Health Services Utilization and Specialist Care in Pediatric Inflammatory Bowel Disease: A Multiprovince Population-Based Cohort Study.

BACKGROUND: Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b). METHODS: Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis. RESULTS: Among the 1165 (65.7% Crohn's) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn's-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01). CONCLUSIONS: Patterns of health services utilization are generally similar when comparing children diagnosed across age groups.

Among 1165 children with inflammatory bowel disease, health services utilization was similar for children diagnosed <10 years of age and those diagnosed ≥10 years of age, except younger children had fewer emergency department visits and Crohn's disease­related surgeries.

Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease : A Population-Based Cohort Study.

BACKGROUND: North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. OBJECTIVE: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. DESIGN: Time-conditional propensity score-matched, new-user cohort study. SETTING: Health insurance databases from the Régie de l'assurance maladie du Québec in Canada. PATIENTS: Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. MEASUREMENTS: The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. RESULTS: The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). LIMITATION: Residual confounding, including from lack of smoking information. CONCLUSION: In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Canadian Lung Association.

Variable selection in high dimensions for discrete-outcome individualized treatment rules: Reducing severity of depression symptoms.

Despite growing interest in estimating individualized treatment rules, little attention has been given the binary outcome setting. Estimation is challenging with nonlinear link functions, especially when variable selection is needed. We use a new computational approach to solve a recently proposed doubly robust regularized estimating equation to accomplish this difficult task in a case study of depression treatment. We demonstrate an application of this new approach in combination with a weighted and penalized estimating equation to this challenging binary outcome setting. We demonstrate the double robustness of the method and its effectiveness for variable selection. The work is motivated by and applied to an analysis of treatment for unipolar depression using a population of patients treated at Kaiser Permanente Washington.

Estimating individualized treatment rules in longitudinal studies with covariate-driven observation times.

The sequential treatment decisions made by physicians to treat chronic diseases are formalized in the statistical literature as dynamic treatment regimes. To date, methods for dynamic treatment regimes have been developed under the assumption that observation times, that is, treatment and outcome monitoring times, are determined by study investigators. That assumption is often not satisfied in electronic health records data in which the outcome, the observation times, and the treatment mechanism are associated with patients' characteristics. The treatment and observation processes can lead to spurious associations between the treatment of interest and the outcome to be optimized under the dynamic treatment regime if not adequately considered in the analysis. We address these associations by incorporating two inverse weights that are functions of a patient's covariates into dynamic weighted ordinary least squares to develop optimal single stage dynamic treatment regimes, known as individualized treatment rules. We show empirically that our methodology yields consistent, multiply robust estimators. In a cohort of new users of antidepressant drugs from the United Kingdom's Clinical Practice Research Datalink, the proposed method is used to develop an optimal treatment rule that chooses between two antidepressants to optimize a utility function related to the change in body mass index.

Generating synthetic data from administrative health records for drug safety and effectiveness studies.

Introduction: Administrative health records (AHRs) are used to conduct population-based post-market drug safety and comparative effectiveness studies to inform healthcare decision making. However, the cost of data extraction, and the challenges associated with privacy and securing approvals can make it challenging for researchers to conduct methodological research in a timely manner using real data. Generating synthetic AHRs that reasonably represent the real-world data are beneficial for developing analytic methods and training analysts to rapidly implement study protocols. We generated synthetic AHRs using two methods and compared these synthetic AHRs to real-world AHRs. We described the challenges associated with using synthetic AHRs for real-world study. Methods: The real-world AHRs comprised prescription drug records for individuals with healthcare insurance coverage in the Population Research Data Repository (PRDR) from Manitoba, Canada for the 10-year period from 2008 to 2017. Synthetic data were generated using the Observational Medical Dataset Simulator II (OSIM2) and a modification (ModOSIM). Synthetic and real-world data were described using frequencies and percentages. Agreement of prescription drug use measures in PRDR, OSIM2 and ModOSIM was estimated with the concordance coefficient. Results: The PRDR cohort included 169,586,633 drug records and 1,395 drug types for 1,604,734 individuals. Synthetic data for 1,000,000 individuals were generated using OSIM2 and ModOSIM. Sex and age group distributions were similar in the real-world and synthetic AHRs. However, there were significant differences in the number of drug records and number of unique drugs per person for OSIM2 and ModOSIM when compared with PRDR. For the average number of days of drug use, concordance with the PRDR was 16% (95% confidence interval [CI]: 12%-19%) for OSIM2 and 88% (95% CI: 87%-90%) for ModOSIM. Conclusions: ModOSIM data were more similar to PRDR than OSIM2 data on many measures. Synthetic AHRs consistent with those found in real-world settings can be generated using ModOSIM. Synthetic data will benefit rapid implementation of methodological studies and data analyst training.

