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Background Comorbidity scores based on medical or prescription claims data are frequently used to control for confounding in pharmacoepidemiological studies. Performance of such scores in predicting the risk of death in community-dwelling elderly adults may be compromised by the absence of mental health and socioeconomic characteristics not captured in claims data. Objective The aim of the study was to assess the impact of adding mental health status and sociodemographic characteristics to the Geriatric Comorbidity Score (GCS), a score derived from prescription claims data in the Quebec community-dwelling elderly population. Methods We used the cohort study from the longitudinal Quebec Seniors' Health Survey (n = 1,494) conducted between 2005 and 2006. For each participant, we obtained mental health and socioeconomic characteristics through validated questionnaires, which we linked with the medical and prescription claims databases of the Quebec Health Insurance Agency [Régie de l'assurance maladie du Québec (RAMQ)]. The main study outcome was death within 1 year, ascertained using the Quebec death registry. The GCS was calculated from prescription claims data, with the c statistic as a measure of performance. Using backward stepwise selection, external variables (marital status, region, family income, social support, daily hassles, perceived physical and mental health status, presence of mental health disorders) were added to the logistic regression model and the marginal effect assessed by comparing the c statistic with and without each covariate. Results Over 1 year, 77 deaths (5.15 %) were reported. The c statistic for the GCS was calculated as 0.67 (95 % confidence interval 0.64, 0.70). Addition of sex and age to the score yielded a 2.4 % increase. The variable with the greatest impact on the c statistic was marital status (6.1 % increase). Though important contributors, social support and perceived mental health status did not significantly improve performance of the score. Conclusions While sex, age and marital status significantly improved performance of a predictive score in the community-dwelling elderly population, the absence of data on mental and physical health status did not appear to compromise the validity of claims-based scores. Combining comorbidity scores with other methods to control for confounding thus remains a useful tool in pharmacoepidemiological research. [ABSTRACT FROM AUTHOR]

Objective: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital‐acquired infection (HAI) incidence rate in critically ill children. Background: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion‐related immunomodulation due to bioactive substances' release as transfused blood ages. Methods: In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre‐storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21–34 days), and 3) transfusion of 'long‐stored' RBCs (≥35 days). All were compared to a 'golden' period (11–20 days), representing the time between 'fresh' and 'stored'. We used quasi‐Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). Results: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long‐stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). Conclusion: Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children. [ABSTRACT FROM AUTHOR]

• YKL-40 is an inflammatory marker increased in blood of CF patients. • Two distinct groups of CF patients were identified: low and high YKL-40 levels. • The high YKL-40 group had a more severe clinical profile, for instance low FEV 1. • The CHI3L1 C/C-rs4950928 genotype is associated to high YKL-40 and dysglycemia in CF. • YKL-40 as a potential biomarker of CF disease severity. YKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease. A prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters. We found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P = 0.027) and dysglycemia (P = 0.015). They were also more colonized with Pseudomonas aeruginosa (P = 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic. Our study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile. [ABSTRACT FROM AUTHOR]

Background Higher rates of influenza-related morbidity and mortality occur in individuals with underlying medical conditions. To improve vaccine effectiveness, cell-based technology for influenza vaccine manufacturing has been developed. Cell-derived inactivated quadrivalent influenza vaccines (cIIV4) may improve protection in seasons in which egg-propagated influenza viruses undergo mutations that affect antigenicity. This study aimed to estimate the relative vaccine effectiveness (rVE) of cIIV4 versus egg-derived inactivated quadrivalent influenza vaccines (eIIV4) in preventing influenza-related medical encounters in individuals with underlying medical conditions putting them at high risk of influenza complications during the 2018–2019 US influenza season. Methods An integrated dataset, linking primary care electronic medical records with claims data, was used to conduct a retrospective cohort study among individuals aged ≥4 years, with ≥1 health condition, vaccinated with cIIV4 or eIIV4 during the 2018–2019 season. Adjusted odds ratios (ORs) were derived using a doubly robust inverse probability of treatment-weighting (IPTW) model, adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness was estimated by (1 − OR) × 100 and presented with 95% confidence intervals (CIs). Results The study cohort included 471 301 cIIV4 and 1 641 915 eIIV4 recipients. Compared with eIIV4, cIIV4 prevented significantly more influenza-related medical encounters among individuals with ≥1 health condition (rVE, 13.4% [95% CI, 11.4%–15.4%]), chronic pulmonary disease (rVE, 18.7% [95% CI, 16.0%–21.3%]), and rheumatic disease (rVE, 11.8% [95% CI, 3.6%–19.3%]). Conclusions Our findings support the use of cIIV4 in individuals ≥4 years of age at high risk of influenza complications and provide further evidence supporting improved effectiveness of cIIV4 compared with eIIV4. [ABSTRACT FROM AUTHOR]

