Biologic therapy has changed the prognosis of patients with juvenile idiopathic arthritis (JIA). The aim of this study was to examine the pattern of use, drug survival, and adverse events of ...biologics in patients with JIA during the period from diagnosis to adulthood.
All patients included in BIOBADASER (Spanish Registry for Adverse Events of Biological Therapy in Rheumatic Diseases), a multicenter prospective registry, diagnosed with JIA between 2000 and 2015 were analyzed. Proportions, means, and SDs were used to describe the population. Incidence rates and 95% CIs were calculated to assess adverse events. Kaplan-Meier analysis was used to compare the drug survival rates.
A total of 469 patients (46.1% women) were included. Their mean age at diagnosis was 9.4 ± 5.3 years. Their mean age at biologic treatment initiation was 23.9 ± 13.9 years. The pattern of use of biologics during their pediatric years showed a linear increase from 24% in 2000 to 65% in 2014. Biologic withdrawal for disease remission was higher in patients who initiated use biologics prior to 16 years of age than in those who were older (25.7% vs 7.9%, p < 0.0001). Serious adverse events had a total incidence rate of 41.4 (35.2-48.7) of 1000 patient-years. Patients younger than 16 years old showed significantly increased infections (p < 0.001).
Survival and suspension by remission of biologics were higher when these compounds were initiated in patients with JIA who had not yet reached 16 years of age. The incidence rate of serious adverse events in pediatric vs adult patients with JIA treated with biologics was similar; however, a significant increase of infection was observed in patients under 16 years old.
The aim of the work was to examine whether abnormalities in the lipid profile that tocilizumab (TCZ), an anti-IL-6 receptor Ab, exerts in rheumatoid arthritis (RA) patients is related to changes in ...either proprotein convertase subtilisin/kexin-9 (PCSK9) serum concentrations or in serum cholesterol efflux capacity (CEC). TOCRIVAR is a one-year prospective clinical trial that analyzes the influence of TCZ on cardiovascular risk factors. Twenty-seven RA patients receiving TCZ (8 mg/kg IV/q4w) were assessed at baseline and weeks 12, 24, and 52. Disease activity indexes, adiposity composition, physical activity, serum CEC, PCSK9, and lipoproteins serum concentrations were assessed at every visit. Basal high-sensitivity C-reactive protein (hs-CRP) and disease activity were markedly reduced throughout one-year TCZ treatment. While initially total cholesterol and LDL cholesterol increased their plasma concentration, decreasing to basal afterwards, lipoprotein(a) was significantly lower than basal in all visits of the study. CEC increased after 24 week of treatment proportionally to hs-CRP reduction, and remained significantly higher after week 52 median % change 32 (3-141), p=0.021. Interestingly, variations in LDL cholesterol basal concentration along the one year of TCZ treatment correlated directly with changes of PCSK9 serum concentration (r=0.37, p=0.003). Basal abdominal adiposity, BMI, and physical activity remained stable during the study. Long-term TCZ-treated RA patients show an increment in CEC inversely proportional to hs-CRP reduction and changes in LDL cholesterol that might be explained, at least in part, by variations in PCSK9 plasma concentration. Overall, TCZ treatment produces a favorable qualitative net effect in terms of atherogenic implication in RA patients.
To estimate the prevalence of Sjögren's syndrome (SS) in the adult Spanish population we performed a population-based multicenter cross-sectional study. Cases were defined by the American-European ...Consensus Group criteria proposed in 2002. A total of 4,916 subjects aged 20 years or over were included. The estimated prevalence of SS (including primary and secondary forms) in the adult population in Spain was 0.33% (95% CI 0.21-0.53). Extrapolating to the total population of the country aged ≥ 20 years (around 37.7 million persons), there would be around 125,000 cases of SS in Spain. Considering only primary SS, the estimated prevalence was 0.25% (95% CI 0.15-0.43) or 1 person in 400. The prevalence of primary SS in Spain is comparable to that reported in other European studies with a similar design and diagnostic criteria. Based on these results, primary SS could not be considered a rare (orphan) disease. Only 50% of cases had already been diagnosed with SS prior EPISER 2016 study, confirming the existence of a non-negligible proportion of undiagnosed cases in the general population.
