Construct, content and face validity of the eoSim laparoscopic simulator on advanced suturing tasks.

BACKGROUND: The purpose of this study was to validate the eoSim, an affordable and mobile inanimate laparoscopic simulator with instrument tracking capabilities, regarding face, content and construct validity on complex suturing tasks. METHODS: Participants recruited for this study were novices (no laparoscopic experience), target group for this training (surgical/gynaecologic/urologic residents, > 10 basic and < 20 advanced laparoscopic procedures) and experts (> 20 advanced laparoscopic procedures). Each participant performed the intracorporeal suturing exercise (Task 1), an upside down needle transfer (Task 2, developed for this study) and an anastomosis needle transfer (Task 3). Following, the participants completed a questionnaire regarding their demographics and opinion on the eoSim in terms of realism, didactic value and usability. Measured outcome parameters were time, distance, percentage of instrument tip off-screen, working area, speed, acceleration and smoothness. RESULTS: In total, 104 participants completed the study, of which 60 novices, 31 residents and 13 experts. Face and content validity results showed a mean positive opinion on realism (3.9 Task 1, 3.6 Task 2 and 3.7 Task 3), didactic value (4.0, 3.4 and 3.7, respectively) and usability (4.2. 3.7 and 4.0, respectively). There were no significant differences in these outcomes between the specified expertise groups. Construct validity results showed significant differences between experts, target group or novices for Task 1 in terms of time (means 339, 607 and 1224 s, respectively, p < 0.001) and distance (means 8.1, 15.6 and 21.7 m, respectively, p < 0.001). Task 2 showed significant differences between groups regarding time (p < 0.001), distance (p 0.003), off-screen (p < 0.001) and working area (p < 0.001). Task 3 showed significant differences between groups, after subanalyses, on total number of stitches (p < 0.001), time per stitch (p < 0.001) and distance per stitch (p < 0.001). CONCLUSIONS: The results of this study indicate that the eoSim is a potential meaningful and valuable simulator in the training of suturing tasks.

Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. METHODS: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. RESULTS: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). CONCLUSIONS: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

Low disease activity (DAS28≤3.2) reduces the risk of first cardiovascular event in rheumatoid arthritis: a time-dependent Cox regression analysis in a large cohort study.

OBJECTIVE: Systemic inflammation appears to contribute to the excess risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objective of this study was to investigate the effect of different levels of disease activity over time, particularly low disease activity and remission, on CVD risk in patients with RA. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events within the first 10 years of follow-up. Cut points of the DAS28 for remission (<2.6) and low (≤3.2), moderate (3.2-5.1) and high (>5.1) disease activity were used. The effect of disease activity on CVD risk was analysed using Cox-proportional hazards regression with DAS28 as a time-dependent covariate and also conventionally with time-averaged DAS28 as the primary dependent variable. RESULTS: Low DAS28 (≤3.2) was significantly associated with a reduced risk of CVD (HR 0.65, 95% CI 0.43 to 0.99) compared with DAS28 >3.2, both when included as a time-dependent covariate and as time-averaged DAS28 ≤3.2 (HR 0.52, 95% CI 0.33 to 0.81). Remission had a modest, non-significant protective effect against CVD (HR 0.67, 95% CI 0.43 to 1.07). CONCLUSION: Results of this study suggest that low disease activity is sufficient to achieve a protective effect against CVD in RA. Apparently, remission defined as DAS28 <2.6 has no additional protective effect against CVD compared with low disease activity. Our results strengthen the use of tight control strategies in daily clinical practice to achieve low stable disease activity or remission in patients with RA as soon as possible.

The effect of disease duration and disease activity on the risk of cardiovascular disease in rheumatoid arthritis patients.

OBJECTIVE: Disease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA. METHODS: RA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged  28 joint disease activity score (DAS28) for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were used for the analyses. RESULTS: During follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders. CONCLUSIONS: Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.

Interactive virtual reality training to improve socio-emotional functioning in adolescents with developmental language disorders: A feasibility study.

