Secukinumab Significantly Reduces Psoriasis-Related Work Impairment and Indirect Costs Compared With Ustekinumab and Etanercept in the United Kingdom.

PubMed

Warren, R B; Halliday, A; Graham, C N; Gilloteau, I; Miles, L; McBride, D

2018-05-30

Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (1) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (2) weekly/annual work productivity loss by PASI response level; (3) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (4) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different timepoints and with patient cohorts, including FIXTURE. In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI <50: 22.8%/7.60 hours; PASI 50-74: 13.3%/4.45 hours; PASI 75-89: 6.4%/2.14 hours; PASI ≥90: 4.9%/1.65 hours. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P=0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρ<0.0001). Average annual indirect cost savings with secukinumab were £355 versus ustekinumab and £1,061 versus etanercept. Results at 52 weeks were similar. Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis

Poor early response to methotrexate portends inadequate long-term outcomes in patients with moderate-to-severe psoriasis: Evidence from 2 phase 3 clinical trials.

PubMed

Gordon, Kenneth B; Betts, Keith A; Sundaram, Murali; Signorovitch, James E; Li, Junlong; Xie, Meng; Wu, Eric Q; Okun, Martin M

2017-12-01

Most methotrexate-treated psoriasis patients do not achieve a long-term PASI75 (75% reduction from baseline Psoriasis Area and Severity Index score) response. Indications of nonresponse can be apparent after only 4 weeks of treatment. To develop a prediction rule to identify patients unlikely to respond adequately to methotrexate. Patient-level data from CHAMPION (NCT00235820, N = 110) was used to construct a prediction model for week 16 PASI75 by using patient baseline characteristics and week 4 PASI25. A prediction rule was determined on the basis of the sensitivity and specificity and validated in terms of week 16 PASI75 response in an independent validation sample from trial M10-255 (NCT00679731, N = 163). PASI25 achievement at week 4 (odds ratio = 8.917) was highly predictive of response with methotrexate at week 16. Patients with a predicted response probability <30% were recommended to discontinue methotrexate. The rates of week 16 PASI75 response were 65.8% and 21.1% (P < .001) for patients recommended to continue and discontinue methotrexate, respectively. The CHAMPION trial excluded patients previously treated with biologics, and the M10-255 trial had no restrictions. A prediction rule was developed and validated to identify patients unlikely to respond adequately to methotrexate. The rule indicates that 4 weeks of methotrexate might be sufficient to predict long-term response with limited safety risk. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Phototherapy with Narrow-Band UVB in Adult Guttate Psoriasis: Results and Patient Assessment.

PubMed

Fernández-Guarino, Montserrat; Aboín-González, Sonsoles; Velázquez, Diana; Barchino, Lucia; Cano, Natividad; Lázaro, Pablo

2016-01-01

Acute guttate psoriasis (AGP) is a distinctive clinical entity with good response to treatment with narrow-band ultraviolet B (NB-UVB). To investigate the results of NB-UVB phototherapy in adult patients with adult guttate psoriasis. We carried out a prospective, open, and observational study. Patients over 18 years with more than 5% of body surface area affected were included. The PASI was assessed prior to and after treatment. The follow-up period was 18 months. After treatment, patients completed a simple questionnaire to assess their overall impression of the treatment. The 67 adult patients with AGP included in this study had an initial PASI of 8.55 (SD 5.03). Patients were treated with a mean of 19.9 sessions (SD 13.5) and mean doses of 14 mJ/cm2 (SD 10.5). Of the 67 patients, 52 achieved PASI90 with 96.15% of PASI reduction, and of these, 46 (88%) maintained PASI90 during the 18 months of follow-up. Patients were very satisfied with the treatment. AGP is a defined clinical entity with a variable course. Phototherapy with NB-UVB appears to be a very good option for treatment of AGP because of the good results obtained and patient satisfaction. © 2016 S. Karger AG, Basel.

Comparison of indirubin concentrations in indigo naturalis ointment for psoriasis treatment: a randomized, double-blind, dosage-controlled trial.

PubMed

Lin, Y-K; See, L-C; Huang, Y-H; Chi, C-C; Hui, R C-Y

2018-01-01

Indigo naturalis and its refined formulation, Lindioil, are effective in treating psoriatic symptoms topically. Indirubin is the active ingredient in indigo naturalis. To determine the efficacy and safety of different concentrations of indirubin in Lindioil ointment for treating psoriasis. In this randomized, double-blind trial, adult patients presenting with chronic plaque psoriasis for > 1 year and with < 20% of the body surface area (BSA) affected were randomized to apply Lindioil ointment containing 200, 100, 50 or 10 μg g -1 of indirubin twice daily for 8 weeks followed by an additional 12-week safety/extension period. The primary end point was the mean percentage change in Psoriasis Area and Severity Index (PASI) score along with the proportion of participants achieving 75% and 90% reductions in PASI scores (PASI 75 and PASI 90, respectively) from baseline to week 8. The results from week 8 revealed that the 200 μg g -1 group had the greatest reduction in PASI score [69·2%, 95% confidence interval (CI) 55·5-82·8], followed by the 100 μg g -1 group (63·1%, 95% CI 52·8-73·5), the 10 μg g -1 group (53·4%, 95% CI 42·8-64·0) and the 50 μg g -1 group (50·3%, 95% CI 37·4-63·2), with a between-group comparison of P = 0·0445. The group with the highest proportion of the patients achieving PASI 75 (57%, P = 0·0474) and PASI 90 (30%, P = 0·0098) was the 200 μg g -1 group. No severe treatment-related adverse events were reported during the 20-week evaluation. An amount of 200 μg g -1 of indirubin in Lindioil ointment is the most effective concentration studied so far for treating psoriasis topically, and is safe. © 2017 British Association of Dermatologists.

The Impact of Changes in Psoriasis Area and Severity Index by Body Region on Quality of Life in Patients with Psoriasis.

PubMed

Sojević Timotijević, Zorica; Majcan, Predrag; Trajković, Goran; Relić, Milijana; Novaković, Tatjana; Mirković, Momčilo; Djurić, Sladjana; Nikolić, Simon; Lazić, Bratislav; Janković, Slavenka

2017-10-01

Psoriasis severity varies by body region, with each affected region having a different impact on patient quality of life (QoL). The aim of this study was to assess the impact of changes in the Psoriasis Area and Severity Index (PASI) scores by body region on QoL in patients with psoriasis after treatment. A total of 100 patients with psoriasis were recruited to the study. All patients completed the generic EuroQol-5D instrument and two specific QoL measures, Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI) at the beginning of the study, and 50 patients successfully completed the same questionnaires four weeks after the end of the treatment. Clinical severity was assessed using PASI total score and PASI body region (head, trunk, arms, and legs) scores. QoL improved after treatment, and PASI improvements on visible body regions (head, legs, and arms) showed significant correlation with the most sub-areas of the Visual Analog Scale (EQ VAS), DLQI, and PDI. Multiple linear regression analysis revealed that PASI improvement (particularly on the head), sex, age, and disease duration were predictors of QoL score changes for most domains of the three instruments. Improvement of psoriasis in visible body regions has an appreciable influence on QoL improvement, and may positively affect treatment success in patients with psoriasis.

Phase 3 randomised study of the proposed biosimilar adalimumab GP2017 in psoriasis - impact of multiple switches.

PubMed

Blauvelt, A; Lacour, J-P; Fowler, J F; Weinberg, J M; Gospodinov, D; Schuck, E; Jauch-Lembach, J; Balfour, A; Leonardi, C L

2018-06-19

The impact of multiple switches between GP2017 and reference adalimumab (ref-ADMB) was assessed following the demonstration of equivalent efficacy and similar safety and immunogenicity, in adult patients with active, clinically stable, moderate-to-severe plaque psoriasis. This 51-week double-blinded, phase 3 study randomly assigned patients to GP2017 (N=231) or ref-ADMB (N=234) 80 mg subcutaneously at Week 0, then 40 mg biweekly from Week 1. At Week 17, patients were re-randomised to switch (n=126) or continue (n=253) treatment. Primary endpoint: patients achieving Psoriasis Area and Severity Index (PASI)75 at Week 16 (equivalence confirmed if the 95% confidence interval [CI] for the difference in PASI75 between treatments was ±18%). Key secondary endpoint: change from baseline to Week 16 in continuous PASI. Other endpoints: PASI over time, PASI 50/75/90/100, pharmacokinetics, safety, tolerability and immunogenicity for the switched and continued treatment groups. Equivalent efficacy between GP2017 and ref-ADMB was confirmed for the primary (66.8% and 65.0%, respectively; 95% CI, -7.46, 11.15) and key secondary (-60.7% and -61.5%, respectively; 95% CI, -3.15, 4.84) endpoints. PASI improved over time and was similar between treatment groups at Week 16, and the switched/continued groups from Weeks 17-51. There were no relevant safety or immunogenicity differences between GP2017 and ref-ADMB at Week 16, or the switched/continued groups from Weeks 17-51. No hypersensitivity to adalimumab was reported upon switching. Following the demonstration of GP2017 biosimilarity to ref-ADMB, switching up to four times between GP2017 and ref-ADMB had no detectable impact on efficacy, safety or immunogenicity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The reliability of three psoriasis assessment tools: Psoriasis area and severity index, body surface area and physician global assessment.

PubMed

Bożek, Agnieszka; Reich, Adam

2017-08-01

A wide variety of psoriasis assessment tools have been proposed to evaluate the severity of psoriasis in clinical trials and daily practice. The most frequently used clinical instrument is the psoriasis area and severity index (PASI); however, none of the currently published severity scores used for psoriasis meets all the validation criteria required for an ideal score. The aim of this study was to compare and assess the reliability of 3 commonly used assessment instruments for psoriasis severity: the psoriasis area and severity index (PASI), body surface area (BSA) and physician global assessment (PGA). On the scoring day, 10 trained dermatologists evaluated 9 adult patients with plaque-type psoriasis using the PASI, BSA and PGA. All the subjects were assessed twice by each physician. Correlations between the assessments were analyzed using the Pearson correlation coefficient. Intra-class correlation coefficient (ICC) was calculated to analyze intra-rater reliability, and the coefficient of variation (CV) was used to assess inter-rater variability. Significant correlations were observed among the 3 scales in both assessments. In all 3 scales the ICCs were > 0.75, indicating high intra-rater reliability. The highest ICC was for the BSA (0.96) and the lowest one for the PGA (0.87). The CV for the PGA and PASI were 29.3 and 36.9, respectively, indicating moderate inter-rater variability. The CV for the BSA was 57.1, indicating high inter-rater variability. Comparing the PASI, PGA and BSA, it was shown that the PGA had the highest inter-rater reliability, whereas the BSA had the highest intra-rater reliability. The PASI showed intermediate values in terms of interand intra-rater reliability. None of the 3 assessment instruments showed a significant advantage over the other. A reliable assessment of psoriasis severity requires the use of several independent evaluations simultaneously.

Balneotherapy in Psoriasis Rehabilitation

PubMed Central

PÉTER, IVÁN; JAGICZA, ANNA; AJTAY, ZÉNÓ; BONCZ, IMRE; KISS, ISTVÁN; SZENDI, KATALIN; KUSTÁN, PÉTER; NÉMETH, BALÁZS

2017-01-01

Background/Aim: This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity. Patients and Methods: Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and high sensitivity C-reactive protein (CRP) were determined on admission and before discharge. Results: The mean PASI score and CRP level –determined on admission and before discharge– decreased significantly after the 3-week-long rehabilitation 7.15±7.3 vs. 2.62±3.05 (p<0.001) and 4.1±3.8 vs. 3.5±3.1 (p=0.026). A negative correlation was found between PASI delta and the number of spa therapies received (r=–0.228). Conclusion: After completing the 3-week-long spa therapy based rehabilitation, both PASI score and CRP levels showed improvement of psoriasis. The complex spa therapy used during the rehabilitation is an effective tool to reduce the symptoms of psoriasis and improve the patient’s well-being. PMID:29102940

Balneotherapy in Psoriasis Rehabilitation.

PubMed

Péter, Iván; Jagicza, Anna; Ajtay, Zénó; Boncz, Imre; Kiss, István; Szendi, Katalin; Kustán, Péter; Németh, Balázs

2017-01-01

This study aimed to report a balneotherapy-based psoriasis rehabilitation protocol and assess its effectivity. Eighty psoriatic patients who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and high sensitivity C-reactive protein (CRP) were determined on admission and before discharge. The mean PASI score and CRP level -determined on admission and before discharge-decreased significantly after the 3-week-long rehabilitation 7.15±7.3 vs. 2.62±3.05 (p<0.001) and 4.1±3.8 vs. 3.5±3.1 (p=0.026). A negative correlation was found between PASI delta and the number of spa therapies received (r=-0.228). After completing the 3-week-long spa therapy based rehabilitation, both PASI score and CRP levels showed improvement of psoriasis. The complex spa therapy used during the rehabilitation is an effective tool to reduce the symptoms of psoriasis and improve the patient's well-being. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: results from the Italian Psocare registry.

PubMed

Piaserico, Stefano; Cazzaniga, Simone; Chimenti, Sergio; Giannetti, Alberto; Maccarone, Mara; Picardo, Mauro; Peserico, Andrea; Naldi, Luigi

2014-02-01

Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). There was a small number of patients with complete follow-up data. PASI 75 response in patients who switched from one anti-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first anti-TNF-alfa. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Efficacy of Methotrexate in patients with plaque type psoriasis

PubMed Central

Haider, Sabiqa; Wahid, Zarnaz; Najam-us-Saher; Riaz, Farzana

2014-01-01

Objective: To assess the efficacy of Methotrexate in patients with plaque type psoriasis. Methods: This descriptive study was conducted in the department of Dermatology, Civil Hospital Karachi from September 2009 to March 2010. Seventy three patients between 18 to 50 years of age suffering from plaque type psoriasis with PASI score of >10 were included in the study after taking the informed consent. Oral methotrexate in a dose of 7.5 mg/week was given for 8 weeks. The data collected included demographic profile (age and gender), duration of disease, site of involvement, size of plaque, severity of plaque measured by Psoriasis Area and Severity Index (PASI) score before starting the treatment and at the end of treatment. Efficacy was labeled with a PASI score of ≤5 at the end of 8 weeks. Results: Out of 73 patients there were 45 (61.6%) males and 28 (38.4%) females. The mean ±SD age was 40.0±12.6 years. The mean baseline PASI score showed clear and comparable improvement from a mean ± SD PASI score of 14.8±4.2 to 4.9±4.3.Twenty nine (40%) patients had an almost complete remission during the 8 weeks of treatment. Partial remission was achieved in 44 (60%) patients. The clearance time for psoriasis ranged from 5-7 weeks (mean 6±0.89 weeks). Conclusion: Treatment with methotrexate for chronic plaque psoriasis brings satisfactory disease control and improved quality of life. PMID:25225524

A Fuzzy Logic Approach to Marine Spatial Management

NASA Astrophysics Data System (ADS)

Teh, Lydia C. L.; Teh, Louise S. L.

2011-04-01

Marine spatial planning tends to prioritise biological conservation targets over socio-economic considerations, which may incur lower user compliance and ultimately compromise management success. We argue for more inclusion of human dimensions in spatial management, so that outcomes not only fulfill biodiversity and conservation objectives, but are also acceptable to resource users. We propose a fuzzy logic framework that will facilitate this task- The protected area suitability index (PASI) combines fishers' spatial preferences with biological criteria to assess site suitability for protection from fishing. We apply the PASI in a spatial evaluation of a small-scale reef fishery in Sabah, Malaysia. While our results pertain to fishers specifically, the PASI can also be customized to include the interests of other stakeholders and resource users, as well as incorporate varying levels of protection.

Comparative efficacy and incremental cost per responder of methotrexate versus apremilast for methotrexate-naïve patients with psoriasis.

PubMed

Armstrong, April W; Betts, Keith A; Sundaram, Murali; Thomason, Darren; Signorovitch, James E

2016-10-01

To our knowledge, no clinical trials directly compare apremilast with methotrexate (the standard of care for initial systemic treatment of psoriasis). We sought to compare apremilast's relative efficacy with that of methotrexate for moderate to severe psoriasis. An anchor-based indirect comparison was conducted for 75% improvement in Psoriasis Area and Severity Index score from baseline to week 16 (PASI 75) rates for systemic-naïve patients from Efficacy and Safety Trial Evaluating the Effects of apreMilast in psoriasis (ESTEEM) 1 and 2 (apremilast vs placebo) and Comparative study of HumirA vs. Methotrexate vs Placebo In psOriasis patieNts (CHAMPION) (adalimumab vs methotrexate vs placebo) trials. The difference-in-difference in PASI 75 response rates was calculated as the difference between the ESTEEM apremilast and placebo rates and the CHAMPION methotrexate versus placebo rates. Number needed to treat and incremental drug cost per responder were also estimated. No statistically significant difference was found between apremilast and methotrexate in PASI 75 (risk difference 13.1%; 95% confidence interval -1.8% to 28.0%; P = .09). Number needed to treat with apremilast versus methotrexate to gain 1 additional PASI 75 responder was 7.6. Annual incremental drug cost of this responder was estimated at $187,888.33. Few trials compare systemic-naïve patients. Only direct medication costs were considered. There was no statistical evidence of greater efficacy for apremilast versus methotrexate. The $187,888 incremental cost per PASI 75 may exceed what payers are willing to pay. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Clinical efficacy of Avène hydrotherapy measured in a large cohort of more than 10,000 atopic or psoriatic patients.

