Comparison of eGFR Equations to Guide Dosing of Medications for Kidney Transplant Recipients.

BACKGROUND: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m2 (milliliter per minute per 1.73 m2, as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m2). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology CollaborationCr/CysC equation. CONCLUSIONS: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.

Comparison of Positive Predictive Values of Biparametric MRI and Multiparametric MRI-directed Transrectal US-guided Targeted Prostate Biopsy.

Background Biparametric MRI (bpMRI) of the prostate is an alternative to multiparametric MRI (mpMRI), with lower cost and increased accessibility. Studies investigating the positive predictive value (PPV) of bpMRI-directed compared with mpMRI-directed targeted biopsy are lacking in the literature. Purpose To compare the PPVs of bpMRI-directed and mpMRI-directed targeted prostate biopsies. Materials and Methods This retrospective cross-sectional study evaluated men who underwent bpMRI-directed or mpMRI-directed transrectal US (TRUS)-guided targeted prostate biopsy at a single institution from January 2015 to December 2022. The PPVs for any prostate cancer (PCa) and clinically significant PCa (International Society of Urological Pathology grade ≥2) were calculated for bpMRI and mpMRI using mixed-effects logistic regression modeling. Results A total of 1538 patients (mean age, 67 years ± 8 [SD]) with 1860 lesions underwent bpMRI-directed (55%, 849 of 1538) or mpMRI-directed (45%, 689 of 1538) prostate biopsy. When adjusted for the number of lesions and Prostate Imaging Reporting and Data System (PI-RADS) score, there was no difference in PPVs for any PCa or clinically significant PCa (P = .61 and .97, respectively) with bpMRI-directed (55% [95% CI: 51, 59] and 34% [95% CI: 30, 38], respectively) or mpMRI-directed (56% [95% CI: 52, 61] and 34% [95% CI: 30, 39], respectively) TRUS-guided targeted biopsy. PPVs for any PCa and clinically significant PCa stratified according to clinical indication were as follows: biopsy-naive men, 64% (95% CI: 59, 69) and 43% (95% CI: 39, 48) for bpMRI, 67% (95% CI: 59, 75) and 51% (95% CI: 43, 59) for mpMRI (P = .65 and .26, respectively); and active surveillance, 59% (95% CI: 49, 69) and 30% (95% CI: 22, 39) for bpMRI, 73% (95% CI: 65, 89) and 38% (95% CI: 31, 47) for mpMRI (P = .04 and .23, respectively). Conclusion There was no evidence of a difference in PPV for clinically significant PCa between bpMRI- and mpMRI-directed TRUS-guided targeted biopsy. © RSNA, 2024 Supplemental material is available for this article.

Ixodes scapularis density and Borrelia burgdorferi prevalence along a residential-woodland gradient in a region of emerging Lyme disease risk.

The environmental risk of Lyme disease, defined by the density of Ixodes scapularis ticks and their prevalence of Borrelia burgdorferi infection, is increasing across the Ottawa, Ontario region, making this a unique location to explore the factors associated with environmental risk along a residential-woodland gradient. In this study, we collected I. scapularis ticks and trapped Peromyscus spp. mice, tested both for tick-borne pathogens, and monitored the intensity of foraging activity by deer in residential, woodland, and residential-woodland interface zones of four neighbourhoods. We constructed mixed-effect models to test for site-specific characteristics associated with densities of questing nymphal and adult ticks and the infection prevalence of nymphal and adult ticks. Compared to residential zones, we found a strong increasing gradient in tick density from interface to woodland zones, with 4 and 15 times as many nymphal ticks, respectively. Infection prevalence of nymphs and adults together was 15 to 24 times greater in non-residential zone habitats. Ecological site characteristics, including soil moisture, leaf litter depth, and understory density, were associated with variations in nymphal density and their infection prevalence. Our results suggest that high environmental risk bordering residential areas poses a concern for human-tick encounters, highlighting the need for targeted disease prevention.

Hospital policy of tranexamic acid to reduce transfusion in major non-cardiac surgery (TRACTION): protocol for a phase IV randomised controlled trial.

INTRODUCTION: Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk. METHODS AND ANALYSIS: A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention. ETHICS AND DISSEMINATION: Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT04803747.

