Rheumatoid arthritis (RA) prevalence is believed to be around 1% worldwide, although it varies considerably among different populations. The aim of EPISER2016 study was to estimate the prevalence of ...RA in the general adult population in Spain. We designed a population-based cross-sectional study. A national survey was conducted between November 2016 and October 2017 involving a probabilistic sample from the general population aged 20 years or older. Subjects were randomly selected for phone screening using a computer-assisted telephone interviewer system. Positive RA screening results were evaluated by a rheumatologist. Cases fulfilled the 1987 ACR and/or the 2010 ACR/EULAR criteria; previous diagnosis established by a rheumatologist and clearly identified in medical records were also accepted regardless of the criteria used. Prevalence estimates with 95% CI were calculated taking into account the design of the sample (weighting based on age, sex, and geographic origin using as a reference the distribution of the population in Spain). 4916 subjects participated in the study and 39 RA cases were confirmed. RA estimated prevalence was 0.82% (95% CI 0.59-1.15). Mean age of RA cases was 60.48 (14.85) years, they were more frequently women (61.5%), from urban areas (74.4%), non-smokers (43.6%), and with a high body mass index (53.8% with overweight). Extrapolating to the population in Spain (approximately 37 million are ≥ 20 years old), it was estimated that there were between 220,000 and 430,000 people aged 20 years or older with RA. No undiagnosed cases were detected, which could be related to the establishment of early arthritis clinics around the country, increasing the rates of diagnosis during early phases of RA.
Neutrophils destroy invading microorganisms by phagocytosis by bringing them into contact with bactericidal substances, among which ROS are the most important. However, ROS also function as important ...physiological regulators of cellular signaling pathways. Here, we addressed the involvement of oxygen derivatives in the regulation of human neutrophil rolling, an essential component of the inflammatory response. Flow experiments using dihydroethidium‐preloaded human neutrophils showed that these cells initiate an early production of intracellular ROS during the rolling phase of the adhesion cascade, a phenomenon that required cell rolling, and the interaction of the chemokine receptor CXCR2 with their ligand CXCL8. Flow cytometry experiments demonstrated that L‐selectin shedding in neutrophils is triggered by ROS through an autocrine–paracrine mechanism. Preincubation of neutrophils with the NADPH oxidase complex inhibitor diphenyleniodonium chloride significantly increased the number of rolling neutrophils on endothelial cells. Interestingly, the same effect was observed when CXCL8 signaling was interfered using either a blocking monoclonal antibody or an inhibitor of its receptor. These findings indicate that, in response to CXCL8, neutrophils initiate ROS production during the rolling phase of the inflammatory response. This very early ROS production might participate in the modulation of the inflammatory response by inducing L‐selectin shedding in neutrophils.
We propose that activation of the NADPH oxidase complex by CXCL8 releases superoxide anions to the extracellular milieu. This superoxide generates an oxidative attack on the prodomain thiol group of ADAM‐17, which is activated and process the extracellular domain of L‐selectin, causing its release from the cell membrane.
Obesity is an established risk factor for renal disease and for disease progression. Therefore, an accurate determination of renal function is necessary in this population. Renal function is ...currently evaluated by estimated glomerular filtration rate (GFR) by formulas, a procedure with a proven high variability. Moreover, the adjustment of GFR by body surface area (BSA) confounds the evaluation of renal function. However, the error of using estimated GFR adjusted by BSA has not been properly evaluated in overweight and obese subjects.
We evaluated the error of 56 creatinine- and/or cystatin-C-based equations and the adjustment of GFR by BSA in 944 subjects with overweight or obesity with or without chronic kidney disease (CKD). The error between estimated (eGFR) and measured GFR (mGFR) was evaluated with statistics of agreement: the total deviation index (TDI), the concordance correlation coefficient (CCC) and the coverage probability (cp).
The error of eGFR by any equation was common and wide: TDI averaged 55%, meaning that 90% of estimations ranged from -55 to 55% of mGFR. CCC and cp averaged 0.8 and 26, respectively. This error was comparable between creatinine and cystatin-C-based formulas both in obese or overweight subjects. The error of eGFR was larger in formulas that included weight or height. The adjustment of mGFR or eGFR led to a relevant underestimation of renal function, reaching at least 10 mL/min in 25% of the cases.
In overweight and obese patients, formulas failed in reflecting real renal function. In addition, the adjustment for BSA led to a relevant underestimation of GFR. Both errors may have important clinical consequences. Thus, whenever possible, the use of a gold standard method to measure renal function is recommended. Moreover, the sense of indexing for BSA should be re-considered and probably abandoned.
Lipid profiles appear to be altered in rheumatoid arthritis (RA) patients because of disease activity and inflammation. Cholesterol efflux capacity (CEC), which is the ability of high-density ...lipoprotein cholesterol to accept cholesterol from macrophages, has been linked not only to cardiovascular events in the general population but also to being impaired in patients with RA. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in patients with RA.
We conducted a cross-sectional study that encompassed 401 individuals, including 178 patients with RA and 223 sex-matched control subjects. CEC, using an in vitro assay, lipoprotein serum concentrations, and standard lipid profile, was assessed in patients and control subjects. Carotid intima-media thickness (CIMT) and carotid plaques were assessed in patients with RA. A multivariable analysis was performed to evaluate the relationship of CEC with RA-related data, lipid profile, and subclinical carotid atherosclerosis.
Mean (SD) CEC was not significantly different between patients with RA (18.9 ± 9.0%) and control subjects (16.9 ± 10.4%) (p = 0.11). Patients with RA with low (β coefficient -5.2 -10.0 to 0.3%, p = 0.039) and moderate disease activity (β coefficient -4.6 -8.5 to 0.7%, p = 0.020) were associated with lower levels of CEC than patients in remission. Although no association with CIMT was found, higher CEC was independently associated with a lower risk for the presence of carotid plaque in patients with RA (odds ratio 0.94 95% CI 0.89-0.98, p = 0.015).
