Christopher J. Swearingen

RAPID3 (Routine Assessment of Patient Index Data 3), a Rheumatoid Arthritis Index Without Formal Joint Counts for Routine Care: Proposed Severity Categories Compared to Disease Activity Score and Clinical Disease Activity Index Categories

Objective To compare 4 categories (high, moderate, and low severity, and near-remission) of RAPID3 (Routine Assessment of Patient Index Data 3), an index without formal joint counts, which is scored in < 10 seconds to 4 categories of the DiseaseActivity Score (DAS28) and Clinical Disease Activity Index (CDAI) in patients with rheumatoid arthritis (RA). Methods All patients complete a Multidimensional Health Assessment Questionnaire (MDHAQ) at each visit. A physician/assessor 28-joint count and erythrocyte sedimentation rate (ESR) were completed in 285 patients with RA in usual care by 3 rheumatologists to score DAS28, CDAI, and RAPID3. RAPID3 includes the 3 MDHAQ patient self-report RA Core Data Set measures for physical function, pain, and patient global estimate. Proposed RAPID3 (range 0–10) severity categories of high (> 4), moderate (2.01–4), low (1.01–2), and near-remission (≤ 1) were compared to DAS (0–10) activity categories of high (> 5.1), moderate (3.21–5.1), low (2.61–3.2), and remission (≤ 2.6), and CDAI (0–76) categories of > 22, 10.1–22.0, 2.9–10.0, and ≤ 2.8. Additional RAPID scores, which add to RAPID3 a physician/assessor or patient self-report joint count and/or assessor global estimate, were also analyzed. Statistical significance was analyzed using Spearman correlations, cross-tabulations, and kappa statistics. Results All RAPID scores were correlated significantly with DAS28 and CDAI (rho > 0.65, p < 0.001). Overall, 78%–84% of patients who met DAS28 or CDAI moderate/high activity criteria met similar RAPID severity criteria, and 68%–77% who met DAS28 or CDAI remission/low activity criteria also met similar RAPID criteria. RAPID3 was as informative as other indices. Conclusion RAPID3 provides a feasible, informative quantitative index for busy clinical settings.

Reproducibility of musculoskeletal ultrasound for determining monosodium urate deposition: concordance between readers.

Criteria for sonographic diagnosis of monosodium urate (MSU) crystal deposition have been developed, but the interreader reproducibility of this modality is not well established. We therefore assessed agreement using a systematic approach.

RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): Agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories, scored in five versus more than ninety seconds

To compare the Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) with the Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and individual core data set measures for correlations, agreement of activity levels, and time to score.

Hemolysis during cardiac extracorporeal membrane oxygenation: a case-control comparison of roller pumps and centrifugal pumps in a pediatric population.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy, which has been used for the support of children with a broad range of diseases. Two pumps of differing mechanisms have been used to generate the extracorporeal flow: roller-head pumps and centrifugal pumps. Seven patients supported during ECMO with Levitronix Centrimag (Centrimag group [CG]) were matched to 14 patients supported with Stockert-Shiley SIII (Stockert-Shiley group [SSG]) at a single institution from July 2007 to July 2009. We hypothesized that hemolysis as measured by plasma-free hemoglobin (PFH) is elevated in the SSG versus the CG during cardiac ECMO. Categorical data were analyzed using Fishers exact test. Plasma-free hemoglobin differences between groups were analyzed using both Wilcoxon rank sum and beta regression. Overall, SSG patients had two times the odds of having a higher PFH than CG patients adjusting for repeated measures (odds ratio [OR] = 1.96, 95% confidence interval [CI]: [1.15–3.34], p < 0.014). Differences between circuit failure in the first 168 hours did not reach statistical significance (1/7 CG vs. 7/14 SSG; p = 0.174). In this population of cardiac patients requiring ECMO support, more hemolysis occurred in the SSG, a roller-head pump supported group, when compared with the CG, a centrifugal pump supported group. Differences in circuit life did not reach statistical significance. This pilot study contrasts with past studies, which have demonstrated more hemolysis occurring with centrifugal pumps when compared with roller-head pumps.