Privacy-preserving estimation of an optimal individualized treatment rule: a case study in maximizing time to severe depression-related outcomes.

Estimating individualized treatment rules-particularly in the context of right-censored outcomes-is challenging because the treatment effect heterogeneity of interest is often small, thus difficult to detect. While this motivates the use of very large datasets such as those from multiple health systems or centres, data privacy may be of concern with participating data centres reluctant to share individual-level data. In this case study on the treatment of depression, we demonstrate an application of distributed regression for privacy protection used in combination with dynamic weighted survival modelling (DWSurv) to estimate an optimal individualized treatment rule whilst obscuring individual-level data. In simulations, we demonstrate the flexibility of this approach to address local treatment practices that may affect confounding, and show that DWSurv retains its double robustness even when performed through a (weighted) distributed regression approach. The work is motivated by, and illustrated with, an analysis of treatment for unipolar depression using the United Kingdom's Clinical Practice Research Datalink.

Intraoperative phlebotomies and bleeding in liver transplantation: a historical cohort study and causal analysis.

BACKGROUND: Liver transplantation is associated with major bleeding and red blood cell (RBC) transfusions. No well-designed causal analysis on interventions used to reduce transfusions, such as an intraoperative phlebotomy, has been conducted in this population. METHODS: We conducted a historical cohort study among liver transplantations performed from July 2008 to January 2021 in a Canadian centre. The exposure was intraoperative phlebotomy. The outcomes were blood loss, perioperative RBC transfusions (intraoperative and up to 48 hr after surgery), intraoperative RBC transfusions, and one-year survival. We estimated marginal multiplicative factors (MFs), risk differences (RDs), and hazard ratios by inverse probability of treatment weighting both among treated patients and the whole population. Estimates are reported with 95% confidence intervals (CIs). RESULTS: We included 679 patients undergoing liver transplantations of which 365 (54%) received an intraoperative phlebotomy. A phlebotomy did not reduce bleeding, transfusion risks, or mortality when estimated among the treated but reduced bleeding and transfusion risks when estimated among the whole population (MF, 0.85; 95% CI, 0.72 to 0.99; perioperative RD, -15.2%; 95% CI, -26.1 to -0.8; intraoperative RD, -14.7%; 95% CI, -23.2 to -2.8). In a subgroup analysis on 584 patients with end-stage liver disease, slightly larger effects were observed on both transfusion risks when estimated among the whole population while beneficial effects were observed on the intraoperative transfusion risk when estimated among the treated population. CONCLUSION: The use of intraoperative phlebotomy was not consistently associated with better outcomes in all targets of inference but may improve outcomes among the whole population. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04826666); registered 1 April 2021.

