31 research outputs found

    Daily Practice Experience of Baricitinib Treatment for Patients with Difficult-to-Treat Atopic Dermatitis:Results from the BioDay Registry

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    Clinical trials have shown that baricitinib, an oral selective Janus kinase 1/2 inhibitor, is effective for the treatment of moderate-to-severe atopic dermatitis. However, daily practice data are limited. Therefore, this multicentre prospective study evaluated the effectiveness and safety of 16-weeks' treatment with baricitinib in adult patients with moderate-to-severe atopic dermatitis in daily practice. A total of 51 patients from the BioDay registry treated with baricitinib were included and evaluated at baseline and after 4, 8 and 16 weeks of treatment. Effectiveness was assessed using clinician- and patient-reported outcome measurements. Adverse events and laboratory assessments were evaluated at every visit. At week 16, the probability (95% confidence interval) of achieving Eczema Area and Severity Index ≀ 7 and numerical rating scale pruritus ≀ 4 was 29.4% (13.1-53.5) and 20.5% (8.8-40.9), respectively. No significant difference in effectiveness was found between dupilumab non-responders and responders. Twenty-two (43.2%) patients discontinued baricitinib treatment due to ineffectiveness, adverse events or both (31.4%, 9.8% and 2.0%, respectively). Most frequently reported adverse events were nausea (n = 6, 11.8%), urinary tract infection (n = 5, 9.8%) and herpes simplex infection (n = 4, 7.8%). In conclusion, baricitinib can be an effective treatment option for moderate-to-severe atopic dermatitis, including patients with non-responsiveness on dupilumab. However, effectiveness of baricitinib is heterogeneous, which is reflected by the high discontinuation rate in this difficult-to-treat cohort

    Identification of Risk Factors for Dupilumab-associated OculaSurface Disease in Patients with Atopic Dermatitis

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    This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface di-sease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupi-lumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (his-tory of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30–11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis ex-cluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis

    Cardiovascular morbidity and mortality in adult patients with repaired aortic coarctation

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    BACKGROUND: The long‐term burden of cardiovascular disease after repair of coarctation of the aorta (CoA) has not been elucidated. We aimed to determine the incidence of and risk factors for cardiovascular events in adult patients with repaired CoA. Additionally, mortality rates were compared between adults with repaired CoA and the general population. METHODS AND RESULTS: Using the Dutch Congenital Corvitia (CONCOR) registry, patients aged ≄16 years with previous surgical or transcatheter CoA repair from 5 tertiary referral centers were included. Cardiovascular events were recorded, comprising coronary artery disease, stroke/transient ischemic attack, aortic complications, arrhythmias, heart failure hospitalizations, endocarditis, and cardiovascular death. In total, 920 patients (median age, 24 years [range 16–74 years]) were included. After a mean follow‐up of 9.3±5.1 years, 191 patients (21%) experienced at least 1 cardiovascular event. A total of 270 cardiovascular events occurred, of which aortic complications and arrhythmias were most frequent. Older age at initial CoA repair (hazard ratio [HR], 1.017; 95% CI, 1.000–1.033 [P=0.048]) and elevated left ventricular mass index (HR, 1.009; 95% CI, 1.005–1.013 [P<0.001]) were independently associated with an increased risk of cardiovascular events. The mortality rate was 3.3 times higher than expected based on an age‐ and sex‐matched cohort from the Dutch general population (standardized mortality ratio, 3.3; 95% CI, 2.3–4.4 [P<0.001]). CONCLUSIONS: This large, prospective cohort of adults with repaired CoA showed a high burden of cardiovascular events, particularly aortic complications and arrhythmias, during long‐term follow‐up. Older age at initial CoA repair and elevated left ventricular mass index were independent risk factors for the occurrence of cardiovascular events. Mortality was 3.3‐fold higher compared with the general population. These results advocate stringent follow‐up after CoA repair and emphasize the need for improved preventive strategies

