level cohort study using linked health administrative databases at ICES (formally, the Institute for Clinical and Evaluative Sciences). Participants were all women who gave birth in Ontario, between 2006/07 and 2017/18. We assessed their intrapartum characteristics and used multivariable regression to determine an association between HIV status and CB, controlling for sociodemographic and clinical variables. RESULTS: Since 2014, the overall proportion of CB among WLWH remained stable and was higher than among women without HIV (39.9% vs 29.0%, P < 0.001). In addition, the proportion of primary CB decreased between 2006 and 2010 and between 2014 and 2018 (28.5%-19.3%), whereas the proportion of repeat CB increased (13.1%-20.5%, P = 0.013). CONCLUSIONS: Because of decreasing HIV-related indications for CB, more practitioners may be following the guidelines for first-time mothers. Currently, no guidelines exist for care of WLWH with a previous CB, and opportunities for vaginal birth may be missed in this population.

Health services use by children identified as heterozygous hemoglobinopathy mutation carriers via newborn screening.

BACKGROUND: Newborn screening (NBS) for sickle cell disease incidentally identifies heterozygous carriers of hemoglobinopathy mutations. In Ontario, Canada, these carrier results are not routinely disclosed, presenting an opportunity to investigate the potential health implications of carrier status. We aimed to compare rates of health services use among children identified as carriers of hemoglobinopathy mutations and those who received negative NBS results. METHODS: Eligible children underwent NBS in Ontario from October 2006 to March 2010 and were identified as carriers or as screen-negative controls, matched to carriers 5:1 based on neighbourhood and timing of birth. We used health care administrative data to determine frequencies of inpatient hospitalizations, emergency department (ED) visits, and physician encounters through March 2012, using multivariable negative binomial regression to compare rates of service use in the two cohorts. We analyzed data from 4987 carriers and 24,935 controls. RESULTS: Adjusted incidence rate ratios (95% CI) for service use in carriers versus controls among children < 1 year of age were: 1.11 (1.06-1.17) for ED visits; 0.97 (0.89-1.06) for inpatient hospitalization; and 1.02 (1.00-1.04) for physician encounters. Among children ≥1 year of age, adjusted rate ratios were: 1.03 (0.98-1.07) for ED visits; 1.14 (1.03-1.25) for inpatient hospitalization and 0.92 (0.90-0.94) for physician encounters. CONCLUSIONS: While we identified statistically significant differences in health services use among carriers of hemoglobinopathy mutations relative to controls, effect sizes were small and directions of association inconsistent across age groups and health service types. Our findings are consistent with the assumption that carrier status is likely benign in early childhood.

A Retrospective Cohort Study Investigating the Impact of Maternal Pre-Pregnancy Body Mass Index on Pediatric Health Service Utilization.

OBJECTIVE: Maternal weight during pregnancy impacts the health of both mother and baby. This project investigated associations between maternal pre-pregnancy body mass index (BMI) and the child's future health service utilization. METHODS: The study population comprised all women who delivered a singleton, live infant in Ontario between 2012 and 2014, and was assembled from data contained in the provincial birth registry. Health service utilization in the 24 months following birth was examined by linking data from the registry with other provincial health administrative databases housed at ICES. RESULTS: A total of 258 005 records were available for analysis. After adjusting for infant sex and maternal age, smoking status, income quintile, and pre-existing or gestational diabetes or hypertension, children born to mothers who were overweight or had obesity prior to pregnancy had increased rates of hospitalization (overweight adjusted incidence rate ratio [aIRR] 1.09, 95% confidence interval [CI] 1.06-1.12; obesity aIRR 1.20, 95% CI 1.17-1.24), physician visits (overweight aIRR 1.03, 95% CI 1.03-1.04; obesity aIRR 1.05, 95% CI 1.04-1.05) and emergency department visits (overweight aIRR 1.12, 95% CI 1.10-1.13; obesity aIRR 1.27, 95% CI 1.25-1.29) than infants born to mothers with normal pre-pregnancy BMI. CONCLUSION: Excess maternal weight was associated with greater pediatric health service utilization. Rates of health service utilization appeared to increase with maternal pre-pregnancy BMI. Future study of the reasons behind this increase may allow for early education, diagnosis, and intervention in this at-risk population.

Postnatal gestational age estimation via newborn screening analysis: application and potential.

Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in 2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for metabolomics to estimate GA by analyzing data captured through routine newborn screening. Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn screening and demographic data, our group developed an algorithm capable of estimating GA postnatally to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by including additional analytes and validating the model's performance through internal and external validation studies, and through implementation of the model internationally. Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible and acceptable to individuals in low-resource settings.

Cardiovascular and Neuropsychiatric Events after Varenicline Use for Smoking Cessation.

RATIONALE: Varenicline aids in smoking cessation but has also been associated with serious adverse events. OBJECTIVES: The aim of this study was to determine the risks of cardiovascular and neuropsychiatric events after varenicline receipt in a real-world setting. METHODS: A population-based, self-controlled risk interval study using linked universal health administrative data from the diverse, multicultural population of Ontario, Canada, was conducted. In two separate analyses, new varenicline users between September 1, 2011 and February 15, 2014 were observed from 1 year before to 1 year after varenicline receipt. The relative incidences of cardiovascular and neuropsychiatric hospitalizations and emergency department visits in the 12 weeks after varenicline receipt (the risk interval) compared with the remaining observation period (the control interval) were estimated in two separate fixed-effect conditional Poisson regressions. Sensitivity analyses tested the robustness of the results. MEASUREMENTS AND MAIN RESULTS: Among 56,851 new users of varenicline, 6,317 cardiovascular and 10,041 neuropsychiatric hospitalizations and emergency department visits occurred from 1 year before to 1 year after receipt. The incidence of cardiovascular events was 34% higher in the risk compared with the control interval (relative incidence, 1.34; 95% confidence interval, 1.25-1.44). Findings were consistent in sensitivity analyses, most notably in those without any history of previous cardiovascular disease. The relative incidence of neuropsychiatric events was marginally significant in the primary (relative incidence, 1.06; 95% confidence interval, 1.00-1.13) but not all sensitivity analyses. CONCLUSIONS: Varenicline appears to be associated with an increased risk of cardiovascular but not neuropsychiatric events.

Association Between Self-reported Prenatal Cannabis Use and Maternal, Perinatal, and Neonatal Outcomes.

Importance: Recent evidence suggests that cannabis use during pregnancy is increasing, although population-based data about perinatal outcomes following in utero exposure remain limited. Objective: To assess whether there are associations between self-reported prenatal cannabis use and adverse maternal and perinatal outcomes. Design, Setting, and Participants: Population-based retrospective cohort study covering live births and stillbirths among women aged 15 years and older in Ontario, Canada, between April 2012 and December 2017. Exposures: Self-reported cannabis exposure in pregnancy was ascertained through routine perinatal care. Main Outcomes and Measures: The primary outcome was preterm birth before 37 weeks' gestation. Indicators were defined for birth occurring at 34 to 36 6/7 weeks' gestation (late preterm), 32 to 33 6/7 weeks' gestation, 28 to 31 6/7 weeks' gestation, and less than 28 weeks' gestation (very preterm birth). Ten secondary outcomes were examined including small for gestational age, placental abruption, transfer to neonatal intensive care, and 5-minute Apgar score. Coarsened exact matching techniques and Poisson regression models were used to estimate the risk difference (RD) and relative risk (RR) of outcomes associated with cannabis exposure and control for confounding. Results: In a cohort of 661 617 women, the mean gestational age was 39.3 weeks and 51% of infants were male. Mothers had a mean age of 30.4 years and 9427 (1.4%) reported cannabis use during pregnancy. Imbalance in measured maternal obstetrical and sociodemographic characteristics between reported cannabis users and nonusers was attenuated using matching, yielding a sample of 5639 reported users and 92 873 nonusers. The crude rate of preterm birth less than 37 weeks' gestation was 6.1% among women who did not report cannabis use and 12.0% among those reporting use in the unmatched cohort (RD, 5.88% [95% CI, 5.22%-6.54%]). In the matched cohort, reported cannabis exposure was significantly associated with an RD of 2.98% (95% CI, 2.63%-3.34%) and an RR of 1.41 (95% CI, 1.36-1.47) for preterm birth. Compared with no reported use, cannabis exposure was significantly associated with greater frequency of small for gestational age (third percentile, 6.1% vs 4.0%; RR, 1.53 [95% CI, 1.45-1.61]), placental abruption (1.6% vs 0.9%; RR, 1.72 [95% CI, 1.54-1.92]), transfer to neonatal intensive care (19.3% vs 13.8%; RR, 1.40 [95% CI, 1.36-1.44]), and 5-minute Apgar score less than 4 (1.1% vs 0.9%; RR, 1.28 [95% CI, 1.13-1.45]). Conclusions and Relevance: Among pregnant women in Ontario, Canada, reported cannabis use was significantly associated with an increased risk of preterm birth. Findings may be limited by residual confounding.

