Marco Di Carlo

Extent and distribution of CPP deposits in patients affected by calcium pyrophosphate dihydrate deposition disease: an ultrasonographic study

Objective To assess the extent of calcium pyrophosphate dihydrate (CPP) crystal deposition and the distribution of affected sites, using ultrasonography (US), in patients affected by CPP deposition disease (CPPD). Patients and methods 42 consecutive patients affected by definite CPPD according to the McCarty criteria were enrolled in the study. All patients underwent an US examination of metacarpophalangeal joints of II, III, IV and V fingers of both hands, wrists and knees, Achilles’ tendons and plantar fascia looking for CPP deposits. A dichotomous score for presence/absence of CPP and a semiquantitative score for extent of deposits (0–3: 0, absent; 1, 1–2 spots; 2, more than two spots covering <50% of the structure; 3, deposits covering >50% of the structure) were assigned to each site examined. A site distribution score (total number of affected sites) was then calculated as well as an extent score equal to the sum of the extent scores of all sites. Results The mean involvement in our patients was 4.7 sites (SD±1.7, range 2–8 sites). The knee was the most affected, site (41 of 42) followed by the wrist (at least one in 37 patients) the Achilles’ tendons (23 patients), plantar fascia (11 patients) and metacarpophalangeal joints (four patients). The highest mean values of the extent score were in the menisci, followed by the hyaline cartilage of the femoral condyles and the entheses. Conclusions The deposition of CPP crystals involves at least two sites with a mean of four sites involved in most patients affected by CPPD and is therefore an oligoarticular or polyarticular disease.

The 12-item Psoriatic Arthritis Impact of Disease Questionnaire: Construct Validity, Reliability, and Interpretability in a Clinical Setting

Objective. To study, in a real-life setting, the construct validity, the reliability, and the interpretability of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire in patients with psoriatic arthritis (PsA). Methods. In 144 consecutive patients with PsA (81 men and 63 women, mean age of 51.4 ± 12.8 yrs, and 77 receiving biologic treatment), the PsAID-12 and other patient-reported outcomes (PRO) were collected, such as the Dermatology Life Quality Index. Each patient underwent articular and skin assessment. Results. Construct validity: Factor analysis revealed a 2-factor result defined as the PsAID Symptom Score and the PsAID Skin Score. In determining convergent validity, significant correlations were found between the PsAID-12 and the clinical Disease Activity index for Psoriatic Arthritis (cDAPSA; ρ = 0.867, p < 0.0001). Multivariable analysis showed that the PsAID-12 is determined by the articular disease activity (cDAPSA, p < 0.0001), severity of psoriasis (PsO; physician’s global assessment, p < 0.0001), and the presence of a coexisting fibromyalgia (FM; p < 0.0001). Reliability: Cronbach’s alpha coefficient was 0.93 for the total PsAID-12. Interpretability: Applying the cDAPSA categorization of disease activity states, the PsAID-12 cutoff values resulted in 1.4 between remission and low disease activity (LDA), 4.1 between LDA and moderate disease activity (MDA), and 6.7 between MDA and high disease activity. Conclusion. The PsAID-12 is an excellent PRO to evaluate the effect of PsA. It should be carefully handled in patients with coexisting FM.

Computer-Aided Tomographic Analysis of Interstitial Lung Disease (ILD) in Patients with Systemic Sclerosis (SSc). Correlation with Pulmonary Physiologic Tests and Patient-Centred Measures of Perceived Dyspnea and Functional Disability

Objectives This study was designed (a) to evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CaM) system in patients with systemic sclerosis (SSc),—related interstitial lung disease (SSc-ILD), (b) to investigate the relationship between physiologic parameters (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO]), patient-centred measures of dyspnea and functional disability and CaM and visual reader-based (CoVR) methods, and (c) to identify potential surrogate measures from quantitative and visual HRCT measurement. Methods 126 patients with SSc underwent chest radiography, HRCT and PFTs. The following patient-centred measures were obtained: modified Borg Dyspnea Index (Borg score), VAS for breathing, and Health Assessment Questionnaire-Disability Index (HAQ-DI). HRCT abnormalities were scored according to the conventional visual reader-based score (CoVR) and by a CaM. The relationships among the HRCT scores, physiologic parameters (FVC and DLCO, % predicted) results and patient-centred measures, were calculated using linear regression analysis and Pearson’s correlation. Multivariate regression models were performed to identify the predictor variables on severity of pulmonary fibrosis. Results Subjects with limited cutaneous SSc had lower HAQ-DI scores than subjects with diffuse cutaneous SSc (p <0.001). CaM and CoVR scores were similar in the 2 groups. In univariate analysis, a strong correlation between CaM and CoVR was observed (p <0.0001). In multivariate analysis the CaM and CoVR scores were predicted by DLco, FVC, Borg score and HAQ-DI. Age, sex, disease duration, anti-topoisomerase antibodies and mRSS were not significantly associated with severity of pulmonary fibrosis on CaM- and CoVR methods. Conclusions Although a close correlation between CaM score results and CoVR total score was found, CaM analysis showed a more significant correlation with DLco (more so than the FVC), patient-centred measures of perceived dyspnea and functional disability. Computer-aided tomographic analysis is computationally efficient, and in combination with physiologic and patient-centred measures, it could allow a means for accurately assessing and monitoring the disease progression or response to therapy.

