Evaluator Global Assessment Research Articles

Emerging Role of Interleukin-38 (IL-38) in the Development of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1β, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1β significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1β among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1β exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Efectividad de un modelo de tratamiento integral de la osteoartrosis

Introduction. Osteoarthrosis (OA) is the most frequent degenerative joint disease causing a significant social burden and being a frequent cause of disability. It also affects the mental health of patients and increases health care costs, including costs of hospitalization or admission to emergency services. The most deteriorated joints are the knees, hands, hips, and spine; above all among female patients. Obesity is the main risk factor. Despite the international recommendations, comprehensive patient management is rare and most therapeutic interventions are isolated and focused on the administration of non-steroidal anti-inflammatory drugs (NSAID), viscosupplementation, or intra-articular administration of corticosteroids. Objective. The objective of this non-comparative retrospective study was to test the effectiveness of a comprehensive medical treatment (CMT) model for OA that has been implenting in Mexico since 2006. Material and Methods. To determine the OA improvement in the patient receiving a CMT scheme that includes phytopharmaceuticals, rehabilitation, nutritional intervention, patient education, and a telephone attention program, the consumption of traditional medicines (NSAID) was compared before and after the intervention and clinimetrically measuring the visual analog evaluation, number of painful joints, number of swollen joints, evaluation global assessment of the disease by the patient, global assessment of the disease by the treating physician, muscle strength, Health Assessment Questionnaire, and adherence to treatment. Results. Approximately 18% (17.92%) of the patients in the sample were taking two or more medications at the beginning of the study; at the end, only 2.79% took them. The proportion of patients with no drug, monotherapy and combination of drugs and/or supplements is significant between the initial visit and the final visit. In the clinimetric domain, a statistically significant decrease (p> 0.01) was found between the value of the initial visit and the final visit. The number of painful joints and swollen joints from the initial visit to the final visit decreased statistically significantly. The global assessment of the disease by the patient from the initial visit to the final visit decreased statistically significantly. Discussion. CMT with periodic monitoring, phytopharmaceutical patient education, nutritional intervention, rehabilitation, and a telephone service program is effective for the control of osteoarthritis.

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis.

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms. This paper examines the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), CFS-like (Fibro-fatigue Scale) symptoms and immune–inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylcer-amide (CD17) in RA. The serum biomarkers were assayed in 118 RA and 50 healthy controls. Results were analyzed using the new precision nomothetic psychiatry approach. We found significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tender and swollen joints, and patient and evaluator global assessment scores. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning psychopathology and RA symptoms was explained by immune–inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. We constructed a new endophenotype class comprising patients with very high immune–inflammatory markers, CD17, RA, affective and CF-like symptoms, and tobacco use disorder. We extracted a reliable and replicable latent vector (pathway phenotype) from immune data, psychopathology, and RA-severity scales. Depression, anxiety, and CFS-like symptoms due to RA are manifestations of the phenome of RA and are mediated by the effects of the same immune–inflammatory, autoimmune, and other pathways that underpin the pathophysiology of RA.

Pain catastrophizing hinders Disease Activity Score 28 – erythrocyte sedimentation rate remission of rheumatoid arthritis in patients with normal C‐reactive protein levels

