Summary
Background
Evidence on the effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis is sparse and based only on retrospective data. The best results are achieved in ...a time‐consuming day‐care setting.
Objectives
To study prospectively the effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis. In addition, the effectiveness, safety, duration of treatment and number of visits between regular day care and day care with telemedicine were compared.
Methods
Data were collected from the prospective observational Child‐CAPTURE registry of children with psoriasis. Effectiveness was measured as the mean percentage improvement in Psoriasis Area and Severity Index (PASI). Safety was assessed by recording adverse events. The number of visits and duration of treatment were reported.
Results
For all patients a mean percentage reduction in PASI score of −69·3% was found, with no significant differences between regular day care and day care with telemedicine. The only adverse event reported was irritation of the skin. Neither the frequency of irritation during treatment nor the mean duration of treatment significantly differed between the two groups. Patients with telemedicine had significantly fewer visits.
Conclusions
This first prospective observational study demonstrates that short‐contact dithranol therapy in paediatric psoriasis is effective and safe. Regular day care and day care with telemedicine are equally effective. Telemedicine can be of additional value as it is less time consuming. We hope it will therefore make dithranol treatment appropriate for a larger number of children with psoriasis.
What's already known about this topic?
Dithranol is a proven effective treatment for psoriasis in adults, without known long‐term side‐effects; in children only retrospective studies have been performed.
The best results with short‐contact dithranol therapy are achieved when it is administered in a day care centre.
What does this study add?
In this first prospective observational study, short‐contact dithranol therapy was demonstrated to be effective and safe in daily clinical practice in paediatric psoriasis.
Short‐contact dithranol therapy by day care with telemedicine has extra advantages for children and parents as it is less time consuming.
There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA ...methylation biomarkers for blood-based detection of colorectal cancer.
We used DNA methylation data from 711 colorectal tumors, 53 matched adjacent-normal colonic tissue samples, 286 healthy blood samples and 4,201 tumor samples of 15 different cancer types. DNA methylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selection to identify candidate markers with high methylation across all colorectal tumors while harboring low methylation in healthy samples and other cancer types. We then used pre-therapeutic plasma and serum samples from 107 colorectal cancer patients and 98 controls without colorectal cancer, confirmed by colonoscopy, to verify candidate markers. We selected two markers for further evaluation: methylated THBD (THBD-M) and methylated C9orf50 (C9orf50-M). When tested on clinical plasma and serum samples these markers outperformed carcinoembryonic antigen (CEA) serum measurement and resulted in a high sensitive and specific test performance for early colorectal cancer detection.
Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. THBD-M in particular showed promising performance in clinical samples, justifying its further optimization and clinical testing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dose reduction (DR) of biologics, where possible, seems promising for more efficient use of expensive biologics. For implementation of DR strategies, it is essential to get insight in factors that ...influence implementation. The objective of this study was to evaluate the attitudes and behaviour regarding dose reduction of biologic therapies for psoriasis among psoriasis expert dermatologists worldwide. A 27-question e-survey was sent through the International Psoriasis Council (IPC) to its 114 dermatologist councilors worldwide. The survey assessed demographics, general and DR prescription behaviour, and motivations for and barriers against application of DR. Of 57 respondents, 53 respondents who prescribed biologics were included for analysis. Thirty-seven (69.8%) applied DR (i.e., ‘DR dermatologists’), and 16 (30.2%) did not (i.e., ‘Non-DR dermatologists’). DR strategies varied among respondents. Regarding criteria for starting DR, differences were reported in required treatment duration, and interpretation and duration of stable low disease activity. In addition, the prolongation of intervals between injections varied between respondents. For most ‘DR dermatologists’ (
n
= 32/37, 86.5%), cost savings were one of the main reasons to apply DR. Fifteen out of 16 ‘Non-DR dermatologists’ (94%) did not apply DR due to lack of scientific evidence. In conclusion, DR of biologics for psoriasis is part of clinical practice in psoriasis experts globally. Barriers for applying DR included lack of evidence or guidelines, and uncertainty on DR effects and risks. Although growing evidence shows DR feasibility, future studies are needed to accumulate and broaden evidence, along with development of (inter)national guidelines on DR strategies.
Falls are a leading cause of death in the elderly and, in a majority of patients with Parkinson's disease (PD), the leading levodopa‐insensitive cause of hospitalization and long‐term care. Falling ...in PD has been attributed to degeneration of forebrain cholinergic neurons that, in interaction with striatal dopamine losses, impairs the cognitive control of balance, gait, and movement. We previously established an animal model of these dual cholinergic–dopaminergic losses (“DL rats”) and a behavioral test system (Michigan Complex Motor Control Task, MCMCT) to measure falls associated with traversing dynamic surfaces and distractors. Because the combined treatment of the acetylcholinesterase inhibitor donepezil and the 5‐HT6 receptor antagonist idalopirdine (Lu AE58054) was reported to exhibit synergistic pro‐cholinergic activity in rats and improved cognition in patients with moderate Alzheimer's disease, here we assessed the effects of this treatment on MCMCT performance and attention in DL rats. Compared with the vehicle‐treated group, the combined treatment greatly reduced (Cohen's d = 0.96) falls in DL rats when traversing dynamic surfaces and when exposed to a passive distractor. However, falls associated with a dual task distractor and sustained attentional performance did not benefit from this treatment. Analyses of the behavior in fall‐prone moments suggested that this treatment improved the efficacy and speed of re‐instating forward movement after relatively short stoppages. This treatment may reduce fall propensity in PD patients via maintaining planned movement sequences in working memory and improving the vigor of executing such movements following brief periods of freezing of gait.
