Derivation and Internal Validation of a Disease-Specific Cardiovascular Risk Prediction Model for Patients With Psoriatic Arthritis and Psoriasis.

OBJECTIVE: To address suboptimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a five-year disease-specific cardiovascular risk prediction model. METHODS: We analyzed data from a prospective cohort of participants with PsD without a history of cardiovascular events. Traditional cardiovascular risk factors and PsD-related measures of disease activity were considered as potential predictors. The study outcome included nonfatal and fatal cardiovascular events. A base prediction model included 10 traditional cardiovascular risk factors. Eight PsD-related factors were assessed by adding them to the base model to create expanded models, which were controlled for PsD therapies. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression with 10-fold cross-validation. Model performance was assessed using measures of discrimination and calibration and measures of sensitivity and specificity. RESULTS: Between 1992 and 2020, 85 of 1,336 participants developed cardiovascular events. Discrimination of the base model (with traditional cardiovascular risk factors alone) was excellent, with an area under the receiver operator characteristic curve (AUC) of 85.5 (95% confidence interval [CI] 81.9-89.1). Optimal models did not select any of the tested disease-specific factors. In a sensitivity analysis, which excluded lipid lowering and antihypertensive treatments, the number of damaged joints was selected in the expanded model. However, this model did not improve risk discrimination compared to the base model (AUC 85.5, 95% CI 82.0-89.1). CONCLUSION: Traditional cardiovascular risk factors alone are effective in predicting cardiovascular risk in patients with PsD. A risk score based on these factors performed well, indicating excellent discrimination and calibration.

Derivation of a Multivariable Psoriatic Arthritis Risk Estimation Tool (PRESTO): A Step Towards Prevention.

OBJECTIVE: A simple, scalable tool that identifies psoriasis patients at high risk for developing psoriatic arthritis (PsA) could improve early diagnosis. We aimed to develop a risk prediction model for the development of PsA and to assess its performance among patients with psoriasis. METHODS: We analyzed data from a prospective cohort of psoriasis patients without PsA at enrollment. Participants were assessed annually by a rheumatologist for the development of PsA. Information about their demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms was used to develop prediction models for PsA. Penalized binary regression models were used for variable selection while adjusting for psoriasis duration. Risks of developing PsA over 1- and 5-year time periods were estimated. Model performance was assessed by the area under the curve (AUC) and calibration plots. RESULTS: Among 635 psoriasis patients, 51 and 71 developed PsA during the 1-year and 5-year follow-up periods, respectively. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (AUC 72.3). The risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesion, psoriasis severity, fatigue, pain, and use of systemic nonbiologic medication or phototherapy (AUC 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities. CONCLUSIONS: The development of PsA within clinically meaningful time frames can be predicted with reasonable accuracy for psoriasis patients using readily available clinical variables.

Persistence of Biologics in the Treatment of Psoriatic Arthritis: Data From a Large Hospital-Based Longitudinal Cohort.

OBJECTIVE: To analyze the trends in biologics use at a specialized center over a period of 20 years. METHODS: We performed a retrospective analysis of 571 patients diagnosed with psoriatic arthritis enrolled in the Toronto cohort who initiated biologic therapy between January 1, 2000, and July 7, 2020. The probability of drug persistence over time was estimated nonparametrically. The time to discontinuation of first and second treatment was analyzed using Cox regression models, whereas a semiparametric failure time model with a gamma frailty was used to analyze the discontinuation of treatment over successive administrations of biologic therapy. RESULTS: The highest 3-year persistence probability was observed with certolizumab when used as first biologic treatment, while interleukin-17 inhibitors had the lowest probability. However, when used as second medication, certolizumab had the lowest drug survival even when accounting for selection bias. Depression and/or anxiety were associated with a higher rate of drug discontinuation due to all causes (relative risk [RR] 1.68, P = 0.01), while having higher education was associated with lower rates (RR 0.65, P = 0.03). In the analysis accommodating multiple courses of biologics, a higher tender joint count was associated with a higher rate of discontinuation due to all causes (RR 1.02, P = 0.01). Older age at the start of first treatment was associated with a higher rate of discontinuation due to side effects (RR 1.03, P = 0.01), while obesity had a protective role (RR 0.56, P = 0.05). CONCLUSION: Persistence in taking biologics depends on whether the biologic was used as first or second treatment. Depression and anxiety, higher tender joint count, and older age lead to drug discontinuation.

