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Objectives: Our primary objective was to determine if more comprehensive advance care planning (ACP) documentation was associated with fewer transfers to hospital in the last year of life. Our secondary objective was to determine the impact of ACP processes and practices on hospital transfers in the last year of life., Design: Retrospective cohort study., Setting and Participants: Long-term care (LTC) residents in Ontario, Canada, 65 years and older who died between January 1, 2017, and May 30, 2018, and resided in a participating LTC home., Methods: We administered a survey to directors of care at LTC homes inquiring about ACP practices. Our exposure of interest was living in a home with comprehensive ACP documentation that includes information beyond preferences for cardiopulmonary resuscitation and hospital transfer. Our primary outcome was the number of transfers to hospital in the last year of life. We fit negative binomial regression models to determine the independent effect of comprehensive ACP and other indicators of ACP quality., Results: A total of 157 LTC homes with 6637 decedent residents were included in our study; 2942 lived in homes with comprehensive ACP documentation and 3695 had non-comprehensive ACP documents. Comprehensive documentation was not associated with fewer hospital transfers in the final year of life [incidence rat ratio (IRR), 1.00; 95% CI, 0.91-1.09]. ACP documentation update frequency, availability of ACP documents in the electronic medical record, referring to ACP documents during a health crisis, inclusion of resident values in ACP documents, and involvement of a multidisciplinary team were all associated with fewer transfers to hospital during follow-up in the last year of life., Conclusions and Implications: ACP documents that contain information beyond preferences for cardiopulmonary resuscitation and hospital transfer had no association with transfers to hospital, but high-quality ACP practices and processes were associated with fewer transfers., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: The COVID-19 pandemic highlighted and exacerbated health inequities worldwide. While several studies have examined the impact of individual social factors on COVID infection, our objective was to examine how interactions of social factors were associated with the risk of testing positive for SARS-CoV-2 during the first two years of the pandemic., Study Design and Setting: We conducted an observational cohort study using linked health administrative data for Ontarians tested for SARS-CoV-2 between January 1st, 2020, and December 31st, 2021. We constructed multivariable models to examine the association between SARS-CoV-2 positivity and key variables including immigration status (immigrants vs. other Ontarians), and neighbourhood variables for household size, income, essential worker status, and visible minority status. We report main and interaction effects using odds ratios and predicted probabilities, with age and sex controlled in all models., Results: Of 6,575,523 Ontarians in the cohort, 88.5 % tested negative, and 11.5 % tested positive for SARS-CoV-2. In all models, immigrants and those living in neighbourhoods with large average household sizes had greater odds of testing positive for SARS-CoV-2. The strength of these associations increased with increasing levels of neighbourhood marginalization for income, essential worker proportion and visible minority proportion. We observed little change in the probability of testing positive across neighbourhood income quintiles among other Ontarians who live in neighbourhoods with smaller households, but a large change in probability among other Ontarians who live in neighbourhoods with larger households., Conclusion: Our study found that SARS-CoV-2 positivity was greater among people with certain combinations of social factors, but in all cases the probability of testing positive was consistently greater for immigrants than for other Ontarians. Examining interactions of social factors can provide a more nuanced and more comprehensive understanding of health inequity than examining factors separately., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claire E. Kendall reports financial support was provided by Canadian Institutes of Health Research. Dr. Bayoumi was supported by the 10.13039/100004702Baxter and Alma Ricard Chair in Inner City Health at Unity Health Toronto and the 10.13039/501100003579University of Toronto. Dr. Claire Kendall was supported by a Clinical Research Chair in Strengthening Primary Care for Integrated Health Equity and the 10.13039/100008572University of Ottawa. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc. CC BY-NC-ND 4.0.)

Background: Group B Streptococcus (GBS) significantly contributes to neonatal sepsis and meningitis, with varying disease rates reported globally and limited population-based data. We estimated infant GBS disease burden in Ontario, Canada and assessed the association of maternal GBS screening (35-37 weeks' gestation) and intrapartum antibiotic prophylaxis (IAP) provision with infant disease rates., Methods: Our population-based cohort study included pregnant individuals and their offspring from April 2012 to March 2018, utilising the provincial birth registry linked to health administrative data. GBS cases were ascertained through culture results and diagnostic codes. We calculated incidence rates for early-onset disease (EOD: 0-6 days), late-onset disease (LOD: 7-89 days), and ultra-LOD (ULOD: 90-365 days). Adjusted incidence rate ratios (aIRR) were derived via log-binomial regression to compare infant GBS rates according to screening and IAP-receipt., Findings: Among 776,148 liveborn infants, we identified 803 with GBS, with multiples exhibiting a threefold incidence increase. Incidence rates of EOD, LOD and ULOD were 0.49, 0.46 and 0.07 per 1000 livebirths, respectively. Of eligible pregnancies, 94% were screened; 23% screened positive, and 81% of them received IAP. Nearly 12% of term EOD infants had mothers who missed IAP despite screening positive. Maternal screening was associated with lower rates of any infant GBS disease (aIRR: 0.60; 95% CI: 0.45, 0.80). Among screen-positive births, IAP-receipt was associated with reduced rates of EOD (aIRR: 0.72, 95% CI: 0.48, 1.29) and LOD/ULOD (aIRR: 0.69; 95% CI: 0.46, 1.05), but confidence intervals included 1.0., Interpretation: Our study, the largest Canadian investigation into infant GBS disease, highlights both widespread adoption and ongoing challenges of the current prevention strategy., Funding: Canadian Institutes of Health Research., Competing Interests: MS has been an investigator on projects funded by Pfizer, Merck, Moderna, Sanofi Pasteur, and GlaxoSmithKline (all unrelated to study). All funds have been paid to his institute, and he has not received any personal payments. KW is the CEO of CANImmunize Inc and served as a member of the independent data safety monitoring committee for the Medicago COVD-19 vaccine trial. When this project was funded and initiated, DBF was employed by the University of Ottawa and had an academic appointment at the Children’s Hospital of Eastern Ontario Research Institute; she is now employed by Pfizer and works on an unrelated topic. DEC has been an investigator on projects funded by Moderna and Pfizer. All funds have been paid to her institute, and she has not received any personal payments. AM has received research funds to her institution from Pfizer and Sanofi Pasteur and received personal fees for advisory boards and DSMBs from Astra-Zeneca, GlaxoSmithKline, Medicago, Merck, Moderna, Pfizer, Roche and Sanofi Pasteur. SB is the director of the Centre for Vaccine Preventable Diseases at the University of Toronto, which has received support from Merck, Sanofi and Pfizer. All funds are paid to the institute and are subject to the University of Toronto’s governance policies., (© 2024 The Author(s).)