Following short freezes, rats with dual cortical cholinergic and striatal dopaminergic deafferentation resumed forward movement relatively slowly, generally with the tail positioned relatively low and with a slouched posture, yielding slips and falls. When treated with donepezil and idalopirdine (DON + IDL), such rats resumed forward movement, sometimes starting with a hop, they quickly regaining regular traversal speed and fluid forward movement, with high and firm tail position and upright posture, thereby preventing slips and falls.
Socially desirable responding (SDR) has been of long-standing interest to the field of marketing. Unfortunately, the construct has not always been well understood by marketing researchers. The ...authors provide a review of the SDR literature organized around three key issues—the conceptualization and measurement of SDR; the nomological constellation of personality traits, values, sociodemographics, and cultural factors associated with SDR; and the vexing issue of substance versus style in SDR measures. The authors review the current "state of the literature," identify unresolved issues, and provide new empirical evidence to assess the generalizability of existing knowledge, which is disproportionately based on U.S. student samples, to a global context. The new evidence is derived from a large international data set involving 12,424 respondents in 26 countries on four continents.
Summary
Background
As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants ...for drug survival.
Objectives
To describe 5‐year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival.
Methods
Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX‐CAPTURE). Drug survival was analysed using Kaplan–Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side‐effects or ineffectiveness.
Results
We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side‐effects (35%), ineffectiveness (26%), combination of side‐effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow‐up. The most reported side‐effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival.
Conclusions
Drug survival of MTX was low with 15% of patients ‘on drug’ after 5 years. Side‐effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone.
What's already known about this topic?
Methotrexate (MTX) is a widely used treatment for moderate‐to‐severe plaque psoriasis.
Drug survival of methotrexate for psoriasis has not been studied in detail.
What does this study add?
This is the first study to describe the long‐term drug survival of MTX in patients with plaque psoriasis in daily practice, split according to side‐effects and ineffectiveness.
This is the first study to identify the determinants for drug survival, split according to reasons for discontinuation.
A high baseline score on the visual analogue scale for disease severity assessed by the patient may play an important role in short drug survival.
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Linked Comment: Kirby. Br J Dermatol 2017; 177:345–346
Background
Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower ...satisfaction with biological treatment in women might add to the lower drug survival rates.
Objectives
To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM).
Methods
Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily‐practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes.
Results
We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for ‘side‐effects’ (P = 0.05) and ‘global satisfaction’ (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005).
Conclusions
This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side‐effects and global satisfaction. Differences in treatment satisfaction and side‐effects might add to the fact that women discontinue biological treatments more often.
We made new estimates of the Galactic escape speed at various Galactocentric radii using the latest data release of the RAdial Velocity Experiment (RAVE DR4). Compared to previous studies we have a ...database that is larger by a factor of 10, as well as reliable distance estimates for almost all stars. Our analysis is based on statistical analysis of a rigorously selected sample of 90 high-velocity halo stars from RAVE and a previously published data set. We calibrated and extensively tested our method using a suite of cosmological simulations of the formation of Milky Way-sized galaxies. Our best estimate of the local Galactic escape speed, which we define as the minimum speed required to reach three virial radii R340, is 533+54-41 km s-1 (90% confidence), with an additional 4% systematic uncertainty, where R340 is the Galactocentric radius encompassing a mean overdensity of 340 times the critical density for closure in the Universe. From the escape speed we further derived estimates of the mass of the Galaxy using a simple mass model with two options for the mass profile of the dark matter halo: an unaltered and an adiabatically contracted Navarro, Frenk & White (NFW) sphere. If we fix the local circular velocity, the latter profile yields a significantly higher mass than the uncontracted halo, but if we instead use the statistics for halo concentration parameters in large cosmological simulations as a constraint, we find very similar masses for both models. Our best estimate for M340, the mass interiorto R340 (dark matter and baryons), is 1.3+0.4-0.3 × 1012 M⊙ (corresponds to M200 = 1.6+0.5-0.4 × 1012 M⊙). This estimate is in good agreement with recently published, independent mass estimates based on the kinematics of more distant halo stars and the satellite galaxy Leo I.
Summary
Background
The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response.
Objectives
We ...aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort.
Methods
We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single‐nucleotide polymorphisms (SNPs) in HLA‐C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ2‐test or Fisher's exact test (PASI 75, secondary analysis).
Results
We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis.
Conclusions
We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.
What's already known about this topic?
Pharmacogenetic studies in psoriasis have identified targets that may be promising in predicting treatment response to biologics.
A genome‐wide association study in rheumatoid arthritis identified a genetic variant in CD84 (rs6427528) as a predictor of response to etanercept.
What does this study add?
Genetic variation in CD84 (rs6427528) predicted etanercept response in our cohort of patients with psoriasis.
Genetic variations in IL12B (rs3213094) and TNFAIP3 (rs610604) were associated with ustekinumab response.
What is the translational message?
Using pharmacogenetics we aim to predict treatment outcome of psoriasis based on genetic factors. In the future, we hope to give patients the therapy expected to be most effective based on their genetic constitution.
With our study we have demonstrated, for instance, that patients carrying an A allele for a genetic variant in CD84 responded better to etanercept than patients with two G alleles at the same position.
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