RéSUMé: CONTEXTE: La transplantation hépatique est associée à des saignements importants et à de multiples transfusions de globules rouges (GR). Aucune analyse causale bien conçue sur l'effet d'interventions servant à réduire les transfusions, comme une phlébotomie peropératoire, n'a été menée dans cette population. MéTHODE: Nous avons mené une étude de cohorte historique incluant toutes les transplantations hépatiques réalisées dans un centre canadien de juillet 2008 à janvier 2021. L'exposition d'intérêt était une phlébotomie peropératoire. Les critères d'évaluation étaient le saignement peropératoire, les transfusions de GR périopératoires (peropératoires et jusqu'à 48 heures après la chirurgie), les transfusions de globules rouges peropératoires et la survie à un an. Des facteurs multiplicatifs (FM), des différences de risque (DR) et des rapports de risques instantanés marginaux ont été estimés en utilisant une pondération par l'inverse de la probabilité de traitement parmi les patients traités et parmi l'ensemble de la population. Les effets estimés ont été rapportés avec des intervalles de confiance (IC) à 95 %. RéSULTATS: Nous avons inclus 679 transplantations hépatiques dont 365 (54 %) ont bénéficié d'une phlébotomie peropératoire. La phlébotomie n'a pas réduit les saignements, le risque de transfusion ou la mortalité lorsque ses effets ont été estimés parmi les patients traités, mais a réduit les risques de saignement et de transfusion lorsque ses effets ont été estimés parmi l'ensemble de la population (FM = 0,85 (IC 95 %, 0,72 à 0,99); DR périopératoire = −15,2 % (IC 95 %, −26,1 % à −0,8 %); DR peropératoire = −14,7 % (IC 95 %, −23,2 % à −2,8 %)). Dans une analyse de sous-groupe portant sur 584 patients atteints d'une hépatopathie terminale, des effets légèrement plus importants ont été observés sur les deux risques transfusionnels lorsqu'estimés dans l'ensemble de la population, tandis que des effets bénéfiques ont été observés sur le risque transfusionnel peropératoire lorsqu'estimés parmi les patients traités. CONCLUSION: L'utilisation de la phlébotomie peropératoire n'a pas été systématiquement associée à de meilleurs résultats dans toutes les populations cibles, mais semble améliorer les résultats lorsque les effets sont estimés dans l'ensemble de la population. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04826666); enregistrée le 1er avril 2021.

Estimating the marginal effect of a continuous exposure on an ordinal outcome using data subject to covariate-driven treatment and visit processes.

In the statistical literature, a number of methods have been proposed to ensure valid inference about marginal effects of variables on a longitudinal outcome in settings with irregular monitoring times. However, the potential biases due to covariate-driven monitoring times and confounding have rarely been considered simultaneously, and never in a setting with an ordinal outcome and a continuous exposure. In this work, we propose and demonstrate a methodology for causal inference in such a setting, relying on a proportional odds model to study the effect of the exposure on the outcome. Irregular observation times are considered via a proportional rate model, and a generalization of inverse probability of treatment weights is used to account for the continuous exposure. We motivate our methodology by the estimation of the marginal (causal) effect of the time spent on video or computer games on suicide attempts in the Add Health study, a longitudinal study in the United States. Although in the Add Health data, observation times are prespecified, our proposed approach is applicable even in more general settings such as when analyzing data from electronic health records where observations are highly irregular. In simulation studies, we let observation times vary across individuals and demonstrate that not accounting for biasing imbalances due to the monitoring and the exposure schemes can bias the estimate for the marginal odds ratio of exposure.

Can the Risk of Severe Depression-Related Outcomes Be Reduced by Tailoring the Antidepressant Therapy to Patient Characteristics?

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for patients with unipolar depression, yet there is little guidance on which SSRI provides the most benefit to a patient, based on personal characteristics. In this work, we explore whether an individualized treatment strategy can be used by health-care providers to adapt their prescription pattern to reduce the risk of a severe depression-related outcome (SDO) when choosing between citalopram and fluoxetine, 2 commonly prescribed SSRIs. Our population-based cohort study used data from the Clinical Practice Research Datalink, the Hospital Episode Statistics repository, and the Office for National Statistics database in the United Kingdom to create a cohort of individuals diagnosed with depression who were prescribed citalopram or fluoxetine between April 1998 and December 2017. Patients were followed from treatment initiation until occurrence of the SDO outcome, treatment discontinuation, or end of study. To find an optimal treatment strategy, we used dynamic weighted survival modeling, considering patient features such as age, sex, body mass index, previous psychiatric diagnoses, and medications. Our findings suggest that using patient characteristics to tailor the antidepressant drug therapy is associated with an increase of 4 days in the median time to SDO (95% confidence interval: 2, 10 days).