Background: It is widely accepted that there is a stepwise increase in the risk of acute ischemic stroke with chronic kidney disease (CKD). However, whether the risk of specific ischemic stroke subtypes varies with CKD remains unclear., Objective: To assess the association between ischemic stroke subtypes (cardioembolic, arterial, lacunar, and other) classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and CKD stage., Design: retrospective cohort study., Setting: Ontario, Canada., Patients: A total of 17 434 adults with an acute ischemic stroke in Ontario, Canada between April 1, 2002 and March 31, 2013, with an estimated glomerular filtration rate (eGFR) measurement or receipt of maintenance dialysis captured in a stroke registry were included., Measurements: Kidney function categorized as an eGFR of ≥60, 30-59, <30 mL/min/1.73 m 2 , or maintenance dialysis. Ischemic stroke classified by TOAST included arterial, cardioembolic, lacunar, and other (dissection, prothrombotic state, cortical vein/sinus thrombosis, and vasculitis) types of strokes., Methods: Adjusted regression models., Results: In our cohort, 58.9% had an eGFR of ≥60, 34.7% an eGFR of 30-59, 6.0% an eGFR of <30 and 0.5% were on maintenance dialysis (mean age of 73 years; 48% women). Cardioembolic stroke was more common in patients with non-dialysis-dependant CKD (eGFR 30-59: 50.4%, adjusted odds ratio [OR] 1.20, 95% confidence interval [CI]: 1.02, 1.44; eGFR<30: 50.6%, OR 1.21, 95% CI: 1.02, 1.44), whereas lacunar stroke was less common (eGFR 30-59: 22.7% OR 0.85, 95% CI: 0.77, 0.93; eGFR <30: 0.73, 95% CI: 0.61, 0.88) compared with those with an eGFR ≥60. In stratified analyses by age and CKD, lacunar strokes were more frequent in those aged less than 65 years, whereas cardioembolic was higher in those aged 65 years and above., Limitations: TOAST classification was not captured for all patients., Conclusion: Non-dialysis CKD was associated with a higher risk of cardioembolic stroke, whereas an eGFR ≥60 mL/min/1.73 m 2 was associated with a higher risk of lacunar stroke. Detailed stroke subtyping in CKD may therefore provide mechanistic insights and refocus treatment strategies in this high-risk population., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author M.M.S. received speaker fees from, and performed consultancy for, AstraZeneca, Bayer, Otsuka, and GlaxoSmithKline. All other authors have no disclosures., (© The Author(s) 2023.)

Background: In February 2018, Canada's National Advisory Committee on Immunization (NACI) recommended tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccination during pregnancy to protect newborns against pertussis infection. We sought to describe pre- and postrecommendation trends in Tdap vaccination coverage among pregnant Ontario residents., Methods: Using linked health administrative databases, we conducted a population-based retrospective cohort study of all pregnant individuals who gave birth in Ontario hospitals between April 2012 and March 2020. We described Tdap vaccination patterns in pregnancy for the entire study period and before and after the NACI recommendation. We used log-binomial regression to identify characteristics associated with Tdap vaccination during pregnancy., Results: Among the 991 850 deliveries included, 7.0% of pregnant individuals received the Tdap vaccination during pregnancy. Vaccine coverage increased from 0.4% in 2011/12 to 29.2% in 2019/20. Coverage was highest among individuals who were older, had no previous live births, had adequate prenatal care and received maternity care primarily from a family physician. After adjustment, characteristics associated with lower coverage included younger maternal age, having a multiple birth, residing in a rural location and higher area material deprivation. In 2019/20, 71.0% of vaccinated individuals received the Tdap vaccination during the recommended gestational window (27-32 wk). Stratified analyses of the pre- and postrecommendation cohorts yielded similar findings to the main analyses with a few gradient differences after adjustment., Interpretation: During pregnancy, Tdap vaccination coverage increased substantially in Ontario between 2011/12 and 2019/20, most notably after recommendations for universal Tdap vaccination during pregnancy began in Canada. To further improve vaccine coverage in the obstetric setting, public health strategies should consider tailoring their programs to reach subpopulations with lower vaccine coverage., Competing Interests: Competing interests: Scott Halperin has received research grants or contracts from and has served on ad hoc advisory boards for GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Janssen, Medicago, Entos IMV, CanSino, VBI, Moderna, Precision Nanosystems, AstraZeneca, Seqirus, Novavax and Dynavax (all unrelated to this study). Manish Sadarangani has been an investigator on projects funded by Pfizer, Merck, Moderna, Sanofi Pasteur, Seqirus, Symvivo, VBI Vaccines and GlaxoSmithKline (all unrelated to this study). All funds have been paid to his institute, and he has not received any personal payments. He is chair/deputy chair of 2 data safety monitoring boards for SARS-CoV-2 vaccine trials, involving different vaccines. Kumanan Wilson is the CEO of CANImmunize Inc. and served as a member of the independent data monitoring committee for the Medicago SARS-CoV-2 vaccine trial (all unrelated to this study)., (© 2022 CMA Impact Inc. or its licensors.)

Importance: There is conflicting evidence on the association between intrapartum epidural analgesia and risk of autism spectrum disorder (ASD) in offspring., Objective: To evaluate the association between intrapartum epidural analgesia and the risk of ASD in offspring., Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada, using the health and administrative records of singleton live births by vaginal delivery between April 1, 2006, and March 31, 2014. Neonates with less than 24 weeks' gestation or weighing less than 500 g were excluded. Offspring were followed up from 18 months of age until ASD diagnosis, loss to follow-up, or the end of the study (December 31, 2020), whichever occurred first. Exposure, covariate, and outcome data were obtained using provincial health administrative databases., Exposures: Any intrapartum exposure to epidural or combined spinal-epidural analgesia., Main Outcomes and Measures: The primary outcome was ASD diagnosis after 18 months of age. Inverse probability of treatment weighting (IPTW) of Cox proportional hazards regression models was used to estimate the hazard ratio (HR) of intrapartum epidural analgesia and ASD in offspring. Offspring head injury was used as a control outcome. Models were adjusted for maternal sociodemographic factors, health behaviors, and medical and obstetrical history as well as labor, delivery, and offspring characteristics. Post hoc analyses included restriction to term neonates, a conditional within-mother analysis, exclusion of records with concomitant intrapartum pain management exposures, a complete case analysis, use of an alternative ASD definition, and estimation of the average treatment effect in the treated group., Results: Among the 650 373 mother-offspring pairs included in the study, 418 761 (64.4%) were exposed to intrapartum epidural analgesia. The mean (SD) maternal age at delivery was 29.7 (5.5) years; the offspring had a mean (SD) gestational age at delivery of 39.1 (1.6) weeks and included 329 808 male newborns (50.7%). The exposed and unexposed groups were similar in all maternal and newborn characteristics after IPTW (standardized difference <0.10). Autism spectrum disorder was diagnosed in 7546 offspring (1.8%) of mothers who received intrapartum epidural analgesia (incidence rate, 18.8 [95% CI, 18.4-19.3] per 10 000 person-years) compared with 3234 offspring (1.4%) who were unexposed (incidence rate, 14.4 [95% CI, 13.9-14.9] per 10 000 person-years). The crude HR for ASD associated with intrapartum epidural analgesia was 1.30 (95% CI, 1.25-1.36), and the IPTW-adjusted HR was 1.14 (95% CI, 1.08-1.21). Results did not qualitatively differ in post hoc analyses., Conclusions and Relevance: Results of this study showed that intrapartum epidural analgesia was associated with a small increase in risk for ASD in offspring. The biological plausibility of this association, however, remains unclear, and the finding must be interpreted with caution.