PubMed

Merial-Kieny, C; Mengual, X; Guerrero, D; Sibaud, V

2011-02-01

Atopic dermatitis (AD) and psoriasis are chronic skin conditions. Local or systemic treatments are effective, but their effects are transient. Hydrotherapy, used alone or in combination with other treatments, could be considered as one form of care in providing effective management of these dermatoses. The objective of this observational study was to evaluate the benefit of a 3-week treatment at Avène Hydrotherapy Centre in a very large cohort of patients suffering from atopic dermatitis and psoriasis and to assess the treatment benefits on patients undergoing hydrotherapy for two consecutive years. This 8-year observational study analysed 14,328 records of patients having a dermatological disease and who came to Avène Hydrotherapy Centre for a 3-week treatment between 2001 and 2009. Among them, patients were suffering from atopic dermatitis (n = 5916) and psoriasis (n = 4887). On admission on D0 (day 0) and at the end of cure on D18 (day 18), the severity of AD and psoriasis were evaluated by SCORing Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI), respectively. In order to assess the cumulative effect of the hydrotherapy treatment, the evolution of SCORAD or PASI of patients who came 2 years in a row was also calculated. A significant improvement in SCORAD was observed between D0 and D18 (-41.6%) (P < 0.0001) and similarly, a significant reduction in PASI was noted between D0 and D18 (-54.4%) (P < 0.0001) after 3-weeks of hydrotherapy. PASI 50 and PASI 75 were 64.3% and 19.5%, respectively. For atopic patients (n = 1102) or patients suffering from psoriasis (n = 833) who came for two consecutive years, a significant SCORAD and PASI improvement was observed on D0 of the second year when compared with D0 of the previous year (P < 0.0001). This study is the first observational study in such a large cohort demonstrating the benefit of a 3-week treatment at the Avène Hydrotherapy Centre for atopic and psoriatic patients. © 2010 The Authors

Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab.

PubMed

Warren, R B; Brnabic, A; Saure, D; Langley, R G; See, K; Wu, J J; Schacht, A; Mallbris, L; Nast, A

2018-05-01

Head-to-head randomized studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available. To assess efficacy and quality of life using matching-adjusted indirect comparisons for treatment with ixekizumab vs. secukinumab. Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) method and two modified versions of the Signorovitch (SG) method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis. In the meta-analysis of studies with active comparators, PASI 90 response rates were 12·7% [95% confidence interval (CI) 5·5-19·8, P = 0·0005], 10·0% (95% CI 2·1-18·0, P = 0·01) and 11·2% (95% CI 3·2-19·1, P = 0·006) higher and PASI 100 response rates were 11·7% (95% CI 5·9-17·5, P < 0·001), 12·7% (95% CI 6·0-19·4, P < 0·001) and 13·1% (95% CI 6·3-19·9, P < 0·001) higher for ixekizumab compared with secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and favoured ixekizumab when the BU method was used. Week 12 DLQI 0/1 response rates did not differ significantly. Ixekizumab had higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using adjusted indirect comparisons. © 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Measurement Properties of the Psoriasis Symptom Inventory Electronic Daily Diary in Patients with Moderate to Severe Plaque Psoriasis.

PubMed

Viswanathan, Hema N; Mutebi, Alex; Milmont, Cassandra E; Gordon, Kenneth; Wilson, Hilary; Zhang, Hao; Klekotka, Paul A; Revicki, Dennis A; Augustin, Matthias; Kricorian, Gregory; Nirula, Ajay; Strober, Bruce

2017-09-01

The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Coffee consumption, metabolic syndrome and clinical severity of psoriasis: good or bad stuff?

PubMed

Barrea, Luigi; Muscogiuri, Giovanna; Di Somma, Carolina; Annunziata, Giuseppe; Megna, Matteo; Falco, Andrea; Balato, Anna; Colao, Annamaria; Savastano, Silvia

2018-05-01

Despite the wide consumption of coffee, its anti-inflammatory effect on clinical severity of psoriasis is still debatable. The aim of this study was to evaluate the association between the coffee consumption and clinical severity of psoriasis in a sample of patients stratified according to the presence of the metabolic syndrome (MetS) and smoking. This cross-sectional case-control observational study was conducted on 221 treatment-naïve psoriatic patients. Lifestyle habits, anthropometric measures, clinical and biochemical evaluations were obtained. Clinical severity of psoriasis was assessed by Psoriasis Area and Severity Index (PASI) score. Data on energy caloric intake and coffee consumption were collected using a 7-day food diary record. The coffee consumption was analyzed as coffee intake (consumers and non-consumers) and daily servings (range 0-4 servings/day). Coffee consumers have a lower PASI score vs non-consumers (p < 0.001). The lowest PASI score and MetS prevalence were found in patients consuming 3 cups of coffee/day (p < 0.001), which was also the most common daily serving (34.8%), whereas the highest PASI score was found among those drinking ≥ 4 cups/day. Grouping the case patients according to smoking and MetS, the best odds of PASI score was observed in those drinking 3 cups of coffee per day and no smokers, after adjusting for total energy intake (OR 74.8; p < 0.001). As a novel finding, we reported a negative association between coffee intake, MetS prevalence and clinical severity of psoriasis. The evaluation of the anti-inflammatory effect of coffee on clinical severity of psoriasis, whose metabolic risk increases along with its clinical severity, could be of great importance from a public health perspective.

Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long-term results from a randomized controlled, double-blind, 52-week, phase III trial in patients with moderate-to-severe plaque psoriasis.

PubMed

Papp, K; Bachelez, H; Costanzo, A; Foley, P; Gooderham, M; Kaur, P; Philipp, S; Spelman, L; Zhang, N; Strober, B

2017-12-01

ABP 501, a U.S.A. Food and Drug Administration- and European Medicines Agency-approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics. To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate-to-severe plaque psoriasis (clinical trial: NCT01970488). Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed. A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8-88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments. ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population. © 2017 British Association of Dermatologists.

Problems in developing an instrument for the rapid assessment of personality status.

PubMed

Van Horn, E; Manley, C; Leddy, D; Cicchetti, D; Tyrer, P

2000-06-01

To assess the validity of a quick assessment instrument (10 minutes) for assessing personality status, the Rapid Personality Assessment Schedule (PAS-R). The PAS-R was evaluated in psychotic patients recruited in one of the centres involved in a multicentre randomised controlled trial of intensive vs standard case management (the UK700 case management trial). Patients were assessed using both a full version of the PAS (PAS-I - ICD version) and the PAS-R. The weighted kappa statistic was used to gauge the (criterion-related) validity of the PAS-R using the PAS-I as the gold standard. Both measure code personality status using a four-point rating of severity in addition to recording individual categories of personality disorder. One hundred fifty-five (77%) of 201 patients recruited were assessed with both instruments. The weighted kappa statistic was 0.31, suggesting only moderate agreement between the PAS-I and PAS-R instruments under the four-point rating format, and 0.39 for the dichotomous personality disorder/no disorder separation. The sensitivity (64%) and specificity (82%) of the PAS-R in predicting PAS-I personality disorder were as satisfactory as for other screening instruments but still somewhat disappointing, and the PAS-R had an overall diagnostic accuracy of 78%. The PAS-R is a quick and rough method of detecting personality abnormality but is not a substitute for a fuller assessment.

Assessing the overall benefit of a medication: cumulative benefit of secukinumab over time in patients with moderate-to-severe plaque psoriasis.

PubMed

Armstrong, April W; Feldman, Steven R; Korman, Neil J; Meng, Xiangyi; Guana, Adriana; Nyirady, Judit; Herrera, Vivian; Zhao, Yang

2017-05-01

Conventional measurements for assessing psoriasis treatment effects capture improvements at fixed, pre-specified timepoints, failing to account for cumulative clinical benefit over time. Explore the innovative concept of "cumulative clinical benefit" by examining the effect of secukinumab over 52 weeks in moderate-to-severe psoriasis patients. Cumulative clinical benefit was determined as the area-under-the-curve of the percentage of responders over 52 weeks (AUC 0-52 wks ), using pooled data from two phase III trials for patients receiving secukinumab (300 or 150 mg) or etanercept. Normalized cumulative benefit with secukinumab 300 mg, secukinumab 150 mg, and etanercept was 74.2%, 63.2%, and 50.5%, respectively, for PASI 75; 58.0%, 42.5%, and 29.5%, respectively, for PASI 90; 32.3%, 18.8%, and 8.7%, respectively, for PASI 100; and 58.3%, 47.9%, and 38.3%, respectively, for DLQI 0/1. 52-week PASI 75 clinical benefit ratios for secukinumab 300 and 150 mg versus etanercept were 1.47 and 1.25, respectively; the ratio of the two secukinumab doses was 1.17, favoring 300 mg. Post hoc analysis. Cumulative clinical benefit estimated by AUC 0-52 wks is a novel measure for comparing psoriasis treatments. Secukinumab 300 mg provides greater cumulative clinical benefit than secukinumab 150 mg; both provide greater cumulative benefit than etanercept.

Efficacy and cost-efficacy of biologic therapies for moderate to severe psoriasis: a meta-analysis and cost-efficacy analysis using the intention-to-treat principle.

PubMed

Chi, Ching-Chi; Wang, Shu-Hui

2014-01-01

Compared to conventional therapies, biologics are more effective but expensive in treating psoriasis. To evaluate the efficacy and cost-efficacy of biologic therapies for psoriasis. We conducted a meta-analysis to calculate the efficacy of etanercept, adalimumab, infliximab, and ustekinumab for at least 75% reduction in the Psoriasis Area and Severity Index score (PASI 75) and Physician's Global Assessment clear/minimal (PGA 0/1). The cost-efficacy was assessed by calculating the incremental cost-effectiveness ratio (ICER) per subject achieving PASI 75 and PGA 0/1. The incremental efficacy regarding PASI 75 was 55% (95% confidence interval (95% CI) 38%-72%), 63% (95% CI 59%-67%), 71% (95% CI 67%-76%), 67% (95% CI 62%-73%), and 72% (95% CI 68%-75%) for etanercept, adalimumab, infliximab, and ustekinumab 45 mg and 90 mg, respectively. The corresponding 6-month ICER regarding PASI 75 was $32,643 (best case $24,936; worst case $47,246), $21,315 (best case $20,043; worst case $22,760), $27,782 (best case $25,954; worst case $29,440), $25,055 (best case $22,996; worst case $27,075), and $46,630 (best case $44,765; worst case $49,373), respectively. The results regarding PGA 0/1 were similar. Infliximab and ustekinumab 90 mg had the highest efficacy. Meanwhile, adalimumab had the best cost-efficacy, followed by ustekinumab 45 mg and infliximab.

Home versus outpatient ultraviolet B phototherapy for mild to severe psoriasis: pragmatic multicentre randomised controlled non-inferiority trial (PLUTO study).

PubMed

Koek, Mayke B G; Buskens, Erik; van Weelden, Huib; Steegmans, Paul H A; Bruijnzeel-Koomen, Carla A F M; Sigurdsson, Vigfús

2009-05-07

To determine whether ultraviolet B phototherapy at home is equally safe and equally effective as ultraviolet B phototherapy in an outpatient setting for patients with psoriasis. Pragmatic multicentre single blind randomised clinical trial (PLUTO study). Dermatology departments of 14 hospitals in the Netherlands. 196 patients with psoriasis who were clinically eligible for narrowband (TL-01) ultraviolet B phototherapy. The first 105 consecutive patients were also followed for one year after therapy. Ultraviolet B phototherapy at home using a TL-01 home phototherapy unit compared with standard narrowband ultraviolet B phototherapy in an outpatient setting. Both therapies were done in a setting reflecting routine daily practice in the Netherlands. The main outcome measure was effectiveness as measured by the proportion of patients with a 50% or more reduction of the baseline psoriasis area and severity index (PASI) or self administered psoriasis area and severity index (SAPASI), called the PASI 50 and SAPASI 50 (relevant treatment effect). Another outcome of effectiveness was the percentage reduction in median scores on the PASI as well as SAPASI. Also the proportions of patients reaching the PASI 75 and SAPASI 75 (successful treatment effect), and the PASI 90 and SAPASI 90 (almost complete clearance) were calculated. Other secondary outcomes were quality of life (SF-36, psoriasis disability index), burden of treatment (questionnaire), patients' preferences and satisfaction (questionnaire), and dosimetry and short term side effects (diary). 82% of the patients treated at home compared with 79% of the patients treated in an outpatient setting reached the SAPASI 50 (difference 2.8%, 95% confidence interval -8.6% to 14.2%), and 70% compared with 73% reached the PASI 50 (-2.3%, -15.7% to 11.1%). For patients treated at home the median SAPASI score decreased 82% (from 6.7 to 1.2) and the median PASI score decreased 74% (from 8.4 to 2.2), compared with 79% (from 7.0 to 1

Balneotherapy for chronic plaque psoriasis at Comano spa in Trentino, Italy.

PubMed

Peroni, Anna; Gisondi, Paolo; Zanoni, Mauro; Girolomoni, Giampiero

2008-07-01

Thermal therapy is used worldwide in the treatment of psoriasis but few controlled studies have evaluated its efficacy and safety. We studied the efficacy and safety of balneotherapy compared to photobalneotherapy performed at Comano spa in Trentino, Italy, in chronic plaque psoriasis in a prospective, nonrandomized, open study. Three hundred adult patients with mild to severe chronic plaque psoriasis were assigned to either balneotherapy or photobalneotherapy with daily narrow-band ultraviolet B for a mean period of 1 or 2 weeks, reflecting the times that most patients can dedicate to thermal therapy. Patients were evaluated at baseline and end of treatment for psoriasis area and severity index (PASI) and body surface area; self-administered PASI (SAPASI) and Skindex-29 were evaluated at the same times, and also at 4 months by a mailed questionnaire. One-week balneotherapy or photobalneotherapy resulted in a significant reduction in PASI score (11.54% +/- 2.76 and 12.76% +/- 3.79, respectively; mean +/- standard deviation; p < 0.001). Two-week therapy induced a greater response with photobalneotherapy than with balneotherapy alone, with PASI reduction of 19.8% +/- 24.5 and 13.5% +/- 23.1 (p < 0.005), respectively. These results were confirmed by SAPASI and Skindex-29 evaluation. The therapy was well tolerated. Skin improvement was mostly lost after 4 months. Short-term balneotherapy and photobalneotherapy could thus be offered to patients willing to temporarily discontinue pharmacologic therapy or as adjuvant therapy.

Treatment of Plaque-Type Psoriasis With Oral CF101: Data from a Phase II/III Multicenter, Randomized, Controlled Trial.

PubMed

David, Michael; Gospodinov, Dimitar Konstantinov; Gheorghe, Nicola; Mateev, Grisha Stefanov; Rusinova, Mariyana Venelinova; Hristakieva, Evgeniya; Solovastru, Laura Gheuca; Patel, Rita V; Giurcaneanu, Calin; Hitova, Mariela Chepileva; Purcaru, Anca Ioana; Horia, Beti; Tsingov, Iliya Iliev; Yankova, Rumyana Kaloferova; Kadurina, Miroslava Ilieva; Ramon, Michal; Rotaru, Maria; Simionescu, Olga; Benea, Vasile; Demerdjieva, Zdravka Velichkova; Cosgarea, Maria Rodica; Morariu, Horia Silviu; Michael, Ziv; Cristodor, Patricia; Nica, Carmen; Silverman, Michael H; Bristol, David R; Harpaz, Zivit; Farbstein, Motti; Cohen, Shira; Fishman, Pnina

2016-08-01

CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.

J Drugs Dermatol. 2016;15(8):931-938.