Intraindividual Change in Cognitive Function Among Adults With Systemic Lupus Erythematosus: A Markov Analysis Over 7 Years.

OBJECTIVE: Cognitive impairment is prevalent in systemic lupus erythematosus (SLE). There remain gaps in understanding cognition and SLE longitudinally. We studied intraindividual change in cognition in SLE over time. METHODS: Data were from the University of California, San Francisco Lupus Outcome Study, which included 1281 adults with SLE. The Hopkins Verbal Learning Test-Revised (HVLT-R) and the Controlled Oral Word Association Test (COWAT) were administered annually over 7 years. A two-state Markov analysis was used to model transition intensities for probabilities of change in cognition. Logistic regression examined the association between clinical variables and cognitive change. RESULTS: Minimal transition between cognitive states was observed in the Markov analysis. Using the COWAT, higher levels of self-reported depression were associated with decreased likelihood of cognitive improvement (Relative Risk [RR]: 0.98; 95% confidence interval [CI]: 0.96-0.99), and higher self-reported disease severity was associated with cognitive decline (RR: 1.05; 95% CI: 1.02-1.09). Using the HVLT-R, increasing age (RR: 1.02; 95% CI: 1.01-1.03) and higher education level (RR: 1.82; 95% CI: 1.28-2.58) were associated with cognitive improvement, and higher self-reported disease severity (RR: 1.02; 95% CI: 1.01-1.03) and depression (RR: 1.05; 95% CI: 1.03-1.07) were associated with cognitive decline. CONCLUSION: Most individuals with SLE did not transition between states of high (Z score ≥ -1.5) or low (Z score < -1.5) cognition in a Markov analysis over a 7-year assessment period, highlighting a degree of relative stability in cognition over time. Increasing age and higher education levels were associated with greater likelihood of cognitive improvement. Greater self-reported SLE disease severity and depression were associated with cognitive decline.

Classical Regression and Predictive Modeling.

BACKGROUND: With the advent of personalized and stratified medicine, there has been much discussion about predictive modeling and the role of classical regression in modern medical research. We describe and distinguish the goals in these 2 frameworks for analysis. METHODS: The assumptions underlying and utility of classical regression are reviewed for continuous and binary outcomes. The tenets of predictive modeling are then discussed and contrasted. Principles are illustrated by simulation and through application of methods to a neurosurgical study. RESULTS: Classical regression can be used for insights into causal mechanisms if careful thought is given to the role of variables of interest and potential confounders. In predictive modeling, interest lies more in accuracy of predictions and so alternative metrics are used to judge adequacy of models and methods; methods which average predictions over several contending models can improve predictive performance but these do not admit a single risk score. CONCLUSIONS: Both classical regression and predictive modeling have important roles in modern medical research. Understanding the distinction between the 2 frameworks for analysis is important to place them in their appropriate context and interpreting findings from published studies appropriately.

Association of Cardiac Biomarkers With Cardiovascular Outcomes in Patients With Psoriatic Arthritis and Psoriasis: A Longitudinal Cohort Study.