This study aimed to assess the relationship between pain catastrophizing and achievement of 28-joint Disease Activity Score-defined remission of rheumatoid arthritis (RA), considering the presence or absence of systemic inflammation, and to evaluate associated factors for pain catastrophizing. This cross-sectional study included 421 RA outpatients. The relationship between pain catastrophizing and remission was analyzed by adjusting several confounding factors. Univariable and multivariable analyses were performed to determine the relationship between pain catastrophizing and RA-related factors, comorbidities, and lifestyle habits. The prevalence of pain catastrophizing was 26%. Pain catastrophizing was negatively associated with remission (odds ratio 0.62, 95% confidence interval 0.38-1.00, P=.048). A multinomial logistic analysis showed that the presence of pain catastrophizing was an independent factor that was negatively correlated with the achievement of remission in the absence of systemic inflammation (odds ratio 0.51, 95% confidence interval 0.28-0.93, P=.029). Factors associated with elevated ratings on the Pain Catastrophizing Scale were a history of falls within the past year, a Health Assessment Questionnaire score >0.5, and smoking habit. Further, patients' subjective symptoms, including patient global assessment minus evaluator global assessment values ≥20 and high tender joint count minus swollen joint counts, were associated with elevated pain catastrophizing. Pain catastrophizing is a major obstacle to achieving remission in RA patients with normal C-reactive protein levels. Advanced physical disability, smoking habit, and history of falls were associated with pain catastrophizing, in addition to patients' subjective symptoms.

Depression, Anxiety, and Chronic Fatigue Symptoms in Acute Rheumatoid Arthritis Are Associated With Immune-Inflammatory, Autoimmune, Endogenous Opioid System and Lactosylceramide Signaling Pathways: A Nomothetic Network Approach

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms. To examine the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), and CFS-like (Fibro-fatigue Scale) symptoms and immune-inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylceramide in RA. Serum biomarkers were assayed in RA patients with (n=59) and without (n=59) increased psychopathology (PP) and 50 healthy controls. There were highly significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tenders and swollen joints, and patient and evaluator global assessment scores. A common latent vector (reflective model) could be extracted from the PP and RA-severity scales, which showed excellent psychometric properties. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning PP and RA symptoms could be explained by the regression on immune-inflammatory pathways, rheumatoid factor and anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. Depression, anxiety, and CFS-like symptoms due to RA are reflective manifestations of the phenome of RA and are mediated via the effects of the same immune-inflammatory, autoimmune, and EOS pathways and lactosylceramide that underpin the pathophysiology of RA. These PP symptoms are clinical manifestations of the pathophysiology of RA. Funding Information: There was no specific funding for this specific study. Declaration of Interests: The authors declare no conflicts of interest which are relevant to the content of this article. Ethics Approval Statement: The ethics committee (IRB) of the University of Kufa, Iraq (243/2020), which complies with the International Guideline for Human Research Protection, approved the study as required by the Helsinki Declaration.

Weekly topical therapy based on plant extracts combined with lokivetmab in canine atopic dermatitis.

Lokivetmab is an effective treatment for atopic dermatitis (AD) in dogs. The aim of this prospective study was to determine if topical products containing plant extracts could enhance the clinical efficacy of lokivetmab. Thirty atopic dogs were included. Dogs were allocated randomly to be treated either with a single injection of lokivetmab (mean dose 1.34 mg/kg; Group A) or to a single injection (mean dose 1.28 mg/kg) coupled with a weekly topical treatment using a shampoo and a spot-on specifically designed to improve skin barrier defect (Group B). Clinical parameters evaluated included pruritus (pruritus Visual Analog Scale) and skin lesions (Canine Atopic Dermatitis Lesion Index, CADLI); cosmetic evaluation, and owner and investigator global assessment of efficacy (OGATE) also were carried out. Dogs were re-examined after 10, 17 and 31 days, and until a clinical relapse occurred. An improvement was noted for all dogs, with scores being significantly better in dogs in Group B than in those in Group A; after 10 days for cosmetic evaluation, 17 days for pruritus (P = 0.039) and OGATE, and 31 days for CADLI (P = 0.043). A longer-lasting remission was noted in Group B compared to Group A; dogs receiving the combined treatment showed an extended time to flare compared to dogs treated with lokivetmab alone (P = 0.012). This study suggests that combining lokivetmab with topical therapies designed to repair the skin barrier potentially have value in the treatment of AD in dogs.

How do central sensitisation features affect symptoms among patients with rheumatoid arthritis? Analysis of pain descriptors and the effect of central sensitivity syndrome on patient and evaluator global assessments.