Methods to effectively improve socio-emotional functioning by adolescents with developmental language disorders (DLD) are scarce. Current methods to improve socio-emotional functioning in adolescents with other neurobiological disorders seem less suitable, as these methods are highly language based. This study therefore examined the feasibility of the virtual reality (VR) training for socio-emotional skills: 'InterAction'. The aims of the present study were to (1) examine whether interactive VR is a feasible training method for adolescents with DLD; (2) investigate adolescents' appreciation of the VR training; (3) examine whether the virtual reality training facilitates the participants' sense of presence during social practice situations in an interactive digital world; and (4) explore whether adolescents socio-emotional skills improved during the six-session training. A sample of nine adolescents (13-16 years) with DLD reported on their presence in VR contexts and their appreciation toward the VR training. They also completed weekly self-reports on their socio-emotional functioning. Results indicated that 'InterAction' was a feasible method to practice socio-emotional functioning with adolescents with DLD. Adolescents highly appreciated the VR training. In addition, adolescents rated the sense of presence as high in the VR training. The individual trajectories showed that improvements in the trained skills varied both between and within participants. The results were also not uniform between the specific skills trained. The findings suggest that interactive virtual reality training may be a promising tool for improving socio-emotional functioning in adolescents with DLD. Future studies should examine the positive indications of this study in a larger sample.

The value of digital 3D models in evaluating surgical outcomes using the uninjured contralateral acetabulum after acetabular fracture repair.

BACKGROUND: Currently, assessment of acetabular fracture reduction is mainly performed by evaluating 2D slices of 3D CT scans. This subjective method can potentially be improved by using 3D models and objective analysis tools. In order to evaluate the potential value of digital 3D reconstructed models in the assessment of acetabular fracture reduction, 3D reconstructions of the fractured acetabulum were compared to the mirrored healthy contralateral side for both the pre-, and post-surgical setting. METHODS: Thirteen patients with one-sided acetabular fractures were included in the study. All patients received a pre-, and postoperative CT scan. The similarity between the healthy acetabulum and the contralateral fractured acetabulum was determined by two observers for both the pre-, and postoperative setting by completing the following four steps; (1) mirroring of the fractured acetabulum, (2) initial manual alignment of this mirrored 3D model to the contralateral version, (3) surface-based matching (iterative closest point registration) using the acetabular cartilage surface, and (4) calculating the surface distances between affected and healthy acetabular 3D models. Descriptive statistics showed the surface distance between pre-, and post-surgical reduction, as well as the interobserver variability. RESULTS: A total of 13 patients with an acetabular fracture were included; 11 males and 2 females with a mean ± SD age of 55.6 ± 14.7 years. Digital mirroring of the fractured acetabula to the healthy acetabula was successful for both preoperative and postoperative situations in all patients. The median distance between both fractured and mirrored healthy contralateral acetabula was significantly larger (p<0.01) for the preoperative group (2.21 mm (interquartile range (IQR): 1.30 mm)) compared to the postoperative group (0.93 mm (IQR: 0.59 mm)). The median distance deviation was not significantly different (p = 0.96) between observers. CONCLUSIONS: The results of comparing 3D model of fractured acetabula with the contra-lateral healthy acetabula before, and after surgical repair indicate that this method can be a suitable tool to objectively assess acetabular fracture reduction. Further research is needed to confirm the usefulness to predict future arthrosis after surgical repair.

Atherogenic index and high-density lipoprotein cholesterol as cardiovascular risk determinants in rheumatoid arthritis: the impact of therapy with biologicals.

Cardiovascular (CV) diseases are a serious concern in rheumatoid arthritis (RA), accounting for approximately one-third to one-half of all RA-related deaths. Besides the attempts to identify new risk factors, the proper management of traditional CV risk factors such as dyslipidemia should become a priority in the periodic evaluation of every RA patient. Atherogenic index has been suggested to be less susceptible to disease activity variation during large periods of time, making him more attractive to be used in CV risk prediction in this group of patients as compared to individual lipids concentrations. Nevertheless, inflammation may negatively impact HDL antiatherogenic properties, suggesting that HDL function assessment is of particular importance when predicting CV risk in these patients. A tight control of inflammation becomes therefore crucial for a successful CV risk management. The present paper debates these hypotheses focusing on the effects of therapy with biologicals on the above mentioned parameters.

The cost-effectiveness of substituting physicians with diabetes nurse specialists: a randomized controlled trial with 2-year follow-up.