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is implicated in elevating the risk for cardiovascular (CV) disease; whether the elevated risk applies to all types of CV diseases or specific types is unclear. This study examined the association of AAV and adverse CV outcomes compared with the non-AAV population., Methods: We conducted a population-based, retrospective cohort study of adults (mean age 61 years, 51% female) with a new diagnosis of AAV in Ontario, Canada from 2007 to 2017. Weighted models were used to examine the association of AAV ( n  = 1520) and CV events in a matched (1:4) control cohort ( n  = 5834). The main outcomes were major adverse CV events (MACE), defined as myocardial infarction (MI), stroke or CV death, its components, atrial fibrillation (AF) and congestive heart failure (CHF)., Results: Over a mean follow-up of 3.8 years, AAV (compared with non-AAV) was associated with a higher risk of stroke: cumulative incidence 7.0% versus 5.2%, sub-distribution hazard ratio (sHR) 1.49 [(95% confidence interval (95% CI) 1.10-2.02]; AF: cumulative incidence 16.4% versus 11.5%, sHR 1.51, 95% CI 1.30-1.75; and CHF: cumulative incidence 20.8% versus 13.3%, sHR 1.41, 95% CI 1.22-1.62; but not for MACE, MI or CV death. The risks for all CV events, except CV death, were significantly elevated in the early period after AAV diagnosis, in particular AF (365-day sHR 2.06, 95% CI 1.71-2.48; 90-day sHR 3.33, 95% CI 2.66-4.18) and CHF (365-day sHR 1.75, 95% CI 1.48-2.07; 90-day sHR 2.65, 95% CI 2.15-3.26)., Conclusion: AAV is associated with a high risk of certain types of CV events, particularly in the early period following diagnosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Importance: Thiazide diuretics are commonly prescribed for the treatment of hypertension, a disease highly prevalent among older individuals and in those with chronic kidney disease. How specific thiazide diuretics compare in regard to safety and clinical outcomes in these populations remains unknown., Objective: To compare safety and clinical outcomes associated with chlorthalidone or hydrochlorothiazide use among older adults with varying levels of kidney function., Design, Setting, and Participants: This population-based retrospective cohort study was conducted in Ontario, Canada, from 2007 to 2015. Participants included adults aged 66 years or older who initiated chlorthalidone or hydrochlorothiazide during this period. Data were analyzed from December 2019 through September 2020., Exposures: New chlorthalidone users were matched 1:4 with new hydrochlorothiazide users by a high-dimensional propensity score. Time-to-event models accounting for competing risks examined the associations between chlorthalidone vs hydrochlorothiazide use and the outcomes of interest overall and within estimated glomerular filtration rate (eGFR) categories (≥60, 45-59, and <45 mL/min/1.73 m2)., Main Outcomes and Measures: The outcomes of interest were adverse kidney events (ie, eGFR decline ≥30%, dialysis, or kidney transplantation), cardiovascular events (composite of myocardial infarction, coronary revascularization, heart failure, or atrial fibrillation), all-cause mortality, and electrolyte anomalies (ie, sodium or potassium levels outside reference ranges)., Results: After propensity score matching, the study cohort included 12 722 adults (mean [SD] age, 74 [7] years; 7063 [56%] women; 5659 [44%] men; mean [SD] eGFR, 69 [19] mL/min/1.73 m2), including 2936 who received chlorthalidone and 9786 who received hydrochlorothiazide. Chlorthalidone use was associated with a higher risk of eGFR decline of 30% or greater (hazard ratio [HR], 1.24 [95% CI, 1.13-1.36]) and cardiovascular events (HR, 1.12 [95% CI, 1.04-1.22]) across all eGFR categories compared with hydrochlorothiazide use. Chlorthalidone use was also associated with a higher risk of hypokalemia compared with hydrochlorothiazide use, which was more pronounced among those with higher eGFR (eGFR ≥60 mL/min/1.73 m2: HR, 1.86 [95% CI, 1.67-2.08]; eGFR 45-59 mL/min/1.73 m2: HR, 1.57 [95% CI, 1.25-1.96]; eGFR <45 mL/min/1.73 m2: HR, 1.10 [95% CI, 0.84-1.45]; P for interaction = .001). No significant differences were observed between chlorthalidone and hydrochlorothiazide for dialysis or kidney transplantation (HR, 1.44 [95% CI, 0.88-2.36]), all-cause mortality (HR, 1.10 [95% CI, 0.93-1.29]), hyperkalemia (HR, 1.05 [95% CI, 0.79-1.39]), or hyponatremia (HR, 1.14 [95% CI, CI 0.98-1.32])., Conclusions and Relevance: This cohort study found that among older adults, chlorthalidone use was associated with a higher risk of eGFR decline, cardiovascular events, and hypokalemia compared with hydrochlorothiazide use. The excess risk of hypokalemia with chlorthalidone was attenuated in participants with reduced kidney function. Placed in context with prior observational studies comparing the safety and clinical outcomes associated with thiazide diuretics, these results suggest that there is no evidence to prefer chlorthalidone over hydrochlorothiazide.

Rationale & Objectives: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown., Study Design: Population-based retrospective cohort study., Settings & Participants: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB., Exposures: New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication., Outcomes: 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality., Analytical Approach: New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m 2 ) were explored., Results: Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m 2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m 2 , respectively., Limitations: Observational design, BP measurement data unavailable., Conclusions: AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Oncoplastic breast surgery (OBS) is increasingly used to decrease the deformity in breast conserving therapy (BCT) for breast cancer. We aimed to evaluate patient reported satisfaction following level II OBS and mastectomy utilizing the BREAST-Q questionnaire., Methods: Patients who underwent level II OBS BCT and those who underwent mastectomies were distributed the BREAST-Q post-reduction/mammoplasty module. Clinicopathological data were collected from review of patient charts. Results were scored using the standardized scoring system (Q-score). Results of the OBS group were compared to those in the mastectomy group., Results: A total of 88 patients who underwent level II OBS and 101 patients who underwent mastectomy completed the questionnaire. Mann-Whitney odds estimator demonstrated higher satisfaction with breasts (1.51, 95% CI [1.04-2.25], p = 0.026) and higher psychosocial well-being (1.51, 95% CI [1.04-2.15], p = 0.022) in those who underwent OBS compared to mastectomy., Conclusion: Results demonstrate a high satisfaction with breasts and improved psychosocial wellbeing in patients who underwent level II OBS compared to those undergoing mastectomy. These results demonstrate that OBS should be considered in patients where mastectomy otherwise would be necessary. Further larger multi-institutional studies are necessary to examine the effect of OBS on the quality of life of breast cancer patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Whether the survival benefit of β-blockers in congestive heart failure (CHF) from randomized trials extends to patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 but not receiving dialysis] is uncertain., Methods: This was a retrospective cohort study using administrative datasets. Older adults from Ontario, Canada, with incident CHF (median age 79 years) from April 2002 to March 2014 were included. We matched new users of β-blockers to nonusers on age, sex, eGFR categories (>60, 30-60, <30), CHF diagnosis date and a high-dimensional propensity score. Using Cox proportional hazards models, we examined the association of β-blocker use versus nonuse with all-cause mortality., Results: We matched 5862 incident β-blocker users (eGFR >60, n = 3136; eGFR 30-60, n = 2368; eGFR <30, n = 358). There were 2361 mortality events during follow-up. β-Blocker use was associated with reduced all-cause mortality [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.54-0.64]. This result was consistent across all eGFR categories (>60: adjusted HR 0.55, 95% CI 0.49-0.62; 30-60: adjusted HR 0.63, 95% CI 0.55-0.71; <30: adjusted HR 0.55, 95% CI 0.41-0.73; interaction term, P = 0.30). The results were consistent in an intention-to-treat analysis and with β-blocker use treated as a time-varying exposure., Conclusions: β-Blocker use is associated with reduced all-cause mortality in elderly patients with CHF and CKD, including those with an eGFR <30. Randomized trials that examine β-blockers in patients with CHF and advanced CKD are needed., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Purpose: Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood., Patients and Methods: We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy., Results: A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group ( P < .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] v 5.02 units [standard deviation, 6.13 units]; P = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, -2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies., Conclusion: In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.