Central sensitivity syndrome (CSS) comprises various symptoms caused by central sensitisation (CS). Using the central sensitisation inventory (CSI), a screening questionnaire developed for detecting CSS, this syndrome was recently identified in patients with long-standing rheumatoid arthritis (RA). However, the descriptors of CS-related pain and the effects of CSS on symptoms in patients with rheumatoid arthritis (RA) remain unknown. We examined the characteristics of pain and influence of CSS on patient and evaluator global assessment among multiple clinical variables. We used the central sensitisation inventory (CSI) and short-form McGill pain questionnaire to evaluate CSS and characteristics of pain in 240 outpatients with RA. Disease activity, fibromyalgia, neuropathic pain, anxiety, depression, pain catastrophising, and health-related quality of life were evaluated. We used multivariate analysis to analyse the characteristics of CS-related pain according to CSI and the effect of CSS on patient global assessment (PGA), evaluator global assessment (EGA), and PGA minus EGA among relevant clinical variables. In patients with RA, the main descriptors of pain according to severity of CSI scores were "sharp" and "stabbing", whereas those of pain according to disease activity were "tender" and "throbbing". CSS was associated with EGA (p=0.000, β=- 0.199) and PGA minus EGA (p=0.021, β=0.147), but not with PGA. In patients with RA, descriptors for CS-related pain differ from those for disease activity-related pain. CSS may have an important impact on EGA and PGA minus EGA. Additionally, CSI may be helpful in identifying why there is discordance between PGA and EGA.

Go Ask Your Patients! PSS-QoL Reported Perception of Dryness Correlates With Lacrimal and Salivary Flow in Primary Sjögren's Syndrome.

Introduction/Objectives: The patient perspective is an essential outcome parameter in the quest for effective therapy in primary Sjögren's Syndrome (PSS). The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is recommended by EULAR to quantify patient's symptom burden and has been used in several clinical trials. Surprisingly, the patient's perception of dryness quantified with ESSPRI does not correlate with objective measures of salivary or lacrimal flow. Thus, we evaluated a newly developed assessment tool-the Primary Sjögren's Syndrome Quality of Life Questionnaire (PSS-QoL)—for quantifying symptoms of dryness in comparison with the ESSPRI and objective measurements of salivary and lacrimal flow.Methods: Data of patients from the PSS registry of the Medical University of Graz fulfilling the 2016 ACR/EULAR classification criteria for PSS were analyzed. The patient perspective was analyzed by PSS-QoL, ESSPRI, Xerostomia Inventory (XI) and Ocular Surface Disease Index (OSDI). Sicca signs were measured with Schirmer's test, unstimulated salivary flow test (USF) and stimulated salivary flow test (SSF). ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) and EGA (Evaluator Global Assessment, numeric rating scale from 0 to 10) were obtained. In addition, free light chains (FLC) κ and λ, rheumatoid factor (RF) IgM and IgA were determined.Results: Data from 123 PSS patients were analyzed; 91.9% (n = 113) were female, with a mean disease duration of 6.2 (±5.3) years and mean age of 60.1 (±12.4) years. PSS-QoL-dryness revealed significant negative correlations with Schirmer's test (r = −0.31, p < 0.05) and SSF-test (r = −0.390, p < 0.01). In contrast, we found no significant correlation between ESSPRI-dryness and any objective dryness test. Lower perceived dryness was associated with higher immunological activity determined by increased levels of IgG, FLC and RF-IgA. Whereas patients with only subjective signs of dryness had lower immunological activity.Discussion: Patients' perception of dryness assessed by PSS-QoL correlates with objective measurements of salivary gland function while ESSPRI-dryness did not. Based on the PSS-QoL and objective measures of dryness two distinct groups of PSS patients could be distinguished, which may have implications in daily practice and future clinical studies.

Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice.