Blood Pressure Management in Early Aneurysmal Subarachnoid Hemorrhage: A National Cross-Sectional Survey of Canadian Intensivists and Cerebrovascular Neurosurgeons.

BACKGROUND: In aneurysmal subarachnoid hemorrhage (aSAH), rebleeding of the culprit aneurysm is associated with significant morbidity and mortality. Blood pressure reduction to specific target levels, with the goal of preventing rebleeding, has been a mainstay of care prior to definitively securing the aneurysm. Clinical practice guidelines have recently changed and no longer recommend specific blood pressure targets. This survey aims to identify the reported practice patterns and beliefs regarding blood pressure management during the early phase of aSAH. METHODS: We conducted a self-administered, Web-based survey of critical care physicians and cerebrovascular neurosurgeons practicing in Canada. The questionnaire contained 21 items, including 3 case-based scenarios to elicit blood pressure target selection, both before and after aneurysm securing. RESULTS: In the presecured period, systolic blood pressures of 160 mm Hg (50% [144 of 287]) and 140 mm Hg (42% [120 of 287]) were the most frequently selected upper-limit targets. In the postsecured period, a systolic blood pressure of 180 mm Hg (32% [93 of 287]) was the most frequently selected upper-limit target, but there was a wide distribution of targets selected across all three cases ranging from 100 to > 200 mm Hg. A mean arterial pressure of 65 mm Hg was the most common lower-limit target in both the presecured and postsecured periods. There was little change in blood pressure targets with increasing clinical severity. Predictors of higher or lower blood pressure target selection and barriers to implementation of the desired target were identified. CONCLUSIONS: During the presecured period, nearly half of the reported upper-limit blood pressure targets are lower than previous guideline recommendations. These targets remain consistent despite increasing clinical severity and could potentially exacerbate cerebral ischemia and negatively impact clinical outcomes. In the postsecured period, there is wide variation in the reported blood pressure targets. A clinical trial is urgently needed to guide decision-making.

Five-Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub-Concussive Overpressures.

BACKGROUND: The Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5-year longitudinal trial was conducted in follow-up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure. PURPOSE: To examine brain MRI findings in military personnel exposed to multiple repeated blast exposures. STUDY TYPE: Five-year longitudinal prospective trial. POPULATION: Ninety-two males aged 23-42 with an average of 9.4 years of blast exposure. FIELD STRENGTH/SEQUENCE: 3 T brain MRI/T1-weighted 3D with reconstruction in three planes, T2-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2-weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging. ASSESSMENT: All MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form. STATISTICAL TESTS: Matching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers. RESULTS: A significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678-1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442-1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513-1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively. DATA CONCLUSION: There were significant changes in brain volume, white matter lesions, and enlargement of VR spaces. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

DERIVATION AND VALIDATION OF A MACHINE LEARNING MODEL FOR THE PREVENTION OF UNPLANNED DIALYSIS.

BACKGROUND: Approximately half of all patients with advanced chronic kidney disease (CKD) who progress to kidney failure initiate dialysis in an unplanned fashion which is associated with high morbidity, mortality, and healthcare costs. A novel prediction model designed to identify advanced CKD patients who are at high risk for developing kidney failure over short time frames (6-12 months) may help reduce the rates of unplanned dialysis and improve the quality of transitions from CKD to kidney failure. METHODS: We performed a retrospective study employing machine learning random forest algorithms incorporating routinely collected age and sex data along with time-varying trends in laboratory measurements to derive and validate six- and 12-month kidney failure risk prediction models in the advanced CKD population. The models were comprehensively characterized in three independent cohorts in Ontario, Canada - derived in a cohort of 1,849 consecutive advanced CKD patients (mean [standard deviation] age 66 [15] years, eGFR 19 [7] mL/min/1.73m2), and validated in two external advanced CKD cohorts (n=1,356; age 69 [14] years, eGFR 22 [7] mL/min/1.73m2). RESULTS: Across all cohorts, 55% of patients experienced kidney failure, of which 35% involved unplanned dialysis. The six- and 12-month models demonstrated excellent discrimination with area under the receiver operating characteristic curve of 0.88 (95%CI: 0.87-0.89) and 0.87 (95%CI: 0.86-0.87) along with high probabilistic accuracy with Brier scores of 0.10 (95%CI 0.09-0.10) and 0.14 (95%CI 0.13-0.14), respectively. The models were also well-calibrated and delivered timely alerts on a significant number of patients who ultimately initiated dialysis in an unplanned fashion. Similar results were found upon external validation testing. CONCLUSION: These machine-learning models using routinely collected patient data accurately predict near-future kidney failure risk among the advanced CKD population, and retrospectively deliver advanced warning on a substantial proportion of unplanned dialysis events. Optimal implementation strategies still need to be elucidated.