Home versus outpatient ultraviolet B phototherapy for mild to severe psoriasis: pragmatic multicentre randomised controlled non-inferiority trial (PLUTO study)

PubMed Central

Buskens, Erik; van Weelden, Huib; Steegmans, Paul H A; Bruijnzeel-Koomen, Carla A F M; Sigurdsson, Vigfús

2009-01-01

Objective To determine whether ultraviolet B phototherapy at home is equally safe and equally effective as ultraviolet B phototherapy in an outpatient setting for patients with psoriasis. Design Pragmatic multicentre single blind randomised clinical trial (PLUTO study). Setting Dermatology departments of 14 hospitals in the Netherlands. Participants 196 patients with psoriasis who were clinically eligible for narrowband (TL-01) ultraviolet B phototherapy. The first 105 consecutive patients were also followed for one year after therapy. Intervention Ultraviolet B phototherapy at home using a TL-01 home phototherapy unit compared with standard narrowband ultraviolet B phototherapy in an outpatient setting. Both therapies were done in a setting reflecting routine daily practice in the Netherlands. Main outcome measures The main outcome measure was effectiveness as measured by the proportion of patients with a 50% or more reduction of the baseline psoriasis area and severity index (PASI) or self administered psoriasis area and severity index (SAPASI), called the PASI 50 and SAPASI 50 (relevant treatment effect). Another outcome of effectiveness was the percentage reduction in median scores on the PASI as well as SAPASI. Also the proportions of patients reaching the PASI 75 and SAPASI 75 (successful treatment effect), and the PASI 90 and SAPASI 90 (almost complete clearance) were calculated. Other secondary outcomes were quality of life (SF-36, psoriasis disability index), burden of treatment (questionnaire), patients’ preferences and satisfaction (questionnaire), and dosimetry and short term side effects (diary). Results 82% of the patients treated at home compared with 79% of the patients treated in an outpatient setting reached the SAPASI 50 (difference 2.8%, 95% confidence interval −8.6% to 14.2%), and 70% compared with 73% reached the PASI 50 (−2.3%, −15.7% to 11.1%). For patients treated at home the median SAPASI score decreased 82% (from 6.7 to 1.2) and

Estimated cost efficacy of systemic treatments that are approved by the US Food and Drug Administration for the treatment of moderate to severe psoriasis.

PubMed

D'Souza, Logan S; Payette, Michael J

2015-04-01

Newer psoriasis treatments tout higher efficacy but are generally more expensive. We sought to estimate the cost efficacy of systemic psoriasis treatments that have been approved by the US Food and Drug Administration (FDA). A literature review of systemic psoriasis treatments that have been approved by the FDA was performed for the primary end point of a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75). Medication cost was referenced by wholesale acquisition cost (WAC), laboratory fees were obtained from the American Medical Association, and office visit fees are standard at our university. Total expenses were standardized by calculating cost per month of treatment considering the number needed to treat (NNT) to achieve PASI 75. Methotrexate ($794.05-1502.51) and cyclosporine ($1410.14-1843.55) had the lowest monthly costs per NNT to achieve PASI 75. The most costly therapies were infliximab ($8704.68-15,235.52) and ustekinumab 90 mg ($12,505.26-14,256.75). Monthly costs per NNT to achieve PASI 75 for other therapies were as follows: narrowband ultraviolet B light phototherapy ($2924.73), adalimumab ($3974.61-7678.78), acitretin ($4137.71-14,148.53), ustekinumab 45 mg ($7177.89-7263.99), psoralen plus ultraviolet A light phototherapy ($7499.46-8834.98), and etanercept ($8284.71-10,674.89). Drug rebates and incentives, potential adverse effects, comorbidity risk reduction, ambassador programs, and combination therapies were excluded. Our study provides meaningful cost efficacy data that may influence psoriasis treatment selection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross-Sectional Study (EPI-PSODE).

PubMed

Song, Hae Jun; Park, Chul Jong; Kim, Tae Yoon; Choe, Yong Beom; Lee, Seok-Jong; Kim, Nack In; Cho, Jae We; Jeon, Jie Hyun; Jang, Min Soo; Youn, Jai Il; Kim, Myung Hwa; Park, Joonsoo; Kim, Ki Ho; Kim, Byung Soo; Youn, Sang Woong; Lee, Joo-Heung; Lee, Min-Geol; Ahn, Sung Ku; Won, Young Ho; Yun, Seok Kweon; Shin, Bong Seok; Seo, Seong Jun; Lee, Ji Yeoun; Kim, Kwang Joong; Ro, Young Suck; Kim, Youngdoe; Yu, Dae Young; Choi, Jee-Ho

2017-08-01

Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m 2 ; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.

Disease Severity, Quality of Life, and Psychiatric Morbidity in Patients With Psoriasis With Reference to Sociodemographic, Lifestyle, and Clinical Variables: A Prospective, Cross-Sectional Study From Lahore, Pakistan

PubMed Central

Khawaja, Abdul Rahman; Bokhari, Syed Muhammad Azam; Rasheed, Tariq; Shahzad, Atif; Hanif, Muhammad; Qadeer, Faisal

2015-01-01

Background: Psoriasis is an immune-mediated, chronic disease with a genetic background that involves skin, nails, and joints. The incidence of psoriasis varies from 2.0% to 4.0% depending on the geographical location, ethnic background, and environmental conditions. Recent research has proved that psoriasis is a systemic inflammatory disease with extensive systemic implications. Objectives of the study were to explore the severity of psoriasis, dermatology-related quality of life, and psychiatric health of the patients with reference to sociodemographic, lifestyle, and clinical characteristics. Method: Consecutive patients with psoriasis (ICD-10 criteria) from skin outpatient clinics of 3 tertiary care hospitals in Lahore, Pakistan, between November 1, 2012, and December 31, 2012, were assessed in this prospective cross-sectional study. The final sample includes 87 patients who were evaluated for severity of psoriasis (Psoriasis Area Severity Index [PASI]), dermatology-related quality of life (Dermatology Life Quality Index [DLQI]), and psychiatric morbidity (12-item General Health Questionnaire [GHQ-12]) and were assessed on 23 sociodemographic, lifestyle, and clinical variables. Results: Of the 23 variables, the PASI was significantly associated with education and habit of drinking alcohol (P < .05), the DLQI was significantly associated with disturbed eating (P < .05), and the GHQ-12 score was significantly associated with hair disease (P < .05), current income (P < .05), and disturbed eating and sleeping (P < .01). The PASI, DLQI, and GHQ-12 were not usually affected by sociodemographic, lifestyle, and clinical factors, except for some variables such as education of the patient, alcohol intake, eating and sleeping disturbance, and income status. A statistically significant correlation (P < .01) was found between all 3 scores (ie, PASI, DLQI, and GHQ-12). The correlation coefficients of the PASI with the DLQI and GHQ-12 are 0.345 and 0.460, respectively, and

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis.

PubMed

Balak, Deepak M W; van Doorn, Martijn B A; Arbeit, Robert D; Rijneveld, Rianne; Klaassen, Erica; Sullivan, Tim; Brevard, Julie; Thio, Hok Bing; Prens, Errol P; Burggraaf, Jacobus; Rissmann, Robert

2017-01-01

Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI). IMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo. Short-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs. EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729. Copyright © 2016 Elsevier Inc. All rights reserved.

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

PubMed Central

van Bezooijen, Ji Sun; Balak, Deepak M.W.; van Doorn, Martijn B.A.; Looman, Caspar W.N.; Schreurs, Marco W.J.; Koch, Birgit C.P.; van Gelder, Teun; Prens, Errol P.

2016-01-01

Background Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability. PMID:27576483

The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross-Sectional Study (EPI-PSODE)

PubMed Central

Song, Hae Jun; Park, Chul Jong; Kim, Tae Yoon; Choe, Yong Beom; Lee, Seok-Jong; Kim, Nack In; Cho, Jae We; Jeon, Jie Hyun; Jang, Min Soo; Youn, Jai Il; Kim, Myung Hwa; Park, Joonsoo; Kim, Ki Ho; Kim, Byung Soo; Youn, Sang Woong; Lee, Joo-Heung; Lee, Min-Geol; Ahn, Sung Ku; Won, Young Ho; Yun, Seok Kweon; Shin, Bong Seok; Seo, Seong Jun; Lee, Ji Yeoun; Kim, Kwang Joong; Ro, Young Suck; Kim, Youngdoe; Yu, Dae Young

2017-01-01

Background Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. Objective To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. Methods This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. Results A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m2; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. Conclusion This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population. PMID:28761295

How Long Does the Benefit of Biologics Last? An Update on Time To Relapse and Potential for Rebound of Biologic Agents for Psoriasis.

PubMed

Kamaria, Monique; Liao, Wilson; Koo, J Y

2010-01-01

The biologic agents vary considerably in terms of their long-term duration of effect. Using the definitions provided by the National Psoriasis Foundation Medical Board, the objective of this review was to compare all biologic agents with respect to time to relapse and potential for rebound. Overall, alefacept had the longest off-treatment benefit (29.9 weeks in Psoriasis Area and Severity Index [PASI] 75 responders), followed by ustekinumab (22 weeks), infliximab (19.5 weeks), adalimumab (18 weeks), etanercept (12.1 weeks in PASI 50 responders), and, lastly, efalizumab (9.6 weeks). Rebound was reported commonly for efalizumab (14%) and, extremely rarely, for etanercept (0.002%).

Psoriasis and psoriatic arthritis video project: an update from the 2012 GRAPPA annual meeting.

PubMed

Callis Duffin, Kristina; Armstrong, April W; Mease, Philip J

2013-08-01

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has developed online videos intended to provide training on the most commonly used physical examination measures for psoriasis and psoriatic arthritis (PsA). At the 2012 GRAPPA annual meeting, attendees were updated on the development, availability, use, and validation of these video modules. To date, 1300 users from 45 different countries have used the Psoriasis Area and Severity Index (PASI) module at least once. Results were presented from a recently completed study of pre- and post-video scoring of the PASI by experienced and naive physicians and patient assessors. Future modifications of the video collection were also discussed.

Comparison of clinical and cost-effectiveness of psoralen + ultraviolet A versus psoralen + sunlight in the treatment of chronic plaque psoriasis in a developing economy.

PubMed

Aggarwal, Komal; Khandpur, Sujay; Khanna, Neena; Sharma, Vinod K; Pandav, Chandrakant S

2013-04-01

Psoralen + ultraviolet A (PUVA) therapy is an established modality for psoriasis. As India is a tropical country that has good availability of natural sunlight psoralen + sunlight (PUVAsol) may be a more convenient option. To compare the efficacy and cost-effectiveness of PUVA versus PUVAsol in chronic plaque psoriasis. Cases of chronic plaque psoriasis with body surface area ≥10% or Psoriasis Area and Severity Index (PASI) ≥10, excluding erythrodermic or pustular psoriasis, were randomized to receive either PUVA or PUVAsol, with endpoint being the achievement of PASI 90 or completion of 12 weeks treatment, whichever is earlier. Cost analysis was also undertaken. Thirty-six cases (16 in PUVA and 20 in PUVAsol group) completed treatment. In the PUVA group, 15 cases (93.75%) responded to therapy while in the PUVAsol group, 15 (75%) responded (P = 0.29). Mean baseline PASI in the PUVA and PUVAsol groups was 16 and 14.4, respectively, and at endpoint was 1.62 and 3.77. There was a significantly greater reduction in PASI in the PUVA group at 2 and 4 weeks but at 8 and 12 weeks and endpoint, it was comparable. Treatment failure occurred in 6.25% and 25% of cases respectively (P = 0.29). Side effects were higher with PUVA. Total cost of therapy was significantly higher in the PUVA group (P = 0.002). Cost-effectiveness ratio was US$0.72 with PUVA and US$0.37 with PUVAsol. Both PUVA and PUVAsol were equally efficacious, with PUVAsol being twice as cost effective. Hence, PUVAsol may be recommended as treatment for psoriasis in a developing economy such as India. © 2013 The International Society of Dermatology.

Clinical features and nail clippings in 52 children with psoriasis.

PubMed

Uber, Marjorie; Carvalho, Vânia O; Abagge, Kerstin T; Robl Imoto, Renata; Werner, Betina

2018-03-01

Nail clipping, the act of cutting the distal portion of a nail for microscopic analysis, can complement the diagnosis of skin diseases with nail involvement, such as psoriasis. This study aimed to describe histopathologic findings on 81 nails from 52 children and adolescents with skin psoriasis and to determine whether these changes correlated with the severity of skin and nail involvement. Children with psoriasis were enrolled in this cross-sectional study to obtain Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores. The most altered nails were processed using periodic acid-Schiff with diastase staining. Fifty-two patients with a median age of 10.5 years were included. The median Nail Psoriasis Severity Index score of the 20 nails from these patients was 17 (range 3-80). The most common findings were pitting (94.2%), leukonychia (73.0%), and longitudinal ridges (63.5%). Eighty-one nail fragments were collected by clipping. Neutrophils were found in 6 samples (7.6%) and serous lakes in 15 (19%). Median nail plate thickness was 0.3 mm (range 0.1-0.63 mm). Patients whose nails had neutrophils had a higher median PASI score (6.1 vs 2.0, P = .03). Patients whose nails had serous lakes had higher median PASI (5.3 vs 1.9, P = .008) and NAPSI (median 45.0 vs 18.0, P = .006) scores. There seems to be a correlation between some microscopic nail features in children with psoriasis and their PASI and NAPSI scores, so nail clippings from children with suspected psoriasis may help with diagnosis, especially in the presence of neutrophils, and in excluding onychomycosis. © 2018 Wiley Periodicals, Inc.

Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L in psoriasis patients.

PubMed

Poór, Adrienn Katalin; Rencz, Fanni; Brodszky, Valentin; Gulácsi, László; Beretzky, Zsuzsanna; Hidvégi, Bernadett; Holló, Péter; Kárpáti, Sarolta; Péntek, Márta

2017-12-01

The purpose of this study is to assess the measurement properties of EQ-5D-5L compared to EQ-5D-3L in psoriasis patients. A cross-sectional survey was carried out at an academic dermatology clinic in Hungary. Psoriasis patients completed the EQ-5D-3L, EQ-5D-5L and Dermatology Life Quality Index (DLQI) questionnaires, and Psoriasis Area and Severity Index (PASI) was assessed. The UK value sets were used to calculate the 3L and 5L index scores. We tested the feasibility, ceiling effect, redistribution properties, the level of inconsistency and informativity (Shannon and Shannon Evenness indices). Spearman's rank-order correlations were performed between EQ-5D, EQ VAS, DLQI and PASI scores. Known-groups validity was evaluated by comparing age groups, clinical subtypes and treatment groups. Mean age of the 238 patients was 47 years, and 36.6% of them received biological therapy. Mean EQ-5D index score was 0.77 (SD: 0.26) with the 3L and 0.84 (SD: 0.19) with the 5L. The overall ceiling effect decreased from 37.1 (3L) to 32.9% (5L). Shannon index improved significantly for most dimensions, but Shannon Evenness index improved only in three dimensions. Compared to the 3L, the 5L version confirmed a better convergent validity with PASI, but not with the DLQI. Known-groups validity was equally demonstrated both for the 5L and 3L. The EQ-5D-5L seems to improve measurement properties by reducing ceiling effects, strengthening correlations with PASI and improving informativity. Follow-up studies are needed to test responsiveness and reliability in psoriasis.

Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study

PubMed Central

Baranauskaite, Asta; Raffayová, Helena; Kungurov, NV; Kubanova, Anna; Venalis, Algirdas; Helmle, Laszlo; Srinivasan, Shankar; Nasonov, Evgeny; Vastesaeger, Nathan

2012-01-01

Objective To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). Methods In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. Results At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group. Conclusions Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237. PMID:21994233

Mesopause region wind, temperature and airglow irradiance above Eureka, Nunavut

NASA Astrophysics Data System (ADS)

Kristoffersen, Samuel; Ward, William E.; Vail, Christopher; Shepherd, Marianna

2016-07-01

The PEARL All Sky Imager (PASI, airglow images), the Spectral Airglow Temperature Imager (SATI, airglow irradiance and temperature) and the E-Region Wind Interferometer II (ERWIN2, wind, airglow irradiance and temperature) are co-located at the Polar Environment Atmospheric Research Laboratory (PEARL)in Eureka, Nunavut (80 N, 86 W). These instruments view the wind, temperature and airglow irradiance of hydroxyl (all three) O2 (ERWIN2 and SATI), sodium (PASI), and oxygen green line (PASI and ERWIN2). The viewing locations and specific emissions of the various instruments differ. Nevertheless, the co-location of these instruments provides an excellent opportunity for case studies of specific events and for intercomparison between the different techniques. In this paper we discuss the approach we are using to combine observations from the different instruments. Case studies show that at times the various instruments are in good agreement but at other times they differ. Of particular interest are situations where gravity wave signatures are evident for an extended period of time and one such situation is presented. The discussion includes consideration of the filtering effect of viewing through airglow layers and the extent to which wind, airglow and temperature variations can be associated with the same gravity wave.

Secukinumab is Efficacious and Safe in Hispanic Patients with Moderate-to-Severe Plaque Psoriasis: Pooled Analysis of Four Phase 3 Trials.