OBJECTIVE: In patients with psoriatic disease (PsD), we determined whether cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with carotid plaque burden and the development of cardiovascular events independent of the Framingham Risk Score (FRS). METHODS: Among 1,000 patients with PsD, carotid total plaque area (TPA) was measured in 358 participants at baseline. Cardiac troponin I and NT-proBNP were measured using automated clinical assays. The association between cardiac biomarkers and carotid atherosclerosis was assessed by multivariable regression after adjusting for cardiovascular risk factors. Improvement in the prediction of cardiovascular events beyond the FRS was tested using measures of risk discrimination and reclassification. RESULTS: In univariate analyses, cTnI (ß coefficient 0.52 [95% confidence interval (95% CI) 0.3, 0.74], P < 0.001) and NT-proBNP (ß coefficient 0.24 [95% CI 0.1, 0.39], P < 0.001) were associated with TPA. After adjusting for cardiovascular risk factors, the association remained statistically significant for cTnI (adjusted ß coefficient 0.21 [95% CI 0, 0.41], P = 0.047) but not for NT-proBNP (P = 0.21). Among the 1,000 patients with PsD assessed for cardiovascular risk prediction, 64 patients had incident cardiovascular events. When comparing a base model (with the FRS alone) to expanded models (with the FRS plus cardiac biomarkers), there was no improvement in predictive performance. CONCLUSION: In patients with PsD, cTnI may reflect the burden of atherosclerosis, independent of traditional cardiovascular risk factors. Cardiac troponin I and NT-proBNP are associated with incident cardiovascular events independent of the FRS, but further study of their role in cardiovascular risk stratification is warranted.

Oligoarticular vs Polyarticular Psoriatic Arthritis: A Longitudinal Study Showing Similar Characteristics.

OBJECTIVE: The objectives of this study were to determine whether patients with oligoarticular presentation differ from those with polyarticular presentation and to identify potential predictors for evolution of oligoarthritis to polyarthritis in patients with psoriatic arthritis (PsA). METHODS: Patients who entered the University of Toronto PsA clinic between 1978 and 2018 within 12 months of diagnosis were identified. Only patients with ≥ 2 clinic visits were included. Patients were followed at 6- to 12-month intervals according to standard protocol, which included demographics, clinical history, detailed clinical examination, laboratory information, and patient questionnaires. Radiographs were done at 2-year intervals. Oligoarthritiswas defined by the presence of ≤ 4 inflamed joints and progressionas an increase to ≥ 5 joints. Statistical analyses included logistic regression models as well as Weibull regression models, adjusted for age, disease duration, and sex. RESULTS: Of 407 patients, 192 (47%) presented with oligoarthritis. Whereas demographic features were similar to those with polyarthritis, more patients with polyarthritis presented with dactylitis and enthesitis. Similar joint distribution was observed, with small joints of the hands and feet being most commonly affected. Patients with polyarthritis had higher Health Assessment Questionnaire and lower 36-item Short Form Health Survey (SF-36) scores. Of the 192 oligoarticular patients, 117 (61%) remained oligoarticular and 75 (39%) progressed to polyarthritis. A lower SF-36 mental component summary (MCS) score was the predictor for progressing to polyarthritis. CONCLUSION: Oligoarticular PsA occurs in 47% of patients with PsA and is similar to polyarticular disease, with most patients having small joint involvement. The only predictor for progression to polyarthritis was lower SF-36 MCS.

Targeted metabolomic profiling and prediction of cardiovascular events: a prospective study of patients with psoriatic arthritis and psoriasis.