The aim of this study was to investigate the clinical characteristics of patients with difficult-to-treat RA (D2T RA) and the usefulness of switching to drugs with different modes of action in real-world. We reviewed all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017 with a definition of D2T RA. We analysed clinical characteristics and evaluated the usefulness of changing drugs according to mode of action. Among 1709 patients with RA, 173 (10.1%) were D2T RA. The reason for the D2T RA was multi-drug resistance in 59 patients (34.1%), comorbidity in 17 (9.8%), and socio-economic reasons in 97 (56.1%). The multi-drug-resistance group had significantly higher tender joint count and evaluator global assessment than the other groups, despite receiving the most intensive treatment. The comorbidity group showed a significantly older age and higher rheumatic disease comorbidity index. Although changing the drug to another with a different mode of action was useful, the proportion of patients who achieved remission or low disease activity decreased as the number of switches increased. Of the patients with RA, 10.1% were still difficult to treat in clinical practice, despite intensive treatment. Their characteristics were distinct by the reasons of D2T RA, which suggests the need for a personalized approach to D2T RA.

Central sensitisation features are associated with neuropathic pain-like symptoms in patients with longstanding rheumatoid arthritis: a cross-sectional study using the central sensitisation inventory.

Several studies have indicated that arthralgia may be driven by central sensitisation. Central sensitivity syndrome (CSS) is a concept that unifies various symptoms due to central sensitisation. Recently, the central sensitisation inventory (CSI) was developed as a screening questionnaire to detect CSS. Using the CSI, we examined the prevalence, the clinical characteristics of CSS, and the association between CSS and neuropathic pain (NP)-like symptoms among rheumatoid arthritis (RA) patients. The CSI was administered to 240 RA outpatients. We evaluated their disease activity and several potentially relevant patient-reported outcomes. We compared the clinical parameters depending on the severity of CSS and examined the effect of the CSI score on NP-like symptoms among the relevant clinical parameters using multivariate analyses. The mean disease duration was 9.58 ± 7.76 years. Eighteen (7.5 %) patients had CSS, which was associated with evaluator global assessment (EGA) (odds ratio (OR) 0.860); fibromyalgia symptom scale (OR 1.46); painDETECT questionnaire score (OR 1.24); hospital anxiety and depression scale-anxiety (OR 1.35); and physical (OR 0.898), mental (OR 0.828), and role-social (OR 0.946) component summary scores on the Short-Form 36-Item Health Survey. CSI score was the factor that contributed most to NP-like symptoms (p=0.000, β=0.266). NP-like symptoms might be one of the symptoms of CSS in longstanding RA patients. In longstanding RA patients who have disproportionately greater NP-like symptoms and/or widespread pain compared with degree of inflammation, detecting CSS using CSI might help to understand the pathogenesis of patients.

Structured patient interview to assess clinical outcomes in complicated urinary tract infections in the APEKS-cUTI study: pilot investigation.

Background:The APEKS-cUTI study demonstrated the non-inferiority of cefiderocol to imipenem−cilastatin in the primary endpoint of the composite of clinical and microbiological outcome in patients with complicated urinary tract infections (cUTIs). We piloted a structured patient interview (SPI) to evaluate clinical outcomes based on patient-reported symptoms while conducting this pivotal randomized, double-blind, phase-2 study. The objectives were to assess the value of the SPI, using its performance relative to physician assessment, and also to strengthen the value of patient-reported measures in conducting clinical trials for cUTI treatment.Methods:In addition to the protocol-defined clinical and microbiological outcomes, patients randomized in the APEKS-cUTI study were interviewed by the investigator or qualified study personnel at screening/baseline, early assessment (EA), end of treatment (EOT), test of cure (TOC), and follow-up (FUP). The 14-element questionnaire graded cUTI symptoms as absent or present, and if present, as mild, moderate, or severe. Changes in post-baseline symptoms based on patients’ responses were rated by the interviewer. The overall clinical outcome was evaluated based on the responses provided by patients at each time point.Results:Among the 371 patients in the modified intention-to-treat population, the rate of SPI completion in each treatment arm exceeded 90% at each time point. SPI-assessed clinical cure rates were 89.7% in the cefiderocol arm and 84.9% in the imipenem–cilastatin arm. There was substantial agreement between SPI evaluation and investigator global assessment of clinical outcome at TOC and FUP, with lower agreement at EA and EOT.Conclusion:This analysis suggests that patient-reported symptoms can be effectively captured in hospitalized patients with cUTI in a clinical trial setting. Development of a validated patient-reported outcome for use in such a setting is warranted.Registration:NCT02321800 (registered on 22 December 2014).

