Joan M. Von Feldt

Adherence, Discontinuation, and Switching of Biologic Therapies in Medicaid Enrollees with Rheumatoid Arthritis

OBJECTIVE This study examined adherence, discontinuation, and switching of rheumatoid arthritis (RA) biologics over a 1-year period after initiation of the biologic treatment in Medicaid patients with RA. METHODS The study sample consisted of Medicaid patients with RA in California, Florida and New York who had newly initiated etanercept (n=1359), anakinra (n=267), or infliximab (n=1012) between January 1, 2000 and December 31, 2002. Adherence (proportion of days covered (PDC)≥0.80), discontinuation (90-day continuous gap), and switching (initiation of second biologic within 90days of discontinuation date of index biologic) were measured during the 12-month postindex biologic initiation. Sensitivity analyses were conducted by varying the thresholds to define these measures. Logistic regressions examined the factors associated with RA biologic adherence and discontinuation. RESULTS Anakinra users had the lowest mean PDC (0.36) and percent adherent patients (11%) followed by etanercept users (mean PDC: 0.57; % adherent: 32%) and infliximab users (mean PDC: 0.64; % adherent: 43%). All three groups had high discontinuation rates (41% etanercept, 76% anakinra, and 41% infliximab). Few patients who discontinued the index biologic switched to another biologic. Logistic regressions found that patients in Florida had lower odds of being adherent and higher odds of discontinuing their index biologic than patients in California. Anakinra users had lower odds and infliximab users had higher odds of being adherent than etanercept users. Anakinra users had higher odds of discontinuation than etanercept users. CONCLUSION This study highlights the poor adherence to and premature discontinuation without concurrent switching of RA biologics that should raise concern for clinicians as well as payers.

Vitamin D, metabolic dyslipidemia, and metabolic syndrome in rheumatoid arthritis.

PURPOSE Vitamin D deficiency is a potential risk factor for cardiometabolic disease. We investigated the associations between vitamin D and dyslipidemia and the metabolic syndrome in patients with rheumatoid arthritis, a group at high risk for cardiovascular disease. METHODS Serum 25(OH)vitamin D and lipoprotein levels were measured at baseline in a random sample of 499 participants, ages 18-85 years, enrolled in a randomized trial of golimumab (GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset or GO-BEFORE Trial). Participants had rheumatoid arthritis with active disease, and were naïve to methotrexate and biologic therapies. Multivariable linear regression was performed to assess associations between vitamin D levels and lipoprotein fractions. Multivariable logistic regression was performed to determine the odds of hyperlipidemia and the metabolic syndrome in participants with vitamin D deficiency (<20 ng/mL). RESULTS In multivariable linear regression, vitamin D levels (per 10 ng/mL) were associated inversely with low-density lipoprotein (β: -0.029 [-0.049, -0.0091], P=.004) and triglyceride (β: -0.094 [-0.15, -0.039] P=.001) levels, adjusted for demographic, cardiovascular, and disease-specific variables. Vitamin D and high-density lipoprotein levels were not associated in univariate or multivariate analyses. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia (odds ratio 1.72; 95% confidence interval, 1.10-2.45; P=.014) and metabolic syndrome (odds ratio 3.45; 95% confidence interval, 1.75-6.80; P <.001) in adjusted models. CONCLUSIONS In conclusion, vitamin D deficiency was associated with the metabolic syndrome and dyslipidemia in rheumatoid arthritis, suggesting a potential role in cardiovascular disease risk. Large-scale, prospective studies are needed to determine if vitamin D supplementation improves lipoprotein levels and reduces cardiovascular risk in rheumatoid arthritis.

Seen Through Their Eyes: Residents’ Reflections on the Cognitive and Contextual Components of Diagnostic Errors in Medicine

Purpose Diagnostic errors in medicine are common and costly. Cognitive bias causes are increasingly recognized contributors to diagnostic error but remain difficult targets for medical educators and patient safety experts. The authors explored the cognitive and contextual components of diagnostic errors described by internal medicine resident physicians through the use of an educational intervention. Method Forty-one internal medicine residents at University of Pennsylvania participated in an educational intervention in 2010 that comprised reflective writing and facilitated small-group discussion about experiences with diagnostic error from cognitive bias. Narratives and discussion were transcribed and analyzed iteratively to identify types of cognitive bias and contextual factors present. Results All residents described a personal experience with a case of diagnostic error that contained at least one cognitive bias and one contextual factor that may have influenced the outcome. The most common cognitive biases identified by the residents were anchoring bias (36; 88%), availability bias (31; 76%), and framing effect (23; 56%). Prominent contextual factors included caring for patients on a subspecialty service (31; 76%), complex illness (26; 63%), and time pressures (22; 54%). Eighty-five percent of residents described at least one strategy to avoid a similar error in the future. Conclusions Residents can easily recall diagnostic errors, analyze the errors for cognitive bias, and richly describe their context. The use of reflective writing and narrative discussion is an educational strategy to teach recognition, analysis, and cognitive-bias-avoidance strategies for diagnostic error in residency education.

