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"Cook, Richard J."
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Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion
2016
In a pragmatic trial, more than 30,000 patients requiring blood transfusion were randomly assigned to receive blood after short-term storage or long-term storage. In-hospital mortality did not differ significantly between the two groups.
Red-cell transfusion is one of the most common medical interventions.
1
Blood is stored for up to 42 days before transfusion. Biochemical, structural, and functional changes during storage may reduce oxygen delivery to tissues, and the release of extracellular vesicles and cell-free DNA during storage may cause a hypercoagulable state.
2
Observational studies have suggested that prolonged blood storage is associated with an increased risk of cardiovascular events.
3
Randomized, controlled trials have not shown harm in transfusing red-cell units with a longer duration versus a shorter duration of storage. However, most of these trials have been restricted to high-risk populations and have . . .
Journal Article
South Korea's Foreign Policy Shifts Under President Yoon and Implications for the Sino-US Peer Competition
2024
South Korea, caught amid the intensifying Sino-US peer competition, has begun to re-orientate its foreign policy under President Yoon Suk-yeol, significantly shifting it away from his predecessor President Moon Jae-in. At the crux of these policy changes is a shift away from the so-called “Three Noes”, which have existed as a policy stopgap in order to stabilize Seoul's position between China and the US following the 2017 THAAD debacle. This policy shift indicates that the Yoon administration has begun removing policy stopgaps that facilitated hedging behavior and is trimming South Korea's hedge tacking harder on the US for security and aligning as a core Asian state with the Rules-based International Order. Nevertheless, careful strategic calculus is required to avoid backlash from Beijing, despite Yoon seeking closer alignment with Washington. The policy shift underway has the geostrategic potential to solidify the Northeast Asian flank of Washington's efforts to counter Beijing, with a phalanx of Asia-Pacific allies and partners.
Journal Article
Robustness and Efficiency Considerations When Testing Process Reliability with a Limit of Detection
2025
Processes in biotechnology are considered reliable if they produce samples satisfying regulatory benchmarks. For example, laboratories may be required to show that levels of an undesirable analyte rarely (e.g., in less than 5% of samples) exceed a tolerance threshold. This can be challenging when measurement systems feature a lower limit of detection, rendering some observations left-censored. We investigate the implications of detection limits on location-scale model-based inference in reliability studies, including their impact on large and finite sample properties of various estimators and the sensitivity of results to model misspecification. To address the need for robust methods, we introduce a flexible weakly parametric model in which the right tail of the response distribution is approximated using a piecewise-constant hazard model. Simulation studies are reported that investigate the performance of the established and proposed methods, and an illustrative application is given to a study of drinking can weights. We conclude with a discussion of areas warranting future work.
Journal Article
Association between musculoskeletal sonographic features and response to treatment in patients with psoriatic arthritis
by
Gutierrez, Jessica
,
Cook, Richard J
,
Eder, Lihi
in
Adult
,
Antirheumatic Agents - therapeutic use
,
Arthritis, Psoriatic - diagnostic imaging
2024
ObjectiveTo investigate the association between musculoskeletal sonographic features and clinical features, as well as treatment outcomes, in patients with active psoriatic arthritis (PsA).MethodsA prospective cohort study was conducted involving patients with active PsA. Disease activity was assessed clinically at baseline and 3–6 months after initiating therapy, with a Disease Activity Index for PsA (DAPSA) score calculated. A baseline ultrasound examination of 64 joints, 28 tendons and 16 entheses evaluated the following lesions: synovitis, peritenonitis, enthesitis, tenosynovitis, new bone formation and erosions. Total scores for each lesion and total inflammatory and structural scores were calculated. The association between baseline sonographic scores and treatment outcomes was assessed using Cox proportional hazards models (for drug persistence) and generalised estimating equation models for DAPSA change.ResultsA total of 135 treatment periods (107 patients) were analysed. Multivariable analysis showed that a greater reduction in DAPSA score at follow-up was associated with higher baseline synovitis (β −3.89), peritenonitis (β −3.93) and enthesitis structural scores (β −2.91). Additionally, the total inflammatory score independently predicted DAPSA change (β −5.23) regardless of the total structural damage score. Drug persistence was analysed in 105 treatment periods, revealing that a higher sonographic erosion score was associated with earlier drug discontinuation (adjusted HR 1.28, 95% CI 1.03 to 1.61).ConclusionThe study results provide preliminary evidence supporting the utility of musculoskeletal ultrasound in predicting treatment response and drug persistence in PsA.