PubMed

Adsit, Sandra; Zaldivar, Enrique Rivas; Sofen, Howard; Dei-Cas, Ignacio; Maldonado-García, César; Peñaranda, Elkin O; Puig, Luís; Meng, Xiangyi; Fox, Todd; Guana, Adriana

2017-06-01

There is little evidence available on the efficacy and safety of biologic therapies for the treatment of psoriasis in Hispanic patients. Secukinumab is demonstrated to be highly effective for clearing psoriasis. The aim of this study was to compare the efficacy and safety of secukinumab in Hispanic and non-Hispanic patients. Data were pooled from four phase 3 studies of secukinumab in patients with moderate-to-severe plaque psoriasis. Patients who self-identified as Hispanic were included in the Hispanic subgroup. Efficacy responses (Psoriasis Area and Severity Index [PASI] 75/90/100 and Investigator's Global Assessment 2011 modified version 0/1) for secukinumab 300 mg were greater than for etanercept at week 12 in the Hispanic and non-Hispanic patient subgroups. At week 12 with secukinumab 300 mg, PASI 90/100 responses were achieved by 70.6%/35.9% of Hispanic patients and 58.0%/28.1% of non-Hispanic patients. At week 12 with secukinumab 150 mg, PASI 90/100 responses were achieved by 59.5%/25.1% of Hispanic patients and 41.2%/13.4% of non-Hispanic patients. In both subgroups, peak efficacy responses with secukinumab were observed at week 16 and were maintained to week 52. Secukinumab is highly effective for clearing psoriasis in both Hispanic and non-Hispanic patients. Novartis Pharmaceutical Corporation.

Serum Squamous Cell Carcinoma Antigen in Psoriasis: A Potential Quantitative Biomarker for Disease Severity.

PubMed

Sun, Ziwen; Shi, Xiaomin; Wang, Yun; Zhao, Yi

2018-06-05

An objective and quantitative method to evaluate psoriasis severity is important for practice and research in the precision care of psoriasis. We aimed to explore serum biomarkers quantitatively in association with disease severity and treatment response in psoriasis patients, with serum squamous cell carcinoma antigen (SCCA) evaluated in this pilot study. 15 psoriasis patients were treated with adalimumab. At different visits before and after treatment, quantitative body surface area (qBSA) was obtained from standardized digital body images of the patients, and the psoriasis area severity index (PASI) was also monitored. SCCA were detected by using microparticle enzyme immunoassay. The serum biomarkers were also tested in healthy volunteers as normal controls. Receiver-operating characteristic (ROC) curve analysis was used to explore the optimal cutoff point of SCCA to differentiate mild and moderate-to-severe psoriasis. The serum SCCA level in the psoriasis group was significantly higher (p < 0.05) than in the normal control group. After treatment, the serum SCCA levels were significantly decreased (p < 0.05). The SCCA level was well correlated with PASI and qBSA. In ROC analysis, when taking PASI = 10 or qBSA = 10% as the threshold, an optimal cutoff point of SCCA was found at 2.0 ng/mL with the highest Youden index. Serum SCCA might be a useful quantitative biomarker for psoriasis disease severity. © 2018 S. Karger AG, Basel.

Open-label study of etanercept treatment in patients with moderate-to-severe plaque psoriasis who lost a satisfactory response to adalimumab.

PubMed

Bagel, J; Tyring, S; Rice, K C; Collier, D H; Kricorian, G; Chung, J; Iles, J; Stolshek, B S; Kaliyaperumal, A; Papp, K A

2017-08-01

Some patients with plaque psoriasis experience secondary failure of tumour necrosis factor inhibitor therapy. To evaluate efficacy, safety and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure. This phase IV open-label single-arm estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static Physician's Global Assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥ 3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥ 10%, sPGA ≥ 3 and PASI ≥ 10. Antiadalimumab antibodies (ADAs) were measured at screening. Patients received etanercept 50 mg twice weekly for 12 weeks, followed by 50 mg weekly. The primary end point was sPGA 0/1 at week 12 (intention-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain and flaking, Dermatology Life Quality Index, treatment satisfaction and Work Productivity and Activity Impairment questionnaire. Sixty-four patients enrolled; 67% had ADAs. sPGA 0/1 rates at week 12 were 39·7% [95% confidence interval (CI) 27·6-52·8; primary end point] and 45% (95% CI 29·3-61·5) for patients positive for ADAs and 35% (95% CI 15·4-59·2) for patients negative for ADAs. PASI 75 response rates at week 12 were 47·5% (95% CI 31·5-63·9) for patients who were positive for ADAs and 50% (95% CI 27·2-72·8) for patients negative for ADAs. No new safety signals were observed. PROs of itch, pain and flaking consistently improved at week 12 and were maintained through week 24. Patients with psoriasis who experienced secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Influence of internal current and pacing current on pacemaker longevity.

PubMed

Schuchert, A; Kuck, K H

1994-01-01

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

Pharmacokinetic Characteristics of Tofacitinib in Adult Patients With Moderate to Severe Chronic Plaque Psoriasis.

PubMed

Ma, Guangli; Xie, Rujia; Strober, Bruce; Langley, Richard; Ito, Kaori; Krishnaswami, Sriram; Wolk, Robert; Valdez, Hernan; Rottinghaus, Scott; Tallman, Anna; Gupta, Pankaj

2018-06-01

Tofacitinib is an oral Janus kinase (JAK) inhibitor. This study characterized the pharmacokinetics of tofacitinib in patients with psoriasis and evaluated the impact of patient factors on disposition. Pooled phase 2/3 data (2981 patients: 9735 concentrations, dose range: 2-15 mg twice daily) up to 56 weeks were used for modeling. A one-compartment model parameterized in terms of apparent oral clearance (CL/F), apparent volume of distribution, zero-order absorption (duration, D), with interindividual variability and inter-occasion variability terms, described tofacitinib pharmacokinetics. A full covariate model incorporated effects for age, sex, race, ethnicity, and baseline variables (body weight, Psoriasis Area Severity Index [PASI], C-reactive protein [CRP], creatinine clearance [CrCl]). The parameter estimates (95%CI) for CL/F, Vd/F, and D in a typical individual (white, male, 86 kg, 46 years, CrCl 121 mL/min, PASI 19.8, and CRP 0.267 mg/dL) were 26.7 (25.9, 27.5) L/h, 125 (120.8, 128.3) liters, and 0.69 (0.646, 0.735) hours, respectively. Only CrCl led to clinically relevant changes in exposure. The analysis suggested no dosing modifications for age, body weight, sex, race, ethnicity, baseline PASI, or CRP based on the magnitude of exposure change. Dosing adjustments for renal impairment were derived from a separate phase 1 study. © 2018, The American College of Clinical Pharmacology.

Biologics and dermatology life quality index (DLQI) in the Australasian psoriasis population.

PubMed

Norris, Diana; Photiou, Louise; Tacey, Mark; Dolianitis, Con; Varigos, George; Foley, Peter; Baker, Chris

2017-12-01

Psoriasis is a chronic condition that may require long-term treatment for disease control. This analysis utilizes data from the Australasian Psoriasis Registry with particular attention to the impact of biologic therapy on DLQI, and the differences between the biologics in terms of DLQI score change. A retrospective review of patients enrolled in the Australasian Psoriasis Registry from April 2008 to August 2016 was conducted. All subjects from the registry that had DLQI and Psoriasis Assessment Severity Index (PASI) scores recorded at a baseline time point of treatment commencement, in addition to week 12 and 24 post commencement were included in the study. A window of ±3 weeks was permitted at these time points. Multivariate linear regression analysis was undertaken to identify significant predictors associated with change in DLQI. Significant predictors of reduction in DLQI and PASI score from baseline to week 24 include use of adalimumab, infliximab, secukinumab and ustekinumab. Other therapies, including etanercept and oral systemic agents did not show significant change. Each class of biologic showed significant reductions in DLQI score, with IL-12/23 blockade showing the greatest reduction. Significant predictors of lack of reduction in DLQI score include a baseline PASI score <16, and history of diabetes, alcoholism or uveitis. Patients with moderate to severe chronic plaque psoriasis who are treated with biologics show the greatest reduction in DLQI score, compared with other treatments. Australian dermatologists are prescribing biologics when patients qualify for them in keeping with current guidelines.

Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial.

PubMed

David, M; Akerman, L; Ziv, M; Kadurina, M; Gospodinov, D; Pavlotsky, F; Yankova, R; Kouzeva, V; Ramon, M; Silverman, M H; Fishman, P

2012-03-01

CF101 demonstrated a marked anti-inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome. The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque-type psoriasis. This was a phase 2, multicentre, randomized, double-blind, dose-ranging, placebo-controlled study. Seventy five patients with moderate to severe plaque-type psoriasis were enrolled, randomized and treated with CF101 (1, 2, or 4 mg) or placebo administered orally twice daily for 12 weeks. Safety and change from base line of Psoriasis Area and Severity Index (PASI) score and physician's global assessment (PGA) score over 12 weeks. In the 2 mg CF101-treated group, a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed, with a statistically significant difference on weeks 8 and 12 (P = 0.047; P = 0.031, respectively). In this group, 35.3% of the patients achieved PASI ≥ 50 response, and 23.5% of the patients achieved a PGA score of 0 or 1. CF101 was safe and well tolerated. CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

PubMed

Shibuya, Takashi; Honma, Masaru; Iinuma, Shin; Iwasaki, Takeshi; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

2018-06-01

Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible. © 2018 Japanese Dermatological Association.

Nutrition: a key environmental dietary factor in clinical severity and cardio-metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire.

PubMed

Barrea, Luigi; Macchia, Paolo Emidio; Tarantino, Giovanni; Di Somma, Carolina; Pane, Elena; Balato, Nicola; Napolitano, Maddalena; Colao, Annamaria; Savastano, Silvia

2015-09-16

Western dietary pattern is included among the environmental dietary factors involved in the pathogenesis of psoriasis. Nutritional data collection methods and gender differences might affect the association between diet and psoriasis. The 7-day food records is considered the "gold standard" of self-administered food frequency questionnaires. In this study, we evaluated the differences in the dietary intake, anthropometric measurements and cardio-metabolic risk profile in a group of psoriatic patients compared with an age and Body Mass Index (BMI)-matched control group. In addition, in the group of psoriatic patients we investigated the association between the dietary intake and clinical severity of psoriasis. Cross-sectional case control observational study. A total of 82 adult males, 41 treatment-naïve patients with psoriasis and 41 healthy subjects matched for age and BMI were included in the study. The clinical severity of psoriasis was by assessed by Psoriasis Area and Severity Index (PASI) score. The dietary interview data were collected by a 7-day food records. Anthropometric measures, glucose and lipid profile, liver function tests and C-reactive protein levels were measured. Homeostasis Model Assessment of Insulin Resistance (HoMA-IR), Visceral Adiposity Index (VAI) and the Fatty Liver Index (FLI) were calculated. Psoriatic patients consumed a higher percentage of total and simple carbohydrates, total fat, polyunsaturated fatty acid (PUFA) and n-6/n-3 PUFAs ratio, and cholesterol, while the consumption of protein, complex carbohydrates, monounsaturated fatty acid (MUFA), n-3 PUFA and fiber was lower than in the control group. In addition, psoriatic patients presented altered anthropometric measurements, glucose and lipid profile, liver function tests, and elevated values of HoMA-IR, VAI and FLI. PASI score well correlated with anthropometric measures, glucose and lipid profile, liver function tests, cardio-metabolic indices, and the dietary components

Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam is Effective, Independent of Body Mass Index and the Extent and Severity of Psoriasis.

PubMed

Stein Gold, Linda; Villumsen, John; Rosen, Monika

2016-12-01

Good treatment adherence is important in the effective management of psoriasis and is related to both the frequency of applications and the amount of product used versus the recommended dose. The efficacy and safety of fixed combination calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) in the treatment of psoriasis is well established; an aerosol foam formulation has been developed to enhance adherence. This subanalysis from the Phase III PSO-FAST study evaluates the amount of Cal/BD foam used during treatment and the association between the extent and severity of baseline disease. Patients (≥18 years) with mild-to-severe body psoriasis were randomized 3:1 to once-daily Cal/BD foam or vehicle. The amount of Cal/BD foam and vehicle used over the 4-week study period was evaluated according to three baseline disease assessments: extent of body surface area (BSA) affected by psoriasis, physician's global assessment of disease severity (PGA) and modified psoriasis area and severity index (mPASI). Treatment success and mPASI75 rates were assessed according to body mass index (BMI) and body weight. 323 patients were randomized to Cal/BD foam and 103 to vehicle. At week 4, the mean total amount of Cal/BD foam used was 120.8 g (n = 293), which was similar to the amount of vehicle used (128.9 g; n = 98). The total amount of Cal/BD foam used at week 4 was greater with increasing BSA and increasing severity of baseline PGA and mPASI. Throughout the study, 93.1% of patients in the Cal/BD foam group and 99.0% of patients in the vehicle group missed ≤10% of treatment applications. Treatment success and mPASI75 rates were generally similar when stratified according to BMI and body weight. This subanalysis demonstrates that Cal/BD aerosol foam is used appropriately and is effective for the treatment of psoriasis, independent of BMI and the extent or severity of disease. NCT01866163. LEO Pharma A/S.

Impact of active and stable psoriasis on health-related quality of life: the PSO-LIFE study.

PubMed

Daudén, E; Herrera, E; Puig, L; Sánchez-Carazo, J L; Toribio, J; Perulero, N

2013-10-01

The aim of this study was to assess the impact of psoriasis on health-related quality of life (HRQOL) using different questionnaires. Prospective observational study of patients with plaque psoriasis of at least 6 months' duration stratified by active and stable disease. The patients were evaluated at baseline, 7 days, and 12 weeks. At the 3 visits, the investigators recorded sociodemographic and clinical data and the patients completed the following HRQOL questionnaires: the Dermatology Life Quality Index (DLQI), the Psoriasis Disability Index (PDI), and psoriasis quality of life questionnaire (PSO-LIFE). In total, 304 patients (182 with active psoriasis and 122 with stable psoriasis) were evaluated. The mean (SD) age was 45.3 (14.5) years, and 56.3% of the group were men. At baseline, the mean (SD) psoriasis and area severity index (PASI) score was 17.0 (7.4) in patients with active disease and 5.6 (5.3) in those with stable disease; a reduction was seen in PASI scores during the evaluation period (P<.01). The mean (SD) score on the PSO-LIFE questionnaire increased significantly from 57.4 (20.4) to 72.2 (19.6) in patients with active psoriasis and from 76.4 (20.6) to 82.3 (18.3) in those with stable disease (P<0.01 in both groups). The difference in standardized mean scores between the 2 groups was 0.79 for the DLQI, 0.62 for the PDI, and 0.85 for the PSO-LIFE questionnaire. The impact of psoriasis on HRQOL as assessed by the PSO-LIFE questionnaire was greater in patients with lesions in visible areas than in those with less visible lesions (P<.01). Changes in PSO-LIFE and PASI scores were moderately and significantly correlated (r=-0.4). The impact of psoriasis on HRQOL is higher in patients with active disease. The PSO-LIFE questionnaire showed a greater tendency to discriminate between active and stable psoriasis than either the DLQI or the PDI. PSO-LIFE scores correlated significantly with lesion site and disease severity as measured by PASI. Copyright �

Chronic stress experience and burnout syndrome have appreciable influence on health-related quality of life in patients with psoriasis.

PubMed

Breuer, K; Göldner, F M; Jäger, B; Werfel, T; Schmid-Ott, G

2015-10-01

Psoriasis has a negative impact on health-related quality of life (HRQoL) and may favour mental comorbidity. To investigate the contribution of chronic stress and burnout experience to HRQoL and how mental health influences the efficacy of an inpatient rehabilitation measure in psoriasis patients. Eighty-four psoriasis patients taking part in a 3-week inpatient rehabilitation measure participated in the study. Severity of psoriasis was assessed with the Psoriasis Area and Severity Index (PASI) and by patients' self-evaluation at the beginning and end of treatment. The following aspects of mental health were explored using validated questionnaires. Symptoms of chronic stress and burnout experience: Trier Inventory for the Assessment of Chronic Stress (TICS) and Shirom Melamed Burnout Measure (SMBM). Symptoms of depression: depression scale of the Patient Health Questionnaire in the German version (PHQ-D). HRQoL: Dermatology Life Quality Index (DLQI) and Short Form Health Survey-8 (SF-8). Linear regression analyses revealed that chronic stress, burnout experience and perceived symptom severity but not clinician-assessed severity of psoriasis had independent negative effects on HRQoL. Patients who achieved a PASI reduction of <75% at discharge from the rehabilitation measure had lower baseline QoL and showed more symptoms of depression, chronic stress and burnout than patients who achieved a PASI improvement of ≥75. Chronic stress and burnout have appreciable influence on HRQoL and may adversely affect treatment success in psoriasis patients. Our data underscore the importance of a multidimensional approach in the management of psoriasis. © 2015 European Academy of Dermatology and Venereology.

Efficacy of Tofacitinib for the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis in Patient Subgroups from Two Randomised Phase 3 Trials.