New Anticancer Drugs: Reliably Assessing "Value" While Addressing High Prices.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how "incremental cost-effectiveness ratios" (ICERs) based on measures such as gains in "quality-adjusted life-years" (QALYs) may be used to determine a drug's value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Population Survival Kinetics Derived from Clinical Trials of Potentially Curable Lung Cancers.

Using digitized data from progression-free survival (PFS) and overall survival Kaplan-Meier curves, one can assess population survival kinetics through exponential decay nonlinear regression analyses. To demonstrate their utility, we analyzed PFS curves from published curative-intent trials of non-small cell lung cancer (NSCLC) adjuvant chemotherapy, adjuvant osimertinib in resected EGFR-mutant NSCLC (ADAURA trial), chemoradiotherapy for inoperable NSCLC, and limited small cell lung cancer (SCLC). These analyses permit assessment of log-linear curve shape and estimation of the proportion of patients cured, PFS half-lives for subpopulations destined to eventually relapse, and probability of eventual relapse in patients remaining progression-free at different time points. The proportion of patients potentially cured was 41% for adjuvant controls, 58% with adjuvant chemotherapy, 17% for ADAURA controls, not assessable with adjuvant osimertinib, 15% with chemoradiotherapy, and 12% for SCLC. Median PFS half-life for relapsing subpopulations was 11.9 months for adjuvant controls, 17.4 months with adjuvant chemotherapy, 24.4 months for ADAURA controls, not assessable with osimertinib, 9.3 months with chemoradiotherapy, and 10.7 months for SCLC. For those remaining relapse-free at 2 and 5 years, the cure probability was 74%/96% for adjuvant controls, 77%/93% with adjuvant chemotherapy, 51%/94% with chemoradiation, and 39%/87% with limited SCLC. Relatively easy population kinetic analyses add useful information.

Knowledge, protective behaviours, and perception of Lyme disease in an area of emerging risk: results from a cross-sectional survey of adults in Ottawa, Ontario.

BACKGROUND: The number of Lyme disease risk areas in Canada is growing. In regions with emerging tick populations, it is important to emphasize peridomestic risk and the importance of protective behaviours in local public health communication. This study aims to identify characteristics associated with high levels of Lyme disease knowledge and adoption of protective behaviours among residents in the Ottawa, Ontario region. METHODS: A geographically stratified web survey was conducted in November 2020 (n = 2018) to determine knowledge, attitudes, and practices regarding Lyme disease among adult residents. Responses were used to calculate: (i) composite scores for knowledge and adoption of protective practices; and (ii) an exposure risk index based on reported activity in woodlands during the spring-to-fall tick exposure risk period. RESULTS: 60% of respondents had a high knowledge of Lyme disease, yet only 14% indicated they often use five or more measures to protect themselves. Factors strongly associated with a high level of Lyme disease knowledge included being 55 or older (Odds Ratio (OR) = 2.04), living on a property with a yard (OR = 3.22), having a high exposure index (OR = 1.59), and knowing someone previously infected with Lyme disease (OR = 2.05). Strong associations with the adoption of a high number of protective behaviours were observed with membership in a non-Indigenous racialized group (OR = 1.70), living on a property with a yard (OR = 2.37), previous infection with Lyme disease (OR = 2.13), prior tick bite exposure (OR = 1.62), and primarily occupational activity in wooded areas (OR = 2.31). CONCLUSIONS: This study highlights the dynamics between Lyme disease knowledge, patterns of exposure risk awareness, and vigilance of personal protection in a Canadian region with emerging Lyme disease risk. Notably, this study identified gaps between perceived local risk and protective behaviours, presenting opportunities for targeted enhanced communication efforts in areas of Lyme disease emergence.

Prediction Models for Forecasting Risk of Development of Surgical Site Infection after Lower Limb Revascularization Surgery: A Systematic Review.