Weighted regression analysis to correct for informative monitoring times and confounders in longitudinal studies.

We address estimation of the marginal effect of a time-varying binary treatment on a continuous longitudinal outcome in the context of observational studies using electronic health records, when the relationship of interest is confounded, mediated, and further distorted by an informative visit process. We allow the longitudinal outcome to be recorded only sporadically and assume that its monitoring timing is informed by patients' characteristics. We propose two novel estimators based on linear models for the mean outcome that incorporate an adjustment for confounding and informative monitoring process through generalized inverse probability of treatment weights and a proportional intensity model, respectively. We allow for a flexible modeling of the intercept function as a function of time. Our estimators have closed-form solutions, and their asymptotic distributions can be derived. Extensive simulation studies show that both estimators outperform standard methods such as the ordinary least squares estimator or estimators that only account for informative monitoring or confounders. We illustrate our methods using data from the Add Health study, assessing the effect of depressive mood on weight in adolescents.

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010. METHODS: The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database. RESULTS: We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD. CONCLUSIONS: The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.

Core-binding factor acute myeloid leukemia with t(8;21): Risk factors and a novel scoring system (I-CBFit).

BACKGROUND: Although the prognosis of core-binding factor (CBF) acute myeloid leukemia (AML) is better than other subtypes of AML, 30% of patients still relapse and may require allogeneic hematopoietic cell transplantation (alloHCT). However, there is no validated widely accepted scoring system to predict patient subsets with higher risk of relapse. METHODS: Eleven centers in the US and Europe evaluated 247 patients with t(8;21)(q22;q22). RESULTS: Complete remission (CR) rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of 24.7% of patients received alloHCT. The median disease-free (DFS) and overall (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high white blood cell counts (WBC), and pseudodiploidy compared with hyper- or hypodiploidy were included in a scoring system (named I-CBFit). DFS rate at 2 years was 76% for patients with a low-risk I-CBFit score compared with 36% for those with a high-risk I-CBFit score (P < 0.0001). Low- vs high-risk OS at 2 years was 89% vs 51% (P < 0.0001). CONCLUSIONS: I-CBFit composed of readily available risk factors can be useful to tailor the therapy of patients, especially for whom alloHCT is not need in CR1 (ie, patients with a low-risk I-CBFit score).

Author Correction: Altered Cerebellar Biochemical Profiles in Infants Born Prematurely.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Comparative effectiveness of novel oral anticoagulants in UK patients with non-valvular atrial fibrillation and chronic kidney disease: a matched cohort study.

OBJECTIVES: To evaluate the effectiveness and safety of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) among patients with non-valvular atrial fibrillation (NVAF), particularly those with chronic kidney disease (CKD). DESIGN: Population-based matched cohort study. SETTING: Over 670 primary care practices in the UK, contributing to the Clinical Practice Research Datalink. PARTICIPANTS: Up to 6818 adult patients newly treated with NOACs between 2011 and 2016, matched 1:1 to new users of VKAs on age, sex and high-dimensional propensity score. INTERVENTIONS: Current exposure to NOACs compared with current exposure to VKAs. MAIN OUTCOME MEASURES: HRs of ischaemic stroke and systemic embolism (SE), major bleeding, gastrointestinal (GI) bleeding, intracranial bleeding, myocardial infarction and all-cause mortality. RESULTS: In as-treated analyses, the rates of ischaemic stroke/SE were similar between NOACs and VKAs (HR 0.94; 95% CI 0.62 to 1.42), as were the rates of major bleeding (HR 0.86; 95% CI 0.56 to 1.33). NOACs also significantly increased the risk of GI bleeding (HR 1.78; 95% CI 1.27 to 2.48). In patients with NVAF and CKD, NOACs and VKAs remained comparable with respect to the risk of ischaemic stroke/SE (HR 0.79; 95% CI 0.40 to 1.58) and major bleeding (HR 0.88; 95% CI 0.47 to 1.62), with no difference in the risk of GI bleeding (HR 0.99; 95% CI 0.63 to 1.55). Similar results were obtained in on-treatment analyses using a time-dependent exposure definition. CONCLUSIONS: Our results suggest that in the UK primary care, NOACs are overall effective and safe alternatives to VKAs, among patients with NVAF altogether, as well as in patients with NVAF and CKD.