PubMed

Menter, M Alan; Papp, Kim A; Cather, Jennifer; Leonardi, Craig; Pariser, David M; Krueger, James G; Wohlrab, Johannes; Amaya-Guerra, Mario; Kaszuba, Andrzej; Nadashkevich, Oleg; Tsai, Tsen-Fang; Gupta, Pankaj; Tan, Huaming; Valdez, Hernan; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is a Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. We report efficacy of tofacitinib in patient subgroups based on pooled data from two Phase 3 trials (NCT01276639, NCT01309737).
To assess consistency of treatment effects of tofacitinib versus placebo in subgroups defined by baseline characteristics, and to ascertain whether baseline characteristics are of value in optimizing tofacitinib use.
Pooled data from the two trials were used to evaluate ≥75% reduction in PASI from baseline (PASI75 response) in subgroups defined by age, age at psoriasis onset, gender, race, geographical region, weight, body mass index, diabetes, metabolic syndrome, tobacco/alcohol use, psoriatic arthritis, disease activity, and prior therapy.
Week 16 PASI75 response rates (N=1843) were 43%, 59% and 9% with tofacitinib 5 and 10mg twice daily (BID) and placebo, respectively (each P<0.0001 versus placebo). Tofacitinib 5 and 10mg BID were effective regardless of baseline characteristics. Across subgroups, tofacitinib generally produced greater response rates with the 10 versus 5mg BID dosage. Lower absolute response rates were seen in heavier patients and patients with prior biologic experience.
Both tofacitinib dosages demonstrated consistent efficacy versus placebo across subgroups. Lower response rates were seen in heavier patients and those with prior biologic experience. Tofacitinib 10mg BID resulted in a substantial proportion of responders regardless of baseline characteristics.

J Drugs Dermatol. 2016;15(5):568-580.

The efficacy and safety of tofacitinib in Asian patients with moderate to severe chronic plaque psoriasis: A Phase 3, randomized, double-blind, placebo-controlled study.

PubMed

Zhang, JianZhong; Tsai, Tsen-Fang; Lee, Min-Geol; Zheng, Min; Wang, Gang; Jin, HongZhong; Gu, Jun; Li, RuoYu; Liu, QuanZhong; Chen, Jin; Tu, CaiXia; Qi, ChunMei; Zhu, Hua; Ports, William C; Crook, Tim

2017-10-01

Tofacitinib is an oral Janus kinase inhibitor. This study assessed tofacitinib efficacy and safety vs placebo in Asian patients with moderate to severe chronic plaque psoriasis. Patients from China mainland, Taiwan, and Korea were randomized 2:2:1:1 to tofacitinib 5mg (N=88), tofacitinib 10mg (N=90), placebo→5mg (N=44), or placebo→10mg (N=44), twice daily (BID) for 52 weeks. Placebo-treated patients advanced to tofacitinib at Week 16. Co-primary efficacy endpoints: proportions of patients achieving Physician's Global Assessment (PGA) response ('clear' or 'almost clear') and proportion achieving ≥75% reduction from baseline Psoriasis Area and Severity Index (PASI75) at Week 16. At Week 16, more patients achieved PGA and PASI75 responses with tofacitinib 5mg (52.3%; 54.6%) and 10mg (75.6%; 81.1%) BID vs placebo (19.3%; 12.5%; all p<0.0001). Of patients with a Week 16 response, 73.6% and 75.0% maintained PGA response, and 76.8% and 84.9% maintained PASI75 to Week 52 with tofacitinib 5mg and 10mg BID, respectively. Over 52 weeks, 2.2-4.5% of patients across treatment groups experienced serious adverse events, and 1.1-6.8% discontinued due to adverse events. Tofacitinib demonstrated efficacy vs placebo at Week 16 in Asian patients with moderate to severe plaque psoriasis; efficacy was maintained through Week 52. No unexpected safety findings were observed. [NCT01815424]. Copyright © 2017 The Authors and Pfizer Inc. Published by Elsevier B.V. All rights reserved.

Therapeutic drug monitoring of patients with psoriasis during tumour necrosis factor (TNF)-α antagonist treatment using a novel interleukin-8 reporter cell line.

PubMed

Kimura, Y; Shimada-Omori, R; Takahashi, T; Tsuchiyama, K; Kusakari, Y; Yamasaki, K; Nishikawa, R; Nishigori, C; Aiba, S

2016-11-01

Tumour necrosis factor (TNF)-α antagonist therapy is currently used for moderate and severe psoriasis. However, this treatment has several drawbacks, including interindividual variability in clinical response and secondary loss of effectiveness. To evaluate quantitatively the TNF-α-neutralizing activity of the plasma of patients with psoriasis during TNF-α antagonist therapy and to determine poor responders objectively. We used a human interleukin-8 reporter monocyte cell line, THP-G8, that harbours a stable luciferase orange (SLO) gene under the control of the interleukin-8 promoter. After confirming its dose-dependent response to exogenous TNF-α, we examined the suppressive activity of TNF-α antagonists and of the patients' plasma during TNF-α antagonist therapy on TNF-α-induced SLO luciferase activity (TNF-SLO-LA). Pretreatment of TNF-α with TNF-α antagonists or with the plasma of patients with psoriasis who achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) dose dependently suppressed TNF-SLO-LA. There was a significant correlation between change in PASI and percentage suppression (inhibitory rate of a 1 : 2 dilution of patient plasma on TNF-SLO-LA). A percentage suppression of 50·3% has a positive predictive value of 87% of achieving PASI 75, with a sensitivity of 93% and a specificity of 80%. Therapeutic monitoring of patients with psoriasis during TNF-α antagonist therapy using THP-G8 can provide a useful tool to determine objectively the efficacy of the administered TNF-α antagonists. © 2016 British Association of Dermatologists.

Improvement of depressive symptoms in patients with moderate-to-severe psoriasis treated with ustekinumab: an open label trial validated using beck depression inventory, Hamilton depression rating scale measures and 18fluorodeoxyglucose (FDG) positron emission tomography (PET).

PubMed

Kim, Seong-Jang; Park, Min-Young; Pak, Kyoungjune; Han, Junhee; Kim, Gun-Wook; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Byung-Soo

2018-05-07

Psoriasis is a chronic skin disease associated with psychiatric co-morbidities, especially depression. Early detection of psychological vulnerability in patients with psoriasis seems to be of great clinical importance and significantly impacts the quality of life of the patients. We sought to clarify the association between psoriasis and depressive symptoms in patients with moderate-to-severe psoriasis, and to determine the risk factors for depressive symptoms and analyze the effect of ustekinumab on the symptoms. We also aimed to evaluate the changes in glucose metabolism using 18 fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET). Fifteen patients with moderate-to-severe psoriasis scheduled to be treated with ustekinumab were enrolled. At baseline and after achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI75), all patients underwent a psychiatric interview and FDG-PET. Fifteen healthy volunteers were enrolled for comparison. Patients with moderate-to-severe psoriasis were more depressed than those in the control group were (p < .05). The severity of psoriasis at baseline did not correlate with the depression symptoms. Treatment with ustekinumab significantly reduced the depressive symptoms, as verified using Beck Depression Inventory and Hamilton Depression Rating Scale psychiatric interviews (p < .05). However, FDG-PET of the brain showed no significant difference before and after PASI75 achievement using ustekinumab injection. Patients with moderate-to-severe psoriasis are at an increased risk for depressive symptoms, and treatment with ustekinumab may be beneficial. FDG-PET does not reflect the changes in depressive symptoms in such patients.

Global Education Reform: How Privatization and Public Investment Influence Education Outcomes

ERIC Educational Resources Information Center

Adamson, Frank, Ed.; Astrand, Bjorn, Ed.; Darling-Hammond, Linda, Ed.

2016-01-01

With contributions from Linda Darling-Hammond, Michael Fullan, Pasi Sahlberg, and Martin Carnoy, "Global Education Reform" is an eye-opening analysis of national educational reforms and the types of high-achieving systems needed to serve all students equitably.The collection documents the ideologically and educationally distinctive…

Effects of treatment adherence on clinical and economic outcomes in patients with psoriasis.

PubMed

Jevtić, Tatjana; Bukumirić, Zoran; Janković, Slobodan M

2013-02-01

To compare clinical and cost outcomes of psoriasis in non-biological treatment of adherent and non-adherent patients in a developing Balkans country going through socio-economic transition. The study was designed as a retrospective cohort study involving patients with psoriasis adherent and non-adherent to the prescribed treatment regimen. The patients were followed for a period of one year, through four visits with intervals of three months. The adherence to the prescribed regimen was measured at the end of the follow-up period by the medication possession ratio. Clinical outcomes of the treatment were estimated by the Psoriasis Area Severity Index (PASI) at each visit and the treatment costs were collected from patients' files at each visit. The study enrolled 108 patients, 61 (56.5%) were adherent to the prescribed treatment, and 47 (43.5%) were non-adherent. A signiicant decrease of PASI score was noted in the patients adherent to prescribed therapy (p < 0.001). The costs also decreased significantly in the group of adherent patients (p=0.001), and the drop of costs was the highest from the visit 3. The decrease in PASI score and costs were less rapid in non-adherent patients. Better treatment adherence leads to faster clinical improvement and a more rapid decrease in costs of treatment, which diminish overall expenditure of the health system and society, leaving room for treatment of other diseases more efficiently. Therefore, health systems of developing countries should support additional research of causes of treatment non-adherence in patients with psoriasis, in order to minimize this fenomenon more efficiently, and make significant savings.

Metabolic syndrome and psoriasis severity in South-East Asian patients: An investigation of potential association using current and chronological assessments.

PubMed

Chularojanamontri, Leena; Wongpraparut, Chanisada; Silpa-Archa, Narumol; Chaweekulrat, Pichanee

2016-12-01

Although studies regarding prevalence of metabolic syndrome (MS) in Asian psoriatic patients are limited and show varying results, a previous report describes a significant increase in prevalence of MS in Thai psoriatic patients, as compared with rates in the general population. However, no significant association between MS and psoriasis severity using the Psoriasis Area and Severity Index (PASI) was found, which differs from the findings of Korean and Japanese studies. This study aimed at re-evaluating the association between MS and psoriasis severity in Thai patients using current assessment (PASI) and chronological assessment (historical course and interventions). A total of 273 psoriatic patients were recruited. After controlling for age and sex, 96 patients were assigned to the MS group and 96 patients to the non-MS group. Similar to the previous study, no significant differences were identified between metabolic and non-metabolic patients regarding PASI, age of onset, disease duration and family history of psoriasis. However, the numbers of hospitalizations (P = 0.018) and interventions (P = 0.028) were significantly higher in metabolic patients than in non-metabolic patients. Further, a greater number of metabolic components was significantly associated with a higher number of hospitalizations (P = 0.012), pustular or erythrodermic psoriasis episodes (P = 0.049), and interventions (P = 0.005). Body mass index of 23 kg/m 2 or more, abdominal obesity and high blood pressure were associated with an increased risk of treatment failure. Using chronological assessment, our study supported that MS negatively affects psoriasis severity and treatment outcomes. Screening for MS is highly recommended for psoriatic patients. © 2016 Japanese Dermatological Association.

Exposure-Response Modeling to Characterize the Relationship Between Ixekizumab Serum Drug Concentrations and Efficacy Responses at Week 12 in Patients With Moderate to Severe Plaque Psoriasis.

PubMed

Chigutsa, Emmanuel; de Mendizabal, Nieves Velez; Chua, Laiyi; Heathman, Michael; Friedrich, Stuart; Jackson, Kimberley; Reich, Kristian

2018-06-07

Ixekizumab, a high-affinity monoclonal antibody, selectively targets interleukin-17A and has been shown to be efficacious in the treatment of moderate to severe psoriasis. The objective was to describe the relationship between ixekizumab concentrations and efficacy response (static Physician Global Assessment [sPGA] and the Psoriasis Activity and Severity Index [PASI) scores] after 12 weeks of ixekizumab treatment in psoriasis patients from 3 phase 3 studies. Data from 2888 psoriasis patients randomized to receive placebo or 80 mg ixekizumab every 2 weeks or every 4 weeks were analyzed. Separate logistic regression models describing the relationship between ixekizumab concentrations and sPGA or PASI scores at week 12 were used to determine the probability of patients achieving a response and to investigate the impact of various patient factors other than drug concentrations on response rates. Both dosing regimens were efficacious, with higher rates of response achieved with the higher range of observed ixekizumab concentrations after every-2-week dosing. Although higher bodyweight, palmoplantar involvement, lower baseline disease state, or high baseline C-reactive protein were associated with slightly lower response rates, the magnitude of effect of these factors on sPGA(0,1) response was small, with all subgroups able to achieve high levels of response. Other factors tested had no effect including age, sex, and antidrug antibody status. Logistic regression modeling of ixekizumab concentration and efficacy data accurately identified the proportion of responders using sPGA or PASI end points. The higher concentration ranges achieved with 80 mg every 2 weeks versus every 4 weeks were associated with higher response levels. © 2018, The American College of Clinical Pharmacology.

Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat syndrome: a multi-center, double-blind, randomized, placebo-controlled trial.

PubMed

Li, Nuo; Zhao, Wenbin; Xing, Jianmin; Liu, Jianping; Zhang, Guangzhong; Zhang, Yunbi; Li, Yuanwen; Liu, Wali; Shi, Fei; Bai, Yanping

2017-05-15

Traditional Chinese medicine (TCM) has a long history in the treatment of psoriasis vulgaris. We aimed to evaluate the clinical efficacy and safety of Chinese herbal Pulian ointment in treating psoriasis vulgaris of blood-heat syndrome. A multicenter, randomized, double-blind, placebo-controlled trial was conducted. Participants with psoriasis vulgaris of blood-heat syndrome were blinded and randomized to receive Pulian ointment or placebo ointment twice daily for 4 weeks, with follow-up 8 weeks after treatment. Psoriasis Area Severity Index (PASI) scores, severity of each symptom and area of skin lesion and quality of life were assessed at baseline, 2 weeks, and 4 weeks. Adverse events were recorded during the study. SAS 9.4 software and SPSS 17.0 software was applied for data analysis. A total of 300 participants with psoriasis vulgaris of blood-heat syndrome were assessed for eligibility, and 294 were randomly assigned to the Pulian ointment and placebo group from six study centers. Full analysis set (FAS): after 4 weeks of treatment, there were significant differences between groups in PASI score and the separate score of skin lesion area, favoring Pulian ointment group (P < 0.05). However, no significant differences were observed in scores of scaling, erythema and induration/thickness (P > 0.05). Per protocol set (PPS): There was no statistically significant difference in PASI score and separate score of each symptom and area of skin lesion between two groups (P > 0.05). Quality of life measured by Hamilton Anxiety Rating Scale (HAMA) and 36-Item Short Form Health Survey (SF-36) improved after treatment in both groups, but there was no significant difference between the two groups (P > 0.05). After being followed up for 8 weeks, the total relapse rates of the Pulian Ointment group and placebo group were 5.88 and 8.45%, respectively, and the difference was not statistically significant between the two groups (P > 0.05). No adverse

Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A.

PubMed

Schopf, R E; Hultsch, T; Lotz, J; Bräutigam, M

1998-11-01

The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus. We compared the number of blood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate. Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA (n = 21) or etretinate (n = 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0-3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters. After CyA treatment the PASI-score amounted to 24 +/- 4%, after etretinate to 56 +/- 6% of the initial values (mean +/- SEM). One week after CyA treatment, esosinophils dropped from 190 +/- 21 to 137 +/- 16/microliter (P = 0.038, Wilcoxon test), after 10 weeks to 127 +/- 18/microliter (P = 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 +/- 1.30 (CyA) and 15.3 +/- 5.53 micrograms/l (etretinate) were measured (normal range 3-16 micrograms/l), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional. We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.

Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study.

PubMed

Ohtsuki, Mamitaro; Kubo, Hiroshi; Morishima, Hitomi; Goto, Ryosuke; Zheng, Richuan; Nakagawa, Hidemi

2018-06-15

Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52-week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque-type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross-over to guselkumab 50 mg or 100 mg at week 16. Co-primary end-points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI-90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI-90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI-75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment-emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque-type psoriasis. © 2018 Janssen Pharmaceutical K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Influence of dermal exposure to ultraviolet radiation and coal tar (polycyclic aromatic hydrocarbons) on the skin aging process.

PubMed

Borska, Lenka; Andrys, Ctirad; Krejsek, Jan; Palicka, Vladimir; Vorisek, Viktor; Hamakova, Kvetoslava; Kremlacek, Jan; Borsky, Pavel; Fiala, Zdenek

2016-03-01

Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J).

PubMed

Saeki, Hidehisa; Nakagawa, Hidemi; Nakajo, Ko; Ishii, Taeko; Morisaki, Yoji; Aoki, Takehiro; Cameron, Gregory S; Osuntokun, Olawale O

2017-04-01

Psoriasis, a chronic, immune-mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open-label study was to evaluate the long-term efficacy and safety of ixekizumab, a humanized, anti-interleukin-17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment-emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52-week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis. © 2016 Eli Lilly Japan K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial

PubMed Central

Tarcha, Eric J.; Probst, Peter; Peckham, David; Muñoz-Elías, Ernesto J.; Kruger, James G.; Iadonato, Shawn P.

2017-01-01

Background Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. Objective The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations. Methods Patients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires. Results The most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells. Limitations The study was small and drug treatment was for a short duration (4 weeks). Conclusion This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted. PMID:28723914

Autologous Adipose-Derived Mesenchymal Stromal Cells for the Treatment of Psoriasis Vulgaris and Psoriatic Arthritis: A Case Report.