Understanding ecosystem resilience requires long data series provided by palaeoecological studies, the best tool for reconstructing vegetation dynamics. Here, we analyzed a continuous and well-dated ...record of pollen, non-pollen palynomorphs, macrocharcoal remains, loss-on-ignition and magnetic susceptibility from one of the most singular peatlands in the Toledo Mountains (central Spain), in order to delineate the anthropogenic and/or climate impact on the peatland and the ecosystem’s response. La Ventilla mire is an isolated site of birch woodland dominated by Betula pubescens subsp. celtiberica (Rothm. & Vasc.) Rivas Mart. This mire, acting as a refugium for this species, is located in Cabañeros National Park and is recognized as ‘Special Area of Conservation’ according to Habitats Directive of the Natura 2000 network. We describe major patterns and trends in the development of this palaeorefugium since the mid-Holocene (∼6145 cal BP) and provide historical context for some natural and/or human-induced dynamics. Around 1500 cal BP, the lotic depositional environment with slow moving backwaters developed into a minerotrophic mire. Until the Middle Ages, macroclimate and autogenic succession appear to have been the main drivers of both local and regional development of vegetation. Between 1500 and 500 cal BP, an abrupt decline in birch cover started, coincident with the Visigothic period. The pronounced peaks in the coprophilous fungi record ca. 1000 and 150 cal BP reflect extensive pastoral activities in the area. This study shows how palaeoecological knowledge helps to explain present patterns in the composition of a valuable protected site, which may be used in prioritizing conservation.
•La Ventilla birch forest confirms the antiquity of birch in the Toledo Mountains.•Toledo Mountains mires have been important refugia for certain species.•Human groups lived and exploited the Toledo Mountains environment since Neolithic.•Palynological studies are useful tools for conservation and landscape management.
This is a response to critical comments concerning the inappropriate use of the potential natural vegetation (PNV) concept made in a recent contribution to the Commentary section of this journal. We ...consider that the PNV concept has been misinterpreted. PNV has been used extensively in several European countries since the mid-1950s and was never intended to be used to make a prediction of what vegetation would dominate in an area if human influence were removed. PNV maps express hypothetical assumptions of what corresponds to dominant or natural vegetation in each area. Remnants of the vegetation of the past provided by palaeopalynology and other disciplines provide valuable information for interpreting modern vegetation, but natural changes and anthropogenic influences operating over the last millennia have to be taken into account. Annex I of the Habitats Directive provides a balanced list of habitat types for implementing conservation policies within the European Union.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation, and which has been linked to ...cardiovascular risk. The purpose of the present study was to examine whether PCSK9 serum levels are disrupted in patients with systemic sclerosis (SS) compared to controls, and if PCSK9 is related to disease-related data and the subclinical atherosclerosis that occurs in these patients.
Cross-sectional study that encompassed 146 individuals; 73 patients with SS and 73 age- and sex-matched controls. PCSK9, lipoproteins serum concentrations, and standard lipid profiles were assessed in patients and controls. Carotid intima-media thickness (cIMT) and the presence of carotid plaques were evaluated in SS patients. A multivariable analysis, adjusted for traditional cardiovascular risk factors, was performed to evaluate the differences in PCSK9 between patients and controls, the association of SS-related manifestations with PCSK9 levels, and if PCSK9 was associated with subclinical carotid atherosclerosis in SS patients.
After multivariable analysis, PCSK9 was downregulated in SS patients compared to controls (beta coefficient -78 (95%CI -106 - -50) ng/ml, p=0.000) and skin thickness was associated with higher serum levels of PCSK9 (beta coef. 22 (7-37) units, p=0.005). PCSK9 was significantly and positively associated with cIMT (beta coef. 0.65 (0.06-1.24) ng/ml, p=0.031) in SS patients after multivariable adjustment.
PCSK9 serum concentration is downregulated in SS patients compared to controls and is directly associated with disease severity subrogated parameters. PCSK9 was independently related to cIMT in SS patients.
Background
Post-transplant diabetes mellitus (PTDM) beyond 12 months (late PTDM) is a severe complication after renal transplantation. Late PTDM develops mostly in subjects with prediabetes. Although ...exercise may have a potential role in preventing late PTDM, there are no previous data on the effect of exercise in patients with prediabetes.