AIMS: To evaluate the cost-effectiveness of an intervention substituting physicians with nurse specialists. BACKGROUND: Increasing populations of people with diabetes in most Western countries require creative solutions that give high-quality chronic care while controlling costs. Instigating nurse specialists as a substitute for physicians yields positive results in this area. Research about such interventions in a hospital-based setting is limited. METHODS: This paper is a report of a study of a randomized, non-blinded clinical trial including people with diabetes mellitus types 1 and 2. In the intervention group nurse specialists were the central carers, providing care that conformed to a preset protocol. Patients were included between 2004 and 2007. Costs, quality of life and adverse events were measured, cost-effect ratios and incremental cost-effect ratios were calculated based on health-resource utilization rates, corresponding market prices and national tariffs from 2007. RESULTS: Health related quality of life scores did not differ significantly between the control and the intervention group. In the intervention group, fewer patients were hospitalized and fewer side effects from drugs were reported compared to controls. Nurse specialists as central care givers generated a modest reduction in costs per quality adjusted life year gained compared to usual care. CONCLUSION: Nurse specialists give diabetes care that is similar to care provided by physicians in terms of quality of life and economic value. Instigating a nurse specialist as central carer yields opportunities to generate cost savings. Developing interventions which also focus on prevention of complications is recommended when aiming for long-term organisational cost savings.

Improving social emotional functioning in adolescents with Developmental Language Disorders: A mini review and recommendations.

Adolescents with Developmental Language Disorders (DLD) have more difficulties in social emotional functioning than their typically developing peers (TD), such as shyness and anxiety in social situations, fewer peer relations, greater risk of victimization, social isolation and depression. In addition, they are more likely to report higher levels of hyperactivity and conduct problems. These problems derive from a complex interplay between difficulties in language, social communication, underlying cognitive deficits in Theory of Mind (ToM), Executive Functioning (EF) and self-directed speech (SDS). The aim of this mini review is to provide an overview of studies examining the effectiveness of interventions targeting the factors underlying social emotional functioning of school-aged children and adolescents with DLD. We found that studies dedicated to social emotional functioning in school-aged children and adolescents with DLD were relatively scarce. Based on this overview, we give suggestions to improve social emotional functioning in adolescents with DLD. We propose that intervention programs should target the social, linguistic and cognitive functions underlying social emotional functioning and create opportunities to practice these skills in daily, real-life situations with peers.

The value of 3D reconstructions in determining post-operative reduction in acetabular fractures: a pilot study.

BACKGROUND: In patients with acetabular fractures, the reconstructed three-dimensional (3D) model of the contralateral acetabulum could be used as a mirrored template for the anatomical configuration of the affected joint. This has not been validated. OBJECTIVE: To investigate whether the right and left acetabula, as reconstructed 3D models, are valid mirrored duplicates that can be used as a reference model for the contralateral side. METHODS: CT scans of twenty patients with unaffected acetabula were used. The symmetry of the generated 3D models was evaluated through: (1) mirroring of the acetabulum; (2) initial rough matching; (3) automatic optimisation of the matching via surface-based matching; (4) calculation of distances between surfaces by evaluating the Euclidean (straight-line) error distance between the closest points between left and right. The percentages of surface points of the left and right acetabulum with a distance smaller than 0.5, 1.0, 1.5 and 2.0 mm were calculated and evaluated, in relation to Matta's criteria, for acetabular fracture reductions. RESULTS: The mean distance deviation was less than 0.75 mm in all 40 comparisons. The calculated distances in 90.7% of the surface points of the left and right acetabulum were below the tolerance threshold of 1.0 mm, based on Matta's anatomical reduction criteria, and 98.7% of the surface points scored below Matta's imperfect tolerance threshold of 2.0 mm. CONCLUSION: This study demonstrates 3D reconstructed models of healthy left and right acetabula are highly similar and could potentially be used as mirrored duplicates. The next step will be to investigate these results in patients with reduced acetabular fractures.

Training benchmarks based on validated composite scores for the RobotiX robot-assisted surgery simulator on basic tasks.

The RobotiX robot-assisted virtual reality simulator aims to aid in the training of novice surgeons outside of the operating room. This study aimed to determine the validity evidence on multiple levels of the RobotiX simulator for basic skills. Participants were divided in either the novice, laparoscopic or robotic experienced group based on their minimally invasive surgical experience. Two basic tasks were performed: wristed manipulation (Task 1) and vessel energy dissection (Task 2). The performance scores and a questionnaire regarding the realism, didactic value, and usability were gathered (content). Composite scores (0-100), pass/fail values, and alternative benchmark scores were calculated. Twenty-seven novices, 21 laparoscopic, and 13 robotic experienced participants were recruited. Content validity evidence was scored positively overall. Statistically significant differences between novices and robotic experienced participants (construct) was found for movements left (Task 1 p = 0.009), movements right (Task 1 p = 0.009, Task 2 p = 0.021), path length left (Task 1 p = 0.020), and time (Task 1 p = 0.040, Task 2 p < 0.001). Composite scores were statistically significantly different between robotic experienced and novice participants for Task 1 (85.5 versus 77.1, p = 0.044) and Task 2 (80.6 versus 64.9, p = 0.001). The pass/fail score with false-positive/false-negative percentage resulted in a value of 75/100, 46/9.1% (Task 1) and 71/100, 39/7.0% (Task 2). Calculated benchmark scores resulted in a minority of novices passing multiple parameters. Validity evidence on multiple levels was assessed for two basic robot-assisted surgical simulation tasks. The calculated benchmark scores can be used for future surgical simulation training.