Long-term Use of Inhaled Corticosteroids in COPD and the Risk of Fracture.

BACKGROUND: It is uncertain whether long-term use of inhaled corticosteroids (ICSs), widely used to treat COPD, increases the risk of fracture, particularly in women, in view of the postmenopausal risks. We assessed whether long-term ICS use in patients with COPD increases the risk of hip or upper extremity fractures, and examined sex-related differences. METHODS: The Quebec health-care databases were used to form a cohort of patients with COPD over 1990 to 2005, followed until 2007 for the first hip or upper extremity fracture. In a nested case-control analysis, each case of fracture was matched with 20 control subjects on age, sex, and follow-up time. The adjusted rate ratio (RR) of fracture with ICS use, by duration and dose, was estimated using conditional logistic regression, with an interaction term to compare the risk in men and women. RESULTS: In the cohort of 240,110 subjects, 19,396 sustained a fracture during a mean 5.3 years (rate, 15.2 per 1,000 per year). Any use of ICSs was not associated with an increased rate of fracture (RR, 1.00; 95% CI, 0.97-1.03). The fracture rate was increased with > 4 years of ICS use at daily doses ≥ 1,000 µg in fluticasone equivalents (RR, 1.10; 95% CI, 1.02-1.19). This risk increase did not differ between men and women. CONCLUSIONS: Long-term ICS use at high doses is associated with a modest increase in the risk of hip and upper extremity fractures in patients with COPD. This dose-duration risk increase does not appear to be higher for women.

Temporal trends in outpatient management of incident pulmonary embolism and associated mortality.

INTRODUCTION: In clinical trial settings, outpatient management of pulmonary embolism (PE) is feasible and safe, but less is known on its use in routine care. We determined trends in outpatient management of PE and associated mortality in a large non-select patient population. METHODS: All residents of Quebec, Canada with a first-ever work-up for suspected PE in the emergency department (ED) over 10years were included. Patients could transition to outpatient management and from unconfirmed to confirmed PE in a time-varying fashion. Comparing the years 2005-9 with 2000-4, we assessed the odds ratio (OR) for outpatient management, and relative risk (RR) for all-cause mortality, readmissions for PE, and major bleeding in 30days. We adjusted the RR for a mortality risk score. RESULTS: Of 15,217 patients included, 7583 were outpatients (7.5% confirmed PE) and 7634 were inpatients (60.6% confirmed PE). In all, 10.9% of patients with confirmed PE were outpatients, but outpatient management of confirmed PE was more likely in the latter study period (OR 1.73, 95%CI 1.44-2.09). Among outpatients with confirmed PE, mortality (RR 0.84, 95%CI 0.15-4.61) and readmission (RR 1.25, 95%CI 0.45-3.48) rates were stable, and only 3 major bleeding events were noted. Inpatients with confirmed PE had stable mortality rates (RR 0.95, 95%CI 0.72-1.24). CONCLUSION: Outpatient PE management increased over 10years while remaining fairly uncommon. Nevertheless, stable mortality and readmission rates indicate this practice is safe in routine care, and add to the growing evidence in support of outpatient PE management.

Patterns of long-term use of non-vitamin K antagonist oral anticoagulants for non-valvular atrial fibrillation: Quebec observational study.