PubMed

De Jesus, Miguel M; Santiago, Jayson S; Trinidad, Camille V; See, Melvin E; Semon, Kimberly R; Fernandez, Manuel O; Chung, Francisco S

2016-11-01

Psoriasis is a dermatologic disease of immune origins with no definitive cure. We report the Makati Medical Center experience of utilizing autologous mesenchymal stromal cells (MSCs) for one patient with psoriasis vulgaris (PV) and another with psoriatic arthritis (PA). Patients were educated and gave informed consent, according to the principles of the Declaration of Helsinki. The protocol was approved by the Cellular Transplantation Ethics Committee of the Makati Medical Center. Autologous MSCs were cultured from lipoaspirate and expanded in a clean room class 100 facility (Cellular Therapeutics Center, Makati Medical Center). MSCs were infused intravenously at a dose of 0.5-3.1 million cells/kg after complying with quality control parameters. Psoriasis area and severity index (PASI) evaluations were conducted by third-party dermatologists. The PA patient, who was previously unresponsive to standard treatment modalities, demonstrated a decrease in PASI (from 21.6 to 9.0, mild state after two infusions). No improvements were noted in joint pain until further treatment with etanercept and infliximab. The PV patient, who was previously dependent on methotrexate, showed a decrease in PASI from 24.0 to 8.3 after three infusions; this clinical improvement was sustained for 292 days (9.7 months) without methotrexate. The PV patient illustrated a marginal reduction in serum tumor necrosis factor-α (TNF-α), while significant (3.5- to 5-fold) decreases in reactive oxygen species (ROS) activity were noted. The ROS levels correlated with the clinical improvement of the PV patient. No serious adverse events were noted for either patient as a result of MSC infusions. This report demonstrates safe and tolerable transplantation of autologous MSCs for the treatment of psoriasis and warrants large clinical studies to investigate the long-term safety and efficacy of this approach.

Subject-enabled analytics model on measurement statistics in health risk expert system for public health informatics.

PubMed

Chung, Chi-Jung; Kuo, Yu-Chen; Hsieh, Yun-Yu; Li, Tsai-Chung; Lin, Cheng-Chieh; Liang, Wen-Miin; Liao, Li-Na; Li, Chia-Ing; Lin, Hsueh-Chun

2017-11-01

This study applied open source technology to establish a subject-enabled analytics model that can enhance measurement statistics of case studies with the public health data in cloud computing. The infrastructure of the proposed model comprises three domains: 1) the health measurement data warehouse (HMDW) for the case study repository, 2) the self-developed modules of online health risk information statistics (HRIStat) for cloud computing, and 3) the prototype of a Web-based process automation system in statistics (PASIS) for the health risk assessment of case studies with subject-enabled evaluation. The system design employed freeware including Java applications, MySQL, and R packages to drive a health risk expert system (HRES). In the design, the HRIStat modules enforce the typical analytics methods for biomedical statistics, and the PASIS interfaces enable process automation of the HRES for cloud computing. The Web-based model supports both modes, step-by-step analysis and auto-computing process, respectively for preliminary evaluation and real time computation. The proposed model was evaluated by computing prior researches in relation to the epidemiological measurement of diseases that were caused by either heavy metal exposures in the environment or clinical complications in hospital. The simulation validity was approved by the commercial statistics software. The model was installed in a stand-alone computer and in a cloud-server workstation to verify computing performance for a data amount of more than 230K sets. Both setups reached efficiency of about 10 5 sets per second. The Web-based PASIS interface can be used for cloud computing, and the HRIStat module can be flexibly expanded with advanced subjects for measurement statistics. The analytics procedure of the HRES prototype is capable of providing assessment criteria prior to estimating the potential risk to public health. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-of-illness in patients with moderate to severe psoriasis: a cross-sectional survey in Hungarian dermatological centres.

PubMed

Balogh, Orsolya; Brodszky, Valentin; Gulácsi, László; Herédi, Emese; Herszényi, Krisztina; Jókai, Hajnalka; Kárpáti, Sarolta; Baji, Petra; Remenyik, Éva; Szegedi, Andrea; Holló, Péter

2014-05-01

Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies. To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary. Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures. Two-hundred patients were involved (females 32%) with a mean age of 51 (SD 13) years, 103 (52%) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86%. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups. Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.

Easy-interactive and quick psoriasis lesion segmentation

NASA Astrophysics Data System (ADS)

Ma, Guoli; He, Bei; Yang, Wenming; Shu, Chang

2013-12-01

This paper proposes an interactive psoriasis lesion segmentation algorithm based on Gaussian Mixture Model (GMM). Psoriasis is an incurable skin disease and affects large population in the world. PASI (Psoriasis Area and Severity Index) is the gold standard utilized by dermatologists to monitor the severity of psoriasis. Computer aid methods of calculating PASI are more objective and accurate than human visual assessment. Psoriasis lesion segmentation is the basis of the whole calculating. This segmentation is different from the common foreground/background segmentation problems. Our algorithm is inspired by GrabCut and consists of three main stages. First, skin area is extracted from the background scene by transforming the RGB values into the YCbCr color space. Second, a rough segmentation of normal skin and psoriasis lesion is given. This is an initial segmentation given by thresholding a single gaussian model and the thresholds are adjustable, which enables user interaction. Third, two GMMs, one for the initial normal skin and one for psoriasis lesion, are built to refine the segmentation. Experimental results demonstrate the effectiveness of the proposed algorithm.

Medical Fitness for Expeditionary Missions: A NATO Guide for Assessing Deployability for Military Personnel with Medical Conditions. Task Group 174, Human Factors and Medicine Panel

DTIC Science & Technology

2013-07-30

preventing movement of the thrombus toward the lungs. Pulmonary embolism is the obstruction of a pulmonary artery due to the presence of air, fat , blood...Organization NSAID Nonsteroidal anti-inflammatory drugs OCD Obsessive-Compulsive Disorder PASI Psoriasis Area & Severity Index PE Pulmonary embolism PEF...as cancer, infection, cauda equina syndrome, spinal stenosis or radiculopathy, vertebral compression fracture or ankylosing spondylitis); OR

Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

PubMed

Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui

2017-10-01

Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

PASIS: A Distributed Framework for Perpetually Available and Secure Information Systems

DTIC Science & Technology

2005-07-01

6.5.3 Random over-requesting vs . intelligent server selection ......................... 76 6.5.4 Which server selection algorithm to use; which r value...of 16 KB blocks. .................................................................................. 98 Figure 8-4. Mean response time vs . Total

Psoriasis and polycystic ovary syndrome: a new link in different phenotypes.

PubMed

Moro, Francesca; Tropea, Anna; Scarinci, Elisa; Federico, Alex; De Simone, Clara; Caldarola, Giacomo; Leoncini, Emanuele; Boccia, Stefania; Lanzone, Antonio; Apa, Rosanna

2015-08-01

Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A - patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B - patients with H plus O (without PCO); C - patients with H plus PCO (ovulatory phenotype); D - patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59-13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40-211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01-0.51). The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group. Copyright © 2015 Elsevier Ireland Ltd. All rights

Educational and motivational support service: a pilot study for mobile-phone-based interventions in patients with psoriasis.

PubMed

Balato, N; Megna, M; Di Costanzo, L; Balato, A; Ayala, F

2013-01-01

 Psoriasis is a chronic disease which requires long-term therapy. Therefore, adherence to therapy and patient motivation are key points in controlling the disease. Mobile-phone-based interventions, and in particular text messages (TM), have already been used effectively to motivate patients and improve treatment adherence in many different chronic diseases such as diabetes, cardiovascular disease and asthma. To evaluate the use of TM in improving treatment adherence and several patient outcomes such as quality of life, disease severity, patient-perceived disease severity and the patient-physician relationship. Daily TM, providing reminders and educational tools, were sent for 12 weeks to a group of 20 patients with psoriasis. At the beginning and end of the study the following assessments were performed: Psoriasis Area Severity Index (PASI), Self-Administered Psoriasis Area Severity Index (SAPASI), body surface area (BSA), Physician Global Assessment (PGA), Dermatology Life Quality Index (DLQI), evaluation of patient-physician relationship and adherence to therapy. A matched control group of 20 patients with psoriasis was used for comparison of the same outcomes. Both patient groups had similar scores for PASI, SAPASI, BSA, PGA and DLQI at baseline. However, after 12 weeks the intervention group reported a significantly better improvement of disease severity as well as quality of life, showing lower values of PASI, SAPASI, BSA, PGA and DLQI with respect to the control group (P<0·05). Moreover, adherence to therapy improved in a statistically significant way (P<0·001) whereas it remained stable in the control group. Similarly, TM interventions led to an optimization of patient-physician communication.  TM interventions seem to be a very promising tool for the long-term management of patients with psoriasis, leading to an increased compliance to therapy, positive changes in self-care behaviours and better patient-physician relationship allowing improved

Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis.

PubMed

Papp, Kim A; Blauvelt, Andrew; Bukhalo, Michael; Gooderham, Melinda; Krueger, James G; Lacour, Jean-Philippe; Menter, Alan; Philipp, Sandra; Sofen, Howard; Tyring, Stephen; Berner, Beate R; Visvanathan, Sudha; Pamulapati, Chandrasena; Bennett, Nathan; Flack, Mary; Scholl, Paul; Padula, Steven J

2017-04-20

Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12. At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group. In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).

Effects of Rusanda Spa balneotherapy combined with calcipotriol on plaque psoriasis.

PubMed

Golusin, Zoran; Jovanović, Marina; Magda, Natasa; Stojanović, Slobodan; Matić, Milan; Petrović, Aleksandra

2015-11-01

Treatment of psoriasis is very complex and there are no still universal, nor unique treatment modalities. Apart from conventional treatment, which includes topical calcipotriol (vitamin D3 analogue), balneotherapy is drawing increased attention worldwide. Being part of climatotherapy, balneotherapy is defined as the use of natural environmental factors in the treatment of health conditions, whereas in the treatment of psoriasis it means the use of mineral baths and peloids. The aim of this study was to examine the therapeutic efficacy of mineral waters and peloids of the Rusanda Spa on plaque psoriasis in patients also treated with calcipotriol. The study included 60 patients divided into two groups. The first group included patients treated with mineral waters, peloids and calcipotriol in the Rusanda Spa, while the second one included those treated only with calcipotriol. The study took 21 days, and each patient was followed up for at least one month after ending the treatment. The treatment efficacy was measured by psoriasis area severity index (PASI) scores on the days 0, 7, 14 and 21 during the treatment and 30 after the end of the therapy. After a 3-week treatment in the Rusanda Spa, the first group showed a decrease in PASI score by 59.45%, whereas in the group of outpatients treated by calcipotriol it was 39.34%. On the day 30 following the treatment, the first group presented with the PASI score reduction of 58.44%, and the second group of 34.78%. The therapeutic efficacy of mineral waters and peloids combined with calcipotriol showed to be significantly higher in regard to monotherapy with calcipotriol (p < 0.05). In regard to clinical symptoms, the best results were obtained in the reduction of desquamation (p < 0.001). The results of our study show that in the treatment of plaque-type psoriasis, topical calcipotriol combined with Spa Rusanda balineotherapy is more effective than topical calcipotriol alone. Randomized controlled trials are needed to

An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

PubMed

Warren, Richard B; Mrowietz, Ulrich; von Kiedrowski, Ralph; Niesmann, Johannes; Wilsmann-Theis, Dagmar; Ghoreschi, Kamran; Zschocke, Ina; Falk, Thomas M; Blödorn-Schlicht, Norbert; Reich, Kristian

2017-02-04

Methotrexate is one of the most commonly used systemic drugs for the treatment of moderate to severe psoriasis; however, high-quality evidence for its use is sparse and limited to use of oral dosing. We aimed to assess the effect of an intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis. We did this prospective, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (METOP) at 16 sites in Germany, France, the Netherlands, and the UK. Eligible patients were aged 18 years or older, had a diagnosis of chronic plaque psoriasis for at least 6 months before baseline, had currently moderate to severe disease, and were methotrexate treatment-naive. Participants were randomly assigned (3:1), via a computer-generated random number sequence integrated into an electronic data capture system, to receive either methotrexate at a starting dose of 17·5 mg/week or placebo for the first 16 weeks, followed by methotrexate treatment of all patients up to 52 weeks (methotrexate-methotrexate vs placebo-methotrexate groups). Dose escalation to 22·5 mg/week was allowed after 8 weeks of methotrexate treatment if patients had not achieved at least a 50% reduction in baseline Psoriasis Area and Severity Index score (PASI), with corresponding volume increases in placebo injections. Treatment was combined with folic acid 5 mg/week. Group allocation was concealed from participants and investigators from the time of randomisation until an interim database lock at week 16, and was open label from week 16 onwards, with no masking of participants or investigators. The primary efficacy endpoint was a 75% reduction in PASI score (PASI 75) from baseline to week 16. We did analysis by modified intention to treat, with non-responder imputation. This study is registered with EudraCT, number 2012-002716-10. Between Feb 22, 2013, and May 13, 2015, we randomly assigned 120 patients to receive methotrexate (n=91) or placebo (n

Proceedings of the Navy Symposium on Aeroballistics (10th) Held at the Sheraton Motor Inn, Fredericksburg, Virginia on 15-16-17 July 1975. Volume 1

DTIC Science & Technology

1975-07-17

Impact Thomas B. McDonough Aeronautical Research Associates of Princeton. Inc. Princeton, New Jersey ...32460 [whi Naval Surface Weapons Center Dahigren Laboratory PASI UK , L. Code DG-40 Naval Sea Systems Comond Dah~gren, VA 22448 SEA -03513 (703...perturbation upwa h veLoci- tieas -inued by -the constant u-velocitv panels. ’?he axial an side force coponents, 6F and LFy, are then ca, u.,, -- -f

Jojoba Oil Soft Colloidal Nanocarrier of a Synthetic Retinoid: Preparation, Characterization and Clinical Efficacy in Psoriatic Patients.

PubMed

Nasr, Maha; Abdel-Hamid, Sameh; Moftah, Noha H; Fadel, Maha; Alyoussef, Abdullah A

2017-01-01

Nanotechnology has provided substantial benefits in drug delivery, especially in the treatment of dermatological diseases. Psoriasis is a chronic inflammatory skin disease in which topical delivery of antipsoriatic agents is considered the first line treatment. To investigate whether the encapsulation of the synthetic retinoid tazarotene in a nanocarrier based on jojoba oil would decrease its irritation potential and clinically improve its therapeutic outcome in psoriatic patients. A microemulsion system based on jojoba wax and labrasol/plurol isostearique was prepared and characterized. The selected formula displayed spherical morphology, particle size of 15.49±2.41 nm, polydispersity index of 0.20 ±0.08, negative charge and low viscosity. The microemulsion provided two folds increase in skin deposition of tazarotene, correlating with higher reduction in psoriatic patients PASI scores after treatment (68% reduction in PASI scores versus 8.96% reduction with the marketed gel). No irritation was encountered in patients using microemulsion, with redness and inflammation reported with the marketed gel-treated patients. Jojoba oil microemulsion proved to be advantageous in reducing the irritancy of tazarotene, enhancing its skin deposition and achieving better therapeutic outcome in psoriatic patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial.

PubMed

Papp, Kim; Thaçi, Diamant; Marcoux, Danielle; Weibel, Lisa; Philipp, Sandra; Ghislain, Pierre-Dominique; Landells, Ian; Hoeger, Peter; Kotkin, Carol; Unnebrink, Kristina; Seyger, Marieke; Williams, David

2017-07-01

Adalimumab is indicated for the treatment of moderate to severe psoriasis in adults. We assessed the efficacy and safety of adalimumab in children and adolescents with severe plaque psoriasis. This randomised, double-blind, multiperiod, phase 3 trial was done at 38 clinics in 13 countries. Patients (aged ≥4 to <18 years) with severe plaque psoriasis who had not responded to topical therapy were randomly assigned with an interactive voice or web-response system (1:1:1) to receive adalimumab 0·8 mg/kg or 0·4 mg/kg subcutaneously at week 0, then every other week starting at week 1, or oral methotrexate once weekly (0·1-0·4 mg/kg) for 16 weeks. Randomisation was stratified by history of etanercept treatment, with a block size of three. Responders were withdrawn from treatment (for up to 36 weeks) and re-treated with adalimumab (for 16 weeks) if disease became uncontrolled. Ranked primary efficacy endpoints were the proportion of patients who achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75) score and clear or minimal physician global assessment (PGA) score at week 16, comparing adalimumab 0·8 mg/kg with methotrexate. Efficacy analysis was by intention to treat, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01251614, and has been completed. Between Dec 14, 2010, and Feb 5, 2015, 114 patients were randomly assigned to adalimumab 0·8 mg/kg (n=38), adalimumab 0·4 mg/kg (n=39) or methotrexate (n=37). At week 16, PASI75 was achieved in 22 (58%) of 38 patients in the adalimumab 0·8 mg/kg group compared with 12 (32%) of 37 patients in the methotrexate group (p=0·027). 23 (61%) of 38 patients in the adalimumab 0·8 mg/kg group and 15 (41%) of 37 in the methotrexate group achieved clear or minimal PGA (p=0·083). In the adalimumab 0·4 mg/kg group, 17 (44%) of 39 patients achieved PASI75 and 16 (41%) achieved clear or

Secukinumab Self-Administration by Prefilled Syringe Maintains Reduction of Plaque Psoriasis Severity Over 52 Weeks: Results of the FEATURE Trial.