Younger age and female gender are determinants of underestimated cardiovascular risk in rheumatoid arthritis patients: a prospective cohort study.

BACKGROUND: Rheumatoid arthritis (RA) patients have an increased cardiovascular (CV) risk. Here, we aimed to investigate whether gender and age are contributing to the misclassification of CV risk in RA patients. METHODS: Prospectively collected data on cardiovascular risk factors and incident events from the Nijmegen inception cohort were analyzed, with up to 10 years follow-up. Original as well as the EULAR-modified (M)_SCORE algorithms were used to calculate CV risk. Patients were stratified in deciles according to predicted risk; the Hosmer-Lemeshow test was used to check concordance between observed and predicted risk, in subgroups of gender and age. RESULTS: There were 863 RA patients included with 128 incident CV events. When using SCORE in the whole group, there was evidence of a discrepancy between the predicted and observed CV risk (H-L test p < 0.003), mainly present in the female subgroup (H-L test p < 0.001). Interestingly, 36% of females who developed an event belonged to the low CV risk group, whereas this was just 10% in RA males. When analyzing the subgroups based on age, a discrepancy was present only in the youngest patients (H-L test p < 0.001 in patients < 55 years) consisting of an underestimation of CV risk (5.3% predicted vs. 8.0% observed). Similar results were obtained when the M_SCORE was applied. CONCLUSION: CV risk is especially underestimated in female and younger RA patients. This suggests that modifying the weight for the female gender and/or younger age in currently used CV risk algorithms might improve their predictive value in RA, contributing to better CV risk management.

Prediction of cardiovascular events in rheumatoid arthritis using risk age calculations: evaluation of concordance across risk age models.

BACKGROUND: In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics. METHODS: RA patients aged 30-70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up. RESULTS: A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15-32% of patients. C-statistics ranged 0.68-0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results. CONCLUSIONS: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.

Face, Content, and Construct Validity of the Take-Home EoSim Augmented Reality Laparoscopy Simulator for Basic Laparoscopic Tasks.

Background: The eoSim® laparoscopic augmented reality (AR) simulator has instrument tracking capabilities that may be suitable for implementation in laparoscopic training. The objective is to assess face, content, and construct validity of this simulator for basic laparoscopic skills training. Methods: Participants were divided into three groups: novices (no training), intermediates (<50 laparoscopic procedures), and experts (>50 laparoscopic procedures). Three basic tasks were completed on the simulator: thread transfer (1), cyst dissection (2), and tube ligation (3). A questionnaire was completed on realism, didactic value, and usability of the simulator. Measured outcome parameters were as follows: time, distance, time off screen, average speed, acceleration, and smoothness. Results: Mean ± standard deviation scores on realism were positive (Task 1 or T1; 3.9 ± 0.7, P = .13, T2; 3.7 ± 0.7, P = .07, T3; 3.7 ± 0.07), as well as didactic value (T1; 3.9 ± 0.8, P = .71, T2; 3.9 ± 0.8, P = .31, T3; 4.0 ± 0.8, P = .40). Usability was valued the highest, with mean scores between 3.9 and 4.3 (T1; P = .71, T2; P = .80, T3; P = .85). Scores did not differ significantly between groups. Experts were significantly faster (Task 1; P < .001, Task 2; P = .042, Task 3: P < .001) with higher handling speed for tasks 2 and 3 (Task 1; P = .20, task 2; P = .034, task 3; P = .049). Results for other outcome parameters also indicated experts had better instrument control and efficiency than novices, although these differences did not reach statistical significance. Conclusions: The eoSim laparoscopic AR simulator is regarded as a realistic, accessible, and useful tool for the training of basic laparoscopic skills, with good face validity. Construct validity of the eoSim AR simulator was demonstrated on several core variables, but not all.

Anticyclic Citrullinated Peptide Antibodies and Rheumatoid Factor as Risk Factors for 10-year Cardiovascular Morbidity in Patients with Rheumatoid Arthritis: A Large Inception Cohort Study.