BACKGROUND: Surgical site infections (SSIs) are a common and potentially preventable complication of lower limb revascularization surgery associated with increased healthcare resource utilization and patient morbidity. We conducted a systematic review to evaluate multivariable prediction models designed to forecast risk of SSI development after these procedures. METHODS: After protocol registration (CRD42022331292), we searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies describing multivariable prediction models designed to forecast risk of SSI in adults after lower limb revascularization surgery. Two investigators independently screened abstracts and full-text articles, extracted data, and assessed risk of bias. A narrative synthesis was performed to summarize predictors included in the models and their calibration and discrimination, validation status, and clinical applicability. RESULTS: Among the 6,671 citations identified, we included 5 studies (n = 23,063 patients). The included studies described 5 unique multivariable prediction models generated through forward selection, backward selection, or Akaike Information Criterion-based methods. Two models were designed to predict any SSI and 3 Szyilagyi grade II (extending into subcutaneous tissue) SSI. Across the 5 models, 18 adjusted predictors (10 of which were preoperative, 3 intraoperative, and 5 postoperative) significantly predicted any SSI and 14 adjusted predictors significantly predict Szilagyi grade II SSI. Female sex, obesity, and chronic obstructive pulmonary disease significantly predicted SSI in more than one model. All models had a "good fit" according to the Hosmer-Lemeshow test (P > 0.05). Model discrimination was quantified using the area under the curve, which ranged from 0.66 to 0.75 across models. Two models were internally validated using non-exhaustive twofold cross-validation and bootstrap resampling. No model was externally validated. Three studies had a high overall risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). CONCLUSIONS: Five multivariable prediction models with moderate discrimination have been developed to forecast risk of SSI development after lower limb revascularization surgery. Given the frequency and consequences of SSI after these procedures, development and external validation of novel prediction models and comparison of these models to the existing models evaluated in this systematic review is warranted.

Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study.

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

Edge-to-edge with partial band mitral valve repair compared to replacement and undersized restrictive annuloplasty for ischemic mitral regurgitation.

Objective: Evidence supports replacement over repair for ischemic mitral regurgitation due to improved durability; however, the latter often involves an undersized ring annuloplasty that does not include edge-to-edge approximation. The objective of this study was to evaluate the outcomes of replacement, edge-to-edge leaflet approximation with mild-undersized annuloplasty and undersized ring annuloplasty for ischemic mitral regurgitation. Methods: This is a single-center retrospective study of patients undergoing mitral surgery for moderate-severe or greater ischemic mitral regurgitation, between 2004 and 2020, with mild-undersized annuloplasty, mitral valve replacement, or undersized restrictive annuloplasty (undersized ring annuloplasty). The primary outcome was all-cause mortality. Secondary outcomes included first recurrence of mitral regurgitation, heart failure hospitalization, and composite of valve-related events (bleeding, thromboembolism, endocarditis, and mitral valve reoperation). Results: There were 121, 93, and 78 patients in the mitral valve replacement, mild-undersized annuloplasty, and undersized restrictive annuloplasty groups, respectively, with a median follow-up of 3.1, 5.9, and 3.8 years, respectively. Both mitral valve replacement (hazard ratio, 1.87; 95% CI, 1.029-3.415) and undersized restrictive annuloplasty (hazard ratio, 2.73; 95% CI, 1.480-5.061) were associated with worse survival compared with mild-undersized annuloplasty. At 2 years, the rate of mild-moderate mitral regurgitation was greater in the mild-undersized annuloplasty group compared with the mitral valve replacement group (P = .001) but less than in the undersized restrictive annuloplasty group (P = .001). The rate of recurrent moderate or greater mitral regurgitation at 2 years was similar between mild-undersized annuloplasty and mitral valve replacement groups but significantly higher after undersized restrictive annuloplasty (P < .0001). Mitral valve replacement and undersized restrictive annuloplasty were associated with a significant increase in the incidence of first heart failure hospitalization compared with mild-undersized annuloplasty (P < .001 and P = .001, respectively). Mitral valve replacement was associated with an increased incidence of valve-related events compared with mild-undersized annuloplasty (P = .002). Conclusions: Surgical edge-to-edge approximation in addition to a mild-undersizing annuloplasty offers similar durability compared with replacement, with a lower rate of hospitalization for heart failure, and may confer a survival advantage.