PubMed

Gottlieb, Alice B; Blauvelt, Andrew; Prinz, Jörg C; Papanastasiou, Philemon; Pathan, Rashidkhan; Nyirady, Judit; Fox, Todd; Papavassilis, Charis

2016-10-01

Secukinumab, a human monoclonal antibody that selectively targets interleukin-17A, is highly efficacious in the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg, or placebo self-administered by prefilled syringe at baseline, weeks 1, 2, and 3, and then every four weeks from week 4 to 48. Efficacy responses (≥ 75/90/100% improvement in Psoriasis Area and Severity Index [PASI 75/90/100] and clear/almost clear skin by Investigator's Global Assessment 2011 modified version [IGA mod 2011 0/1]) were measured to week 52. Patient-reported usability of the prefilled syringe was evaluated by the Self-Injection Assessment Questionnaire to week 48. The efficacy of secukinumab increased to week 16 and was maintained to week 52. With secukinumab 300 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 83.5%/68.0%/47.5% and 71.5% of patients when analyzed by multiple imputation, respectively, and by 75.9%/62.1%/43.1% and 63.8% of patients when analyzed by nonresponder imputation, respectively. With secukinumab 150 mg at week 52, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 63.5%/50.3%/31.1% and 43.6% of patients when analyzed by multiple imputation, respectively, and by 61.0%/49.2%/30.5% and 42.4% of patients when analyzed by nonresponder imputation, respectively. Self-reported acceptability of the prefilled syringe was high throughout the study. The incidence of adverse events (AE) was well balanced between groups, with AEs reported in 74.4% of patients receiving secukinumab 300 mg and 77.3% of patients receiving secukinumab 150 mg. Nasopharyngitis was the most common AE across both secukinumab groups. Self-administration of secukinumab by prefilled syringe was associated with robust and sustained efficacy and a favorable safety profile up to week

Work Productivity and Costs Related to Patients with Ankylosing Spondylitis, Rheumatoid Arthritis, and Psoriasis.

PubMed

Kruntorádová, Klára; Klimeš, Jiří; Šedová, Liliana; Štolfa, Jiří; Doležal, Tomáš; Petříková, Alena

2014-09-01

To determine and compare the impact of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis on work productivity, to calculate the productivity costs (PC), and to map out factors that influence (functional status and disease activity) work productivity. The Work Productivity and Activity Impairment questionnaire was used to evaluate productivity losses of patients with RA (n = 77), AS (n = 230), and psoriasis (n = 93). Demographic data, patient-reported outcomes (PROs) (Health Assessment Questionnaire [HAQ] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and clinical parameters (Disease Activity Score in 28 joints [DAS28], body surface area [BSA], and Psoriasis Area and Severity Index [PASI]) were collected. The correlations among PROs, clinical parameters, and overall productivity loss were examined, and multiple regression models were used to examine relationships among parameters and productivity loss. PC were calculated using the friction cost approach. Mean patient age and disease duration were 47.1 and 15.7 years, respectively. The mean HAQ and DAS28 in patients with RA were 1.22 and 5.6, respectively. The mean BASDAI score in patients with AS was 4.43. The mean BSA and PASI score in patients with psoriasis were 21.1% and 12.9, respectively. The percentage of patients with psoriatic arthritis (in those with psoriasis) was 24.7%. We did not find significant differences in Work Productivity and Activity Impairment domains among various diagnoses. Patients with AS, RA, and psoriasis reported overall work productivity losses of 40.9%, 42.9%, and 42.8%, respectively. Daily activity impairments were approximately 50.0%. Overall work productivity loss strongly correlated with PROs, whereas correlations with clinical parameters were weak. The HAQ and BASDAI were identified as major predictors of productivity impairment. The greatest loss in productivity was in those with psoriatic arthritis; however, it was not significant. In

A NATO Guide for Assessing Deployability for Military Personnel with Medical Conditions (Guide OTAN d’evaluation de l’aptitude medicale a la projection du personnel militaire)

DTIC Science & Technology

2014-06-01

Pulmonary Embolism (PE) / Deep Venous Thrombosis (DVT) 3-9 3.2.16.3 Venous Insufficiency 3-9 3.2.17 Vision/Ophthalmology 3-9 3.2.17.1 Refractive Surgery...Thoracic Aortic Aneurysms 3-63 3.3.16.2 History of Pulmonary Embolism (PE) or Deep Venous Thrombosis 3-65 (DVT) 3.3.16.3 Venous Insufficiency 3-67...Drugs OCD Obsessive-Compulsive Disorder PASI Psoriasis Area and Severity Index PE Pulmonary Embolism PEF Peak Expiratory Flow PHA Periodic

Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels.

PubMed

Baran, A; Świderska, M; Myśliwiec, H; Flisiak, I

2017-03-01

Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment. Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement. Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis.

PubMed

Amin, M; Darji, K; No, D J; Wu, J J

2017-10-01

The development of monoclonal antibodies targeting IL-12 and IL-23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL-23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti-IL-23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti-IL-23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL-17 inhibitors with a favourable short-term safety profile. The results of the phase III trials support the notion that IL-23 is a potential target in psoriasis treatment. © 2017 European Academy of Dermatology and Venereology.

Serum YKL-40 as a potential biomarker of inflammation in psoriasis.

PubMed

Baran, Anna; Myśliwiec, Hanna; Szterling-Jaworowska, Malgorzata; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona

2018-02-01

YKL-40 is an inflammatory glycoprotein associated with atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of the study was to assess serum YKL-40 level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and treatment. A total of 37 individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and topical therapy. Median YKL-40 serum levels were significantly increased in psoriatic patients in comparison to the controls (p < .0001). No significant correlations between investigated protein and metabolic parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found. Significant positive relation with CRP (p = .003) or alanine aminotransferase (p = .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level remained unchanged (p = .5) after topical treatment, despite clinical improvement. YKL-40 might be a biomarker of psoriasis and inflammation in psoriatic patients, but not a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of the treatment.

Physical and Mental Impact of Psoriasis Severity as Measured by the Compact Short Form-12 Health Survey (SF-12) Quality of Life Tool

PubMed Central

Grozdev, Ivan; Kast, Douglas; Cao, Lauren; Carlson, Diana; Pujari, Prasad; Schmotzer, Brian; Babineau, Denise; Kern, Elizabeth; McCormick, Thomas; Cooper, Kevin D.; Korman, Neil J.

2012-01-01

The Short Form-12 Health Survey (SF-12) is used to assess the patient’s quality of life (QoL) using the physical component score (PCS) and the mental component score (MCS). The purpose of this study was to determine whether the SF-12 PCS and MCS are associated with psoriasis severity and to compare QoL between Murdough Family Center for Psoriasis (MFCP) patients and patients with other major chronic diseases included in the National Survey of Functional Health Status data. We used data from 429 adult patients enrolled in MFCP. Psoriasis Area Severity Index (PASI) was used to assess psoriasis severity at the time of completion of the SF-12 questionnaire. Other variables included age, sex, body mass index, psoriatic arthritis, psychiatric disorders, and comorbidities. Linear regression models were used to estimate effect sizes ±95% confidence intervals. For every 10-point increase in PASI, there was a 1.1±1.3 unit decrease in MCS (P = 0.100) and a 2.4±1.3 unit decrease in PCS (P<0.001). Psoriasis severity was associated with PCS and MCS after adjusting for variables, although the strength of the relationship was attenuated in some models. Psoriasis severity is associated with decreased QoL. SF-12 may be a useful tool for assessing QoL among psoriasis patients. PMID:22205305

Patterns of clinical nail appearances in patients with cutaneous psoriasis

PubMed Central

MARINA, ELENA MIHAELA; BOTAR-JID, CAROLINA; BOLBOACA, SORANA DANIELA; ROMAN, IULIA IOANA; SENILA, CORINA SIMONA; MIHU, CARMEN MIHAELA; TATARU, DUMITRU ALEXANDRU

2017-01-01

Background and aim Nail manifestations are often an overlooked aspect in psoriatic disease, cutaneous and joint involvement being far more often reported and investigated. The reported prevalence of nail changes varies in literature, specific fingernail clinical features having different degrees of occurrence. The aim of this study was to describe specific clinical patterns of fingernail alterations in adult patients with plaque-type psoriasis in a university hospital in the North-West of Romania. Methods Clinical data of 35 patients with fingernail psoriasis were collected and analyzed. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were used to quantify disease extension in each patient. Results PASI score proved linearly correlated with NAPSI score (p<0.05). The age of onset of fingernail psoriasis was positively correlated with age of onset cutaneous psoriasis (p<0.0001). Furthermore, the duration of cutaneous involvement and NAPSI proved significantly related (p<0.05). The third fingernail in the right hand and first fingernail in the left hand were in most of the cases severely affected. The most common observed nail pattern was pitting, followed by salmon patches and subungual hyperkeratosis. Conclusion Important nail changes appear even in moderate forms of cutaneous psoriasis. Particular localization of specific fingernail psoriasis pattern enables the possibility of detecting early stage disease. PMID:28246493

Serum irisin levels in patients with psoriasis.

PubMed

Baran, Anna; Myśliwiec, Hanna; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona

2017-06-01

Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p = 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p = 0.37) or PASI (p = 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p = 0.02), age (p = 0.02) and disease duration (p = 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p = 0.31), despite clinical improvement. Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.

9th Transgenic Technology Meeting (TT2010) in Berlin, Germany: a meeting report.

PubMed

Saunders, Thomas L; Sobieszczuk, Peter

2010-12-01

The first Transgenic Technology (TT) Meeting was organized in 1999 by Johannes Wilbertz, Karolinska Institute, Stockholm, Sweden as a regional meeting. The TT Meetings continued in this way, constantly gathering additional practitioners of transgenic methodologies until the breakthrough in 2005 when the 6th TT Meeting in Barcelona, Spain, hosted by Lluis Montoliu (Centro Nacional de Biotecnologia, Madrid, Spain), generated the momentum to establish the International Society for Transgenic Technologies (ISTT). Since 2006, the ISTT has continued to promote the TT Meetings and provide its membership with a forum to discuss best practices and new methods in the field. The TT2010 Meeting was held at the Max Delbrück Center for Molecular Medicine (Berlin, Germany). Participation at the TT2010 Meeting exceeded the registration capacity and set a new attendance record. Session topics included methods for the generation of rat and mouse models of human disease, fundamental and advanced topics in rodent embryonic stem cells, and the newest transgenic technologies. Short presentations from selected abstracts were of especial interest. Roundtable discussions on transgenic facility establishment and cryoarchiving of mouse lines were favorably received. Students, technical staff, and professors participated in numerous discussions and came away with practical methods and new ideas for research.

Novel Magnetic Devices

DTIC Science & Technology

2007-10-12

Vincent, Magnetism Magnetic Materials (LAW3MO5), Vifia del Mar, Chile, December 11-15, 2005. 5. Nanomagnetism, Ivan K. Schuller, Pan America Advanced Study Institute, PASI 2007, Zacatecas , Mexico , June 19, 2007. 6 ...project explored the design, preparation, measurement and theoretical study of these novel magnetic devices. Modem thin film techniques (sputtering and...results to motion associated with the unstable nature of mechanical contacts In order to exploit BMR from a device point of view (or to make it useful in a

Apremilast and Narrowband Ultraviolet-B Combination Therapy for Treating Moderate-to-Severe Plaque Psoriasis.

PubMed

Bagel, Jerry; Nelson, Elise; Keegan, Brian R

2017-10-01

Combining narrowband UVB (NB-UVB) phototherapy with biologics has been shown to enhance the therapeutic response of plaque psoriasis patients. The objective of this study was to evaluate the effectiveness of apremilast combined with NB-UVB in patients with moderate to severe plaque psoriasis. This was a 12-week, open-label study of 29 patients diagnosed with moderate to severe psoriasis. Patients received apremilast 30 mg twice daily, and increasing doses of NB-UVB (310-312 nm) 3 times per week for 12 weeks. Twenty-two of 29 patients (76%) completed the 12-week apremilast and NB-UVB combination therapy; 73% (16 of 22 completers) achieved a PASI 75 response at week 12. Mean scores for PASI, VAS pain, VAS itch, DLQI, and PGA improved by 77%, 77%, 69%, 70%, and 67%, respectively, at week 12. The most commonly reported adverse events (AEs) were mild and moderate first-degree burns related to NB-UVB (n=11 [38%] patients). A second-degree NB-UVB burn was reported (likely due to an underlying photosensitivity) and was considered a serious AE. The combination of apremilast with NB-UVB was effective for the treatment of moderate to severe plaque psoriasis, without any unexpected safety signals. Apremilast combined with NB-UVB provided a high treatment response in patients with moderate to severe plaque psoriasis, and may be an option for patients to enhance a patient's initial therapeutic response.

J Drugs Dermatol. 2017;16(10):957-962.

Identification of multidrug resistant protein 1 of mouse leukemia P388 cells on a PVDF membrane using 6-aminoquinolyl-carbamyl (AQC)-amino acid analysis and World Wide Web (WWW)-accessible tools.

PubMed

Shindo, N; Fujimura, T; Nojima-Kazuno, S; Mineki, R; Furusawa, S; Sasaki, K; Murayama, K

1998-11-15

Multidrug resistant protein 1 (MDR1) in a doxorubicin-resistant mouse leukemia cell line (P388/DOX) was identified using its amino acid composition combined with protein database searching (ExPASy and EMBL PROPSEARCH) via the World Wide Web. The proteins were separated by one-dimensional SDS-polyacrylamide gel electrophoresis, blotted onto a polyvinylidene fluoride membrane, and stained with Coomassie brilliant blue. A 160-kDa protein band was acid-hydrolyzed in the vapor phase (6 N HC1) and converted to 6-aminoquinolyl-carbamyl (AQC)-amino acids without extraction of the amino acids from the membrane. The amino acid composition of the protein was determined using the sensitive AQC-amino acid analysis method, improving our previously described method. The improved method involved using a Cosmosil 5C8-MS column instead of a Pegasil C8; replacement of the mobile phase A, constituent, 75 mM ammonium phosphate (pH 7.5), with 30 mM sodium phosphate buffer (pH 7.2); and slight modification of the separation program (9). All manipulations for protein hydrolysis and AQC derivatization were carried out in a hood using clean tools. This minimized contamination of amino acids at the low femtomolar level. A database search was carried out with bovine serum albumin as a calibration protein. MDR1 in P388/DOX was ranked first by both databases with high reliability (score 14 for ExPASy, distance 1.34 for EMBL).

Development of sedentary communities in the Maya lowlands: coexisting mobile groups and public ceremonies at Ceibal, Guatemala.

PubMed

Inomata, Takeshi; MacLellan, Jessica; Triadan, Daniela; Munson, Jessica; Burham, Melissa; Aoyama, Kazuo; Nasu, Hiroo; Pinzón, Flory; Yonenobu, Hitoshi

2015-04-07

Our archaeological investigations at Ceibal, a lowland Maya site located in the Pasión region, documented that a formal ceremonial complex was built around 950 B.C. at the onset of the Middle Preclassic period, when ceramics began to be used in the Maya lowlands. Our refined chronology allowed us to trace the subsequent social changes in a resolution that had not been possible before. Many residents of Ceibal appear to have remained relatively mobile during the following centuries, living in ephemeral post-in-ground structures and frequently changing their residential localities. In other parts of the Pasión region, there may have existed more mobile populations who maintained the traditional lifestyle of the preceramic period. Although the emerging elite of Ceibal began to live in a substantial residential complex by 700 B.C., advanced sedentism with durable residences rebuilt in the same locations and burials placed under house floors was not adopted in most residential areas until 500 B.C., and did not become common until 300 B.C. or the Late Preclassic period. During the Middle Preclassic period, substantial formal ceremonial complexes appear to have been built only at a small number of important communities in the Maya lowlands, and groups with different levels of sedentism probably gathered for their constructions and for public rituals held in them. These collaborative activities likely played a central role in socially integrating diverse groups with different lifestyles and, eventually, in developing fully established sedentary communities.

Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis.

