Description of Study Protocol. Data Collection Summary

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AND Evidence Analysis Worksheet Citation Kostoglou-athanassiou I, AthanassiouP, Lyraki A, Raftakis I, Antoniadis C. Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab. 2012; 3(6):181-7. Study Design Case Control Study Class C Research Purpose The evaluation of the relationship between vitamin D and rheumatoid arthritis as well as disease activity relation between the two. Inclusion Criteria - fulfilled the 2010 American College of Rheumatology/European League against Rheumatism Rheumatoid Arthritis Classification Criteria - receiving treatment at the specific Rheumatology Department s outpatient clinic Exclusion Criteria - did not fulfill the 2010 American College of Rheumatology/European Description of Study Protocol Data Collection Summary League against Rheumatism Rheumatoid Arthritis Classification Criteria Study cohort of 44 patients with RA that fulfilled the 2010 American College of Rheumatology/European League against Rheumatism Rheumatoid Arthritis Classification Criteria, had: 25-hydroxyvitamin D3 [25(OH)D3] levels, parathyroid hormone levels, C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ) disability index, visual analogue scale (VAS) pain score, and 28-joint Disease Activity Score (DAS28) was calculated and used to evaluate disease activity measured. A control group of 44 with age and sex matched were also studied. -25-hydroxyvitamin D3 [25(OH)D3] levels were measured in a two-step radioimmunoassay process. 25-hydroxy vitamin D test is the most accurate way to measure how much vitamin D is in your body. In the kidney, 25- hydroxy vitamin D changes into an active form of the vitamin. The active form of vitamin D helps control calcium and phosphate levels in the body. -Parathyroid hormone was measured by an immunoradiometric assay. -Full clinical and lab evaluations were performed on all patients. Independent Variables: -Patient and control group selection -Measurement procedure of 25(OH)D3 by a two-step radioimmunoassay process Dependent Variables: -Tests in comparison to 25(OH)D3 levels - Patients treatment regimen for RA Control Variables: control group did not fulfill the 2010 American College of Rheumatology/European League against Rheumatism Rheumatoid Arthritis Classification Criteria SPSS19 was used to perform statistical analysis. Student s t-test was used for comparison between the patient and control groups. Disease activity and

25(OH)D3 level relationship were compared with regression analysis. Summary of Results -The 44 patients with RA were found to have 25(OH)D3 levels lower than the control group. Values consisted of: 15.26 ± 1.07 ng/ ml [mean ± standard error of the mean (SEM)], range 7.00 44.8 ng/ml and 25.8±1.6 ng/ml, range 6.8 80.0 ng/ml in the patient and control group with student s t-test, p < 0.001 (see figure below). -Parathyroid levels were tested and values of 71.08 ± 7.02 pg/ml (mean ± SEM) were recorded (normal parathyroid values are: 10.0 65.0 pg/ml), CRP 7.6 ± 1.57 mg/liter (with normal values < 3 mg/liter) and ESR 38.0 ± 4.6 mm/h in the patients group, with DAS28 index of 4.26 ± 0.26. -25(OH)D3 levels were found to be negatively correlated to the DAS28 score, (correlation coefficient being 0.084, r being 0.084) (see figure below).

-25(OH)D3 levels were found to be negatively correlated to CRP (see figure below) -25(OH)D3 levels were also found to be negatively correlated to ESR correlation coefficient being 0.115 and 0.18 and r being 0.115 and 0.18. (see figure below) Author Conclusion Reviewer Comments The authors concluded that RA patients have a higher prevalence of vitamin D deficiency, with a negative correlation between RA disease activity and vitamin D levels. Strengths: - findings of statistical significance - no conflict of interest in preparing this study (author reported) - funding for this research was conducted without outside funding (no bias) Weaknesses: - small sample size (44 patients, 44 control) - few details about the patient and control groups provided - few details about the specific study, bulk of the article is comparisons to past studies

Citation Study Design Class Research Purpose Inclusion Criteria Exclusion Criteria Description of Study Protocol AND Evidence Analysis Worksheet Sabbagh Z, Markland J, Vatanparast H. Vitamin D status is associated with disease activity among rheumatology outpatients. Nutrients. 2013;5(7):2268-75. Case Control C Determine serum vitamin D status of diagnosed cases of most usual autoimmune diseases and compare to those with non-autoimmune diseases as well as evaluating the impact of vitamin D levels on disease activity. -Patients with measured plasma 25-hydroxy vitamin D (25(OH)D), categorized into case and control groups. -Patients who visited one of the private rheumatology clinics in Saskatoon, Alaska from January-December 2010. -Patients without measured plasma 25-hydroxy vitamin D (25(OH)D). Study cohort of 60 patients with rheumatic autoimmune disease that had plasma 25-hydroxy vitamin D (25(OH)D) levels measured at above specified clinics had: Calcium supplement use Disease Activity Score (DAS 28-ESR) was calculated and used to evaluate disease activity in rheumatoid arthritis patients Serum calcium Serum phosphate Erythrocyte sedimentation rate C-reactive protein Glomerular filtration rate measured. A control group of 56 patients were also studied. Data Collection Summary Summary of Results Independent Variables: Case or control group Dependent Variables: Plasma vitamin D status 25(OH)D and Disease activity scores Statistical methods: -Independent t-test -Pearson Correlation -Chi-squared -Logistical regression -SPSS IBM The case and control groups were suffering from varying diseases. In the case group, 39 were suffering from rheumatoid arthritis. Age and sex were not matched for in the two groups and both had more female than men (13 male participants in total).

Author Conclusion Reviewer Comments (plasma concentration of 25(OH)D in both case and control groups) In both the case and control groups, patients were vitamin D deficient with levels < 50nmol/L. Patients distribution of plasma 25(OH)D groups (deficient, optimal) presented a borderline significant difference (p = 0.05). Evaluation of seasonal differences in evaluation between groups showed no statistical differences. To evaluate association between vitamin D status and disease activity scores in rheumatoid arthritis cases, the odds of having active disease was 5.15 times higher in patients with low plasma 25(OH)D compared to those with adequate vitamin D (OR = 5.15 95% CI 1.16, 22.9; p = 0.031). The authors concluded that low plasma vitamin D 25(OH)D concentration shows a need for evaluation of vitamin D status in patients with systematic autoimmune rheumatic diseases. Training to make sure patients are getting the proper amount of vitamin D should be provided. Strengths: -No conflict of interest in preparing this study (author reported) -All authors read and approved final manuscript -Ethics approval granted. Weaknesses: -Case-control study -Small sample sizes (60 case and 56 control) -Groups not matched for age or gender