Background: Widespread increases in caesarean section (CS) rates have sparked concerns about risks to mothers and infants and rising healthcare costs. A multicentre, two-arm, cluster-randomized trial in Quebec, Canada assessed whether an audit and feedback intervention targeting health professionals would reduce CS rates for pregnant women compared to usual care, and concluded that it reduced CS rates without adverse effects on maternal or neonatal health. The effect was statistically significant but clinically small. We assessed cost-effectiveness to inform scale-up decisions.Methods: A prospective economic evaluation was undertaken using individual patient data from the Quality of Care, Obstetrics Risk Management, and Mode of Delivery (QUARISMA) trial (April 2008 to October 2011). Analyses took a healthcare payer perspective. The time horizon captured hospital-based costs and clinical events for mothers and neonates from labour onset to 3 months postpartum. Resource use was identified and measured from patient charts and valued using standardized government sources. We estimated the changes in CS rates and costs for the intervention group (versus controls) between the baseline and post-intervention periods. We examined heterogeneity between clinical subgroups of high-risk versus low-risk pregnancies and estimated the joint uncertainty in cost-effectiveness over 20,000 trial simulations. We decomposed costs to identify drivers of change.Results: The intervention group experienced per-patient reductions of 0.005 CS (95% confidence interval (CI): -0.015 to 0.004, P = 0.09) and $180 (95% CI: -$277 to - $83, P < 0.001). Women with low-risk pregnancies experienced statistically significant reductions in CS rates and costs; changes for the high-risk subgroup were not significant. The intervention was "dominant" (effective in reducing CS and less costly than usual care) in 86.08% of simulations. It reduced costs in 99.99% of simulations. Cost reductions were driven by lower rates of neonatal complications in the intervention group (-$190, 95% CI: -$255 to - $125, P < 0.001). Given 88,000 annual provincial births, a similar intervention could save $15.8 million (range: $7.3 to $24.4 million) in Quebec annually.Conclusions: From a healthcare payer perspective, a multifaceted intervention involving audits and feedback resulted in a small reduction in caesarean deliveries and important cost savings. Cost reductions are consistent with improved quality of care in intervention group hospitals.Trial Registration: International Clinical Trials Registry Platform, ISRCTN95086407 . Registered on 23 October 2007. [ABSTRACT FROM AUTHOR]

Background: Two sets of diagnostic criteria of paediatric multiple organ dysfunction syndrome (MODS) were published by Proulx in 1996 and by Goldstein in 2005. We hypothesized that this changes the epidemiology of MODS. Thus, we determined the epidemiology of MODS, according to these two sets of diagnostic criteria, we studied the intra- and inter-observer reproducibility of each set of diagnostic criteria, and we compared the association between cases of MODS at paediatric intensive care unit (PICU) entry, as diagnosed by each set of diagnostic criteria, and 90-day all-cause mortality. Methods: All consecutive patients admitted to the tertiary care PICU of Sainte-Justine Hospital, from April 21, 2009 to April 20, 2010, were considered eligible for enrolment into this prospective observational cohort study. The exclusion criteria were gestational age < 40 weeks, age < 3 days or > 18 years at PICU entry, pregnancy, admission immediately after delivery. No patients were censored. Daily monitoring using medical chart ended when the patient died or was discharged from PICU. Mortality was monitored up to death, hospital discharge, or 90 days post PICU entry, whatever happened first. Concordance rate and kappa score were calculated to assess reproducibility. The number of MODS identified with Proulx and Goldstein definitions was compared using 2-by-2 contingency tables. Student's t test or Wilcoxon signed-ranked test was used to compare continuous variables with normal or abnormal distribution, respectively. We performed a Kaplan-Meier survival analysis to assess the association between MODS at PICU entry and 90-day mortality. Results: The occurrence of MODS was monitored daily and prospectively in 842 consecutive patients admitted to the PICU of Sainte-Justine Hospital over 1 year. According to Proulx and Goldstein diagnostic criteria, 180 (21.4 %) and 314 patients (37.3 %) had MODS over PICU stay, respectively. Concordance of MODS diagnosis over PICU stay was 81.3 % (95 % CI 78.6-83.9 %), and kappa score was 0.56 (95 % CI 0.50-0.61). Discordance was mainly attributable to cardiovascular or neurological dysfunction criteria. The proportion of patients with MODS at PICU entry who died within 90 days was higher with MODS diagnosed with Proulx criteria (17.8 vs. 11.5 %, p = 0.038), as well as the likelihood ratio of death (4.84 vs. 2.37). On the other hand, 90-day survival rate of patients without MODS at PICU entry was similar (98.6 vs. 98.9 % ( p = 0.73). Conclusions: Proulx and Goldstein diagnostic criteria of paediatric MODS are not equivalent. The epidemiology of paediatric MODS varies depending on which set of diagnostic criteria is applied. [ABSTRACT FROM AUTHOR]

The article investigates the potential association between long-term use of benzodiazepines and risks of developing Alzheimer's disease among older people. Topics discussed include the correlation between the length of time that a patient has been using the drug and the patient's chances of developing Alzheimer's disease and the experts' warning that benzodiazepine may not be the cause of Alzheimer's disease but may just be an early marker of increased risk.

The article discusses a study regarding the comparison and efficacy of elastic compression stockings (ECS) with placebo stockings to prevent post-thrombotic syndrome (PTS). Topics include the use of a multicentre randomised placebo-controlled trial and Cox regression analysis for PTS prevention, the primary of outcome of patients with PTS, and the estimation of cumulative incidence of the primary outcome.

Abstract: Background: Although for the great majority of indications, practice guidelines recommend that antidepressants (ADs) be used for at least 6 months, premature discontinuation is very frequent in a “real-life” setting. Previous studies have assessed the economic impact of such nonpersistence, but differences across antidepressant products remain inadequately explored. Objective: To compare treatment persistence and incremental cost/persistence ratios (ICPRs) across individual new ADs (selective serotonin reuptake inhibitors and atypical ADs) as well as the associated direct health-care costs in the adult population covered by the public drug program of Quebec. Methods: A retrospective cohort study was conducted in 13,936 adults aged 18 to 64 years who started an AD treatment in 2003. Persistence was defined as treatment duration of at least 6 months regardless of whether a product switch had occurred. Economic impact was assessed over the first year of treatment through drug, medical services, hospitalization, and total health-care costs. Comparisons across products were conducted using the ICPR. Results: Adjusting for confounders, treatment nonpersistence ranged from 60.4% (paroxetine) to 65.1% (citalopram). The product associated with the highest total health-care costs was citalopram (CDN$2653) and the lowest was venlafaxine (CDN$2168). Fluvoxamine had the lowest mean AD costs (CDN$215) and venlafaxine (CDN$309) the highest. Conclusions: Total health-care costs were similar across products except for citalopram, which was more costly. Comparisons based on the ICPR revealed that paroxetine, fluoxetine, and venlafaxine were more favorable than the other AD alternatives. [Copyright &y& Elsevier]