How to Define Boolean Low Disease Activity in Rheumatoid Arthritis: Experience from a Large Real-world Cohort.

IntroductionThe aim of this work is to propose Boolean-defined low disease activity (LDA) and to test its utility in rheumatoid arthritis (RA).MethodsWe used data from a longitudinal academic clinical database of RA in Peking University First Hospital over a decade. The initial proposal of Boolean-defined LDA was proposed with ascending thresholds from 2 to 5 in steps of 1 (referred to as Boolean-LDA2/3/4/5). Agreement and residual swollen joint count (SJC) pattern with the index-based [Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)] LDA was analyzed. To confirm discovery, we randomly classified RA patients in a 3:2 ratio into either analysis cohort or validation cohort.ResultsIn total, 4881 visits of 672 patients were included in the analysis cohort. Of these visits, the frequencies of achieving LDA were 71.9% (SDAI), 73.6% (CDAI), 52.8% (Boolean-LDA2), 65.2% (Boolean-LDA3), 73.5% (Boolean-LDA4), and 80.7% (Boolean-LDA5). High consistency and similar SJC pattern with SDAI-LDA or CDAI-LDA were observed in Boolean-LDA3 (kappa = 0.796, 0.771). Further analysis found meeting SDAI-LDA but not Boolean-LDA3 was largely attributable to higher patient’s global assessment (PGA) scores (62.9%). In further modification of Boolean-LDA3, better agreement with SDAI-LDA or CDAI-LDA was reached when exclusively increasing PGA cutoffs to 4.0, 4.5 or replacing PGA by evaluator’s global assessment (EGA) with cutoff to 3.0. These findings were further replicated in randomly generated validation cohort of 449 patients with 3306 clinic visits.ConclusionsUsing cutoff of 3 to Boolean-LDA provides great clinical utility with index-based LDA, especially when exclusively increasing PGA cutoffs to 4.0, 4.5 or replacing PGA by EGA with cutoffs to 3.0. This may deserve being considered in clinical practice.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-020-00270-z.

A Critical Disconnect: Residency Selection Factors Lack Correlation With Intern Performance.

Emergency medicine (EM) residency programs want to employ a selection process that will rank best possible applicants for admission into the specialty. We tested if application data are associated with resident performance using EM milestone assessments. We hypothesized that a weak correlation would exist between some selection factors and milestone outcomes. Utilizing data from 5 collaborating residency programs, a secondary analysis was performed on residents trained from 2013 to 2018. Factors in the model were gender, underrepresented in medicine status, United States Medical Licensing Examination Step 1 and 2 Clinical Knowledge (CK), Alpha Omega Alpha (AOA), grades (EM, medicine, surgery, pediatrics), advanced degree, Standardized Letter of Evaluation global assessment, rank list position, and controls for year assessed and program. The primary outcomes were milestone level achieved in the core competencies. Multivariate linear regression models were fitted for each of the 23 competencies with comparisons made between each model's results. For the most part, academic performance in medical school (Step 1, 2 CK, grades, AOA) was not associated with residency clinical performance on milestones. Isolated correlations were found between specific milestones (eg, higher surgical grade increased wound care score), but most had no correlation with residency performance. Our study did not find consistent, meaningful correlations between the most common selection factors and milestones at any point in training. This may indicate our current selection process cannot consistently identify the medical students who are most likely to be high performers as residents.