Alpha-blockers (ABs) are commonly prescribed as part of a multidrug regimen in the management of hypertension. We set out to assess the risk of hypotension and related adverse events with AB use compared with other blood pressure (BP) lowering drugs using a population-based, retrospective cohort study of women (≥66 years) between 1995 and 2015 in Ontario, Canada. Cox proportional hazards examined the association of AB use and hypotension and related events (syncope, fall, and fracture) compared with other BP lowering drugs matched via a high dimensional propensity score. The primary outcome was a composite of hospitalizations for hypotension and related events (syncope, fractures, and falls) within 1 year. From 734 907 eligible women, 14 106 were dispensed an AB (mean age, 75.7; standard deviation 6.9 years, median follow-up 1 year) and matched to 14 106 dispensed other BP lowering agents. The crude incidence rate of hypotension and related events was 95.7 (95% CI [confidence interval], 90.4-101.1, events 1214 [8.6%]) with AB and 79.8 (95% CI, 74.9-84.7 per 1000 person-years, events 1025 [7.3%]) with other BP lowering medications (incident rate ratio, 1.20; 95% CI, 1.10-1.30). The risk was higher for hypotension (hazard ratio, 1.71; 95% CI, 1.33-2.20) and syncope (hazard ratio, 1.44; 95% CI, 1.18-1.75) with no difference in falls, fractures, adverse cardiac events, or all-cause mortality. Treatment of hypertension in women with ABs is associated with a higher risk of hypotension and hypotension-related events compared with other BP lowering agents. Our findings suggest that ABs should be used with caution, even as add on therapy for hypertension.

Importance: Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use., Objective: To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age., Design, Setting, and Participants: Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level., Exposure: Dispensed sodium polystyrene sulfonate in an outpatient setting., Main Outcomes and Measures: The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription., Results: From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury., Conclusions and Relevance: The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

Background and Purpose- Early hematoma expansion after intracerebral hemorrhage is a potentially modifiable predictor of outcome and a promising therapeutic target. Radiological markers seen on noncontrast computed tomography can help predict hematoma expansion and risk stratify patients presenting with intracerebral hemorrhage. Our objective was to assess the interrater and intrarater reliability of 5 commonly reported noncontrast computed tomographic markers of hematoma expansion. Methods- Four readers independently reviewed images from 40 patients from 2 intracerebral hemorrhage imaging databases (PREDICT Collaboration [Predicting Haematoma Growth and Outcome in Intracerebral Haemorrhage Using Contrast Bolus CT] and Massachusetts General Hospital). Readers were blind to all demographic and outcome data and used accepted definitions to establish the presence or absence of intrahematoma hypodensities, blend sign, fluid level, irregular hematoma morphology, and heterogeneous hematoma density. We calculated interrater and intrarater agreement and stratified kappas for the 5 imaging markers. Results- Interrater agreement was excellent for all 5 markers, ranging from 94% to 98%. Interrater kappas ranged from 0.67 to 0.91 (the lowest for fluid level). Interrater agreement had a similar pattern, ranging from 89% to 93%, with Kappas ranging from 0.60 to 0.89. Conclusions- We show that 5 commonly used noncontrast computed tomographic imaging findings all have good-to-excellent interrater and intrarater reliabilities, with the best kappa for blend sign, hypodensities, and heterogeneity.

Purpose To evaluate whether journal-level variables (impact factor, cited half-life, and Standards for Reporting of Diagnostic Accuracy Studies [STARD] endorsement) and study-level variables (citation rate, timing of publication, and order of publication) are associated with the distance between primary study results and summary estimates from meta-analyses. Materials and Methods MEDLINE was searched for meta-analyses of imaging diagnostic accuracy studies, published from January 2005 to April 2016. Data on journal-level and primary-study variables were extracted for each meta-analysis. Primary studies were dichotomized by variable as first versus subsequent publication, publication before versus after STARD introduction, STARD endorsement, or by median split. The mean absolute deviation of primary study estimates from the corresponding summary estimates for sensitivity and specificity was compared between groups. Means and confidence intervals were obtained by using bootstrap resampling; P values were calculated by using a t test. Results Ninety-eight meta-analyses summarizing 1458 primary studies met the inclusion criteria. There was substantial variability, but no significant differences, in deviations from the summary estimate between paired groups (P > .0041 in all comparisons). The largest difference found was in mean deviation for sensitivity, which was observed for publication timing, where studies published first on a topic demonstrated a mean deviation that was 2.5 percentage points smaller than subsequently published studies (P = .005). For journal-level factors, the greatest difference found (1.8 percentage points; P = .088) was in mean deviation for sensitivity in journals with impact factors above the median compared with those below the median. Conclusion Journal- and study-level variables considered important when evaluating diagnostic accuracy information to guide clinical decisions are not systematically associated with distance from the truth; critical appraisal of individual articles is recommended. © RSNA, 2017 Online supplemental material is available for this article.

Background: Epidemiological analyses demonstrate that pneumonia survivors have a higher risk of myocardial infarction than people with similar load of risk factors for atherosclerotic cardiovascular disease (ASCVD) but without pneumonia. This may be due to a higher baseline burden of ASCVD in patients with pneumonia that is not captured by the accounting of known ASCVD risk factors in epidemiological analyses or to unfavorable accelerating effects of pneumonia on atherosclerosis., Methods: We analyzed data from the Multi-Ethnic Study of Atherosclerosis. We identified 54 participants that were hospitalized for pneumonia during study follow-up and that also had assessment of coronary artery calcium (CAC, an objective marker of coronary atherosclerotic burden) before and after this hospitalization. We matched them to 54 participants who were not hospitalized for pneumonia but that had CAC assessments at the same study visits as the pneumonia cases. We compared baseline CAC scores and their progression between groups., Results: Baseline CAC scores were similar in both groups (median [IQR]; 6.3 [0-356.8] in pneumonia participants vs. 10.8 [0-178.3] in controls; p = 0.25). After a median of 4.8 years, the direction and magnitude of CAC score change, and the slope of CAC score progression between groups was also similar (median change [IQR], 21.8 [0 to 287.29] in participants with pneumonia versus 15.8 [0 to 140.94] in controls, p = 0.28; difference in slope, 7.7, 95% CI -9.0 to 24.6, p = 0.18). However, among participants with high baseline ASCVD risk (i.e. ACC/AHA 10-year risk estimate ≥7.5%), participants with pneumonia showed a larger increase in CAC scores (median change [IQR]; 159.10 [38.55-407.34] versus 48.72 [0.97-246.99] in controls; p = 0.02) and a trend towards a steeper slope of CAC score progression (difference in slope, 19.7, 95% CI -6.6 to 45.6, p = 0.07)., Conclusion: Pneumonia may accelerate the progression of atherosclerosis in people with high baseline ASCVD risk.

Objective: The purpose of this study was to compare the efficacy of gelatin sponge with that of coils for splenic artery embolization in the treatment of blunt splenic injury., Materials and Methods: A single-center retrospective review was performed with the records of 63 patients (45 men, 18 women; mean age, 45.5 years; range, 16-84 years) with blunt splenic injury treated at a tertiary care trauma center by splenic artery embolization with gelatin sponge (n = 30 patients) or metallic coils (n = 33 patients) between 2005 and 2014. The two groups had comparable median American Association for the Surgery of Trauma grades of IV and comparable angiographic appearances regarding active extravasation and pseudoaneurysm formation at preembolization splenic arteriography (p = 0.32). Clinical outcomes and procedure-related outcomes were evaluated., Results: The success rates were similar in the two groups: splenic artery embolization failed in 6.6% (2/30) of patients in the gelatin sponge group and 12.1% (4/33) in the coil embolization group (p = 0.45; 95% CI, -30.1% to 19.2%). Major complications occurred in six patients (20.0%) in the gelatin sponge group and in six patients (18.1%) in the coil group (p = 0.85; 95% CI, -23.0% to 26.6%). Minor complications occurred in three patients (10.0%) in the gelatin sponge group and seven patients (21.2%) in the coil group (p = 0.21; 95% CI, -35.4% to 14.0%). Procedure time was significantly shorter in the gelatin sponge group (median, 32 minutes; interquartile range, 18-48 minutes) than in the coil group (median, 53 minutes; interquartile range, 30-76 minutes) (p = 0.01)., Conclusion: Splenic artery embolization with gelatin sponge appears to be as effective and as safe as coil embolization and can be completed in a shorter time.