The Psoriatic Arthritis Impact of Disease 12-item questionnaire: equivalence, reliability, validity, and feasibility of the touch-screen administration versus the paper-and-pencil version.

Background Over the last few years, there has been a shift toward a more patient-centered perspective of the disease by adopting patient-reported outcomes. Touch-screen formats are increasingly being used for data collection in routine care and research. Objectives The aim of this study is to examine the equivalence, reliability, validity and respondent preference for a computerized touch-screen version of the Psoriatic Arthritis Impact of Disease 12-item (PsAID-12) questionnaire in comparison with the original paper-and-pencil version, in a cohort of patients with psoriatic arthritis (PsA). Methods One hundred and fifty-nine patients with PsA completed both the touch screen- and the conventional paper-and-pencil administered PsAID-12 questionnaire. Agreement between formats was assessed by intraclass correlation coefficients. Spearman’s rho correlation coefficient was used to test convergent validity of the touch screen format of PsAID-12, while receiver operating characteristic curve analysis was performed to test discriminant validity. In order to assess the patient’s preference, the participants filled in an additional questionnaire. The time taken to complete both formats was measured. Results A high concordance between the responses to the two modes of the PsAID-12 tested was found, with no significant mean differences. Intraclass correlation coefficients between data obtained for touch-screen and paper versions ranged from 0.801 to 0.962. There was a very high degree of correlation between the touch-screen format of PsAID-12 and composite disease activity indices (all at a P level <0.0001), Health Assessment Questionnaire, and Physician Assessment of disease activity. The discriminatory power of the touch-screen format of PsAID-12, assessed using the minimal disease activity – Outcome Measurements in Rheumatology Clinical Trials criteria, was very good, with an area under the receiver operating characteristic curve of 0.937 and a resulting cutoff value of 2.5. The touch-screen questionnaire was readily accepted and preferred. The mean time spent for completing the questionnaire on touch screen was 2 minutes and on paper was 2.7 minutes. Conclusion The touch-screen mode of administration of PsAID-12 can be a feasible and suitable alternative to the paper-and-pencil mode for the assessment of patients with PsA.

Patient Acceptable Symptom State in Self-Report Questionnaires and Composite Clinical Disease Index for Assessing Rheumatoid Arthritis Activity: Identification of Cut-Off Points for Routine Care

Objective. To provide information on the value of Patient Acceptable Symptom State (PASS) in rheumatoid arthritis (RA) by the identification of PASS thresholds for patient-reported outcomes (PROs) composite scores. Methods. The characteristics of RA patients with affirmative and negative assignment to PASS were compared. Contributors to physician response were estimated by logistic regression models and PASS thresholds by the 75th percentile and receiver-operating characteristic (ROC) curve methods. Results. 303 RA patients completed the study. All PROs were different between the PASS (+) and PASS (−) groups (p < 0.0001). The thresholds with the 75th percentile approach were 2.0 for the RA Impact of Disease (RAID) score, 2.5 for the PRO-CLinical ARthritis Activity (PRO-CLARA) index, and 1.0 for the Recent-Onset Arthritis Disability (ROAD) questionnaire. The cut-off values for Clinical Disease Activity Index (CDAI) were in the moderate range of disease activity. Assessing the size of the logistic regression coefficients, the strongest predictors of PASS were the disease activity (p = 0.0007) and functional state level (0.006). Conclusion. PASS thresholds were relatively high and many patients in PASS had moderate disease activity states according to CDAI. Factors such as disease activity and physical function may influence a negative PASS.

Ultrasound Learning Curve in Gout: A Disease‐Oriented Training Program

To describe the learning curve of rheumatologists with limited experience using ultrasound (US) attending an intensive disease‐oriented training program focusing on the skills required to obtain and interpret US signs of monosodium urate (MSU) crystal deposits in joint and periarticular tissues.

Interreader Reliability in Assessment of Nailfold Capillary Abnormalities by Beginners: Pilot Study of an Intensive Videocapillaroscopy Training Program

Objective. To test the learning curve of rheumatologists with different experience in videocapillaroscopy (VCP) attending an intensive training program focused on interpretation of the main capillary nailfold abnormalities, the scleroderma (systemic sclerosis, SSc) pattern, and the normal pattern, and to determine their interreader agreement with an experienced investigator. Methods. Five investigators (1 senior, 1 junior, and 3 beginners) participated in the exercise. The study was composed of 2 steps. First, an independent investigator selected representative VCP images of normal patterns and capillary abnormalities. The second step included the training program, which ran 4 hours per day for 7 days. The senior rheumatologist taught investigators to recognize and interpret the normal pattern, the capillary abnormalities, and the different types of SSc pattern. These abnormalities were considered: homogeneously enlarged capillaries, giant capillaries, irregularly enlarged capillaries, microhemorrhages, neoangiogenesis, avascular areas, and capillary density. Results. A total of 300 VCP images were read from all the investigators. Both κ values and overall agreement percentages of qualitative and quantitative assessments showed progressive improvement from poor to excellent from the beginning to the end of the exercise. The sensitivity and specificity of the participants in the assessment of SSc pattern at the last lecture session were high. Conclusion. Our pilot study suggests that after an intensive 1-week training program, novice investigators with little or no experience in VCP are able to interpret the main capillary abnormalities and SSc pattern and to achieve good interreader agreement rates.