Abstract: Antidepressants are highly prescribed in youth although most products have not been approved for use in this population. Furthermore, regulatory warnings have led to changes in antidepressant use that might have differed across various countries. Our study aimed at determining factors associated with antidepressant prescribing practices and at assessing trends in use from 1997 to 2005 in Quebec youth.A retrospective cohort study was conducted through claims databases of the Quebec public health care program (RAMQ). The study included 5094 children (age 2–14) and 11,121 adolescents (age 15–19) who were incident users of antidepressant between 1997 and 2005. The characteristics of users and prescribers were the main independent variables.Tricyclics were the most frequently dispensed products among children (50.9%) and selective serotonin reuptake inhibitors among adolescents (58.8%). Selection of an antidepressant class was associated with patient characteristics and with prescriber specialty. The number of antidepressant users increased from 1997 until 2001 then decreased thereafter.The selection of an antidepressant class was associated with clinical and non-clinical characteristics. Although antidepressant use decreased after regulatory warnings, there appears to be a care gap between the evidence generated by efficacy studies and the products prescribed in a real-life setting. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer. Methods and Materials: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.0–50.4 Gy in 25–28 fractions with concurrent 5-fluorouracil chemotherapy or HDRBT using 26 Gy in 4 fractions. Results: Thirty patients with initially abnormal profiles were excluded. Profiles included in this study were collected from 51 patients treated with EBRT and 38 patients treated with HDRBT, all of whom had normal hormonal profiles before treatment. Mean follow-up times were 17 months for the entire patient cohort—14 and 20 months, respectively—for the EBRT and HDRBT arms. Dosimetry results revealed a mean cumulative testicular dose of 1.24 Gy received in EBRT patients compared with 0.27 Gy in the HDRBT group. After treatment, FSH and LH were elevated in all patients but were more pronounced in the EBRT group. The testosterone-to-LH ratio was significantly lower (p = 0.0036) in EBRT patients for tumors in the lower third of the rectum. The 2-year hypogonadism rate observed was 2.6% for HDRBT compared with 17.6% for EBRT (p = 0.09) for tumors in the lower two thirds of the rectum. Conclusion: HDRBT allows better hormonal sparing than EBRT during neoadjuvant treatment of patients with rectal cancer. [Copyright &y& Elsevier]

Summary: Objective: To describe and compare the characteristics of children hospitalized with novel influenza A (H1N1) during two successive waves. Methods: This was a medical chart review of all children hospitalized in a French Canadian pediatric hospital in Montreal in the spring and fall of 2009 with a positive real-time polymerase chain reaction for novel influenza A (H1N1) and flu-like symptoms. Results: We included 202 children with a median age of 4.9 (range 0.1–18) years. Demographic and clinical features of the children in the two waves were similar. One or more underlying medical conditions were found in 59% of the children. Clinical findings at admission were: fever (98%), cough (88%), congestion/rhinorrhea (58%), gastrointestinal symptoms (47%), oxygen saturation below 95% (33%), sore throat (20%), and neurological symptoms (9%). Admission to the intensive care unit was required for 22 (11%) children, and 14 patients needed respiratory support. During the second wave, the median duration of stay was shorter (3 vs. 4 days, p =0.003) and oseltamivir was used more often (84% vs. 40%, p <0.001). Conclusions: Children hospitalized during the two successive waves of H1N1 were mainly school-aged and suffered from moderate disease. Although clinical features and severity of disease were similar, oseltamivir was prescribed more frequently and the length of hospital stay was shorter in the second wave. [ABSTRACT FROM AUTHOR]

Background/objectives: This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus the BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19., Methods: In a linked electronic health record/claims dataset, US adults (≥18 years) with ≥1 underlying medical condition of interest who received either the bivalent vaccine between 31 August 2022 and 28 February 2023 were identified. The inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until 31 May 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions., Results: 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%-15.2%) against COVID-19-related hospitalization and 3.2% (1.7%-4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were as follows: diabetes 15.1% (8.7%-21.0%), cerebro- and cardiovascular disease 14.7% (9.0%-20.1%), chronic lung disease 11.9% (5.1%-18.2%), immunocompromised 15.0% (7.2%-22.2%), chronic kidney disease 8.4% (0.5%-15.7%)., Conclusions: Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations.