OBJECTIVE: In patients with psoriatic disease (PsD), we sought serum metabolites associated with cardiovascular (CV) events and investigated whether they could improve CV risk prediction beyond traditional risk factors and the Framingham Risk Score (FRS). METHODS: Nuclear magnetic resonance metabolomics identified biomarkers for incident CV events in patients with PsD. The association of each metabolite with incident CV events was analysed using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for traditional CV risk factors. Variable selection was performed using penalisation with boosting after adjusting for age and sex, and the FRS. RESULTS: Among 977 patients with PsD, 70 patients had incident CV events. In Cox regression models adjusted for CV risk factors, alanine, tyrosine, degree of unsaturation of fatty acids and high-density lipoprotein particles were associated with decreased CV risk. Glycoprotein acetyls, apolipoprotein B and cholesterol remnants were associated with increased CV risk. The age-adjusted and sex-adjusted expanded model with 13 metabolites significantly improved prediction of CV events beyond the model with age and sex alone, with an area under the receiver operator characteristic curve (AUC) of 79.9 versus 72.6, respectively (p=0.02). Compared with the FRS alone (AUC=73.9), the FRS-adjusted expanded model with 11 metabolites (AUC=75.0, p=0.72) did not improve CV risk discrimination. CONCLUSIONS: We identify novel metabolites associated with the development of CV events in patients with PsD. Further study of their underlying causal role may clarify important pathways leading to CV events in this population.

The Pattern of Musculoskeletal Complaints in Patients With Suspected Psoriatic Arthritis and Their Correlation With Physical Examination and Ultrasound.

OBJECTIVE: To describe the pattern of musculoskeletal (MSK) symptoms and their correlation with clinical and sonographic findings among psoriasis patients with suspected psoriatic arthritis (PsA). METHODS: Patients with psoriasis and no prior diagnosis of PsA were referred for assessment of their MSK complaints. The study included the following steps: (1) assessment by an advanced practice physiotherapist, (2) targeted MSK ultrasound, and (3) assessment by a rheumatologist. In addition, patients were asked to complete questionnaires about the nature and duration of their MSK symptoms and to mark the location of their painful joints on a homunculus. Each patient was classified by a rheumatologist as "Not PsA," "Possible PsA," or "PsA". MSK symptoms and patient-reported outcomes (PRO) were compared between patients with PsA and Possible/Not PsA. Agreement between modalities was assessed using κ statistics. RESULTS: Two hundred three patients with psoriasis and MK symptoms were enrolled (8.8% PsA, 23.6% Possible PsA). Patients classified as PsA had worse scores on the PsA Impact of Disease (P = 0.004) and Functional Assessment of Chronic Illness Therapy-Fatigue scale (P = 0.02). There was no difference between the 2 groups in the presence, distribution, and duration of MSK symptoms. Analysis of agreement in physical examination between modalities revealed the strongest agreement between the rheumatologist and physiotherapist (κ = 0.28). The lowest levels of agreement were found between ultrasound and patient (κ = 0.08) and physiotherapist and ultrasound (κ = 0.08). CONCLUSION: The results of this study suggest that the intensity, rather than the type, duration, or distribution of MSK symptoms, is associated with PsA among patients with psoriasis.

Malignancy in psoriatic disease: Results from prospective longitudinal cohorts.

OBJECTIVES: To estimate the prevalence and incidence of malignancy and its types in psoriatic arthritis (PsA) and psoriasis without arthritis (PsC) patients, in comparison to the general population, and to identify the predictive factors for developing cancer in psoriatic disease (PsD). METHODS: PsA patients followed prospectively since 1978 and PsC patients followed since 2006 at 6-to-12 month intervals according to a standard protocol were included. Malignancies were recorded prospectively and linkages with Cancer Care Ontario and the Death Registry were carried out to confirm the presence and type of malignancy up to December 2016. Standardized incidence ratios (SIR) were calculated for overall cancers and by age and sex. Cox regression analysis was conducted to identify risk factors associated with the development of malignancy after the diagnosis of PsD. RESULTS: 2051 patients (PsD) were included of whom 228 (11%) developed cancer. 168 patients developed cancer after first clinic visit and are included in this report. Overall SIR for malignancy was 0.83 (0.68, 1.00), SIR for females was 1.06 (0.80, 1.37), and for males was 0.67 (0.50, 0.88). The most common malignancies were skin, breast, and hematological. Skin cancer was the only specific cancer that had a higher incidence than the general population with SIR = 3.37 (1.84, 5.66). There was insufficient evidence to suggest an increased risk of malignancy associated with biologics use. CONCLUSIONS: In this long-term prospective follow-up of patients with PsA and PsC the overall malignancy risk was not found to be higher than the general population, while skin cancer increased.