Associations between body mass, radiographic joint damage, adipokines and risk factors for bone loss in rheumatoid arthritis

OBJECTIVE To evaluate the association between BMI and radiographic joint damage (RJD) in RA. METHODS van der Heijde-Sharp (vdHS) erosion scores were determined in 499 participants with RA, ages 18-85 years, while enrolled in a clinical trial of golimumab (GO-BEFORE trial). Subjects were MTX and biologic therapy naïve. Multivariable logistic regressions determined the odds of prevalent RJD (defined as vdHS score >10) according to BMI category. Longitudinal analyses evaluated the association between BMI category and progression of vdHS score over 52 weeks. Analyses in a subset of 100 participants examined the association between adipokines and vdHS scores. RESULTS At enrolment and 52 weeks, 37.6 and 43.6% of participants had RJD. Compared with normal weight, obese subjects had lower odds of RJD [0.40 (95% CI 0.22, 0.74); P = 0.003], and underweight subjects had greater odds [3.86 (95% CI 1.66, 9.00); P = 0.002] at baseline, adjusted for demographic and disease characteristics. The baseline associations between BMI category and RJD were greater among participants with multiple risk factors for bone loss (female >50 years, smoking, glucocorticoid exposure and vitamin D deficiency); test for interaction P = 0.05. Adjustment for adiponectin levels did not attenuate the association between BMI and vdHS scores. Baseline BMI and change in weight did not independently predict radiographic progression (P > 0.1). CONCLUSIONS Higher BMI was independently associated with less RJD and was greatest in participants with risk factors for bone loss. Future studies are needed to examine the associations between RJD, obesity, weight loss and osteoporosis.

Deficits in Muscle Mass, Muscle Density, and Modified Associations With Fat in Rheumatoid Arthritis

To quantify muscle outcomes, independent of fat mass, in rheumatoid arthritis (RA) patients compared to healthy controls.

Resistin Levels in Lupus and Associations with Disease-specific Measures, Insulin Resistance, and Coronary Calcification

Objective. To evaluate levels of resistin in female subjects with systemic lupus erythematosus (SLE) compared to age and race-matched controls and to determine the relationship between resistin and systemic inflammation, disease measures, and coronary artery calcification (CAC). Methods. Resistin levels were measured on stored samples from 159 women with SLE and 70 controls as an extension of a previous cross-sectional study. Spearman correlations and multivariable regressions were used to examine whether resistin levels were associated with SLE, disease-specific and inflammatory markers, insulin resistance, and CAC. Results. In a multivariable linear regression model, a diagnosis of SLE was significantly associated with higher resistin levels independent of age, race, renal function, body mass index (BMI), high-sensitivity CRP (hsCRP), hypertension, diabetes, and steroid use. In SLE, resistin levels correlated positively with Systemic Lupus International Collaborating Clinics Damage Index, glomerular filtration rate (GFR), hsCRP, erythrocyte sedimentation rate, homocysteine, and disease duration (all p < 0.03). Resistin level did not correlate with markers of insulin resistance or body adiposity, including homeostatic model assessment or BMI. Resistin levels were significantly elevated in SLE cases with CAC compared to cases without CAC (16.58 vs 13.10 ng/ml, respectively; p = 0.04). In multivariate logistic regression, the association was not present after adjustment for age, race, and GFR. Conclusion. SLE was independently associated with higher resistin levels. Among subjects with SLE, higher resistin level correlated positively with renal dysfunction, inflammatory markers, and disease damage but not with insulin resistance or BMI. SLE cases with CAC had higher resistin levels than cases without CAC; however, this relationship was dependent on other established risk factors.