Health Services Use during Transition from Pediatric to Adult Care for Inflammatory Bowel Disease: A Population-Based Study Using Health Administrative Data.

OBJECTIVES: To evaluate the impact of the transfer from pediatric to adult care on health services use for adolescents with inflammatory bowel disease (IBD). STUDY DESIGN: A population-based retrospective cohort study identified all children diagnosed with IBD from 1994 to 2008 and treated by pediatric gastroenterologists in Ontario, Canada, using health administrative data. Self-controlled case series analyses compared health service use in the 2 years before and 2 years after transfer with adult gastroenterologists, with a 6-month washout period at transfer. Outcomes evaluated included IBD-specific and IBD-related hospitalizations, emergency department use, outpatient visits, and laboratory use. The relative incidence (RI) in the post-transfer period was compared with pretransfer periods using Poisson regression analysis controlling for transfer starting age. Analyses were stratified by IBD type: Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: There were 536 patients included in the study (388 CD, 148 UC). Emergency department use rate was higher after transfer for both CD (RI, 2.12; 95% CI, 1.53-2.93) and UC (RI, 2.34; 95% CI, 1.09-5.03), as were outpatient visits (CD: RI, 1.56; 95% CI, 1.42-1.72; UC: RI, 1.48; 95% CI, 1.24-1.76), and laboratory investigations (CD: RI, 1.43; 95% CI, 1.26-1.63; UC: 1.38; 95% CI, 1.13-1.68). There was no change in the hospitalization rate (CD: RI, 0.70; 95% CI, 0.42-1.18; UC: RI, 2.41; 95% CI, 0.62-9.40). CONCLUSIONS: Health services use in Canada increases after transfer from pediatric to adult care for outpatient visits, emergency department use, and laboratory tests, but not hospitalizations. This study has implications for the planning and budgeting of care for adolescents transitioning to adult care.

Effectiveness of a hospital-initiated smoking cessation programme: 2-year health and healthcare outcomes.

BACKGROUND: Tobacco-related illnesses are leading causes of death and healthcare use. Our objective was to determine whether implementation of a hospital-initiated smoking cessation intervention would reduce mortality and downstream healthcare usage. METHODS: A 2-group effectiveness study was completed comparing patients who received the 'Ottawa Model' for Smoking Cessation intervention (n=726) to usual care controls (n=641). Participants were current smokers, >17 years old, and recruited during admission to 1 of 14 participating hospitals in Ontario, Canada. Baseline data were linked to healthcare administrative data. Competing-risks regression analysis was used to compare outcomes between groups. RESULTS: The intervention group experienced significantly lower rates of all-cause readmissions, smoking-related readmissions, and all-cause emergency department (ED) visits at all time points. The largest absolute risk reductions (ARR) were observed for all-cause readmissions at 30 days (13.3% vs 7.1%; ARR, 6.1% (2.9% to 9.3%); p<0.001), 1 year (38.4% vs 26.7%; ARR, 11.7% (6.7% to 16.6%); p<0.001), and 2 years (45.2% vs 33.6%; ARR, 11.6% (6.5% to 16.8%); p<0.001). The greatest reduction in risk of all-cause ED visits was at 30 days (20.9% vs 16.4%; ARR, 4.5% (0.4% to 8.7%); p=0.03). Reduction in mortality was not evident at 30 days, but significant reductions were observed by year 1 (11.4% vs 5.4%; ARR 6.0% (3.1% to 9.0%); p<0.001) and year 2 (15.1% vs 7.9%; ARR, 7.3% (3.9% to 10.7%); p<0.001). CONCLUSIONS: Considering the relatively low cost, greater adoption of hospital-initiated tobacco cessation interventions should be considered to improve patient outcomes and decrease subsequent healthcare usage.

Accurate prediction of gestational age using newborn screening analyte data.