Mortality in psoriatic arthritis: Risk, causes of death, predictors for death.

BACKGROUND/OBJECTIVES: Mortality studies in psoriatic arthritis (PsA) have provided inconsistent results. This study aimed to: 1) Estimate trends in mortality rates among PsA patients over calendar time; 2) Evaluate cause-specific mortality rates in patients with PsA compared to the general population; 3) Identify predictors for mortality in PsA. METHODS: The study was carried out at the University of Toronto Psoriatic Arthritis Clinic where patients are followed prospectively according to a standard protocol at 6- to 12- month intervals. Standardized mortality ratios (SMRs) were calculated overall, by age, and by sex with reference to the Ontario population. Causes of death were recorded by ICD9 and ICD10 codes and cause-specific SMRs were computed. Cox regression models were used to identify predictors for mortality among PsA patients. RESULTS: Among 1490 patients followed over 15062.8 patient-years, 225 (15%) confirmed deaths were recorded (111 females, 114 males). The overall SMR was 0.92 (95% CI: 0.81-1.05), the sex-specific SMRs were 1.08 (95% CI: 0.89-1.30) for females and 0.81 (95% CI: 0.66-0.97) for males. The age-specific SMRs were 3.36 (95% CI: 1.61-6.18), 0.97 (95% CI: 0.68-1.34), 0.88 (95% CI: 0.73-1.06) and 0.86 (95% CI: 0.66-1.11) for 20-39, 40-59, 60-79 and above 80 years of age, respectively. Major causes of death included malignant neoplasms (n=61; SMR=0.97, 95% CI: 0.72-1.28), acute myocardial infarction (n=32; SMR=1.11, 95% CI: 0.74-1.58), and pneumonia (n=14; SMR=2.46, 95% CI: 1.27-4.31). Factors found to be associated with increased mortality include elevated acute phase reactants, presence of comorbidities such as heart disease and cancer, and lower education level. CONCLUSION: Young patients with PsA are at increased mortality risk. Better control of comorbidities may reduce this risk.

Remission in psoriatic arthritis: Definition and predictors.

OBJECTIVE: To determine the frequency of remission defined by the absence of the various disease manifestations of psoriatic arthritis (PsA) and identify predictors for remission. METHODS: Patients followed at the PsA clinic between 2000 and 2015 were included. Patients are assessed at 6- to 12-month intervals according to a standard protocol. Remission was defined as a visit that patients had no tender or swollen joints, no inflammatory back pain, no tender entheseal sites, minimal skin involvement with BSA<1%, patient pain on visual analog scale (VAS) score of <15, patient global disease activity VAS score of <20, Health Assessment Questionnaire (HAQ) score <0.5. We used imputation approach to determine remission status for visits with incomplete criteria for each patient. RESULTS: Data from 985 patients (57% males, average age of 47.4 years) were included in this study. From 2000 to 2015, 175 (18%) patients achieved remission at least once and 92 (9%) experienced sustained remission over at least 2 consecutive visits. In a multivariate Weibull regression analysis for the time to remission, higher BMI was associated with lower chance of remission (HR = 0.96, p = 0.012), while the use of biologics increased the chance of achieving remission (HR = 1.48, p = 0.034). The effect of biologics was also significant on the chance of achieving sustained remission for 2 or more consecutive visits (HR = 1.76, p = 0.020). However, biologics were not significantly associated with sustained remission when it was defined based on 3 or more consecutive visits. CONCLUSION: Remission occurred at least once in 18% of the patients with PsA while sustained remission occurred in 9% of the study sample. Having higher BMI would reduce the achievement of remission. The use of biologic agents increased not only the chance of remission, but also the chance of sustained remission for at least 12 months.