Objectives: While studies have demonstrated increased morbidity and mortality risk in infancy among children who are HIV-exposed and uninfected (CHEU), longitudinal data are limited. The objective of this study was to assess long-term risk of hospitalization among CHEU compared to children who are HIV-unexposed and uninfected (CHUU), and determine risk factors for hospitalization among CHEU., Design: Longitudinal cohort study (1988-2015) linking the Centre maternel et infantile sur le SIDA cohort (Montreal, Quebec) to administrative data from the Régie de l'assurance maladie du Québec (RAMQ), a universal health insurance provider in the province of Quebec., Methods: CHEU from the CMIS cohort were matched 1:3 by age, sex and postal code with CHUU controls from the RAMQ database. Incidence and causes of hospitalization between CHEU and CHUU were compared using Poisson regression., Results: 726 CHEU were matched to 2178 CHUU. Risk of first hospitalization was significantly higher among CHEU at 1 year (IRR 2.22, [1.86-2.66]), 5 years (IRR 1.62, [1.39-1.90]) and over the lifespan (IRR 1.55, [1.33-1.81]). Among CHEU, significant risk factors for hospitalization on univariate regression analysis included birth year before 2005, prematurity, small for gestational age (SGA), detectable maternal viral load (dVL) at delivery, and maternal hepatitis C co-infection. In the adjusted analysis, small for gestational age and dVL remained significant risk factors., Conclusions: CHEU had a higher rate of hospitalization than CHUU controls across their lifespan. Significant risk factors included SGA and detectable maternal dVL, suggesting a need enhanced pediatric care for these children., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A universal newborn screening program for sickle cell disease (uNS-SCD) was implemented in the province of Québec (Qc) in November 2013, close in time to the recommendation of early initiation of hydroxyurea (HU) therapy for children. This retrospective cohort study evaluated the impact of such a program on children first seen between January 2000 and December 2019. Cohorts pre-SCD-uNS in Qc (pre-QcNS) ( n  = 253) and post-QcNS ( n  = 157) for patients seen prior to or after Nov 2013 were compared. Kaplan-Meier curves, Poisson regression, and logistic regressions were used for statistical analysis, using Software R version 4.2.1. Median age at first visit decreased significantly from 14.4 [interquartile range: 2.4-72.0] to 1.2 months [1.2-57.6] ( p  < 0.001). The percentage of children born in Qc undiagnosed at birth and referred after a first SCD-related complication dropped from 42.6% to 0.0% ( p  < 0.0001). The median age of HU introduction for patients with SS/Sβ°-thalassemia decreased from 56.4 [31.2-96.0] to 9.0 months post-QcNS [8.0-12.1] ( p  < 0.001). Event-free survival improved significantly for any type of hospitalization as well as for vaso-occlusive crisis (VOC) (140-257 days ( p  < 0.001) and 1320 vs. 573 days ( p  < 0.002), respectively), resulting in a reduction from 2 [interquartile range: 1.0-3.0] to 1.0 hospitalizations/patient-year [0.6-1.4] ( p  < 0.001). Children with SS/Sβ°-thalassemia referred post-QcNS also had fewer emergency department visits for VOC (RR: 0.69, 95% confidence interval: 0.54-0.88). The Universal NS program allows early detection and referral of children with SCD to comprehensive care centers. Earlier access ensures that children benefit from essential preventive interventions, reducing disease burden. This cohort study highlights that uNS-SCD is an essential public health measure., Competing Interests: The authors declared no conflict of interest., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: The Ross procedure is a surgical option for congenital aortic stenosis that involves replacing the diseased aortic valve with a pulmonary autograft. Little is known about outcomes in children, particularly those younger than 1 year., Methods: A systematic review with pooled analyses was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Inferred individual patient data were extracted from life tables. The primary end points were early (≤30 days) and late (>30 days) mortality rates following the Ross procedure in children. Secondary end points were freedom from reintervention for the right ventricular outflow tract and pulmonary autograft. These end points were assessed in the overall population of children. Sensitivity analyses were performed in subgroups younger than 1 year of age (infants) and in noninfant children., Results: A total of 25 studies on 2737 patients met inclusion criteria. The pooled early survival rate was 96.0% (95% confidence interval [CI]: 95.1%-96.8%) overall and 86.8% (95% CI: 82.1%-90.3%) among infants. Pooled overall 10-year survival, freedom from pulmonary autograft reintervention, and freedom from right ventricular outflow tract reintervention rates were 91.1%, 90.2%, and 79.7%, respectively. Corresponding pooled rates in infants were 79.3%, 87.1%, and 51.2%. Mortality was significantly higher among infants compared with noninfant children (hazard ratio: 3.38, 95% CI: 2.44-4.68; P < 0.001). In metaregression analyses, younger age was strongly associated with poorer survival and higher reintervention rates., Conclusions: Modest survival and autograft reoperation rates were observed following the Ross procedure in children. Surgery in infancy was strongly associated with poorer survival and higher reintervention rates., (© 2024 The Author(s).)

Background: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery., Methods: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559., Findings: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups., Interpretation: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture., Funding: Canadian Institutes of Health Research (CIHR, MOP-142448)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6-16.4%) and 5.1% (95% CI: 3.2-6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5-20.8%) and 10.7% (8.2-13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.

Objective: This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery., Methods: Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death., Results: One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P  = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P  = .49)., Conclusions: In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results., (© 2023 The Author(s).)