Journal Article
Chronic kidney disease in patients with psoriatic arthritis: a cohort study
2024
ObjectivesChronic kidney disease (CKD) is a comorbidity in psoriatic arthritis (PsA). We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes and identify risk factors for CKD development.MethodsWe included patients with PsA followed by our prospective observational cohort. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 for at least 3 months. We characterised long-term renal outcomes of CKD cases identified following clinic entry. We used time-dependent Cox regression models to identify factors associated with CKD development.ResultsOf 1336 patients included in the study, 123 (9.2%) had CKD. Of these, 25 (20.3%) were observed to have CKD at clinic entry and 98 (79.7%) developed CKD during follow-up at a median (IQR) of 8.2 (2.8–14.0) years from baseline. Doubling of baseline creatinine was observed in 18 of 98 (18.3%) new patients with CKD. 49 (50%) patients developed a sustained ≥40% reduction in baseline eGFR. Two patients developed eGFR <15 mL/min/1.73 m2. In the multivariate Cox regression model adjusted for age at study entry, sex and baseline eGFR, factors independently associated with the development of CKD included diabetes mellitus (HR 2.58, p<0.001), kidney stones (HR 2.14, p=0.01), radiographic damaged joint count (HR 1.02, p=0.02), uric acid (HR 1.21, p<0.001; 50-unit increase), daily use of non-steroidal anti-inflammatory drugs (NSAIDs) (HR 1.77, p=0.02) and methotrexate use (HR 0.51, p=0.01).ConclusionCKD is not infrequent in PsA. Its development is associated with related comorbidities, joint damage and NSAID use. Methotrexate seems to be protective.
Journal Article
The association between smoking and the development of psoriatic arthritis among psoriasis patients
by
Gladman, Dafna D
,
Thavaneswaran, Arane
,
Rosen, Cheryl F
in
Adult
,
Age Distribution
,
Alcohol Drinking - adverse effects
2012
Aim To investigate the association between smoking and psoriatic arthritis (PsA) among patients with psoriasis and its interaction with the HLA-C*06 allele. Methods In this exploratory case–control study, smoking status was determined at the time of the diagnosis of arthritis for PsA patients and at their first study visit for psoriasis patients, when they were confirmed not to have PsA. The proportions of patients exposed to smoking were compared in patients with PsA to those with psoriasis alone. A logistic regression model was constructed to test the independent association of smoking and PsA after adjusting for potential confounders. The statistical interaction between HLA-C*06 and smoking was tested through a regression model. Results The proportions of current and past smokers were higher in the psoriasis group compared with the PsA group (30.2% vs 23.4% and 26.7% vs 22.3%, p=0.001, respectively). On multivariate analysis being a current smoker versus a lifetime non-smoker remained inversely associated with PsA (OR 0.57, p=0.002), while past smoker versus lifetime non-smoker status was no longer significant. In a subgroup analysis, smoking remained inversely associated with PsA only among patients who were HLA-C*06 negative. Regression analysis revealed that the interaction between smoking status (ever smoked vs lifetime non-smoker) and HLA-C*06 was statistically significant (p=0.01). Conclusion Smoking may be inversely associated with PsA among psoriasis patients. This association is not present among HLA-C*06-positive individuals.