Trends in the Prevalence and Incidence of Psoriasis and Psoriatic Arthritis in Ontario, Canada: A Population-Based Study.

OBJECTIVE: To estimate the prevalence and incidence of psoriasis and psoriatic arthritis (PsA) over time in Ontario, Canada. METHODS: We performed a population-based study of Ontario health administrative data, using validated case definitions for psoriasis and PsA. We computed the crude and age- and sex-standardized cumulative prevalence and incidence of psoriasis from 2000 to 2015. RESULTS: Among the 10,774,802 individuals ages ≥20 years residing in Ontario in 2015, we identified 273,238 patients with psoriasis and 18,655 patients with PsA, equating to cumulative prevalence estimates of 2.54% and 0.17%, respectively. Correcting the prevalence estimates for imperfect sensitivity and specificity resulted in similar estimates. The male:female ratio was approximately 1.0 for both conditions. For psoriasis, the age- and sex-standardized cumulative prevalence increased from 1.74% in 2000 to 2.32% in 2015. For PsA, the age- and sex-standardized cumulative prevalence increased from 0.09% in 2008 to 0.15% in 2015. Between 2008 and 2015, annual incidence rates for psoriasis decreased, whereas those for PsA remained relatively stable. CONCLUSION: The prevalence and incidence of psoriasis and PsA in Ontario are similar to those observed in Europe and the US. The steady increase in the prevalence of psoriasis and PsA over the past decade may be due to a combination of population aging, population growth, and increasing life expectancy.

Design of cancer trials based on progression-free survival with intermittent assessment.

Therapeutic advances in cancer mean that it is now impractical to performed phase III randomized trials evaluating experimental treatments on the basis of overall survival. As a result, the composite endpoint of progression-free survival has been routinely adopted in recent years as it is viewed as enabling a more timely and cost-effective approach to assessing the clinical benefit of novel interventions. This article considers design of cancer trials directed at the evaluation of treatment effects on progression-free survival. In particular, we derive sample size criteria based on an illness-death model that considers cancer progression and death jointly while accounting for the fact that progression is assessed only intermittently. An alternative approach to design is also considered in which the sample size is derived based on a misspecified Cox model, which uses the documented time of progression as the progression time rather than dealing with the interval censoring. Simulation studies show the validity of the proposed methods.

Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial.

BACKGROUND: No randomised trials have addressed whether exposure to red blood cells (RBCs) stored longer than 35 days is associated with harm in patients. We aimed to assess the risk of in-hospital mortality associated with transfusing blood stored longer than 35 days. METHODS: We did a secondary analysis of the INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic, multicentre, randomised controlled trial of patients (≥18 years) admitted to one of six hospitals in Australia, Canada, Israel, and the USA and expected to need RBC transfusions. Patients were randomly assigned (2:1) to receive blood in inventory stored for the longest time (standard care) or the shortest time, using a random allocation schedule and stratified by centre and patient ABO blood group. The primary objective of the INFORM trial was to assess all-cause in-hospital mortality in patients with blood group A and O who were transfused. For our exploratory secondary analysis, we classified individuals into one of three mutually exclusive exposure categories on the basis of the maximum storage duration of any blood unit patients had received on each day in hospital: exclusively exposed to RBCs stored no longer than 7 days, exposed to at least one unit of RBCs stored 8-35 days, and exposed to least one unit of RBCs stored longer than 35 days. Our primary objective was to determine the effect on risk of in-hospital death of time-dependent exposure to RBCs stored longer than 35 days compared with exclusive exposure to RBCs stored no longer than 7 days, both in patients of blood groups A and O and all patients. The INFORM trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN08118744. FINDINGS: Between April 2, 2012, and Oct 21, 2015, 31 497 patients were recruited, and 24 736 patients were eligible for inclusion in this analysis. We excluded nine patients for whom information about the storage duration of transfused blood was missing and one patient whose sex was unknown. 4480 (18%) patients were exposed to RBCs with longest storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8-35 days. Median follow-up was 11 days (IQR 6-20). Exposure to RBCs stored longer than 35 days was not associated with increased risk of in-hospital death compared with exclusive exposure to the freshest RBC units after adjusting for demographic variables, diagnosis category, and blood product use history (in patients with blood group A or O: hazard ratio 0·94, 95% CI 0·73-1·20, p=0·60; in all patients: 0·91, 0·72-1·14, p=0·40). The risk of in-hospital death also did not differ between patients exposed to blood stored 8-35 days and patients exposed to blood stored 7 days or less (in patients with blood group A or O: 0·92, 0·74-1·15, p=0·48; in all patients: 0·90, 0·73-1·10, p=0·29). INTERPRETATION: These data provide evidence that transfusion of blood stored for longer than 35 days has no effect on in-hospital mortality, which suggests that current approaches to blood storage and inventory management are reasonable. FUNDING: Canadian Institutes for Health Research, Canadian Blood Services, and Health Canada.