Background: Few head-to-head comparisons have been performed on the real-world effectiveness of coronavirus disease 2019 (COVID-19) booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 vs BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against any medically attended, outpatient, and hospitalized COVID-19., Methods: A data set linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients age ≥18 years vaccinated with a primary series between February and October 2021 (Part 1) and a homologous mRNA booster between October 2021 and January 2022 (Part 2). Adjusted hazard ratios (HRs) were derived from 1:1 matching adjusted across potential covariates. rVE was (1 - HR adjusted ) × 100. Additional analysis was performed across regions and age groups., Results: Following adjustment, Part 1 rVE for mRNA-1273 vs BNT162b2 was 23% (95% CI, 22%-25%), 23% (95% CI, 22%-25%), and 19% (95% CI, 14%-24%), while the rVE for mRNA-1273 vs Ad26.COV2.S was 50% (95% CI, 48%-51%), 50% (95% CI, 48%-52%), and 57% (95% CI, 53%-61%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 vs BNT162b2 was 14% (95% CI, 10%-18%), 13% (95% CI, 8%-17%), and 19% (95% CI, 1%-34%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically attended COVID-19 was higher in adults age ≥65 years (35%; 95% CI, 24%-47%) than in those age 18-64 years (13%; 95% CI, 9%-17%) after the booster., Conclusions: In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following a primary series during the Delta-dominant period and more effective than BNT162b2 as a booster during the Omicron-dominant period., Competing Interests: Potential conflicts of interest. J.A.M., N.V.V., D.E., P.B., D.M., and A.R. are employees of and shareholders in Moderna, Inc. A.B., M.S., and M.B. work for Veradigm, V.H.N., C.B., and T.D. are employees of VHN Consulting. Both companies were contracted by Moderna and received fees for data management and statistical analyses. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Healthcare constraints with decreasing bed availability cause strain in acute care units, and patients are more frequently being discharged directly home. Our objective was to describe the population, predictors, and explore PICU readmission rates of patients discharged directly home from PICU, compared with those discharge to the hospital ward, then home., Design: An observational cohort study., Setting: Children admitted to the PICU of CHU Sainte-Justine, between January 2014 and 2020., Patients: Patients less than 18 years old, who survived their PICU stay, and were discharged directly home or to an inpatient ward. Patients discharged directly home were compared with patients discharged to the ward using descriptive statistics. Logistic regression was used to identify factors associated with home discharge. Propensity scores were used to compare PICU readmission rates in patients discharged directly home to those discharged to the ward., Interventions: None., Measurements and Main Results: Among the 5,531 admissions included, 594 (10.7%) were discharged directly home from the PICU. Patients who were more severe ill (odds ratio [OR], 0.93; 95% CI, 0.90-0.97), had invasive ventilation (OR, 0.70; 95% CI, 0.53-0.92), or had vasoactive agents (OR, 0.70; 95% CI, 0.53-0.92) were less likely to be discharged directly home. Diagnoses associated with discharge directly home were acute intoxication, postoperative ear-nose-throat care, and shock states. There was no difference in the rate of readmission to PICU at 2 (relative risk [RR], 0.20 [95% CI, 0.02-1.71]) and 28 days (RR, 1.20 [95% CI, 0.61-3.36]) between propensity matched patients discharged to the ward for 2 or less days, compared with those discharged directly home., Conclusion: Discharge directly home from the PICU is increasing locally. The population includes less severely ill patients with rapidly resolving diagnoses. Rates of PICU readmission between patients discharged directly home from the PICU versus to ward are similar, but safety of the practice requires ongoing evaluation., Competing Interests: Dr. Lacroix received funding from the Editions du Centre Hospitalier Universitaire Sainte-Justine. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: The aim of this study was to establish the feasibility and safety of the use of indocyanine green technology during pediatric intestinal resections. While indocyanine green fluorescence angiography (ICG-FA) has been advocated as an imaging technique to assess bowel perfusion in adults, few studies have evaluated this technology in a pediatric context., Methods: A prospective clinical trial was conducted. Patients 16 years old or younger undergoing a surgery potentially requiring an intestinal resection were eligible. Patients received a standardized intravenous injection of indocyanine green and intestinal perfusion was evaluated. The study endpoints included safety, impact on bowel resection and feasibility and acceptance of ICG-FA in this population., Results: From May 2020 to March 2021, 30 consecutive patients were included in this trial. Final analysis was done on 28 patients with a median age of 15.00 [6.36,85.00] weeks and weight of 5.58 [3.64,11.70] kg at surgery. Adequate fluorescence was achieved in less than one minute for all cases with an average dose of 0.14 mg/kg. No adverse event related to indocyanine green occurred. ICG-FA versus standard assessment of potential resection sites differed in 62% (95% IC 0.41-0.82) of our cases. Qualitative analysis demonstrated that 95% of the surgical team agreed that ICG-FA was safe., Conclusions: The use of ICG-FA is feasible and safe for pediatric intestinal resections. Introduction of ICG-FA was simple and acceptance rates were high within the surgical team. This fluorescence imaging may be a valuable imaging technology for intestinal resections in pediatric surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

MF59 ® -adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose trivalent inactivated influenza vaccine (HD-IIV3) elicit an enhanced immune response in older adults compared to standard, quadrivalent inactivated influenza vaccines (IIV4). We sought to determine the relative vaccine effectiveness (rVE) of aIIV3 versus IIV4 and HD-IIV3 in preventing influenza-related medical encounters in this retrospective cohort study involving adults ≥65 years with ≥1 health condition during the 2017-2018 and 2018-2019 influenza seasons. Data were obtained from primary and specialty care electronic medical records linked with pharmacy and medical claims. Adjusted odds ratios (OR) were derived from an inverse probability of treatment-weighted sample adjusted for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was determined using the formula (% rVE = 1 - OR adjusted ) × 100. Analysis sets included 1,755,420 individuals for the 2017-2018 season and 2,055,012 for the 2018-2019 season. Compared to IIV4, aIIV3 was 7.1% (95% confidence interval 3.3-10.8) and 20.4% (16.2-24.4) more effective at preventing influenza-related medical encounters in the 2017-2018 and 2018-2019 seasons, respectively. Comparable effectiveness was observed with HD-IIV3 across both seasons. Our results support improved effectiveness of aIIV3 vs IIV4 in a vulnerable population of older adults at high risk of influenza and its complications.