    Trajectories of Limitations in Instrumental Activities of Daily Living in Frail Older Adults With Vision, Hearing, or Dual Sensory Loss

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    BACKGROUND: This study investigated the trajectories of decline in individual instrumental activities of daily living (IADL) with aging and the effect of hearing loss, vision loss, or dual sensory loss on these trajectories in community-living frail older persons. METHOD: This longitudinal population-based study was conducted in 9,319 community-living frail Dutch persons aged 60 years and older. Self-reported hearing loss, vision loss, or dual sensory loss and nine IADL were assessed in 15 studies of the Dutch National Care for the Elderly Program (The Older Persons and Informal Caregivers Survey Minimum Dataset). Probabilities of limitations in IADL, odds ratios (per 5 years) for binary, and rate ratios (per 5 years) for score outcomes were calculated using mixed logistic and negative binomial models with age as the underlying timescale, stratified by sensory loss, and corrected for confounders. RESULTS: At baseline, the number of IADL limitations was higher in dual sensory loss (2.00 [interquartile range 1.00-4.00]) and vision loss (2.00 [interquartile range 1.00-4.00]) compared to no sensory loss (1.00 [interquartile range 0.00-2.00]) or hearing loss (1.00 [interquartile range 0.00-3.00]). Trajectories of individual IADL showed an increase in limitations in all IADL with age. Household tasks, traveling, shopping, preparing a meal, and walking showed the most rapid decline. Handling finances, traveling, and walking followed a different pattern of decline based on sensory loss status. CONCLUSIONS: The age effect on limitations in IADL appears to be similar across all types of sensory loss, with the exception of handling finances, traveling, and walking. At baseline, persons with self-reported sensory loss had higher levels of self-reported functional limitations. Trajectories depict a decline in IADL competence with age

    Consumption of a diet high in dairy leads to higher 15:0 in cholesteryl esters of healthy people when compared to diets high in meat and grain

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    Background and aims: A higher dairy product intake has been associated to higher blood concentrations of 15:0 (pentadecanoic acid), 17:0 (margaric acid), and 14:0 (myristic acid). This study investigates whether a diet high in dairy products influences cholesteryl ester fatty acid concentrations of these specific fatty acids (FA). Methods and results: In a randomized multiple cross-over study, 13 men and 17 women aged 22 ± 4 years with a BMI of 21.6 ± 2.2 kg/m2 received 3 isocaloric intervention diets (dairy, meat or grain) in random order. For this post-hoc analysis, FA in plasma cholesteryl esters were measured using gas chromatography. We performed a linear mixed model per centered log-ratio transformed FA, adjusting for period, and the interaction between diet and period. Consumed total fat intake per controlled intervention diet was 31.0 ± 0.9 en%/day (dairy), 31.5 ± 0.6 en%/day (meat), and 28.4 ± 1.2 en%/day (grain), respectively. The dairy diet led to higher relative concentrations of 15:0 when compared to diets high in meat and grain, (ÎČ; 0.27, 95%CI: 0.18,0.37; p = 1.2 × 10−5, and ÎČ: 0.15; 95%CI: 0.06,0.24; p = 1.2 × 10−2, respectively). The dairy diet also led to higher 14:0 when compared to the meat diet (ÎČ: 0.34; 95%CI: 0.21,0.46; p = 6.0 × 10−5), but not when compared to the grain diet. 17:0 did not differ between diets. Conclusion: The plasma cholesteryl ester fraction after a diet high in dairy was characterized by higher 15:0 levels. Concentrations of 14:0 were only higher when comparing the FA profile after a diet high in dairy when compared to a diet high in meat. Clinical trial registration: ClinicalTrials.gov, NCT01314040.</p

    Wassociation between oncostatin m expression and inflammatory phenotype in experimental arthritis models and osteoarthritis patients

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    Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-γ), IL-1α and tumor necrosis factor alpha (TNF-α), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA
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