CEC is independently associated with carotid plaque in patients with RA.
To date a complete characterization of the components of the complement (C) pathways (CLassical, LEctin and ALternative) in patients with systemic lupus erythematosus (SLE) has not been performed. We ...aimed to assess the function of these three C cascades through functional assays and the measurement of individual C proteins. We then studied how they relate to clinical characteristics.
New generation functional assays of the three pathways of the C system were assessed in 284 patients with SLE. Linear regression analysis was performed to study the relationship between the activity, severity, and damage of the disease and C system.
Lower values of the functional tests AL and LE were more frequent than those of the CL pathway. Clinical activity was not related to inferior values of C routes functional assays. The presence of increased DNA binding was negatively linked to all three C pathways and products, except for C1-inh and C3a which were positively related. Disease damage revealed a consistent positive, rather than a negative, relationship with pathways and C elements. Anti-ribosomes and anti-nucleosomes were the autoantibodies that showed a greater relationship with C activation, mainly due to the LE and CL pathways. Regarding antiphospholipid antibodies, the most related with C activation were IgG anti-β2GP, predominantly involving the AL pathway.
Not only the CL route, but also the AL and LE are related to SLE features. C expression patterns are linked to disease profiles. While accrual damage was associated with higher functional tests of C pathways, anti-DNA, anti-ribosomes and anti-nucleosomes antibodies, were the ones that showed a higher relationship with C activation, mainly due to the LE and CL pathways.
Aim
To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors.
Methods
Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) ...database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis RA, axial spondyloarthritis SpA or psoriatic arthritis PsA).
Results
Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0–73.9) at year 1% and 37.7% (95% CI: 33.3–42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first‐line therapy (hazard ratio HR for discontinuation 1.52 for second‐ and 1.79 for third/later‐line vs. first‐line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation.
Conclusion
Based on this retrospective analysis of the BIOBADASER registry, nearly two‐fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.
Autosomal polycystic kidney disease (ADPKD) is the most common genetic form of kidney failure, reflecting unmet needs in management. Prescription of the only approved treatment (tolvaptan) is limited ...to persons with rapidly progressing ADPKD. Rapid progression may be diagnosed by assessing glomerular filtration rate (GFR) decline, usually estimated (eGFR) from equations based on serum creatinine (eGFRcr) or cystatin-C (eGFRcys). We have assessed the concordance between eGFR decline and identification of rapid progression (rapid eGFR loss), and measured GFR (mGFR) declines (rapid mGFR loss) using iohexol clearance in 140 adults with ADPKD with ≥3 mGFR and eGFRcr assessments, of which 97 also had eGFRcys assessments. The agreement between mGFR and eGFR decline was poor: mean concordance correlation coefficients (CCCs) between the method declines were low (0.661, range 0.628 to 0.713), and Bland and Altman limits of agreement between eGFR and mGFR declines were wide. CCC was lower for eGFRcys. From a practical point of view, creatinine-based formulas failed to detect rapid mGFR loss (-3 mL/min/y or faster) in around 37% of the cases. Moreover, formulas falsely indicated around 40% of the cases with moderate or stable decline as rapid progressors. The reliability of formulas in detecting real mGFR decline was lower in the non-rapid-progressors group with respect to that in rapid-progressor patients. The performance of eGFRcys and eGFRcr-cys equations was even worse. In conclusion, eGFR decline may misrepresent mGFR decline in ADPKD in a significant percentage of patients, potentially misclassifying them as progressors or non-progressors and impacting decisions of initiation of tolvaptan therapy.
The error of estimated GFR in predialysis care Escamilla-Cabrera, Beatriz; Luis-Lima, Sergio; Gallego-Valcarce, Eduardo ...
Scientific reports,
03/2024, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) ...by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care.
Abstract Objectives Last recommendations regarding cardiovascular risk (CVR) in rheumatoid arthritis (RA) patients were developed by the EULAR group in 2010. The aim is to update evidence-based ...recommendations about this worrying health problem. Methods We assembled a multidisciplinary workgroup (rheumatologists, endocrinologist, cardiologist, and epidemiologist) and a panel of 28 expert rheumatologists. The study was carried out in two big phases: identifying key areas in the prevention and management of CVR and developing a set of recommendations based on a review of the available scientific evidence and use of the Delphi consensus technique. All this has been developed according to an updating process of evidence-based recommendations. Results Overall, 25 recommendations were made addressing three complementary areas: CVR assessment tools, patient eligibility for assessment, and treatment strategies for control of CVR. The grade of the recommendations was not substantially modified compared to the original EULAR recommendations, except in two of them, which were upgraded from C to B. These two recommendations are the ones related to the use of corticosteroids and smoking cessation. The new developed recommendations address these two areas: CVR assessment and treatment strategies for control of CVR. Conclusions There are substantial gaps in the current knowledge that do not allow classifying properly RA patients based on their actual CVR and to accurately identify those patients who would benefit from CVR assessment. Consequently, studies designed to determine the causal effects of RA disease characteristics on cardiovascular morbidity/mortality and to identify patients at high risk of cardiovascular disease are still needed.
To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), ...or psoriatic arthritis (PsA).
All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young (< 25 years old), adult (25-64 years old), elderly (65-75 years old) or very elderly (> 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression.
2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older IRR elderly: 1.42 (CI95% 1.13-1.77). Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years HR 1.50 (1.01-2.24) and female gender HR 1.42 (1.22-1.64).
Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics.
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