PURPOSE: Studies on long-term utilization of non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) are scarce. We evaluated predictors of use and long-term persistence of NOACs in a real-world setting. METHODS: This population-based cohort study used the computerized databases of the Canadian Province of Quebec's health insurance. Patients with a first NVAF diagnosis from 2011 until 2014 were included. A logistic regression model yielded adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of treatment initiation with NOACs versus VKAs. Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% CIs for predictors of switching from VKAs to NOACs versus remaining on VKAs, and for predictors of discontinuation of anticoagulation treatment. RESULTS: Of the 62 867 newly diagnosed NVAF patients, 14 646 initiated NOACs and 17 685 VKAs. Initiation with NOACs was less likely for patients ≥ 80 years old (OR 0.55, 95% CI 0.41-0.73) or with CHA2 DS2 -VASc ≥ 2 (OR 0.49, 95% CI 0.42-0.57). Switching from VKAs to NOACs was less likely for patients with chronic kidney disease (HR 0.53, 95% CI 0.48-0.59). After 3 years, persistence was 54% with NOACs and 25% with VKAs. Discontinuation of anticoagulation treatment was less likely for patients ≥ 80 years old (HR 0.47, 95% CI 0.40-0.55) or with CHA2 DS2 -VASc ≥ 2 (HR 0.64, 95% CI 0.57-0.70). CONCLUSIONS: Older, high-risk patients are less likely to initiate NOACs than VKAs. NOAC users show a higher long-term persistence than VKA users, and older, high-risk patients are less likely to discontinue anticoagulation treatment.

Confounding by Pre-Morbid Functional Status in Studies of Apparent Sex Differences in Severity and Outcome of Stroke.

BACKGROUND AND PURPOSE: Several studies have reported unexplained worse outcomes after stroke in women but none included the full spectrum of symptomatic ischemic cerebrovascular events while adjusting for prior handicap. METHODS: Using a prospective population-based incident cohort of all transient ischemic attack/stroke (OXVASC [Oxford Vascular Study]) recruited between April 2002 and March 2014, we compared pre-morbid and post-event modified Rankin Scale score (mRS) in women and men and change in mRS score 1 month, 6 months, 1 year, and 5 years after stroke. Baseline stroke-related neurological impairment was measured with the National Institutes of Health Stroke Scale. RESULTS: Among 2553 patients (50.6% women) with a first transient ischemic attack/ischemic stroke, women had a worse handicap 1 month after ischemic stroke (age-adjusted odds ratio for mRS score, 1.35; 95% confidence interval, 1.12-1.63). However, women also had a higher pre-morbid mRS score compared with men (age-adjusted odds ratio, 1.58; 95% confidence interval, 1.36-1.84). There was no difference in stroke severity when adjusting for age and pre-morbid mRS (odds ratio, 1.10; 95% confidence interval, 0.90-1.35) and no difference in the pre-/poststroke change in mRS at 1 month (age-adjusted odds ratio, 1.00; 95% confidence interval, 0.82-1.21), 6 months, 1 year, and 5 years. Women had a lower mortality rate, and there was no sex difference in risk of recurrent stroke. CONCLUSIONS: We found no evidence of a worse outcome of stroke in women when adjusting for age and pre-morbid mRS. Failure to account for sex differences in pre-morbid handicap could explain contradictory findings in previous studies. Properties of the mRS may also contribute to these inconsistencies.

Altered Cerebellar Biochemical Profiles in Infants Born Prematurely.

This study aims to compare the cerebellar biochemical profiles in preterm (PT) infants evaluated at term equivalent age (TEA) and healthy full-term newborns using proton magnetic resonance spectroscopy (1H-MRS). We explore the associations between altered cerebellar metabolite profiles and brain injury topography, severity of injury, and prematurity-related clinical complications. We prospectively collected high quality 1H-MRS in 59 premature infants born ≤32 weeks and 61 healthy full term controls. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentration for N-acetyl-aspartate (NAA), choline (Cho) and creatine (Cr). PT infants had significantly lower cerebellar NAA (p < 0.025) and higher Cho (p < 0.001) at TEA when compared to healthy controls. Creatine was not different between the two groups. The presence of cerebellar injury was consistently associated with reduced concentrations for NAA, Cho, and Cr. Postnatal infection was negatively associated with NAA and Cr (p < 005), while cerebral cortical brain injury severity was inversely associated with both Cho and Cr (p < 0.01). We report for the first time that premature birth is associated with altered cerebellar metabolite profiles when compared to term born controls. Infection, cerebellar injury and supratentorial injury are important risk factors for impaired preterm cerebellar biochemistry.