Objective: With the introduction of direct entry (0+5) residency programs in addition to the traditional (5+2) programs, the number of vascular surgery graduates across Canada is expected to increase significantly during the next 5 to 10 years. Society's need for these newly qualified surgeons is unclear. This study evaluated the predicted requirement for vascular surgeons across Canada to 2021. A program director survey was also performed to evaluate program directors' perceptions of the 0+5 residency program, the expected number of new trainees, and faculty recruitment and retirement., Methods: The estimated and projected Canadian population numbers for each year between 2013 and 2021 were determined by the Canadian Socio-economic Information and Management System (CANSIM), Statistics Canada's key socioeconomic database. The number of vascular surgery procedures performed from 2008 to 2012 stratified by age, gender, and province was obtained from the Canadian Institute for Health Information Discharge Abstract Database. The future need for vascular surgeons was calculated by two validated methods: (1) population analysis and (2) workload analysis. In addition, a 12-question survey was sent to each vascular surgery program director in Canada., Results: The estimated Canadian population in 2013 was 35.15 million, and there were 212 vascular surgeons performing a total of 98,339 procedures. The projected Canadian population by 2021 is expected to be 38.41 million, a 9.2% increase from 2013; however, the expected growth rate in the age group 60+ years, who are more likely to require vascular procedures, is expected to be 30% vs 3.4% in the age group <60 years. Using population analysis modeling, there will be a surplus of 10 vascular surgeons in Canada by 2021; however, using workload analysis modeling (which accounts for the more rapid growth and larger proportion of procedures performed in the 60+ age group), there will be a deficit of 11 vascular surgeons by 2021. Program directors in Canada have a positive outlook on graduating 0+5 residents' skill, and the majority of programs will be recruiting at least one new vascular surgeon during the next 5 years., Conclusions: Although population analysis projects a potential surplus of surgeons, workload analysis predicts a deficit of surgeons because it accounts for the rapid growth in the 60+ age group in which the majority of procedures are performed, thus more accurately modeling future need for vascular surgeons. This study suggests that there will be a need for newly graduating vascular surgeons in the next 5 years, which could have an impact on resource allocation across training programs in Canada., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose To evaluate the accuracy of computed tomography (CT) for diagnosis of internal hernia (IH) in patients who have undergone laparoscopic Roux-en-Y gastric bypass and to develop decision tree models to optimize diagnostic accuracy. Materials and Methods This was a retrospective, ethics-approved study of patients who had undergone laparoscopic Roux-en-Y gastric bypass with surgically confirmed IH (n = 76) and without IH (n = 78). Two radiologists independently reviewed each examination for the following previously established CT signs of IH: mesenteric swirl, small-bowel obstruction (SBO), mushroom sign, clustered loops, hurricane eye, small bowel behind the superior mesenteric artery, and right-sided anastomosis. Radiologists also evaluated images for two new signs, superior mesenteric vein (SMV) "beaking" and "criss-cross" of the mesenteric vessels. Overall impressions for diagnosis of IH were recorded. Diagnostic accuracy and interobserver agreement were calculated, and multivariate recursive partitioning was performed to evaluate various decision tree models by using the CT signs. Results Accuracy and interobserver agreement regarding the nine CT signs of IH showed considerable variation. The best signs were mesenteric swirl (sensitivity and specificity, 86%-89% and 86%-90%, respectively; κ = 0.74) and SMV beaking (sensitivity and specificity, 80%-88% and 94%-95%, respectively; κ = 0.83). Overall reader impression yielded the highest sensitivity and specificity (96%-99% and 90%-99%, respectively; κ = 0.79). The decision tree model with the highest overall accuracy and sensitivity included mesenteric swirl and SBO, with a diagnostic odds ratio of 154 (95% confidence interval [CI]: 146, 161), sensitivity of 96% (95% CI: 87%, 99%), and specificity of 87% (95% CI: 75%, 93%). The decision tree with the highest specificity included SMV beaking and SBO, with a diagnostic odds ratio of 105 (95% CI: 101, 109), sensitivity of 90% (95% CI: 79%, 95%), and specificity of 92% (95% CI: 83%, 97%). Conclusion The decision tree with the highest accuracy and sensitivity for diagnosis of IH included mesenteric swirl and SBO, the model with the highest specificity included SMV beaking and SBO, and the remaining signs showed lower accuracy and/or poor to fair interobserver agreement. Overall reader impression yielded the highest accuracy for diagnosis of IH, likely because alternate diagnoses not incorporated in the models were considered. © RSNA, 2016 Online supplemental material is available for this article.

Objectives: HIV prevalence among people who inject drugs (PWID) in Ottawa is estimated at about 10%. The successful integration of peers into outreach efforts and wider access to HIV point-of-care testing (POCT) create opportunities to explore the role of peers in providing HIV testing. The PROUD study, in partnership with Ottawa Public Health (OPH), sought to develop a model for community-based peer-administered HIV POCT., Methods: PROUD draws on community-based participatory research methods to better understand the HIV risk environment of people who use drugs in Ottawa. From March-October 2013, 593 people who reported injecting drugs or smoking crack cocaine were enrolled through street-based recruitment. Trained peer or medical student researchers administered a quantitative survey and offered an HIV POCT (bioLytical INSTI test) to participants who did not self-report as HIV positive., Results: 550 (92.7%) of the 593 participants were offered a POCT, of which 458 (83.3%) consented to testing. Of those participants, 74 (16.2%) had never been tested for HIV. There was no difference in uptake between testing offered by a peer versus a non-peer interviewer (OR = 1.05; 95% CI = 0.67-1.66). Despite testing those at high risk for HIV, only one new reactive test was identified., Conclusion: The findings from PROUD demonstrate high uptake of community-based HIV POCT. Peers were able to successfully provide HIV POCT and reach participants who had not previously been tested for HIV. Community-based and peer testing models provide important insights on ways to scale-up HIV prevention and testing among people who use drugs., Competing Interests: The authors have declared that no competing interests exist.