The Long-Lasting Effects of "Placebo Injections" in Knee Osteoarthritis: A Meta-Analysis.

ObjectivesTo quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated.DesignMeta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines.ResultsOut of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain −13.4 mean difference (MD) (95% confidence interval [CI]: −21.7/−5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain −3.3 MD (95% CI: −3.9/−2.7; P < 0.001). Other significant improvements were WOMAC-stiffness −1.1 MD (95% CI: −1.6/−0.6; P < 0.001), WOMAC-function −10.1 MD (95% CI: −12.2/−8.0; P < 0.001), and Evaluator Global Assessment −21.4 MD (95% CI: −29.2/−13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the “minimal clinically important difference” for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes.ConclusionsThe placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.

Predicting Imaging Remission in Rheumatoid Arthritis: a Case-control Ultrasound Study.

BackgroundTo elucidate the achievement rates of imaging remission and to examine the characteristics associated with imaging remission status among patients with rheumatoid arthritis (RA) who have attained clinical remission.MethodsNinety-seven patients with RA patients who had attained clinical remission, defined by DAS28-ESR < 2.6 were enrolled. Power Doppler ultrasonography (PDUS) was performed on 16 joints and 2 tendons, including the first to third metacarpophalangeal, second and third proximal interphalangeal, radiocarpal (RC), second and third metatarsophalangeal joints, and extensor carpi ulnaris tendons. They were graded based on a dichotomous assessment. The clinical and laboratory data of patients who had attained imaging remission were compared to those of patients who had attained only clinical remission.ResultsThe imaging remission rate was 51.5% in patients who had attained clinical remission. Forty-seven patients (48.5%) were PDUS positive. Power Doppler was detected most frequently in the right RC joint (n = 40). PDUS positive patients had higher evaluator global assessment (EGA) scores (P < 0.001) than PDUS negative patients. PDUS positive patients also had higher clinical disease activity index and simplified clinical disease activity index scores than PDUS negative patients. Patients who had attained imaging remission had lower pain scores and used nonsteroidal anti-inflammatory drugs less frequently. Patients who had attained imaging remission had higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide levels. A low EGA score was found to be a predictor of imaging remission achievement among patients who had attained clinical remission.ConclusionOnly 51.5% of the patients with RA who had attained clinical remission were also in imaging remission. Patients who had attained imaging remission had lower EGA scores and higher RF levels than patients who had attained only clinical remission.

Pain and Self-reported Swollen Joints Are Main Drivers of Patient-reported Flares in Rheumatoid Arthritis: Results from a 12-month Observational Study.

To examine prospectively self-reported flare characteristics and their longitudinal association with disease activity and patient-reported outcomes (PRO) in patients with rheumatoid arthritis (RA). Consecutive RA patients with 28-joint count Disease Activity Score based on C-reactive protein (DAS28-CRP) < 3.2 and no swollen joints were examined at baseline, Month 6, and Month 12. Assessments included joint counts, DAS28-CRP, visual analog scale-evaluator's global assessment (EGA), and PRO. Every third month, patients completed the Flare Assessment in Rheumatoid Arthritis and RA Flare Questionnaire, and disclosed self-management strategies. Flaring and non-flaring patients were compared and longitudinal associations between self-reported flare status (yes/no) and disease activity, PRO, and treatment escalation were explored. Among 80 patients with RA [74% females, mean (SD) age 63 (10) yrs, disease duration 11 (7) yrs, and baseline DAS28-CRP 1.9 (0.6)], 64 (80%) reported flare at least once during 12 months. Fifty-five percent of flares lasted less than 1 week. Common self-management strategies were analgesics (50%) and restricted activities (38%). Patients who reported being in flare had consistently higher disease activity measures and PRO compared to patients without flare. In a partly adjusted model, all flare domains, patient-reported swollen and tender joint counts and disease activity measures were associated with flares. In fully adjusted analyses, present flare was independently associated with pain (OR 1.85, 95% CI 1.34-2.60), patient-reported swollen joints (OR 1.18, 95% CI 1.03-1.36), and higher EGA (OR 1.15, 95% CI 1.04-1.28). Treatment escalation was associated with present flare (p ≤ 0.001). In RA, self-reported flares were frequent, mainly managed by analgesics, substantiated by higher disease activity measures, independently associated with pain and patient-reported swollen joints, and related to treatment escalation.