Efficacy of prednisone 1–4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial

Objective: A randomised double-blind placebo controlled withdrawal clinical trial of prednisone versus placebo in patients with rheumatoid arthritis (RA), treated in usual clinical care with 1–4 mg/day prednisone, withdrawn to the same dose of 1 mg prednisone or identical placebo tablets. Methods: All patients were from one academic setting and all trial visits were conducted in usual clinical care. Patients were taking stable doses of 1–4 mg prednisone with stable clinical status, documented quantitatively by patient questionnaire scores. The protocol included three phases: (1) equivalence: 1–4 study prednisone 1 mg tablets taken for 12 weeks to ascertain their efficacy compared with the patient’s usual tablets before randomisation; (2) transfer: substitution of a 1 mg prednisone or identical placebo tablet every 4 weeks (over 0–12 weeks) to the same number as baseline prednisone; (3) comparison: observation over 24 subsequent weeks taking the same number of either placebo or prednisone tablets as at baseline. The primary outcome was withdrawal due to patient-reported lack of efficacy versus continuation in the trial for 24 weeks. Results: Thirty-one patients were randomised, 15 to prednisone and 16 to placebo, with three administrative discontinuations. In “intent-to-treat” analyses, 3/15 prednisone and 11/16 placebo participants withdrew (p = 0.03). Among participants eligible for the primary outcome, 3/13 prednisone and 11/15 placebo participants withdrew for lack of efficacy (p = 0.02). No meaningful adverse events were reported, as anticipated. Conclusion: Efficacy of 1–4 mg prednisone was documented. Evidence of statistically significant differences with only 31 patients may suggest a robust treatment effect.

Assessing dyspnea and its impact on patients with connective tissue disease-related interstitial lung disease

RATIONALE Dyspnea is the cardinal symptom in patients with any type of interstitial lung disease (ILD); however, there are limited data on dyspnea among patients with connective tissue disease-related ILD (i.e., CTD-ILD). OBJECTIVES To explore the utility of two dyspnea instruments (the University of California San Diego Shortness of Breath Questionnaire [UCSD] and the Dyspnea-12 [D-12]) and use their scores to examine the impact of dyspnea on the lives of patients with CTD-ILD. METHODS Subjects were enrolled from the Autoimmune Lung Database (ALD) at National Jewish Health. Chronbachs alpha was used to assess the internal consistency reliability of the two dyspnea questionnaires. We used the Multi-Dimensional Health Assessment Questionnaire [MDHAQ] as a measure of health status and examined associations between health status and dyspnea by using Pearson product-moment correlation and linear regression. RESULTS The internal consistency reliability of each of the two dyspnea questionnaires was excellent (alpha=0.9 for each). There were significant correlations between either of the two dyspnea measures and MDHAQ components. While controlling for ILD severity, dyspnea as assessed by the UCSD, was a significant predictor of physical function (p=0.04), psychological well-being (p=0.005), and fatigue (p=0.02); dyspnea as assessed the D-12, was a significant predictor of psychological well-being (p=0.01) and global status (p=0.03). CONCLUSION Dyspnea significantly affects day-to-day functioning and global well-being in patients with CTD-ILD. The UCSD and D-12 yield meaningful information about these patients that measures of pulmonary physiology cannot. Future studies should examine other performance characteristics of these self-report measures in patients with CTD-ILD.

A multi-dimensional health assessment questionnaire (MDHAQ) and routine assessment of patient index data (RAPID3) scores are informative in patients with all rheumatic diseases.

Although indices have been developed for many rheumatic diseases in usual care, they are rarely used in usual care. In most visits to rheumatologists, the only quantitative data collected are laboratory tests. Patient history data often are more important in management of patients with rheumatic diseases than other diseases. A two-page multidimensional health assessment questionnaire (MDHAQ) can be completed by the patient in 5 to 10 minutes and reviewed by the physician in 10 seconds, with RAPID3 scored in 5 to 10 seconds. The MDHAQ is useful in rheumatic diseases, to improve management documentation and outcomes. MDHAQ data for physical function, pain, global status, and RAPID3 scores appear preferable to no quantitative data.

