Comparison of clinical burden between patients with erosive hand osteoarthritis and inflammatory arthritis in symptomatic community-dwelling adults: the Keele clinical assessment studies.

OBJECTIVE: To investigate in the general population the clinical impact of erosive OA in interphalangeal joints (IPJs) compared with symptomatic radiographic hand OA and inflammatory arthritis. METHODS: Standardized assessments with hand radiographs were performed in participants of two population-based cohorts in North Staffordshire with hand symptoms lasting ≥1 day in the past month. Erosive OA was defined as the presence of an eroded or remodelled phase in ≥1 IPJ using the Verbruggen-Veys method. Radiographic hand OA was defined as the presence of ≥1 IPJ/first carpometacarpal joint with a Kellgren-Lawrence score of ≥2. Diagnoses of inflammatory arthritis were based on medical records. Hand pain and disability were assessed with the Australian/Canadian Hand Osteoarthritis Index (AUSCAN). Linear regression analyses were used to compare clinical determinants between groups and calculate mean differences with 95% CIs, adjusted for age and sex. RESULTS: Of 1076 participants with hand symptoms [60% women, mean age 64.8 years (s.d. 8.3 years)]; 80 persons (7.4%) had erosive OA. The population prevalence of erosive OA in ≥1 IPJ was 2.4% (95% CI 1.8, 3.0). Persons with erosive OA reported more pain and disability than persons with symptomatic radiographic hand OA [adjusted mean difference 1.3 (95% CI 0.3, 2.3) and 2.3 (95% CI 0.4, 4.2), respectively]. Individuals with inflammatory arthritis (n = 44) reported more pain and disability than those with erosive OA [adjusted mean difference 1.7 (95% CI 0.05, 3.4) and 6.3 (95% CI 2.8, 9.9), respectively]. CONCLUSION: While erosive OA has a greater impact than symptomatic radiographic hand OA in the general population, it is not as severe in terms of hand pain and disability as inflammatory RA

Reference curves for the Australian/Canadian Hand Osteoarthritis Index in the middle-aged Dutch population

Objective. The aim was to establish reference curves of the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), a widely used questionnaire assessing hand complaints. Methods. Analyses were performed in a population-based sample, The Netherlands Epidemiology of Obesity study (n = 6671, aged 45–65 years). Factors associated with AUSCAN scores were analysed with ordered logistic regression, because AUSCAN data were zero inflated, dividing AUSCAN into three categories (0 vs 1–5 vs >5). Age- and sex-specific reference curves for the AUSCAN (range 0–60; higher is worse) were developed using quantile regression in conjunction with fractional polynomials. Observed scores in relevant subgroups were compared with the reference curves. Results. The median age was 56 [interquartile range (IQR): 50–61] years; 56% were women and 12% had hand OA according to ACR criteria. AUSCAN scores were low (median 1; IQR: 0–4). Reference curves where higher for women, and increased moderately with age: 95% percentiles for AUSCAN in men and women were, respectively, 5.0 and 12.3 points for a 45-year-old, and 15.2 and 33.6 points for a 65-year-old individual. Additional associated factors included hand OA, inflammatory rheumatic diseases, FM, socio-economic status and BMI. Median AUSCAN pain subscale scores of women with hand OA lay between the 75th and 90th centiles of the general population. Conclusion. AUSCAN scores in the middle-aged Dutch population were low overall, and higher in women than in men. AUSCAN reference curves could serve as a benchmark in research and clinical practice settings. However, the AUSCAN does not measure hand complaints specific for hand OA

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

Prediction or causality? A scoping review of their conflation within current observational research.

Etiological research aims to uncover causal effects, whilst prediction research aims to forecast an outcome with the best accuracy. Causal and prediction research usually require different methods, and yet their findings may get conflated when reported and interpreted. The aim of the current study is to quantify the frequency of conflation between etiological and prediction research, to discuss common underlying mistakes and provide recommendations on how to avoid these. Observational cohort studies published in January 2018 in the top-ranked journals of six distinct medical fields (Cardiology, Clinical Epidemiology, Clinical Neurology, General and Internal Medicine, Nephrology and Surgery) were included for the current scoping review. Data on conflation was extracted through signaling questions. In total, 180 studies were included. Overall, 26% (n = 46) contained conflation between etiology and prediction. The frequency of conflation varied across medical field and journal impact factor. From the causal studies 22% was conflated, mainly due to the selection of covariates based on their ability to predict without taking the causal structure into account. Within prediction studies 38% was conflated, the most frequent reason was a causal interpretation of covariates included in a prediction model. Conflation of etiology and prediction is a common methodological error in observational medical research and more frequent in prediction studies. As this may lead to biased estimations and erroneous conclusions, researchers must be careful when designing, interpreting and disseminating their research to ensure this conflation is avoided

Associations between Lifestyle Factors and Vitamin E Metabolites in the General Population

The antioxidant vitamin E (α-tocopherol, α-TOH) protects lipids from oxidation by reactive oxygen species. We hypothesized that lifestyle factors associate with vitamin E metabolism marked by urinary α-tocopheronolactone hydroquinone (α-TLHQ) and α-carboxymethyl-hydroxychroman (α-CEHC levels), as potential reflection of lipid oxidation. We conducted a cross-sectional study in the Netherlands Epidemiology of Obesity Study. Serum α-TOH, and urinary α-TLHQ and α-CEHC were quantified by liquid chromatography coupled with tandem mass spectrometry. Information on the lifestyle factors (sleep, physical activity (PA), smoking and alcohol) were collected through questionnaires. Multivariable linear regression analyses were performed to assess the associations between the lifestyle factors and α-TOH measures. A total of 530 participants (46% men) were included with mean (SD) age of 56 (6) years. Of the examined lifestyle factors, only poor sleep was associated with a higher serum α-TOH (mean difference: 4% (95% CI: 1, 7%)). Current smoking was associated with higher urinary α-CEHC (32%: (14%, 53%)), with evidence of a dose-response relationship with smoking intensity (low pack years, 24% (2, 52%); high pack years, 55% (25, 93%)). Moderate physical activity was associated with a lower α-TLHQ relative to α-CEHC (-17%: (-26, -6%), compared with low PA). Only specific lifestyle factors associate with vitamin E metabolism. Examining serum α-TOH does not provide complete insight in vitamin E antioxidant capacity

Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals

Vitamin E (α-tocopherol, α-TOH) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance (NMR) with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-hour urine quantified by LC/MS-MS. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) with vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (45% men) with mean (SD) age of 55.7 (6.0) years. Out of 147 metabolomic measures, 106 were associated (p < 1.34E-3) with serum α-TOH [median beta (IQR): 0.416 (0.383, 0.466)], predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC are with similar directions as those with α-TOH, but effect sizes were smaller and non-significant [median beta (IQR):0.065 (0.047, 0.084)]. However, associations of metabolomic measures with urinary α-TLHQ were markedly different from the associations of metabolomic measures with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most VLDL and amino acids. Therefore, our results highlight the differences of the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not to antioxidative function of vitamin E

Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors

Linda Flinterman and colleagues report on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event