Material and Methods
The design was a 12-month exploratory study to test the capacity of exercise in reverting prediabetes in order to prevent late-PTDM. The outcome was the reversibility of prediabetes, assessed every 3 months with oral glucose tolerance tests (OGTT). The protocol included an incremental plan of aerobic and/or strength training as well as an active plan for promoting adherence (telephone calls, digital technology, and visits). A priori, a sample size cannot be calculated which makes this an exploratory analysis. Based on previous studies, the spontaneous reversibility of prediabetes was 30% and the reversibility induced by exercise will account for another 30%, a total reversibility of 60% (
p
value < 0.05, assuming a potency of 85%). Ad interim analysis was performed during follow-up to test the certainty of this sample calculation. Patients beyond 12 months after renal transplantation with prediabetes were included.
Results
The study was interrupted early due to efficacy after the evaluation of the follow-up of 27 patients. At the end of follow-up, 16 (60%) patients reverted to normal glucose levels at fasting (from 102.13 mg/dL ± 11 to 86.75 ± 6.9,
p
= 0.006) and at 120 min after the OGTTs (154.44 mg/dL ± 30 to 113.0 ± 13.1,
p
= 0.002) and 11 patients had persistent prediabetes (40%). Also, insulin sensitivity improved with the reversibility of prediabetes, compared to those with persistent prediabetes: 0.09 0.08–0.11 versus 0.04 0.01–0.07,
p
= 0.001 (Stumvoll index). Most needed at least one increment in the prescription of exercise and compliance. Finally, measures aimed at the improvement of compliance were successful in 22 (80%) patients.
Conclusion
Exercise training was effective to improve glucose metabolism in renal transplant patients with prediabetes. Exercise prescription must be conducted considering both the clinical characteristics of the patients and pre-defined strategy to promote adherence. The trial registration number of the study was NCT04489043.
Key Points
PTDM is a risk factor for major complications: cardiovascular diseases, infections, and renal cell cancer. Strategies to prevent PTDM are limited.
Exercise training is an effective alternative to improve glucose metabolism in renal transplant patients. Thus, exercise can be considered, together with diet and medications, as a tool to treat and prevent these complications.
A pre-defined strategy to improve compliance must be considered simultaneously with exercise prescription.
The evaluation of renal function changes over time is crucial in day-to-day renal transplant care, and the slope of renal function is a major outcome in clinical trials. Little is known about the ...reliability of estimated glomerular filtration rate (eGFR) in reflecting real glomerular filtration rate (GFR) changes.
We analyzed the variability of eGFR slope by 63 equations in estimating measured GFR (mGFR) changes in 110 renal transplant patients. The agreement between eGFR and mGFR slopes was evaluated by the concordance correlation coefficient and the limits of agreement. Patients were grouped based on mGFR slope in rapid GFR loss: faster than -3 mL/min/y; stable renal function: -3 to +3 mL/min/y; and improvement in GFR: higher than +3 mL/min/y.
Concordance correlation coefficient averaged 0.36 and limits of agreement ±10 mL/min/y, indicating very poor agreement between eGFR and mGFR slopes. The eGFR slope classified patients into the same group of mGFR slope only in 25% of the cases. In about two-thirds of patients, the eGFR slope was either markedly faster or slower than the mGFR slope. In half of these cases, the discrepancy between mGFR and eGFR slopes was ≥50%.
Formulas are neither accurate nor precise in reflecting real GFR decline in renal transplant patients, making them unreliable for clinical practice and trials.
Abstract Objective To establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and ...unexposed individuals attending rheumatology clinics. Methods Analysis of data from the baseline visit of a 10-year prospective study CARdiovascular in rheuMAtology (CARMA) project that includes a cohort of patients with CIRD rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from 67 hospitals in Spain. Prevalence of CV morbidity, CV risk factors, and systematic coronary risk evaluation (SCORE) assessment were analyzed. Results A total of 2234 patients (775 RA, 738 AS, and 721 PsA) and 677 unexposed subjects were included. Patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. The prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%), and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR = 1.58; 95% CI: 0.90–2.76; p = 0.10) and AS (OR = 1.77; 95% CI: 0.96–3.27; p = 0.07). Disease duration in all CIRD groups and functional capacity (HAQ) in RA were associated with an increased risk of CVD (OR = 2.15; 95% CI: 1.29–3.56; p = 0.003). Most patients had a moderate CV risk according to the SCORE charts. Conclusions Despite recent advances in the management of CIRD, incidence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics.
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