Background: Tissue factor pathway inhibitor (TFPI) is an anticoagulant with antimetastatic properties. The homozygous CC polymorphism of TFPI (-33T → C) is associated with higher TFPI levels and lower venous thromboembolism risk. This study was the first to evaluate the impact of this polymorphism on disease-free survival (DFS) in cancer patients after curative resection., Methods: A prospectively maintained tumor bank with clinical data was used to identify patients who underwent curative surgery for colorectal cancer between 1994 and 2006. Germline DNA was extracted from formalin-fixed, paraffin-embedded normal colonic mucosa. Single nucleotide polymorphisms for TFPI (-33T → C), factor V Leiden (G1691A), and prothrombin (G20210A) were determined by polymerase chain reaction. Survival analysis was described using the Kaplan-Meier method. Multivariable regression analysis was performed using the Cox proportional hazard model., Results: Of the 127 patients identified, the CC genotype was found in 11 %. Venous thromboembolism incidence was 18 % in the TT/TC (wild type/heterozygous) genotypes and 7 % in the CC genotype (p = 0.46). The CC genotype was associated with superior DFS (hazard ratio 0.34, 95 % confidence interval 0.14-0.84; p = 0.02) with 5-year DFS of 63 vs. 24 % for CC vs. TT/TC, respectively. In multivariate analysis, CC polymorphism (hazard ratio 0.28, p = 0.008) was independently associated with improved DFS. The prevalence of factor V Leiden (0.8 %) and prothrombin (1.6 %) polymorphisms was too low to detect interaction with TFPI polymorphism or DFS., Conclusions: These findings indicate that the inherited anticoagulant homozygous -33T → C TFPI polymorphism may protect against colon cancer recurrence and suggests a mediating role for the coagulation system in cancer outcomes.

Purpose To determine if adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) is associated with postpublication citation rates. Materials and Methods A comprehensive search of PubMed, EMBASE, and Cochrane Library databases was performed to identify published articles that have evaluated adherence of diagnostic accuracy studies to the STARD statement. These were included if the number of STARD items reported ("STARD result") could be obtained for each evaluated study. The date of publication, journal impact factor, and citation rate (citations per day) were extracted for the diagnostic accuracy studies. Univariate correlations were performed to identify any association between STARD result, impact factor, and citation rate. Multivariate regression analysis was performed to explore the effect of impact factor on postpublication citation rates. Results The authors were able to obtain the STARD results for 1002 "original" diagnostic accuracy studies from eight different "STARD evaluation" articles. The median impact factor was 3.97 (interquartile range [IQR]: 2.32-6.21), the median STARD result was 15 of 25 items (IQR: 12-18), and the median citation rate was 0.007 citations per day (IQR: 0.0032-0.017). The authors identified a weak positive correlation between STARD result and citation rate (r = 0.096; 95% confidence interval [CI]: 0.034, 0.157), a moderate positive correlation between impact factor and citation rate (r = 0.58; 95% CI: 0.535, 0.617), and a weak positive correlation between impact factor and STARD result (r = 0.13; 95% CI: 0.064, 0.186). Multivariate analysis accounting for journal clustering effects revealed that, when impact factor is partialed out, the positive correlation between citation rate and STARD result does not persist (r = 0.029; 95% CI: -0.033, 0.091). Conclusion There is a positive correlation between completeness of reporting, as evaluated with STARD, and citation rate as well as impact factor. When adjusted for impact factor, the positive correlation between completeness of reporting and citation rate does not persist. (©) RSNA, 2016 Online supplemental material is available for this article.

Purpose: A single-center randomized clinical trial was performed to compare postinterventional primary patency rates achieved by cutting balloon angioplasty and high-pressure balloon angioplasty in the treatment of de novo stenoses within autogenous arteriovenous (AV) fistulae for hemodialysis., Materials and Methods: Forty-eight patients undergoing their first angioplasty were prospectively randomized to undergo angioplasty with a cutting balloon or high-pressure balloon 4-8 mm in diameter because cutting balloons larger than 8 mm are not available. Nine patients were excluded after angiography, with seven requiring balloons larger than 8 mm. In the remaining 39 patients, there were 42 stenoses in the following regions: juxtaanastomotic (38%), perianstomotic (38%), midcephalic (9%), and cephalic arch (14%). Patients in the cutting balloon group were younger (mean age difference, 9 y; P = .04), but other demographic variables were comparable (range, P = .08-.89). The mean follow-up period was 8.5 mo (range, 24 d to 32 mo). Kaplan-Meier analysis was used to compare duration of patency. Mann-Whitney rank-sum t test and χ2/Fisher exact tests were used to compare continuous and categoric variables, respectively., Results: Technical success was achieved in all 39 patients. At 3, 6, and 12 months, the postinterventional primary patency rates for the cutting balloon group were 61.1% (95% confidence interval [CI], 35.75%-82.70%), 27.7% (95% CI, 9.69%-53.48%), and 11.1% (95% CI, 1.38%-34.71%), respectively, compared with 70.0% (95% CI, 45.72%-88.11%), 42.1% (95% CI, 20.25%-66.50%), and 26.3% (95% CI, 9.15%-51.20%), respectively, for the high-pressure balloon group (P < .3 at each interval)., Conclusions: Compared with high-pressure balloon angioplasty, cutting balloon angioplasty does not improve postinterventional primary patency of de novo stenotic lesions in autogenous arteriovenous fistulae., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: Current clinical guidelines recommend expedited repair of hip fracture to reduce morbidity and mortality. A significant number of hip fracture patients have concomitant cardiovascular disease requiring anticoagulation. Vitamin K antagonists (VKAs), which have been traditionally used, might be associated with an increased time to surgery (TTS) and it remains unknown what effect direct oral anticoagulants (DOACs) have on this metric. Our objective is to determine how anticoagulation with a VKA or DOAC affects TTS., Materials and Methods: This is a case control study comparing TTS in consecutively admitted hip fracture patients receiving either a DOAC or VKA with age- and gender-matched controls between January 1, 2010 and March 24, 2014. The primary end point is TTS, which is defined as the time elapsed from admission to surgery. Secondary end points include the rate of stroke, death, bleeding and VTE during admission., Results: Of 2258 patients, 233 were on a VKA while 27 were on a DOAC. Median TTS seems to be longer in patients receiving a DOAC or a VKA when compared to controls. (40 h vs. 26.2h). The DOAC group tended to have longer median TTS when compared to the VKA groups (66.9h vs. 39.4h) There was no difference in the rate of stroke, death, bleeding and VTE during admission., Conclusions: Patients on anticoagulation prior to admission for hip fracture experienced longer delays in surgery when compared to patients not receiving anticoagulation. Patients on a DOAC experienced the longest surgical delay., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Purpose: Hematoma expansion in intracerebral hemorrhage is associated with higher morbidity and mortality. The computed tomography (CT) angiographic spot sign is highly predictive of expansion, but other morphological features of intracerebral hemorrhage such as fluid levels, density heterogeneity, and margin irregularity may also predict expansion, particularly in centres where CT angiography is not readily available., Methods: Baseline noncontrast CT scans from patients enrolled in the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study were assessed for the presence of fluid levels and degree of density heterogeneity and margin irregularity using previously validated scales. Presence and grade of these metrics were correlated with the presence of hematoma expansion as defined by the PREDICT study on 24-hour follow-up scan., Results: Three hundred eleven patients were included in the analysis. The presence of fluid levels and increasing heterogeneity and irregularity were associated with 24-hour hematoma expansion (P=0.021, 0.003 and 0.049, respectively) as well as increases in absolute hematoma size. Fluid levels had the highest positive predictive value (50%; 28%-71%), whereas margin irregularity had the highest negative predictive value (78%; 71%-85). Noncontrast metrics had comparable predictive values as spot sign for expansion when controlled for vitamin K, antiplatelet use, and baseline National Institutes of Health Stroke Scale, although in a combined area under the receiver-operating characteristic curve model, spot sign remained the most predictive., Conclusions: Fluid levels, density heterogeneity, and margin irregularity on noncontrast CT are associated with hematoma expansion at 24 hours. These markers may assist in prediction of outcomes in scenarios where CT angiography is not readily available and may be of future help in refining the predictive value of the CT angiography spot sign., (© 2015 American Heart Association, Inc.)