Identifying the symptom and functional domains in patients with fibromyalgia: results of a cross-sectional Internet-based survey in Italy

Objective The aims of this cross-sectional study were to investigate the usefulness of using an Internet survey of patients with fibromyalgia in order to obtain information concerning symptoms and functionality and identify clusters of clinical features that can distinguish patient subsets. Methods An Internet website has been used to collect data. Fibromyalgia Impact Questionnaire Revised version, self-administered Fibromyalgia Activity Score, and Self-Administered Pain Scale were used as questionnaires. Hierarchical agglomerative clustering was applied to the data obtained in order to identify symptoms and functional-based subgroups. Results Three hundred and fifty-three patients completed the study (85.3% women). The highest scored items were those related to sleep quality, fatigue/energy, pain, stiffness, degree of tenderness, balance problems, and environmental sensitivity. A high proportion of patients reported pain in the neck (81.4%), upper back (70.1%), and lower back (83.2%). A three-cluster solution best fitted the data. The variables were significantly different (P<0.0001) among the three clusters: cluster 1 (117 patients) reflected the lowest average scores across all symptoms, cluster 3 (116 patients) the highest scores, and cluster 2 (120 patients) captured moderate symptom levels, with low depression and anxiety. Conclusion Three subgroups of fibromyalgia samples in a large cohort of patients have been identified by using an Internet survey. This approach could provide rationale to support the study of individualized clinical evaluation and may be used to identify optimal treatment strategies.

Validity of the rheumatoid arthritis impact of disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis

OBJECTIVES To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states. METHODS A total of 622 RA patients from an European database have been included. Cross-validation was based on assessment of convergent and discriminant validity. Optimal cut-offs were determined against external criteria by calculating the respective 25th and 75th percentiles mean values of RAID. External criteria included definitions for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA), cut-offs of the 28-joint disease activity score-C-reactive protein (DAS28-CRP) score. RESULTS The RAID showed a moderate degree of correlation with respect to DAS28-CRP (rho=0.417; P<0.0001). The receiver operating characteristic (ROC) curves to discriminate the ability of RAID to distinguish patients with active and non-active disease was very good with an area under the curve (AUC) of 0.847 (95% confidence interval [CI]: 0.816 to 0.878; P<0.0001). Based on the distributions of RAID in the different disease activity groups, we propose the following cut-off values for REM: RAID ≤3; for LDA: RAID >3 and ≤4; for MDA: RAID >4 and ≤6; for HDA: RAID >6. Mean RAID differed significantly between patients classified as REM, LDA, MDA or HDA (P=0.001). CONCLUSIONS The cut-offs revealed good measurement characteristics in cross-validation analysis, had great discriminatory performance in distinguishing patients with different levels of disease activity and are suited for widespread use in everyday practice application and research.

The DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire: development and preliminary testing of a new tool to screen patients with inflammatory bowel disease for the presence of spondyloarthritis

To develop and to test in a preliminary way a new self-administered screening tool, called DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire, in patients suffering from inflammatory bowel disease (IBD) not previously diagnosed as having a spondyloarthritis (SpA). DETAIL questionnaire was realized through the interrogation of 95 experts. They were asked to rate the importance of a list of items, derived from a review of the referral models of SpA, to detect the SpA manifestations in IBD patients. The six top-rated items composed the questionnaire, tested in IBD patients not already diagnosed having a SpA. One-hundred and twenty-eight patients were tested with the DETAIL questionnaire in the gastroenterology setting. After the rheumatologic assessment, in 21 (16.4%) subjects was diagnosed a SpA according to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. Of the six items of the DETAIL questionnaire, the best positive likelihood ratio (LR+) was found in item 2 (LR+ 3.82), exploring dactylitis, and in item 6 (LR+ 3.82) and item 5 (LR+ 3.40), two questions exploring inflammatory low back pain. Enthesitis (item 3—LR+ 2.87) and peripheral synovitis (item 1 – LR+ 2.81) gave similar results, while item 4, exploring the duration of low back pain, resulted in the worst performance (LR+ 1.99). Three of the six items answered in affirmative way gave a post-test probability ≥ 75%. The presence of a fibromyalgia represents a major confounder. The DETAIL questionnaire showed good screening properties that need to be confirmed in broader cohorts.