Utility of the new rheumatoid arthritis 2010 ACR/EULAR classification criteria in routine clinical care

Objectives The new 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been designed to classify early onset RA, but has not been studied to identify RA in patients with arthritis seen in routine clinical care where correct ‘classification’ of patients, when they are not selected for having RA would be important. Design Prospective, consecutive patients cohort. Setting Outpatient clinic of a university rheumatology centre. Participants A total of 126 patients with joint symptoms were consecutively recruited. Interventions The ACR/EULAR RA criteria were applied, with questions followed by a targeted musculoskeletal exam. The gold standard for the diagnosis of RA was the primary rheumatologists diagnosis. Primary outcome measure Number of patients with non-RA diagnosis who were classified as having RA by the new classification criteria. Results The sensitivity and specificity of the 2010 criteria in classifying RA were 97% and 55%, respectively, compared with the 1987 RA criteria which were 93% and 76%, respectively. The 2010 criteria as applied to this group of patients had a poorer positive predictive (44% vs 61%) and a similar negative predictive value (98% vs 97%) compared with the 1987 criteria. More specifically, 66.7% of systemic lupus erythematosus patients, 50% of osteoarthritis, 37.5% of psoriatic arthritis and 27.2% of others fulfilled the new criteria and could have been classified as RA. Conclusions In this, we believe, the first study to examine the new 2010 ACR/EULAR RA criteria among consecutive patients seen in routine care, we found the criteria to have low specificity, and therefore incorrectly label those as having RA when, in fact, they may have a different type of inflammatory arthritis. Physicians need to be aware of this when applying the new criteria for classifying their patients for any purpose.

Ketamine as a neuroprotective and anti-inflammatory agent in children undergoing surgery on cardiopulmonary bypass: a pilot randomized, double-blind, placebo-controlled trial.

Objective: Infants are potentially more susceptible to cell death mediated via glutamate excitotoxicity attributed to cardiopulmonary bypass. We hypothesized that ketamine, via N-methyl D-aspartate receptor blockade and anti-inflammatory effects, would reduce central nervous system injury during cardiopulmonary bypass. Methods: We randomized 24 infants, without chromosomal abnormalities, to receive ketamine (2 mg/kg, n = 13) or placebo (saline, n = 11) before cardiopulmonary bypass for repair of ventricular septal defects. Plasma markers of inflammation and central nervous system injury were compared at the end of surgery, and 6, 24, and 48 hrs after surgery. Magnetic resonance imaging and spectroscopy before cardiopulmonary bypass and at the time of hospital discharge were performed in a subset of cases and controls (n = 5 in each group). Cerebral hemodynamics were monitored postoperatively using near-infrared spectroscopy, and neurodevelopmental outcomes were assessed using Bayley Scales of Infant Development-II before and 2–3 wks after surgery. Results: Statistically significant differences were noted in preoperative inspired oxygen levels, intraoperative cooling and postoperative temperature, respiratory rate, platelet count, and bicarbonate levels. The peak concentration of C-reactive protein was lower in cases compared to controls at 24 hrs (p = .048) and 48 hrs (p = .001). No significant differences were noted in the expression of various cytokines, chemokines, S100, and neuron-specific enolase between the cases and controls. Magnetic resonance imaging with spectroscopy studies showed that ketamine administration led to a significant decrease in choline and glutamate plus glutamine/creatine in frontal white matter. No statistically significant differences occurred between pre- and postoperative Bayley Scales of Infant Development-II scores. Conclusions: We did not find any evidence for neuroprotection or neurotoxicity in our pilot study. A large, adequately powered randomized control trial is needed to discern the central nervous system effect of ketamine on the developing brain. brain. Trial Registration: The trial is registered at www.ClinicalTrials.gov, NCT00556361.

Caffeine and Progression of Parkinson Disease

Objective: Caffeine use is negatively associated with the risk of developing Parkinson disease (PD) and is protective in animal models of PD, but the relationship between caffeine intake and rate of progression of PD is unknown. We assessed this relationship using data from 2 recent clinical trials of PD. Methods: Data were ascertained from 2 recent 1-year clinical trials that together included 413 early PD subjects who did not require symptomatic therapy at the time of study entry. Exploratory analyses compared caffeine intake with rate of progression of PD, as measured by either the likelihood of progression to the point of requiring symptomatic therapy or by change in the total Unified Parkinson Disease Rating Scale score. Results: Rate of progression of PD did not differ significantly between those in the highest and lowest quartiles for caffeine use for either of the primary measures or for secondary analyses of changes in scores on the motor or activities of daily living subsections of the Unified Parkinson Disease Rating Scale. Other secondary analyses yielded variable results. Conclusions: These data do not reveal a consistent relationship between caffeine intake and rate of progression of PD by these measures, although a larger study is required for sufficient power to more fully assess this relationship.