In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver. In this retrospective cross-sectional case-control study, 16 patients with SCD were matched to 50 patients without SCD on known busulfan clearance's covariates (glutathione-S-transferase alpha1 polymorphisms, age, weight). Clearance of the first dose of busulfan was not significantly different independently of genetic or anthropometric factors in patients with or without SCD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: International guidelines recommend using the Villalta score (VS) to diagnose the postthrombotic syndrome (PTS). However, a high proportion of PTS detected with VS could just reflect the presence of preexisting primary venous insufficiency (PVI). Furthermore, it is unclear whether the contralateral VS (cl-VS) can be used to assess for preexisting PVI., Objectives: To estimate whether cl-VS can be used to assess for preexisting PVI, and to assess the proportion of PTS that could be attributable to preexisting PVI., Methods: Subanalysis of the SOX multicenter randomized trial focusing on patients with a first unilateral proximal deep vein thrombosis (DVT) followed for up to 2 years. PVI was defined as a baseline cl-VS > 4, and PTS as VS > 4 in the leg ipsilateral to DVT starting 6 months after DVT., Results: Among 680 patients, mean cl-VS remained stable over time: 1.23 (standard deviation [SD] ±2.49) at baseline and 1.17 (±2.20), 1.59 (±2.81), 1.54 (±2.50), 1.65 (±2.82), and 1.55 (±2.63) at the 1-, 6-, 12-, 18-, and 24-month visits, respectively. Baseline cl-VS and ipsilateral VS measured during follow-up were mildly correlated (Pearson correlation = 0.13-0.25). This association disappeared after subtracting the cl-VS measured at the same visit from the ipsilateral VS. Overall, 48.8% of patients developed PTS of whom 12.8% had baseline cl-VS > 4., Conclusion: In our study of patients with a first unilateral proximal DVT, the proportion of patients with PTS who had a cl-VS > 4 is modest. However, cl-VS appears to be stable over time. Its assessment could constitute a simple way of documenting preexisting PVI and help to classify patients as having PTS., (© 2020 International Society on Thrombosis and Haemostasis.)

Purpose: End-stage kidney disease (ESKD) causes bleeding diathesis; however, whether these findings are extrapolable to acute kidney injury (AKI) remains uncertain. We assessed whether AKI is associated with an increased risk of bleeding., Methods: Single-center retrospective cohort study, excluding readmissions, admissions <24 h, ESKD or kidney transplants. The primary outcome was the development of incident bleeding analyzed by multivariate time-dependent Cox models., Results: In 1001 patients, bleeding occurred in 48% of AKI and 57% of non-AKI patients (p = .007). To identify predictors of incident bleeding, we excluded patients who bled before ICU (n = 488). In bleeding-free patients (n = 513), we observed a trend toward higher risks of bleeding in AKI (22% vs. 16%, p = .06), and a higher risk of bleeding in AKI-requiring dialysis (38% vs. 17%, p = .01). Cirrhosis, AKI-requiring dialysis, anticoagulation, and coronary artery disease were associated with bleeding (HR 3.67, 95%CI:1.33-10.25; HR 2.82, 95%CI:1.26-6.32; HR 2.34, 95%CI:1.45-3.80; and HR 1.84, 95%CI:1.06-3.20, respectively), while SOFA score and sepsis had a protective association (HR 0.92 95%CI:0.84-0.99 and HR 0.55, 95%CI:0.34-0.91, respectively). Incident bleeding was not associated with mortality., Conclusions: AKI-requiring dialysis was associated with incident bleeding, independent of anticoagulant administration. Studies are needed to better understand how AKI affects coagulation and clinical outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury., Methods: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up., Results: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m 2 , and with nephrotic syndrome. No correlation with histological alterations was observed., Conclusions: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

Purpose: Recent studies suggest that acute kidney injury (AKI) can affect distant organ function and increase non-renal complications. We determined whether AKI is associated with an increased risk of incident infections., Material and Methods: We conducted a one-year single-center retrospective cohort study, excluding patients readmitted to the ICU or for <24 h, on chronic dialysis, and kidney transplant recipients. The primary outcome was the development of incident infections analyzed by multivariate time-dependent Cox models., Results: Of the 1001 included patients, infections were more frequent in those with AKI (62% vs. 37% without AKI; p < .001). To characterize predictors of incident infections, we excluded patients with an infection until ICU admission (n = 244). Patients with AKI presented infections more often than without AKI (44% vs. 20%; p < .001). AKI, chronic obstructive pulmonary disease, and mechanical ventilation (MV) were associated with incident infections (HR 1.62, 95%CI:1.15-2.30, HR 1.51, 95%CI 1.04-2.18 and HR 2.14, 95%CI:1.48-3.09, respectively) while age, MV, higher fluid balance, and AKI were independent predictors of mortality., Conclusions: AKI was associated with incident in-hospital infections. However, newly occurring infections were not associated with an increased risk of mortality. Further studies are needed to understand how AKI affects distant organ function and associated clinical outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: There are no well-designed prospective studies evaluating transfusion practices in pediatric trauma. We sought to describe red blood cell (RBC) transfusion practices in trauma patients who were admitted to a pediatric intensive care unit (PICU)., Study Design and Methods: This study is a post-hoc analysis of a prospective, 6-month observational study in 30 PICUs. We studied a total of 580 patients aged less than 18 years who had been admitted to a PICU for more than 48 hours, including 95 who were trauma patients., Results: Trauma patients more frequently received transfusion before PICU admission (p < 0.001), were older (p < 0.0001), and more frequently were mechanically ventilated (p = 0.05). In the PICU, trauma patients received more transfusions (55% vs. 37%; p < 0.001), although admission hemoglobin levels were similar in both groups (p = 0.86). The mean (± standard deviation) pretransfusion hemoglobin level in the PICU was 9.0 ± 2.4 g/dL for trauma patients compared with 8.3 ± 2.4 g/dL for nontrauma patients (p = 0.09). Among the trauma patients, transfusion was associated with younger age, higher Pediatric Logistic Organ Regression scores, mechanical ventilation, bleeding, and transfusion before PICU admission. Multivariate regression demonstrated that receiving an RBC transfusion before admission was strongly associated with receiving a blood transfusion in the PICU (p = 0.008)., Conclusion: Trauma patients are at high risk for receiving an RBC transfusion both before and during their PICU stay, despite a similar transfusion threshold compared with nontrauma patients. Transfusion before PICU admission is a strong determinant, suggesting ongoing bleeding that will require re-transfusion. Further studies are needed to evaluate whether a restrictive transfusion strategy can safely be considered in these patients., (© 2016 AABB.)