Quantification of key red blood cell folates from subjects with defined MTHFR 677C>T genotypes using stable isotope dilution liquid chromatography/mass spectrometry

Red blood cell (RBC) folate levels are established at the time of erythropoiesis and therefore provide a surrogate biomarker for the average folate status of an individual over the preceding four months. Folates are present as folylpolyglutamates, highly polar molecules that cannot be secreted from the RBCs, and must be converted into their monoglutamate forms prior to analysis. This was accomplished using an individuals plasma pteroylpolyglutamate hydrolase by lysing the RBCs in whole blood at pH 5 in the presence of ascorbic acid. Quantitative conversion of formylated tetrahydrofolate derivatives into the stable 5,10-methenyltetrahydrofolate (5,10-MTHF) form was conducted at pH 1.5 in the presence of [(13)C(5)]-5-formyltetrahydrofolate. The resulting [(13)C(5)]-5,10-MTHF was then used as an internal standard for the formylated forms of tetrahydrofolate that had been converted into 5,10-MTHF as well any 5,10-MTHF that had been present in the original sample. A stable isotope dilution liquid chromatography-multiple reaction monitoring/mass spectrometry method was validated and then used for the accurate and precise quantification of RBC folic acid, 5-methyltetrahydrofolate (5-MTHF), tetrahydrofolate (THF), and 5,10-MTHF. The method was sensitive and robust and was used to assess the relationship between different methylenetetrahydrofolate reductase (MTHFR) 677C>T genotypes and RBC folate phenotypes. Four distinct RBC folate phenotypes could be identified. These were classified according to the relative amounts of individual RBC folates as type I (5-MTHF >95%; THF <5%; 5,10-MTHF <5%), type II (5-MTHF <95%; THF 5% to 20%; 5,10-MTHF <5%), type III (5-MTHF >55%; THF >20%; 5,10-MTHF >5%), and type IV (5-MTHF <55%; THF >20%; 5,10-MTHF >5%).

Teaching about how doctors think: a longitudinal curriculum in cognitive bias and diagnostic error for residents

Background Trends in medical education have reflected the patient safety movements initial focus on systems. While the role of cognitive-based diagnostic errors has been increasingly recognised among safety experts, literature describing strategies to teach about this important problem is scarce. Methods 48 PGY-2 internal medicine residents participated in a three-part, 1-year curriculum in cognitive bias and diagnostic error. Residents completed a multiple-choice test designed to assess the recognition and knowledge of common heuristics and biases both before and after the curriculum. Results were compared with PGY-3 residents who did not receive the curriculum. An additional assessment in which residents reviewed video vignettes of clinical scenarios with cognitive bias and debiasing techniques was embedded into the curriculum. Results 38 residents completed all three parts of the curriculum and completed all assessments. Performance on the 13-item multiple-choice knowledge test improved post-curriculum when compared to both pre-curriculum performance (9.26 vs 8.26, p=0.002) and the PGY-3 comparator group (9.26 vs 7.69, p<0.001). All residents correctly identified at least one cognitive bias and proposed at least one debiasing strategy in response to the videos. Conclusions A longitudinal curriculum in diagnostic error and cognitive bias improved internal medicine residents’ knowledge and recognition of cognitive biases as measured by a novel assessment tool. Further study is needed to refine learner assessment tools and examine optimal strategies to teach clinical reasoning and cognitive bias avoidance strategies.

Readability and Suitability Assessment of Patient Education Materials in Rheumatic Diseases

Web‐based patient education materials and printed pamphlets are frequently used by providers to inform patients about their rheumatic disease. Little attention has been given to the readability and appropriateness of patient materials. The objective of this study was to examine the readability and suitability of commonly used patient education materials for osteoarthritis (OA), rheumatoid arthritis, systemic lupus erythematosus, and vasculitis.

A roadmap for education to improve the quality of care in gout

Purpose of reviewTo describe obstacles to optimum management of gout by primary care physicians and to propose educational interventions to improve care. Recent findingsIn the past, gout education has been hampered by infrequency of continuing medical education courses, loss of excitement for a disease in which therapies have not changed (until recently), insufficient evidence-based medicine, and the lack of motivation by physicians to re-learn this disease once in active practice. We identify 10 common myths that impede appropriate treatment of gout, identify gaps in evidence-based medicine that perpetuate those myths, and propose opportunities to improve education on these myths. It is through better gout-centered education that quality of care in gout can be enhanced. Residency may be one of the key points of intervention. As more evidence-based medicine publications address the optimum management of gout, national re-education can occur. More outreach by community rheumatologists to primary care physicians through educational programs and improved referral letters can help re-educate practitioners. Lastly, an often overlooked engine to change physician practices is consumer education, but current patient education programs are lacking. SummaryNovel education interventions for physician trainees, primary care physicians, and patients are proposed to improve the care of patients with gout.