Synthetic data in cancer and cerebrovascular disease research: A novel approach to big data.

OBJECTIVES: Synthetic datasets are artificially manufactured based on real health systems data but do not contain real patient information. We sought to validate the use of synthetic data in stroke and cancer research by conducting a comparison study of cancer patients with ischemic stroke to non-cancer patients with ischemic stroke. DESIGN: retrospective cohort study. SETTING: We used synthetic data generated by MDClone and compared it to its original source data (i.e. real patient data from the Ottawa Hospital Data Warehouse). OUTCOME MEASURES: We compared key differences in demographics, treatment characteristics, length of stay, and costs between cancer patients with ischemic stroke and non-cancer patients with ischemic stroke. We used a binary, multivariable logistic regression model to identify risk factors for recurrent stroke in the cancer population. RESULTS: Using synthetic data, we found cancer patients with ischemic stroke had a lower prevalence of hypertension (52.0% in the cancer cohort vs 57.7% in the non-cancer cohort, p<0.0001), and a higher prevalence of chronic obstructive pulmonary disease (COPD: 8.5% vs 4.7%, p<0.0001), prior ischemic stroke (1.7% vs 0.1%, p<0.001), and prior venous thromboembolism (VTE: 8.2% vs 1.5%, p<0.0001). They also had a longer length of stay (8 days [IQR 3-16] vs 6 days [IQR 3-13], p = 0.011), and higher costs associated with their stroke encounters: $11,498 (IQR $4,440 -$20,668) in the cancer cohort vs $8,084 (IQR $3,947 -$16,706) in the non-cancer cohort (p = 0.0061). A multivariable logistic regression model identified 5 predictors for recurrent ischemic stroke in the cancer cohort using synthetic data; 3 of the same predictors identified using real patient data with similar effect measures. Summary statistics between synthetic and original datasets did not significantly differ, other than slight differences in the distributions of frequencies for numeric data. CONCLUSION: We demonstrated the utility of synthetic data in stroke and cancer research and provided key differences between cancer and non-cancer patients with ischemic stroke. Synthetic data is a powerful tool that can allow researchers to easily explore hypothesis generation, enable data sharing without privacy breaches, and ensure broad access to big data in a rapid, safe, and reliable fashion.

A randomized trial evaluating the utility of non-targeted biopsies for colorectal neoplasia detection in adults with inflammatory bowel disease: a pilot study protocol.

BACKGROUND: Persons with inflammatory bowel diseases are at increased risk of developing colorectal cancer and require frequent colonoscopy surveillance. Guidelines recommend taking 30 to 40 non-targeted biopsies throughout the colorectum to detect "invisible" neoplasia in this setting, despite a lack of evidence supporting this practice. We sought to assess the utility of this practice through a randomized controlled trial. We first propose an internal pilot study to assess recruitment potential, protocol adherence and data capture to guide the full trial. METHODS: We have designed a multi-centre, parallel-group, non-inferiority randomized controlled trial to test the utility of non-targeted biopsies as an adjunct to colonoscopy surveillance for neoplasia detection in persons with inflammatory bowel disease involving the colorectum in routine clinical practice. Participants are randomized 1:1, stratified by study site, to either standard of care high-definition white-light colonoscopy with 32 to 40 non-targeted biopsies of non-neoplastic-appearing mucosa along with a sampling of abnormal-appearing mucosa (control group) or modified colonoscopy with targeted sampling alone (intervention group). The primary outcome for the full trial will be the proportion of persons with ≥ 1 neoplastic focus detected during colonoscopy. For the pilot phase, we will assess the feasibility of recruiting a minimum of 15% of the estimated sample size within 1 year, under identical conditions as the full trial, while maintaining ≥ 90-95% rate of protocol adherence and data capture. These participants will contribute data to the full trial. The trial is being conducted at 12 centres across Canada, with a total sample size of 1952 persons. DISCUSSIONS: The trial protocol has been approved by the ethics committees of all participating sites, and the pilot study has received funding through the Canadian Institutes of Health Research (PJT 159607). If feasibility metrics are met during the pilot phase, we will complete the full trial. The trial outcomes will contribute to update the practice guidelines in this area. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04067778.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn's Disease: A Multicenter Study.

BACKGROUND & AIMS: Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. METHODS: In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. RESULTS: We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. CONCLUSIONS: Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.