The Incidence and Risk Factors for Psoriatic Arthritis in Patients With Psoriasis: A Prospective Cohort Study.

OBJECTIVE: To estimate the incidence of psoriatic arthritis (PsA) in patients with psoriasis, and to identify risk factors for its development. METHODS: The study was designed as a prospective cohort study involving psoriasis patients who did not have a diagnosis of arthritis at the time of study enrollment. Information was collected about lifestyle habits, comorbidities, psoriasis activity, and medications. Patients who developed inflammatory arthritis or spondylitis were classified as having PsA if they fulfilled the criteria of the Classification of Psoriatic Arthritis Study group. The annual incidence of PsA was estimated using an event per person-years analysis. Cox proportional hazards models, involving fixed and time-dependent explanatory variables, were fitted to obtain estimates of the relative risk (RR) of the onset of PsA, determined in multivariate models stratified by sex and controlled for age at onset of psoriasis. RESULTS: The data obtained from the 464 patients who were followed up for 8 years were analyzed. A total of 51 patients developed PsA during the 8 years since enrollment. The annual incidence rate of PsA was 2.7 cases (95% confidence interval 2.1-3.6) per 100 psoriasis patients. The following baseline variables were associated with the development of PsA in multivariate analysis: severe psoriasis (RR 5.4, P = 0.006), low level of education (university/college versus high school incomplete RR 0.22, P = 0.005; high school graduate versus high school incomplete RR 0.30, P = 0.049), and use of retinoid medications (RR 3.4, P = 0.02). In multivariate models with time-dependent variables, psoriatic nail pitting (RR 2.5, P = 0.002) and uveitis (RR 31.5, P = 0.0002) were associated with the development of PsA. CONCLUSION: The incidence of PsA in patients with psoriasis is higher than previously reported. A severe psoriasis phenotype, presence of nail pitting, low level of education, and uveitis are predictive of the development of PsA in patients with psoriasis.

Exposure to ABO-nonidentical blood associated with increased in-hospital mortality in patients with group A blood.