BACKGROUND: Identification of preterm births and accurate estimates of gestational age for newborn infants is vital to guide care. Unfortunately, in developing countries, it can be challenging to obtain estimates of gestational age. Routinely collected newborn infant screening metabolic analytes vary by gestational age and may be useful to estimate gestational age. OBJECTIVE: We sought to develop an algorithm that could estimate gestational age at birth that is based on the analytes that are obtained from newborn infant screening. STUDY DESIGN: We conducted a population-based cross-sectional study of all live births in the province of Ontario that included 249,700 infants who were born between April 2007 and March 2009 and who underwent newborn infant screening. We used multivariable linear and logistic regression analyses to build a model to predict gestational age using newborn infant screening metabolite measurements and readily available physical characteristics data (birthweight and sex). RESULTS: The final model of our metabolic gestational dating algorithm had an average deviation between observed and expected gestational age of approximately 1 week, which suggests excellent predictive ability (adjusted R-square of 0.65; root mean square error, 1.06 weeks). Two-thirds of the gestational ages that were predicted by our model were accurate within ±1 week of the actual gestational age. Our logistic regression model was able to discriminate extremely well between term and increasingly premature categories of infants (c-statistic, >0.99). CONCLUSION: Metabolic gestational dating is accurate for the prediction of gestational age and could have value in low resource settings.

The use of relative incidence ratios in self-controlled case series studies: an overview.

BACKGROUND: The self-controlled case series (SCCS) is a useful design for investigating associations between outcomes and transient exposures. The SCCS design controls for all fixed covariates, but effect modification can still occur. This can be evaluated by including interaction terms in the model which, when exponentiated, can be interpreted as a relative incidence ratio (RIR): the change in relative incidence (RI) for a unit change in an effect modifier. METHODS: We conducted a scoping review to investigate the use of RIRs in published primary SCCS studies, and conducted a case-study in one of our own primary SCCS studies to illustrate the use of RIRs within an SCCS analysis to investigate subgroup effects in the context of comparing whole cell (wcp) and acellular (acp) pertussis vaccines. Using this case study, we also illustrated the potential utility of RIRs in addressing the healthy vaccinee effect (HVE) in vaccine safety surveillance studies. RESULTS: Our scoping review identified 122 primary studies reporting an SCCS analysis. Of these, 24 described the use of interaction terms to test for effect modification. 21 of 24 studies reported stratum specific RIs, 22 of 24 reported the p-value for interaction, and less than half (10 of 24) reported the estimate of the interaction term/RIR, the stratum specific RIs and interaction p-values. Our case-study demonstrated that there was a nearly two-fold greater RI of ER visits and admissions following wcp vaccination relative to acp vaccination (RIR = 1.82, 95 % CI 1.64-2.01), where RI estimates in each subgroup were clearly impacted by a strong healthy vaccinee effect. CONCLUSIONS: We demonstrated in our scoping review that calculating RIRs is not a widely utilized strategy. We showed that calculating RIRs across time periods is useful for the detection of relative changes in adverse event rates that might otherwise be missed due to the HVE. Many published studies of vaccine-associated adverse events could have missed/underestimated important safety signals masked by the HVE. With further development, our application of RIRs could be an important tool to address the HVE, particularly in the context of self-controlled study designs.

Simulation study of the effect of influenza and influenza vaccination on risk of acquiring Guillain-Barré syndrome.

It is unclear whether seasonal influenza vaccination results in a net increase or decrease in the risk for Guillain-Barré syndrome (GBS). To assess the effect of seasonal influenza vaccination on the absolute risk of acquiring GBS, we used simulation models and published estimates of age- and sex-specific risks for GBS, influenza incidence, and vaccine effectiveness. For a hypothetical 45-year-old woman and 75-year-old man, excess GBS risk for influenza vaccination versus no vaccination was -0.36/1 million vaccinations (95% credible interval -1.22% to 0.28) and -0.42/1 million vaccinations (95% credible interval, -3.68 to 2.44), respectively. These numbers represent a small absolute reduction in GBS risk with vaccination. Under typical conditions (e.g. influenza incidence rates >5% and vaccine effectiveness >60%), vaccination reduced GBS risk. These findings should strengthen confidence in the safety of influenza vaccine and allow health professionals to better put GBS risk in context when discussing influenza vaccination with patients.