Clinical and Instrumental Objective Evidence of the Efficacy of a New Water-Based Nail-Strengthening Solution Containing Pistacia lentiscus and Hyaluronic Acid Applied for Up to 6 Months to Improve the Appearance of Weak, Brittle Nails.

IntroductionBrittle nails are fragile or split nails; they affect 20% of the population and may be primary or secondary to different conditions. The aim of our studies was to evaluate the efficacy and tolerability of a new water-based nail-strengthening treatment containing hyaluronic acid and Pistacia lentiscus with daily application for a period of 1–3 months for one study (n = 30) and up to 6 months for a second study (n = 30).MethodsIn total, we enrolled 60 patients of both sexes with brittle and weak nails due to primary or secondary causes and evaluated the efficacy of this new product using subjective and objective methods: clinical evaluation, assessment of photographs, onychoscopy evaluation, investigator and patient global assessment, dynamic optical coherence tomography (D-OCT) and reflectance confocal microscopy (RCM).ResultsStudies subjects presented a statistically significant improvement in global assessment scale (GAS) scores at 14 days (GAS = 1.7 ± 0.6), 1 month (GAS = 1.4 ± 0.7) and at 3 months (GAS = 1±0.7) versus the GAS score obtained before treatment (1.9 ± 0.5) (p < 0.0001). From the Italian study at 6 months (n = 30) 76% of the patients had an improvement in their nail appearance. Reduction in nail plate roughness with improved nail resistance and decreased distal breakage were the most evident benefits, demonstrated on clinical and instrumental evaluations. No side effects were reported. All patients reported an improvement in nail appearance after using the product for 1 month, 3 months and 6 months, and had a positive opinion on the product.ConclusionsThis new product is an effective, safe, and easy-to-use option for topical treatment of brittle nails and primary nail fragility and an adjuvant therapy in secondary nail fragility. Moreover, its ease of application and cosmetic qualities allow good compliance.FundingISDIN.

How do neuropathic pain-like symptoms affect health-related quality of life among patients with rheumatoid arthritis?: A comparison of multiple pain-related parameters

Objectives: Rheumatoid arthritis (RA) pain is thought to be nociceptive. However, recent studies indicate that RA also involves the neuropathic pain (NP) mechanism. We examined pain features and the effect of NP-like symptoms on health-related quality of life (HRQOL) among patients with RA.Methods: The painDETECT questionnaire (PDQ) was used to evaluate NP-like symptoms among 145 outpatients with RA. Disease activity, pain quality, and HRQOL were evaluated. We compared clinical parameters between patients with and without NP-like symptoms and analyzed pain features and the effect of NP-like symptoms on HRQOL, along with multiple other pain-related parameters.Results: Thirty (20.7%) patients had NP-like symptoms (PDQ ≥13). Patient global assessment and evaluator global assessment diverged for patients with RA who had NP-like symptoms. Of the examined pain-related parameters, PDQ score (p = .038, ß = −.173) was associated with the Short-Form 36-Item Health Survey role–social component summary score, but not with the physical or mental component summary scores.Conclusion: NP-like symptoms affected HRQOL among patients with RA. There was discordance between global assessments by patients and by evaluators for patients with RA who had NP-like symptoms. Therefore, NP-like symptoms should be given somewhat more attention when treating patients with RA.

Exposure-response modeling of tocilizumab in rheumatoid arthritis using continuous composite measures and their individual components.