OBJECTIVE: To determine whether anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) are risk factors for 10-year cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). METHODS: Analyses were performed using data from the Nijmegen early RA inception cohort, in which patients with newly diagnosed RA, consecutively included since 1985, were regularly followed up. Anti-CCP and RF were determined at baseline (diagnosis). Outcome was the first cardiovascular disease (CVD) event [ischemic heart disease, nonhemorrhagic cerebrovascular accident (CVA), or peripheral artery disease (PAD)] after baseline as retrieved from physician diagnosis. Fatality was checked against death certificates. Cox regression including correction for baseline confounders was performed to estimate the effect of anti-CCP, RF, and their interaction on 10-year CVD-free survival. RESULTS: Of 929 patients included, 628 were anti-CCP-positive and 697 were RF-positive. During followup, with a median of 7.5 years, 162 CV events were observed (101 ischemic heart disease, 45 CVA, and 16 PAD), of which 15 were fatal. The HRadjusted for anti-CCP was 1.17 (95% CI 0.82-1.67) and the HRadjusted for RF was 1.52 (95% CI 1.00-2.30). The association of RF positivity with CVD was even stronger in the anti-CCP-negative patients: HRadjusted 2.09 (95% CI 1.18-3.71). There was no significant interaction (p = 0.098) between anti-CCP and RF. CONCLUSION: Rather than anti-CCP, presence of RF was associated with CVD in this cohort of patients with RA.

Cost-Effectiveness of Cardiovascular Screening in Patients With Rheumatoid Arthritis.

OBJECTIVE: Early detection and preemptive treatment of patients at risk is of great importance in reducing the excess risk of cardiovascular (CV) disease in rheumatoid arthritis (RA). However, it is unclear how much screening is cost-effective in RA. The objective is to assess whether CV screening in RA proves to be cost-effective from a medical perspective, using different scenarios based on different guidelines. METHODS: A Markov chain model was used with a time horizon of 10 years. Parameter values were mainly obtained from literature and from RA patients screened for CV diseases at the Radboud University Medical Centre, Nijmegen, The Netherlands. The primary outcome was incremental cost-effectiveness expressed as costs per quality-adjusted life year (QALY) gained. Probabilistic sensitivity analysis was performed and described in willingness-to-pay curves; several scenarios were built. RESULTS: In the base case scenario, in 82% of the simulations, screening proved to be dominant compared to no screening. The mean QALY gain was 0.09 (95% percentile -0.07, 0.27), and the mean cost savings were €-1,057 (95% percentile -€2,825, €333). Different scenarios showed small differences in cost-effectiveness; the probability that screening is dominant remained high with the lowest probability being 50% for a very conservative scenario. CONCLUSION: Screening for CV events in RA patients was estimated to be cost-effective with high chances of being less expensive and more effective. These results support endorsement of screening for CV risk in patients with RA.

Serum samples that have been stored long-term (>10 years) can be used as a suitable data source for developing cardiovascular risk prediction models in large observational rheumatoid arthritis cohorts.

OBJECTIVE: There is an unmet need for a specific cardiovascular risk (CV) algorithm for rheumatoid arthritis (RA) patients. Lipoprotein data are often not available in RA cohorts but could be obtained from frozen blood samples. The objective of this study was to estimate the storage effect on lipoproteins in long-term (>10 years) frozen serum samples. METHODS: Data were used from an inception RA cohort. Multiple serum samples from 152 patients were analyzed for lipoproteins, being frozen for 1-26 years at -20°C. Storage effect on lipoproteins was estimated using longitudinal regression analyses and a lipid decay correction factor was developed. Clinical impact of the storage effect on lipoproteins was assessed by calculating the number of patients reclassified to another CV risk group according to the SCORE risk calculator after applying the decay correction factor. RESULTS: There was a significant effect of storage time on total cholesterol (TC) (P<0.001) and high density lipoprotein cholesterol (HDL-c) levels (P<0.001), not LDL-c (P=0.83). The lipid decay correction factor was 0.03 mmol/L and 0.024 mmol/L per additional year of storage for TC and HDL-c, respectively. The TC:HDL ratio decreased after correction for storage effect. After correction, only 5% of patients were reclassified to another CV risk group. CONCLUSION: A modest storage decay effect on lipoproteins was found that is unlikely to significantly affect CV risk stratification. Serum samples that have been stored long-term (>10 years) can be used to obtain valid lipid levels for developing CV risk prediction models in RA cohorts, even without applying a decay correction factor.

High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study.

INTRODUCTION: Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity. METHODS: Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol. RESULTS: HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186). CONCLUSIONS: Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.