Background: Direct oral anticoagulants (DOACs) are used for treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (AF). Given the shorter half-life and lack of laboratory monitoring compared to vitamin-K antagonists (VKAs), adequate adherence to DOACs is important. Reported anticoagulation adherence is unclear in clinical practice., Objectives: To assess self-reported anticoagulation adherence in a tertiary center anticoagulation clinic., Patients/methods: Cross-sectional study of patients on oral anticoagulants (VKAs, rivaroxaban, dabigatran and apixaban). Anticoagulation adherence was assessed using the 4-item Morisky score. Baseline characteristics were evaluated for association with adherence., Results: Five hundred patients completed the survey; 74% were on VKAs and 26% on DOACs: rivaroxaban 102 (79%); dabigatran 26 (19%); apixaban 2 (2%). Main indications for anticoagulation were VTE (72%) and AF (18%). Self-reported anticoagulation adherence using the 4-item Morisky scale was 56.2% for patients on VKAs and 57.1% for patients on DOACs. Predictors of anticoagulation adherence were age (OR=1.02; 95% CI:1.01-1.03), female gender (OR=1.58; 95% CI:1.10-2.27), use of additional oral medications (OR=2.78; 95% CI:1.67-4.63), and retired employment status (OR=2.31; 95% CI:1.51-3.55). In backward selection multivariate analyses age, female gender and use of other oral medications remained significantly associated with anticoagulation adherence., Conclusions: Self-reported anticoagulation adherence was similar between VKAs and DOACs. Until laboratory assays are universally available to evaluate DOAC adherence, physicians should emphasize the importance of anticoagulation adherence at each patient encounter. The Morisky scale provides simple assessment of anticoagulation adherence; however it has not yet been validation for this purpose., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: The ability to accurately characterize a pulmonary air leak is an essential skill in chest medicine and surgery. The objective was to evaluate interobserver variability in air leak assessments using analogue and digital pleural drainage systems., Methods: Air leak severity in lung resection patients with a pulmonary air leak was prospectively evaluated by at least one thoracic surgeon, one surgical resident and one to two nurses using a standardized questionnaire. The first assessment was performed with pleural drains connected to an analogue system. Subsequently, patients were re-assessed after changing from the analogue to a digital drainage system. The thoracic surgeon's evaluation was considered the reference standard for comparison. Agreement between observers was quantified using the kappa (κ) statistic., Results: A total of 128 air leak evaluations were completed in 30 patients (thoracic surgeon = 30; nurses = 56; resident = 30; physiotherapists = 12). The mean time between analogue and digital assessment was 2.16 (±1.66) h. The level of observer agreement regarding air leak severity significantly increased from very slight to substantial when using the digital drainage system [analogue κ = 0.03; confidence interval (CI): 0.04-0.11; P = 0.40) (digital κ = 0.61; CI: 0.49-0.73; P < 0.01]. Similar improvements were observed in subgroups of health-care professionals using digital technology., Conclusions: Digital pleural drainage technology improves the agreement level between members of the health-care team when assessing the severity of a pulmonary air leak after lung resection., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Purpose: The purpose of this study is to determine whether study quality and completeness of reporting of systematic reviews (SR) and meta-analyses (MA) published in high impact factor (IF) radiology journals is associated with citation rates., Methods: All SR and MA published in English between Jan 2007-Dec 2011, in radiology journals with an IF >2.75, were identified on Ovid MEDLINE. The Assessing the Methodologic Quality of Systematic Reviews (AMSTAR) checklist for study quality, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for study completeness, was applied to each SR & MA. Each SR & MA was then searched in Google Scholar to yield a citation rate. Spearman correlation coefficients were used to assess the relationship between AMSTAR and PRISMA results with citation rate. Multivariate analyses were performed to account for the effect of journal IF and journal 5-year IF on correlation with citation rate. Values were reported as medians with interquartile range (IQR) provided., Results: 129 studies from 11 journals were included (50 SR and 79 MA). Median AMSTAR result was 8.0/11 (IQR: 5-9) and median PRISMA result was 23.0/27 (IQR: 21-25). The median citation rate for SR & MA was 0.73 citations/month post-publication (IQR: 0.40-1.17). There was a positive correlation between both AMSTAR and PRISMA results and SR & MA citation rate; ρ=0.323 (P=0.0002) and ρ=0.327 (P=0.0002) respectively. Positive correlation persisted for AMSTAR and PRISMA results after journal IF was partialed out; ρ=0.243 (P=0.006) and ρ=0.256 (P=0.004), and after journal 5-year IF was partialed out; ρ=0.235 (P=0.008) and ρ=0.243 (P=0.006) respectively., Conclusion: There is a positive correlation between the quality and the completeness of a reported SR or MA with citation rate which persists when adjusted for journal IF and journal 5-year IF.

Background: Thrombocytopenia occurs commonly after hematopoietic progenitor cell transplantation (HPCT) and is associated with potential morbidity and mortality. Few studies have examined the impact of platelet (PLT) transfusion on clinical outcomes in HPCT while optimal PLT transfusion strategies after HSCT remain uncertain., Study Design and Methods: A retrospective single-center cohort study was conducted on 522 patients undergoing HPCT between January 2002 and December 2007. Associations between PLT transfusion events and clinical characteristics with transplant-related outcomes were assessed using univariate and multivariate analysis., Results: Mean number of PLT transfusion events before Day +60 posttransplant was 7.5 (95% confidence interval, 6.7-8.4) with greater number of events after allogeneic compared with autologous HPCT (p < 0.01). Univariate and multivariate analysis confirmed that the number of PLT transfusion events was associated with increased 100-day nonrelapse mortality (p < 0.01), posttransplant length of hospital stay (p < 0.01), need for intensive care unit admission (p < 0.01), and number of organs affected by severe toxicity (p < 0.01)., Conclusion: HPCT-related toxicity and mortality are associated with increased PLT transfusion events. Alternative strategies to reduce PLT transfusions after HPCT may warrant future study., (© 2014 AABB.)

Introduction: Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions and the benefits of treatment are unknown. This study investigated the treatment of SCLC in the third-line setting., Patients and Methods: An international, multicenter retrospective analysis of patients who received at least 3 lines of chemotherapy for their SCLC was performed., Results: From 2000 to 2010, 120 patients were identified from 5 centers: median age 61, 40% (n = 72) limited stage, and 79% (n = 95) Eastern Cooperative Oncology Group performance status of 0 to 1. Only 22% of these patients received 3 distinct lines of chemotherapy. The remainder were rechallenged with a chemotherapy regimen used at least once previously. Six percent received platinum-based chemotherapy in all 3 lines. In third-line, response rate was 18% and median overall survival was 4.7 months. Factors associated with longer survival included normal baseline LDH levels and response to second-line chemotherapy. On multivariate analysis only normal baseline LDH retained statistical significance. Thirty-five patients went on to receive chemotherapy beyond the third line., Conclusion: Few SCLC patients receive 3 chemotherapy lines. Most patients were rechallenged with a similar regimen at least once. Response and survival in the third-line setting are modest. Lack of response to second-line chemotherapy and elevated baseline LDH level might predict lack of benefit from third-line treatment. This data set does not include patients receiving fewer lines for comparison., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Rationale and Objectives: Patients presenting with transient ischemic attack or stroke may have symptom-related lesions on acute computed tomography angiography (CTA) such as free-floating intraluminal thrombus (FFT). It is difficult to distinguish FFT from carotid plaque, but the distinction is critical as management differs. By contouring the shape of these vascular lesions ("virtual endarterectomy"), advanced morphometric analysis can be performed. The objective of our study is to determine whether quantitative shape analysis can accurately differentiate FFT from atherosclerotic plaque., Materials and Methods: We collected 23 consecutive cases of suspected carotid FFT seen on CTA (13 men, 65 ± 10 years; 10 women, 65.5 ± 8.8 years). True-positive FFT cases (FFT+) were defined as filling defects resolving with anticoagulant therapy versus false-positives (FFT-), which remained unchanged. Lesion volumes were extracted from CTA images and quantitative shape descriptors were computed. The five most discriminative features were used to construct receiver operator characteristic (ROC) curves and to generate three machine-learning classifiers. Average classification accuracy was determined by cross-validation., Results: Follow-up imaging confirmed sixteen FFT+ and seven FFT- cases. Five shape descriptors delineated FFT+ from FFT- cases. The logistic regression model produced from combining all five shape features demonstrated a sensitivity of 87.5% and a specificity of 71.4% with an area under the ROC curve = 0.85 ± 0.09. Average accuracy for each classifier ranged from 65.2%-76.4%., Conclusions: We identified five quantitative shape descriptors of carotid FFT. This shape "signature" shows potential for supplementing conventional lesion characterization in cases of suspected FFT., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