Tocilizumab has a direct effect on inflammatory markers. Therefore, composite measures for disease activity assessment in rheumatoid arthritis (RA) using these inflammatory markers may not be suitable for tocilizumab treatment. We used a modelling approach to describe the tocilizumab exposure-response relationship and to investigate the different dynamics of the individual components of the routinely used continuous composite measures. Pharmacokinetic (PK), clinical and laboratory data were obtained from a prospective, observational, single-centre study involving 35 subjects with RA treated with intravenous tocilizumab. A population PK/pharmacodynamic analysis was performed using nonlinear mixed effects models. The population for model development comprised 1086, 1083 and 1082 observations calculated with the disease activity score based on 28 joint (DAS28) and the simplified and clinical disease activity scores (SDAI, CDAI). The tocilizumab exposure-response relationship was described with an indirect-response model. Two main groups of individual components were identified based on their different dynamics under tocilizumab treatment: (i) tender and swollen joint counts and patient and evaluator global assessment showed a slower decrease of their baseline value (half-life: 4.6weeks, RSE: 24%) and the need for higher serum drug concentration (EC50 : 4.60μg/mL, RSE: 103%, IIV: 359%) than (ii) C-reactive protein and erythrocyte sedimentation rate (half-life: 2.3weeks, RSE 19%; EC50 : 0.878μg/mL, RSE: 41%, IIV: 238%). Our study confirms a different dynamics of the individual components of the most frequently used continuous composite measures under tocilizumab treatment which should be taken into account to avoid misassessment of disease activity.

Is cachexia associated with chemotherapy toxicities in gastrointestinal cancer patients? A prospective study.

BackgroundChemotherapy is an effective treatment with good clinical response in patients with cancer. However, it can cause exacerbated toxicities in patients and consequently change the course of treatment. Some factors may interfere with this toxicity such as body composition, especially in gastrointestinal cancer. The aim of this study was to evaluate the effects of body composition, nutritional status, and functional capacity scale in predicting the occurrence of toxicities in gastrointestinal cancer patients during chemotherapy treatment.MethodsThis is a prospective study with gastrointestinal cancer patients at the beginning of chemotherapy treatment. Sarcopenia and muscle attenuation were assessed using the skeletal muscle index from computerized tomography by measuring cross‐sectional areas of the L3 tissue (cm2/m2). Cachexia was graded according to involuntary weight loss associated with sarcopenia. Nutritional status was assessed by using anthropometric evaluation and Patient‐Generated Subjective Global Assessment. Functional capacity was evaluated by handgrip strength and Eastern Cooperative Oncology Group (ECOG) Performance Status scale. Haematological gastrointestinal and dose‐limiting toxicities (DLTs) were defined according to National Cancer Institute Common Toxicity Criteria. The associations among sarcopenia, cachexia, nutritional status, and functional capacity with DLT were assessed by univariate and multivariate Cox regression model.ResultsA total of 60 patients were evaluated (55% male, 60.9 ± 14.0 years) and followed up for a mean of 55 days. Most patients had normal weight (44.2%) and good ECOG Performance Status (≤1) at baseline (78%). During the chemotherapy period, the most prevalent toxicities were diarrhoea, nausea, and anorexia, but the presence of DLT was similar between cycles (P > 0.05). Cachexia was associated with a higher toxicity manifested by diarrhoea (P = 0.02), nausea (P = 0.02), and anorexia (P < 0.01 and P = 0.03 at Cycles 1 and 2, respectively). Sarcopenic and cachetic individuals experienced more toxicities and DLT during chemotherapy. The only factors associated with DLT in the multivariate Cox regression analyses including the presence of metastasis and the chemotherapy protocol were cachexia and the ECOG scale (P < 0.001 for both).ConclusionsCachexia and ECOG score may identify patients with an increased risk for developing severe toxicity events during chemotherapy treatment for gastrointestinal cancer.