BACKGROUND: Transfusing ABO-compatible blood avoids most acute hemolytic reactions, but donor units that are ABO compatible are not necessarily ABO identical. Emerging data have raised concerns that ABO-nonidentical blood products lead to adverse outcomes. STUDY DESIGN AND METHODS: A large multihospital registry (Transfusion Registry for Utilization, Surveillance, and Tracking) was used to determine the association between exposure to ABO-nonidentical blood and in-hospital mortality. Cox regression analyses controlled for sex, age, hemoglobin, creatinine, and in-hospital interventions and stratified by age of blood and admission year. RESULTS: Data from 18,843 non-group O patients admitted between 2002 and 2011 and receiving at least 1 unit of blood were analyzed. Overall, group A patients had significantly increased risk of in-hospital death upon receiving a nonidentical unit (RR , 1.79; 95% CI, 1.20-2.67; p = 0.005). There was no evidence of increased risk for group B or AB patients. Similar results were seen when only patients with circulatory disorders were considered. When patients with an injury or poisoning diagnosis were excluded, the risk of in-hospital death after receiving a non-identical unit was significantly higher in group A patients and significantly lower in Group B patients. CONCLUSION: Our study demonstrates an adverse effect of ABO-nonidentical blood in a broad range of patients with group A blood, after adjustment for potential confounders. Further research in this area is required to study possible mechanisms. Increased mortality associated with exposure to nonidentical blood in these patients would have a substantial impact at the population level; it would challenge how blood suppliers manage inventory and recruit donors and how health care providers administer blood.

Changing Pattern of Sputum Cell Counts During Successive Exacerbations of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease exacerbations are associated with worsening of airway inflammation, the nature of which may be neutrophilic, eosinophilic, or both. OBJECTIVE: The primary objective was to examine the cellular nature of airway inflammation in successive COPD exacerbations in order to ascertain if they changed in individual patients. The secondary objective was to estimate the relative risk indicating the extent to which a particular type of exacerbation changed as a function of the most recent exacerbation. DESIGN: This was a retrospective survey performed on a computerised sputum cell count database of a referral respiratory service in Hamilton, Canada. Recurrent event analyses were used to model the incidence of exacerbations and subtypes of exacerbations. RESULTS: 359 patients and 148 patients had sputum examined during stable condition and during exacerbations, respectively. It was found 65 patients had sputum examined during both situations. The exacerbations were eosinophilic in 15.9%, neutrophilic in 18%, combined in 2.6%, of unknown clinical significance in 19.6% and normal in 19.6%. There were missing counts for 24.3% samples. In 85.2% of patients, a different subtype of bronchitis was noted in successive exacerbations. The relative risk of a subsequent neutrophilic or eosinophilic exacerbation was 6.24 (p = 0.02) and 2.8 (p = 0.24) when the previous exacerbation was neutrophilic or eosinophilic respectively. CONCLUSIONS: This non-intervention study suggests that the cellular nature of bronchitis is largely unpredictable and needs to be examined at each COPD exacerbation This has important implications in choosing the appropriate therapy. Future intervention studies would provide further evidence.

A copula model for marked point processes.

Many chronic diseases feature recurring clinically important events. In addition, however, there often exists a random variable which is realized upon the occurrence of each event reflecting the severity of the event, a cost associated with it, or possibly a short term response indicating the effect of a therapeutic intervention. We describe a novel model for a marked point process which incorporates a dependence between continuous marks and the event process through the use of a copula function. The copula formulation ensures that event times can be modeled by any intensity function for point processes, and any multivariate model can be specified for the continuous marks. The relative efficiency of joint versus separate analyses of the event times and the marks is examined through simulation under random censoring. An application to data from a recent trial in transfusion medicine is given for illustration.

Inverse probability weighted estimating equations for randomized trials in transfusion medicine.

Thrombocytopenia is a condition characterized by extremely low platelet counts, which puts patients at elevated risk of morbidity and mortality because of bleeding. Trials in transfusion medicine are routinely designed to assess the effect of experimental platelet products on patients' platelet counts. In such trials, patients may receive multiple platelet transfusions over a predefined period of treatment, and a response is available from each such administration. The resulting data comprised multiple responses per patient, and although it is natural to want to use this data in testing for treatment effects, naive analyses of the multiple responses can yield biased estimates of the probability of response and associated treatment effects. These biases arise because only subsets of the patients randomized contribute response data on the second and subsequent administrations of therapy and the balance between treatment groups with respect to potential confounding factors is lost. We discuss the design and analysis issues involved in this setting and make recommendations for the design of future platelet transfusion trials.