Introduction: Filling defects at the internal carotid artery (ICA) origin in the work-up of stroke or transient ischemic attack may be an ulcerated plaque or free-floating thrombus (FFT). This may be challenging to distinguish, as they can appear morphologically similar. This is an important distinction as FFT can potentially embolize distally, and its management differs. We describe a series of patients with suspected FFT and evaluate its imaging appearance, clinical features, and evolution with therapy., Methods: Between 2008 and 2013, we prospectively collected consecutive patients with proximal ICA filling defects in the axial plane surrounded by contrast on CT/MR angiography. We defined FFT as a filling defect that resolved on follow-up imaging. We assessed the cranial-caudal dimension of the filling defect and receiver operating characteristics to identify clinical and radiological variables that distinguished FFT from complex ulcerated plaque., Results: Intraluminal filling defects were identified in 32 patients. Filling defects and resolved or decreased in 25 patients (78 %) and felt to be FFT; there was no change in 7 (22 %). Resolved defects and those that decreased in size extended more cranially than those that remained unchanged: 7.3 mm (4.2-15.9) versus 3.1 mm (2.7-3.7; p = 0.0038). Receiver operating characteristic analysis established a threshold of 3.8 mm (filling defect length), sensitivity of 88 %, specificity of 86 %, and area under the curve of 0.86 (p < 0.0001) for distinguishing FFT from plaque., Conclusion: Filling defects in the proximal ICA extending cranially >3.8 mm were more likely to be FFT than complex ulcerated plaque. Further studies evaluating filling defect length as a predictor for FFT are warranted.

Background and Purpose: CT angiography spot sign predicts hematoma expansion in patients with acute intracerebral hemorrhage (ICH). The spot sign may represent a site of active extravasation, a locus of arrested hemorrhage forming fibrin globes, or represent associated epiphenomena such as hypertensive microaneurysms. We sought to describe the evolution of spot signs over 60 seconds in acute ICH using dynamic CT angiography and determine whether they grow and diffuse into the hematoma as would be expected with active extravasation., Methods: We prospectively identified consecutive patients presenting with spontaneous ICH<6 hours from symptom onset that completed dynamic CT angiography imaging over a 60-second acquisition protocol. We determined spot positivity, quantified spot volumes, and then used repeated-measures ANOVA to assess changes in spot volume over time., Results: We collected data on 35 patients; 13 of 35 (37%) patients were spot-positive. Spot-positive patients had larger median ICH volume compared with spot-negative patients (median 10.7 versus 49.2 mL; P=0.007). Maximal spot sign volumes ranged from 0.02 to 2.8 mL (median 0.17 mL). Spot sign volumes increased significantly with time (P<0.001) and seemed to disperse into the hematoma in all cases. Three of 13 (23%) spot-positive patients presented with 2 distinct spot signs, but the remaining patients either had only 1 spot sign or different contiguous components of an irregularly shaped spot sign., Conclusions: In this dynamic CT angiography study of ICH, spot signs evolve consistent with sites of active extravasation.

Introduction: The true incidence of symptomatic implanted port related venous thromboembolism (VTE) in cancer patients is unclear and there is very limited data on its associated risk factors., Materials and Methods: We performed a retrospective cohort study of consecutive cancer outpatients who received an ultrasound guided implanted port insertion for the administration of chemotherapy. The primary outcome measure was symptomatic VTE. Univariable and multivariable logistic regression analyses were used to identify risk factors for symptomatic VTE., Results: A total of 400 cancer patients with a newly inserted implanted port for deliverance of chemotherapy were included in the study. Median age was 58years (range of 21 to 85years) and 120 (30%) were males. Patients were followed for a median of 12months and none received thrombophrophylaxis. Of the 400 patients included in the analysis, 34 patients (8.5%; 95% CI: 6.0 to 11.7%) had symptomatic VTE (16 DVTs, 16 PEs, and 2 with both). In the univariate analyses, metastatic disease, male gender and right sided implanted port insertion were significantly associated with the risk of VTE. In the multiple-variable analysis, male gender (OR 2.17, p=0.04) and presence of metastases (OR 8.22, p<0.01) were the two significant independent predictors of implanted port related VTE., Conclusion: Symptomatic VTE is a frequent complication in cancer patients with implanted port receiving chemotherapy. Gender and presence of metastatic disease are independent risk factors for symptomatic VTE. Future trials assessing the role of thromboprophylaxis among these higher risk patients are needed., (© 2013. Published by Elsevier Ltd. All rights reserved.)

Background: Some children feel pain during wound closures using tissue adhesives. We sought to determine whether a topically applied analgesic solution of lidocaine-epinephrine-tetracaine would decrease pain during tissue adhesive repair., Methods: We conducted a randomized, placebo-controlled, blinded trial involving 221 children between the ages of 3 months and 17 years. Patients were enrolled between March 2011 and January 2012 when presenting to a tertiary-care pediatric emergency department with lacerations requiring closure with tissue adhesive. Patients received either lidocaine-epinephrine-tetracaine or placebo before undergoing wound closure. Our primary outcome was the pain rating of adhesive application according to the colour Visual Analogue Scale and the Faces Pain Scale--Revised. Our secondary outcomes were physician ratings of difficulty of wound closure and wound hemostasis, in addition to their prediction as to which treatment the patient had received., Results: Children who received the analgesic before wound closure reported less pain (median 0.5, interquartile range [IQR] 0.25-1.50) than those who received placebo (median 1.00, IQR 0.38-2.50) as rated using the colour Visual Analogue Scale (p=0.01) and Faces Pain Scale--Revised (median 0.00, IQR 0.00-2.00, for analgesic v. median 2.00, IQR 0.00-4.00, for placebo, p<0.01). Patients who received the analgesic were significantly more likely to report having or to appear to have a pain-free procedure (relative risk [RR] of pain 0.54, 95% confidence interval [CI] 0.37-0.80). Complete hemostasis of the wound was also more common among patients who received lidocaine-epinephrine-tetracaine than among those who received placebo (78.2% v. 59.3%, p=0.008)., Interpretation: Treating minor lacerations with lidocaine-epinephrine-tetracaine before wound closure with tissue adhesive reduced ratings of pain and increased the proportion of pain-free repairs among children aged 3 months to 17 years. This low-risk intervention may benefit children with lacerations requiring tissue adhesives instead of sutures., Trial Registration: ClinicalTrials.gov, no. PR 6138378804.