The optimal red blood cell transfusion threshold for postoperative pediatric cardiac surgery patients is unknown. This study describes the stated red blood cell transfusion practice of physicians who treat postoperative pediatric cardiac surgery patients in intensive care units. A scenario-based survey was sent to physicians involved in postoperative intensive care of pediatric cardiac surgery patients in all Canadian centers that perform such surgery. Respondents reported their red blood cell transfusion practice in four postoperative scenarios: acyanotic or cyanotic cardiac lesion, in a neonate or an infant. In part A of each scenario, the patient was critically ill, but stabilized; in part B, the patient became unstable. Response rate was 58 % (71 of 123), with 45 respondents indicating direct involvement in postoperative intensive care. There was a wide variability in stated transfusion threshold, ranging from <7.0-14.0 g/dL for stabilized cases. There was no significant difference between neonates and infants in stated transfusion threshold. The mean hemoglobin level below which respondents would transfuse a stabilized patient was 9 g/dL for acyanotic and 11.2 g/dL for cyanotic patients, a statistically significant difference (2.2 ± 0.9 g/dL, p < 0.001). All clinical determinants of instability significantly increased transfusion threshold. Hemodynamic instability increased transfusion threshold by 2.3 ± 1.3 g/dL in acyanotic patients and by 1.3 ± 1.1 g/dL in cyanotic patients. Cyanotic lesion and clinical instability, but not patient age, increased stated red blood cell transfusion threshold. Significant variation in reported red blood cell transfusion practice exists among physicians treating pediatric patients in intensive care following cardiac surgery.

Objectives: To investigate the relation between the risk of Alzheimer's disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment., Design: Case-control study., Setting: The Quebec health insurance program database (RAMQ)., Participants: 1796 people with a first diagnosis of Alzheimer's disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09., Main Outcome Measure: The association between Alzheimer's disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life., Results: Benzodiazepine ever use was associated with an increased risk of Alzheimer's disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones)., Conclusion: Benzodiazepine use is associated with an increased risk of Alzheimer's disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern., (© Billioti de Gage et al 2014.)

Objective: Most studies determining risk of preterm birth in a twin pregnancy subsequent to a previous preterm birth are based on linkage studies or small sample size. We wished to identify recurrent risk factors in a cohort of mothers with a twin pregnancy, eliminating all known confounders., Methods: We conducted a retrospective cohort study of twin births at a tertiary care centre in Montreal, Quebec, between 1994 and 2008, extracting information, including chorionicity, from patient charts. To avoid the effect of confounding factors, we included only women with a preceding singleton pregnancy and excluded twin-to-twin transfusion syndrome, fetal chromosomal/structural anomalies, fetal demise, and preterm iatrogenic delivery for reasons not encountered in both pregnancies. We used multiple regression and sensitivity analyses to determine recurrent risk factors., Results: Of 1474 twin pregnancies, 576 met the inclusion criteria. Of these, 309 (53.6%) delivered before 37 weeks. Preterm birth in twins was strongly associated with preterm birth of the preceding singleton (adjusted OR 3.23; 95% CI 1.75 to 5.98). The only other risk factors were monochorionic twins (adjusted OR 1.82; 95% CI 1.21 to 2.73) and oldest or youngest maternal ages. Chronic or gestational hypertension, preeclampsia, and insulin-dependent diabetes during the singleton pregnancy did not significantly affect risk., Conclusion: Preterm birth in a previous singleton pregnancy was confirmed as an independent risk factor for preterm birth in a subsequent twin pregnancy. This three-fold increase in risk remained stable regardless of year of birth, inclusion/exclusion of pregnancies following assisted reproduction, or defining preterm birth as < 34 or < 37 weeks' gestational age. Until the advent of optimal preventive strategies, close obstetric surveillance of twin pregnancies is warranted.

Background: With the aging of the population, age-related macular degeneration (AMD) is becoming a public health concern. Few studies have assessed its consequences on morbidity and mortality, and the findings are conflicting., Objectives: To assess the risk of depression, fracture, institutionalization, and death among elderly patients with suspected exudative AMD and the impact of the depletion of susceptibles effect in a burden-of-illness study., Methods: A population-based retrospective cohort study was conducted in the community-dwelling elderly population of Quebec. The cohort was assembled through the Quebec medical claims database (RAMQ). Among patients age 65 and older with a claim involving a diagnosis of AMD over the years 2000 to 2004, those with suspected exudative AMD (n=2,071) were retained, using fluorescein angiography as a marker. The reference cohort consisted of a sample of 16,932 elderly without a claim involving AMD or visual impairment., Results: Suspected exudative AMD was associated with an increased risk of depression (hazard ratio HR=1.3, 95%CI 1.18-1.43) and fracture (HR=1.19, 95%CI 1.03-1.37), but a decreased risk of institutionalization (HR=0.55, 95%CI 0.42-0.71) and death (HR=0.68, 95%CI 0.59-0.78). After adjustment for the incident/prevalent status of the AMD, the association between suspected exudative AMD and institutionalization was no longer statistically significant (HR=0.75, 95%CI 0.5-1.12)., Conclusions: These findings enhance the need to detect visual loss and to consider patients' ability to adapt to AMD, to maintain their quality of life. Failure to account for duration of illness and the depletion of susceptibles effect may bias results of burden-of-illness studies.

