Nasim A. Khan

Serum metabolomic profiles from patients with acute kidney injury: A pilot study

Low sensitivity of current clinical markers (serum creatinine and blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients.

Reevaluation of the Role of Duration of Morning Stiffness in the Assessment of Rheumatoid Arthritis Activity

Objective. To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. Methods. We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 ≤ 3.2) RA. Mixed-effect analysis of covariance (ANCOVA) models were used to assess the utility of adding MS duration to Routine Assessment of Patient Index Data (RAPID)3, a PRO index based on physical function, pain, and general health (GH), in predicting the 3-variable DAS28 (DAS28v3). Results. MS duration had moderate correlation (r = 0.41–0.48) with pain, Health Assessment Questionnaire, and GH; and weak correlation (r = 0.23–0.39) with joint counts and erythrocyte sedimentation rate. MS duration differed significantly among patients with different RA activity (p < 0.001). The area under the ROC curve of 0.74 (95% CI 0.72–0.75) showed moderate ability of MS duration to differentiate clinically active from less active RA. ANCOVA showed significant interactive effects between RAPID3 and the MS duration categories (p = 0.0005) in predicting DAS28v3. The effect of MS was found to be clinically important in patients with the low RAPID3 scores (< 6) in whom the presence of MS may indicate clinically active disease (DAS28v3 > 3.2). Conclusion. MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

Methemoglobinemia Induced by Topical Anesthesia: A Case Report and Review

Topical anesthetic drugs are widely used by clinicians during hospital and outpatient procedures and are also available to the public in a variety of over-the-counter preparations. Although generally safe, they may cause potentially life-threatening methemoglobinemia. We describe a patient who developed repeated episodes of severe methemoglobinemia after administration of topical Cetacaine spray (a proprietary mixture of benzocaine, tetracaine, and butamben) employed for pharyngeal anesthesia before endotracheal intubation, and briefly review the etiology and pathophysiology of this disorder. Cautious interpretation of oxyhemoglobin saturation values obtained by pulse oximetry or estimated from arterial blood gas analysis is crucial lest the diagnosis of severe methemoglobinemia and the resulting hypoxemia are overlooked. If necessary, the condition is usually readily corrected by intravenous administration of methylene blue.

Patient's global assessment of disease activity and patient's assessment of general health for rheumatoid arthritis activity assessment: are they equivalent?

Objectives To assess (A) determinants of patients global assessment of disease activity (PTGL) and patients assessment of general health (GH) scores of rheumatoid arthritis (RA) patients; (B) whether they are equivalent as individual variables; and (C) whether they may be used interchangeably in calculating common RA activity assessment composite indices. Methods Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lins coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using κ statistics. Results Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of −4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95–0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement (κ statistics 0.75–0.84) in RA activity state classification for all three indices. Conclusions PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.

Diastolic Dysfunction in Rheumatoid Arthritis: A Meta-Analysis and Systematic Review

To determine if the prevalence of diastolic dysfunction is increased in rheumatoid arthritis (RA) patients.

Association of industry funding with the outcome and quality of randomized controlled trials of drug therapy for rheumatoid arthritis

OBJECTIVE To assess the association of industry funding with the characteristics, outcome, and reported quality of randomized controlled trials (RCTs) of drug therapy for rheumatoid arthritis (RA). METHODS The Medline and Cochrane Central Register of Controlled Trials databases were searched to identify original RA drug therapy RCTs published in 2002-2003 and 2006-2007. Two reviewers independently assessed each RCT for the funding source, characteristics, outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or not positive), and reporting of methodologic measures whose inadequate performance may have biased the assessment of treatment effect. RCTs that were registered at ClinicalTrials.gov and completed during the study years were assessed for publication bias. RESULTS Of the 103 eligible RCTs identified, 58 (56.3%) were funded by industry, 19 (18.4%) were funded by nonprofit sources, 6 (5.8%) had mixed funding, and funding for 20 (19.4%) was not specified. Industry-funded RCTs had significantly more study centers and subjects, while nonprofit agency-funded RCTs had longer duration and were more likely to study different treatment strategies. Outcome could be assessed for 86 (83.5%) of the 103 RCTs studied. The funding source was not associated with a higher likelihood of positive outcomes favoring the sponsored experimental drug (75.5% of industry-funded RCTs had a positive outcome, compared with 68.8% of non-industry-funded RCTs, 40% of RCTs with mixed funding, and 81.2% of RCTs for which funding was not specified). Industry-funded RCTs showed a trend toward a higher likelihood of nonpublication (P=0.093). Industry-funded RCTs were more frequently associated with double-blinding, an adequate description of participant flow, and performance of an intent-to-treat analysis. CONCLUSION Industry funding was not associated with a higher likelihood of positive outcomes of published RCTs of drug therapy for RA, and industry-funded RCTs performed significantly better than non-industry-funded RCTs in terms of reporting the use of some key methodologic quality measures.

Body mass index and the rheumatoid arthritis swollen joint count: An observational study

Obesity is a prevalent condition and a serious health concern. The relationship between obesity and rheumatoid arthritis (RA) disease activity and severity has not been adequately examined, and there are concerns that periarticular adipose tissue may reduce the utility of the joint examination.

Smoking cessation advice by rheumatologists: results of an international survey

OBJECTIVE The aim of this study was to understand practices regarding smoking cessation among rheumatologists for patients with inflammatory rheumatic diseases. METHODS A survey was sent to the rheumatologists participating in the multinational Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) group. The survey inquired about the clinical practice characteristics and practices regarding smoking cessation (proportion of smokers with inflammatory rheumatic diseases given smoking cessation advice, specific protocols and written advice material, availability of dedicated smoking cessation clinic). RESULTS Rheumatologists from 44 departments in 25 countries (16 European) completed the survey. The survey involved 395 rheumatologists, of whom 25 (6.3%) were smokers, and 199 nurses for patient education, of whom 44 (22.1%) were smokers. Eight departments (18.1 %) had a specific protocol for smoking cessation; 255 (64.5%) rheumatologists reported giving smoking cessation advice to all or almost all smokers with inflammatory diseases. In a regression model, early arthritis clinics (P = 0.01) and high gross domestic product countries (P = 0.001) were both independently associated with advice by the rheumatologist. Nurse gives advice to most patients in 11 of the 36 (30.5%) departments with nurses for patient education. CONCLUSION Advice for smoking cessation within rheumatology departments is not homogeneous. In half of the departments, most doctors give advice to quit smoking to all or almost all patients with inflammatory diseases. However, only one in five departments have a specific protocol for smoking cessation. Our data highlight the need to improve awareness of the importance of and better practice implementation of smoking cessation advice for inflammatory rheumatic disease patients.

Isolated eosinophilic mesenteric vasculitis with extensive thrombosis and splenic infarction in a 13-year-old boy

There are no generally accepted diagnostic criteria for primary systemic vasculitis, and the application of classification as diagnostic criteria is not feasible and may even be misleading. We report a case of a 13-year-old boy with acute abdomen who was found to have isolated eosinophilic mesenteric vasculitis with extensive thrombosis and splenic infarction. All serological tests were negative, including antineutrophil cytoplasmic antibody. The vasculitis had been successfully controlled with surgical intervention, steroid, and cyclophosphamide therapy. This may be an atypical presentation of Churg–Strauss syndrome.

Randomized controlled trials of rheumatoid arthritis registered at ClinicalTrials.gov: what gets published and when.

To examine characteristics associated with the publication and timeliness of publication of randomized controlled trials (RCTs) of treatment of rheumatoid arthritis (RA).