Journal Article
Incidence rate and risk factors of arrhythmias in patients with psoriatic arthritis
by
Akhtari, Shadi
,
Almansouri, Abdulrahman Y
,
Gladman, Dafna D
in
Adult
,
Aged
,
Arrhythmias, Cardiac - diagnosis
2026
ObjectivesTo assess the incidence and risk factors for arrhythmias in patients with psoriatic arthritis (PsA).MethodsWe performed a cohort analysis of patients followed prospectively from 1994 to 2024. Participants were evaluated using standard protocols at 6-to-12-month intervals. The following events were assessed: (1) atrial tachyarrhythmia (including atrial fibrillation and supraventricular tachycardia); (2) ventricular tachyarrhythmia and (3) bradycardia/pacemaker. The cumulative incidence rate (CIR) of each arrhythmia was calculated. Cox proportional hazards models (reported as the current level HR (measured just prior to the event) and the adjusted mean HR) were fitted to assess the association between selected measures of PsA disease activity and the age of occurrence of arrhythmia events. Each model was adjusted for sex, PsA duration, cardiovascular risk factors and medications.ResultsA total of 1670 patients with PsA were analysed (80 atrial tachyarrhythmias, 17 bradyarrhythmias/pacemakers and 11 ventricular tachyarrhythmias). By age 70, the CIRs were 7.82%, 0.67% and 0.45% for atrial, ventricular and bradycardia, respectively. In multivariable analysis, remission/low versus high disease activity state was associated with lower risk of atrial tachyarrhythmia (current HR 0.49, 95% CI 0.26 to 0.92; adjusted mean HR 0.46, 95% CI 0.23 to 0.91). Similarly, a higher three-item Visual Analogue Scale (3-VAS) was associated with a higher risk of atrial tachyarrhythmia (current level HR 1.18, 95% CI 1.04 to 1.33; adjusted mean HR 1.22, 95% CI 1.04 to 1.44).ConclusionsHigher PsA disease activity is associated with higher atrial tachyarrhythmia risk. These findings reinforce the importance of controlling inflammation in PsA to optimise cardiac health.
Journal Article
Obesity is associated with a lower probability of achieving sustained minimal disease activity state among patients with psoriatic arthritis
by
Chandran, Vinod
,
Gladman, Dafna D
,
Cook, Richard J
in
Adult
,
Aged
,
Antirheumatic Agents - therapeutic use
2015
Aim To assess whether overweight and obese patients with psoriatic arthritis (PsA) are less likely to achieve sustained minimal disease activity (MDA) state compared to patients with normal weight. Methods A cohort of patients was assessed at the University of Toronto PsA clinic at 6–12-month intervals according to a standard protocol from 2003 to 2012. Patients were categorised into the following groups according to their body mass index (BMI): normal (<25), overweight (25–30), and obese (>30). Sustained MDA was defined as achieving low disease activity state in five or more of the following domains for at least 1 year: skin, enthesitis, tender and swollen joint counts, pain, patient global assessment and function. Proportional odds discrete time to event analysis was used to investigate the association between BMI category and the achievement of sustained MDA. Results Of the 557 patients included in the study, 36.2% were classified as overweight and 35.4% were obese. Overall, 66.1% of the patients achieved sustained MDA during the follow-up period. A dose–response association was found between obesity and the probability of achieving sustained MDA in the multivariate regression analysis. Patients in the higher BMI categories were less likely to achieve sustained MDA compared those in the lowest BMI category (overweight: OR 0.66 p=0.003; obese: OR 0.53 p<0.0001) after adjusting for potential confounding variables. Conclusions Overweight and obese patients with PsA are less likely to achieve sustained MDA compared to those of normal weight.
Journal Article
Prognostic factors for skeletal complications from metastatic bone disease in breast cancer
by
Costa, Luis
,
Lipton, Allan
,
Brown, Janet E
in
Aged
,
Alkaline phosphatase
,
Antineoplastic Agents
2010
Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients' functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox-regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P < 0.05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included. Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase. Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy. In conclusion, this model identified several prognostic factors that may be useful in routine clinical care. Validation of these factors in a separate dataset and generation of a prognostic risk score are recommended next steps.
Journal Article