Context: The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother's behavior or her interaction with the infant., Objective: To assess whether prolonged and exclusive breastfeeding improves children's cognitive ability at age 6.5 years., Design: Cluster-randomized trial, with enrollment from June 17, 1996, to December 31, 1997, and follow-up from December 21, 2002, to April 27, 2005., Setting: Thirty-one Belarussian maternity hospitals and their affiliated polyclinics., Participants: A total of 17,046 healthy breastfeeding infants were enrolled, of whom 13,889 (81.5%) were followed up at age 6.5 years., Intervention: Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF., Main Outcome Measures: Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence, and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects., Results: The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months (43.3% for the experimental group vs 6.4% for the control group; P < .001) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months. The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures, with cluster-adjusted mean differences (95% confidence intervals) of +7.5 (+0.8 to +14.3) for verbal IQ, +2.9 (-3.3 to +9.1) for performance IQ, and +5.9 (-1.0 to +12.8) for full-scale IQ. Teachers' academic ratings were significantly higher in the experimental group for both reading and writing., Conclusion: These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children's cognitive development., Trial Registration: isrctn.org Identifier: ISRCTN37687716.

Background: The objective of this study was to perform an economic analysis of the cost-effectiveness of prostaglandin analogues for the treatment of increased intraocular pressure (IOP). Prostaglandin analogues for ophthalmic use are more costly than alternative agents for the lowering of IOP. An important policy decision is whether to support continued open listing of these agents or to restrict them to limited use status., Methods: The cost-effectiveness of prostaglandin analogues was assessed using a decision analytic model. Latanoprost was compared with timolol, dorzolamide, and brimonidine, and travoprost was compared with timolol separately. The effectiveness data used for this economic analysis were the number of millilitres of mercury of IOP reduction compared with baseline and the incidence of adverse events resulting in a withdrawal of the patient from the study. Sensitivity analyses were conducted to assess the robustness of the study results., Results: Compared with latanoprost, dorzolamide was not a cost-effective strategy. Compared with brimonidine, latanoprost provided a higher IOP reduction with an incremental cost-effectiveness ratio of $16.17 (base case), but the additional IOP reduction with latanoprost was obtained at a cost higher than the average cost per millimetre of mercury reduction obtained with brimonidine. Compared with timolol, latanoprost and travoprost had a positive incremental cost-effectiveness ratio of $34.48 and $39.06, respectively., Interpretation: For the first-line treatment of glaucoma and elevated IOP, latanoprost is a more cost-effective strategy than dorzolamide and brimonidine. Latanoprost and travoprost are more effective than timolol but also more expensive. For those for whom timolol is not contraindicated, it would be preferable, from a cost-effectiveness standpoint, to initiate treatment with timolol and reserve the prostaglandin analogues as an alternative treatment or as add-on therapy for patients not achieving a clinical response with timolol. Better treatment compliance associated with these analogues improves their cost-effectiveness.

Background: Adverse events associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) have led to the publication of Canadian prescription guidelines. Prescription practices following the publication of these guidelines and the introduction of COX-2 inhibitors in the Quebec formulary of reimbursed medications remain largely unexplored., Objectives: To compare the prevalence of contra-indications and selected risk factors for NSAID-toxicity among COX-2 inhibitor users and non-selective NSAID users., Methods: A case-control analysis was conducted in a random sample of Quebec adult drug plan members who were treated with celecoxib (n=42,422 cases), rofecoxib (n=25,674 cases), full-dose (anti-inflammatory doses) of non-selective NSAIDs (n=9,673 cases), or low-dose NSAIDs (n=2,745 controls) in the year 2000. Data were obtained from the Quebec prescription and medical services databases (RAMQ)., Results: Patients with a history of gastropathy were more likely to be prescribed COX-2 inhibitors than low-dose NSAIDs; the odds ratios were 1.73 (95%CI: 1.56-1.91) and 1.49 (1.33-1.66), respectively for celecoxib and rofecoxib. Corresponding results for concomitant use of anticoagulants were 1.95 (1.34-2.83) for celecoxib and 1.87 (1.26-2.77) for rofecoxib, and for use of corticosteroids they were 1.29 (1.08-1.54) and 1.23 (1.01-1.49). Conversely, patients with the following characteristics were less likely to receive COX-2 inhibitors than low-dose non-selective NSAIDs: age 75+ (OR=0.64; 0.56-0.72 for celecoxib, OR=0.48; 0.76-0.99 for rofecoxib), hypertension (OR=0.83; 0.75-0.92 for celecoxib, OR=0.87; 0.77-0.97 for rofecoxib), and concomitant use of diuretics (OR=0.72; 0.63-0.82 for celecoxib; OR=0.77; 0.66-0.89 for rofecoxib)., Conclusion: Patients with risk factors for NSAID gastropathy were more likely prescribed COX-2 inhibitors, while the presence of other contra-indications led to the prescription of low-dose non-selective NSAIDs. However, 12.7% of users of full-dose non-selective NSAIDs were age 75+ and 12.0% had a history of gastropathy, which are considered important risk factors for adverse events.