PubMed

Cheng, Hui-Man; Wu, Yang-Chang; Wang, Qingmin; Song, Michael; Wu, Jackson; Chen, Dion; Li, Katherine; Wadman, Eric; Kao, Shung-Te; Li, Tsai-Chung; Leon, Francisco; Hayden, Karen; Brodmerkel, Carrie; Chris Huang, C

2017-09-02

Indigo naturalis is a Traditional Chinese Medicine (TCM) ingredient long-recognized as a therapy for several inflammatory conditions, including psoriasis. However, its mechanism is unknown due to lack of knowledge about the responsible chemical entity. We took a different approach to this challenge by investigating the molecular profile of Indigo naturalis treatment and impacted pathways. A randomized, double-blind, placebo-controlled clinical study was conducted using Indigo naturalis as topical monotherapy to treat moderate plaque psoriasis in a Chinese cohort (n = 24). Patients were treated with Indigo naturalis ointment (n = 16) or matched placebo (n = 8) twice daily for 8 weeks, with 1 week of follow-up. At week 8, significant improvements in Psoriasis Area and Severity Index (PASI) scores from baseline were observed in Indigo naturalis-treated patients (56.3% had 75% improvement [PASI 75] response) compared with placebo (0.0%). A gene expression signature of moderate psoriasis was established from baseline skin biopsies, which included the up-regulation of the interleukin (IL)-17 pathway as a key component; Indigo naturalis treatment resulted in most of these signature genes returning toward normal, including down-regulation of the IL-17 pathway. Using an in vitro keratinocyte assay, an IL-17-inhibitory effect was observed for tryptanthrin, a component of Indigo naturalis. This study demonstrated the clinical efficacy of Indigo naturalis in moderate psoriasis, and exemplified a novel experimental medicine approach to understand TCM targeting mechanisms. NCT01901705 .

The association between etanercept serum concentration and psoriasis severity is highly age-dependent.

PubMed

Detrez, Iris; Van Steen, Kristel; Segaert, Siegfried; Gils, Ann

2017-06-01

The association between etanercept serum concentration and psoriasis disease severity is poorly investigated, and currently etanercept serum concentration monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every 3 months for a period of 1 year. The present study demonstrated that the association between etanercept concentration and psoriasis severity is age-dependent: when patients were stratified into three groups, patients in the youngest age group (-50 years) showed a lower PASI at a higher etanercept concentration (β = -0.26), whereas patients in the oldest age group (+59 years) showed the opposite trend (β =0.22). Similar age effects were observed in the relation of etanercept concentration with BSA ( P =0.02) and PGA ( P =0.02). The influence of age and length of time in therapy on the etanercept concentration-disease severity relation was unaffected by body mass index (BMI) or any other possible confounder. Incidence of anti-etanercept antibodies was low (2%). The age-dependent relation between etanercept serum concentrations is both unexpected and intriguing and needs further investigation. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Impact of fumaric acid esters on cardiovascular risk factors and depression in psoriasis: a prospective pilot study.

PubMed

Schmieder, Astrid; Poppe, Manuel; Hametner, Christian; Meyer-Schraml, Hanna; Schaarschmidt, Marthe-Lisa; Findeisen, Peter; Benoit, Sandrine; Bauer, Boris; Schmid, Sybille; Goebeler, Matthias; Goerdt, Sergij; Ludwig-Peitsch, Wiebke K

2015-07-01

Patients with psoriasis have an increased risk of cardiovascular disease that is partly attributable to chronic systemic inflammation. The aim of our prospective pilot study was to investigate the impact of fumaric acid esters (FAE), a first-line systemic antipsoriatic treatment in Germany, on cardiovascular risk parameters. Participants with moderate-to-severe psoriasis from the University Medical Center Mannheim and the University Hospital Würzburg were treated with FAE for 16 weeks according to standard dosage recommendations. Disease severity, life quality and depression scores as well as biomarkers of inflammation, lipid and glucose metabolism were assessed prior to initiation of FAE and after 16 weeks. Out of 39 participants recruited, 27 completed the study. 44% of all participants and 63% of those completing the 16-week treatment achieved PASI 50 response and 27 or 37% PASI 75 response. Clinical improvement was paralleled by significant improvement in quality of life, high treatment satisfaction and significant reduction of depressive symptoms. Adverse events, most frequently mild gastrointestinal complaints, flush and lymphocytopenia occurred in 89%. FAE did not modify glucose metabolism or inflammatory parameters substantially. However, a highly significant increase in serum levels of the atheroprotective cytokine adiponectin was noted after 16 weeks (median 4.7 vs. 8.9 µg/ml; p = 0.0002). Our study demonstrates a significant beneficial impact of FAE on adiponectin, indicating a potential cardioprotective effect. It will be interesting to verify this finding in larger cohorts and to assess the long-term influence of FAE on cardiovascular risk and disease.

The expression of selected molecular markers of immune tolerance in psoriatic patients.

PubMed

Bartosińska, Joanna; Purkot, Joanna; Kowal, Małgorzata; Michalak-Stoma, Anna; Krasowska, Dorota; Chodorowska, Grażyna; Giannopoulos, Krzysztof

2018-04-24

Psoriasis is a chronic autoinflammatory disease whose underlying molecular mechanisms remain unclear. The disease is mediated by the cells and molecules of both the innate and adaptive immune systems. Some T cell surface molecules, including neuropilin-1 (NRP1), programmed death 1 (PD-1) and the human leukocyte antigen G (HLA-G), are known to play a role in the maintenance of immune tolerance. The aim of this study was to investigate HLA-G, NRP1 and programmed cell death gene (PDCD1) mRNA expression in psoriatic patients. The study included 72 psoriatic patients and 35 healthy individuals. Twentyone patients (29.17%) suffered from concomitant psoriatic arthritis. The mRNA expression of HLA-G, NRP1, and PDCD1 were determined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The severity of skin lesions was assessed by means of the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), the Patient Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI). The median value of the PASI was 11.5, and of BSA was 15.8%. The expressions of NRP1 and PDCD1, but not HLA-G, were significantly lower in psoriatic patients in comparison with the control group. The expression of HLA-G, NRP1 and PDCD1 were not significantly different in the psoriatic arthritis and psoriasis vulgaris patients. The results of this study suggest that the molecular markers of immune tolerance, i.e., HLA-G, NRP1, and PD-1, may be involved in the immune response in psoriatic patients.

No association of psoriasis with autoimmune thyroiditis.

PubMed

Vassilatou, E; Papadavid, E; Papastamatakis, P; Alexakos, D; Koumaki, D; Katsimbri, P; Hadjidakis, D; Dimitriadis, G; Rigopoulos, D

2017-01-01

Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P < 0.01). Detected cases with hypothyroidism due to autoimmune thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis. © 2016 European Academy of Dermatology and Venereology.

Development of sedentary communities in the Maya lowlands: Coexisting mobile groups and public ceremonies at Ceibal, Guatemala

PubMed Central

Inomata, Takeshi; MacLellan, Jessica; Triadan, Daniela; Munson, Jessica; Burham, Melissa; Aoyama, Kazuo; Nasu, Hiroo; Pinzón, Flory; Yonenobu, Hitoshi

2015-01-01

Our archaeological investigations at Ceibal, a lowland Maya site located in the Pasión region, documented that a formal ceremonial complex was built around 950 B.C. at the onset of the Middle Preclassic period, when ceramics began to be used in the Maya lowlands. Our refined chronology allowed us to trace the subsequent social changes in a resolution that had not been possible before. Many residents of Ceibal appear to have remained relatively mobile during the following centuries, living in ephemeral post-in-ground structures and frequently changing their residential localities. In other parts of the Pasión region, there may have existed more mobile populations who maintained the traditional lifestyle of the preceramic period. Although the emerging elite of Ceibal began to live in a substantial residential complex by 700 B.C., advanced sedentism with durable residences rebuilt in the same locations and burials placed under house floors was not adopted in most residential areas until 500 B.C., and did not become common until 300 B.C. or the Late Preclassic period. During the Middle Preclassic period, substantial formal ceremonial complexes appear to have been built only at a small number of important communities in the Maya lowlands, and groups with different levels of sedentism probably gathered for their constructions and for public rituals held in them. These collaborative activities likely played a central role in socially integrating diverse groups with different lifestyles and, eventually, in developing fully established sedentary communities. PMID:25831523

Serum fatty acid profile in psoriasis and its comorbidity.

PubMed

Myśliwiec, Hanna; Baran, Anna; Harasim-Symbor, Ewa; Myśliwiec, Piotr; Milewska, Anna Justyna; Chabowski, Adrian; Flisiak, Iwona

2017-07-01

Psoriasis is a chronic inflammatory skin disease that is accompanied by metabolic disturbances and cardio-metabolic disorders. Fatty acids (FAs) might be a link between psoriasis and its comorbidity. The aim of the study was to evaluate serum concentrations of FAs and to investigate their association with the disease activity, markers of inflammation and possible involvement in psoriatic comorbidity: obesity, type 2 diabetes and hypertension. We measured 14 total serum fatty acids content and composition by gas-liquid chromatography and flame-ionization detector after direct in situ transesterification in 85 patients with exacerbated plaque psoriasis and in 32 healthy controls. FAs were grouped according to their biologic properties to saturated FA (SFA), unsaturated FA (UFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA) and n-6 PUFA. Generally, patients characteristic included: Psoriasis Area and Severity Index (PASI), Body Mass Index, inflammatory and biochemical markers, lipid profile and presence of psoriatic comorbidity. We have observed highly abnormal FAs pattern in psoriatic patients both with and without obesity compared to the control group. We have demonstrated association of PASI with low levels of circulating DHA, n-3 PUFA (p = 0.044 and p = 0.048, respectively) and high percent of MUFA (p = 0.024) in the non-obese psoriatic group. The SFA/UFA ratio increased with the duration of the disease (p = 0.03) in all psoriatic patients. These findings indicate abnormal FAs profile in psoriasis which may reflect metabolic disturbances and might play a role in the psoriatic comorbidity.

Continuous dosing versus interrupted therapy with ixekizumab: an integrated analysis of two phase 3 trials in psoriasis.

PubMed

Blauvelt, A; Papp, K A; Sofen, H; Augustin, M; Yosipovitch, G; Katoh, N; Mrowietz, U; Ohtsuki, M; Poulin, Y; Shrom, D; Burge, R; See, K; Mallbris, L; Gordon, K B

2017-06-01

Continuous treatment is recommended for patients with moderate-to-severe psoriasis; however, treatment may need to be interrupted in routine clinical practice. To assess outcomes in patients continuously treated with ixekizumab versus those who interrupted therapy and were subsequently retreated with ixekizumab (IXE). This analysis used data pooled from two phase 3 trials, UNCOVER-1 and UNCOVER-2. Patients were randomized to placebo (PBO), IXE every 4 (Q4W) or IXE every 2 weeks (Q2W) for 12 weeks. Patients with a static Physician's Global Assessment (sPGA) 0, 1 at Week 12 were rerandomized to IXEQ4W, IXE every 12 weeks (not presented) or PBO. We examined outcomes in patients who were continuously treated (IXEQ2W/IXEQ4W; IXEQ4W/IXEQ4W) or withdrawn (IXEQ2W/PBO; IXEQ4W/PBO), and in patients who were withdrawn and retreated with IXEQ4W for 24 weeks after disease relapse (sPGA ≥3). A total of 1226 treated patients achieved an sPGA 0, 1 at Week 12 and entered the maintenance phase; of these patients, 402 and 416 were rerandomized to PBO and IXEQ4W, respectively. Among patients interrupting treatment, 157 (82.2%) of IXEQ4W/PBO and 176 (83.4%) of IXEQ2W/PBO had an sPGA ≥3 by Week 60; median time to relapse was approximately 20 weeks irrespective of induction dose. At Week 60, continuously treated patients maintained high levels of PASI and sPGA responses (90.0% PASI 75 IXEQ2W/IXEQ4W; 81.9% sPGA 0, 1 IXEQ2W/IXEQ4W, non-responder imputation). After 24 weeks of retreatment with IXEQ4W (IXEQ2W/PBO/IXEQ4W and IXEQ4W/PBO/IXEQ4W), 87.0% (107 of 123) and 95.1% (97 of 102) (observed), respectively, of patients recaptured PASI 75 and 70.7% (104 of 147) and 82.3% (107 of 130) (observed) recaptured an sPGA 0, 1. Overall, adverse events in continuously treated and retreated patients were comparable. High levels of response were sustained with continuous ixekizumab treatment through 60 weeks. Most patients who were withdrawn experienced disease relapse, and most of those patients

Demographic characteristics and health-related quality of life of patients with moderate-to-severe psoriasis: The VACAP study.

PubMed

Daudén, E; Pujol, R M; Sánchez-Carazo, J L; Toribio, J; Vanaclocha, F; Puig, L; Yébenes, M; Sabater, E; Casado, M A; Caloto, M T; Aragón, B

2013-11-01

Psoriasis is associated with a deterioration in the health-related quality of life (HRQoL) of affected patients. The aim of this study was to assess the HRQoL of patients with moderate-to-severe psoriasis. A prospective observational study (the VACAP Study) was carried out in 123 centers in Spain with 1217 patients. Patients were evaluated at baseline (visit 1 [V1]) and again four months later (visit 2 [V2]). The severity of psoriasis was determined using the following indices: (i) Psoriasis Area and Severity Index (PASI) (score range 0-72, higher score indicates more severe disease), (ii) the body surface area (BSA) affected, and (iii) the Physicians Global Assessment (PGA) (range 1-7, higher score indicates more severe disease). Four questionnaires were used for the assessment of the HRQoL: (i) the Short-Form 36 quality-of-life questionnaire (SF-36) (score range 0-100, higher score indicates better HRQoL); (ii) Euroqol (EQ-5D) (range from 1 to 3, lower score indicates better HRQoL); (iii) Dermatology Life Quality Index (DLQI) (ranges 0-30; from best to worst HRQoL); and (iv) Psoriasis Disability Index (PDI) (ranges 0-45; higher score indicates better HRQoL). The mean (SD) age of the patients was 45.11 (13.92) years at V1. The mean age at the onset of psoriasis was 26.08 (14.19) years. The majority of patients were female (61%) and were employed (68%). The mean PASI score was 13.24 (9.50) at V1 and 5.07 (6.03) at V2 (P<.001). Scores from the generic HRQoL questionnaires (EQ-5D, SF-36) showed significant improvement between visits in all dimensions measured (P<.001). The disease-specific questionnaires also revealed overall improvements in quality of life over time: the DLQI mean total score was 8.97 (7.28) at V1 and 4.76 (5.72) at V2 (P<.001), and the PDI mean total score was 9.24 (8.76) V1 and 4.88 (6.65) at V2 (P<.001). Multivariate analysis using PDI as the dependent variable showed that the principal factors related to HRQoL were severity of psoriasis as

Conference Committees

NASA Astrophysics Data System (ADS)

2015-11-01

Scientific Committee Silvia Arrese-Igor Irigoyen (CFM, CSIC - UPV/EHU, Donostia), Javier Campo (ICMA-CSIC, Zaragoza), Carlos Frontera (ICMAB-CSIC, Barcelona), Victoria García Sakai (ISIS, Chilton), Cristina Gómez-Polo (UPNa, Pamplona), Miguel Ángel González (ILL, Grenoble), Pedro Gorría (Universidad Oviedo), Jon Gutiérrez Echevarría (EHU/UPV, Bilbao), J. Iñaki Pérez Landazábal (UPNa, Pamplona), Vicente Recarte (UPNa, Pamplona), Jesús Ruíz Hervías (UPM, Madrid), Vicente Sánchez-Alarcos (UPNa, Pamplona), Antonio Urbina (UPC, Cartagena) Organizing Committee J. Iñaki Pérez Landazábal (Co-Chair), Vicente Recarte ( Co-Chair), Cristina Gómez-Polo, Silvia Larumbe Abuin, Vicente Sánchez-Alarcos Editors of the Proceedings J. Iñaki Pérez Landazábal, Vicente Recarte Plenary speakers Charles Simon (Institut Laue-Langevin, Grenoble, France), Miguel Angel Alario Franco (Universidad Complutense, Madrid, Spain), Dieter Richter (Jülich Centre for Neutron Science, Jülich, Germany), James Yeck (European Spallation Source, Lund, Sweden) Invited speakers Manu Barandiarán (BCMaterials & EHU/UPV), Arantxa Arbe (MFC, CSIC- UPV/EHU), José Luis Martínez (Consorcio ESS-Bilbao), Marta Castellote, IETcc-CSIC), Josep Lluis Tamarit (UPC), Diego Alba-Venero (ISIS), Elizabeth Castillo (CIC Energigune), Josu M. Igartua (EHU/UPV), Antonio Dos Santos (UPM), Alex Masalles (Museu Nacional d'Art de Catalunya), José Abad (UPCT), Claudia Mondelli (ILL), Oscar Fabelo (ILL), Aurora Nogales (IEM-CSIC), Jesús Rodríguez (UC), Gerardo

Pictorial representation of illness and self measure (PRISM): an effective tool to assess the burden of psoriasis.

PubMed

Fotiou, K; Hofmann, M; Kaufmann, R; Thaci, D

2015-12-01

Psoriasis has a negative impact on patient's' quality of life, which may reflect the physical and psychosocial impact of the disease. However, little is known about the perceived burden of disease. Pictorial Representation of Illness and Self Measure (PRISM), a pictorial tool, was developed to measure this global suffering. Capturing quality of life impairments in psoriasis is an integral part of assessing the overall disease severity and planning effective treatment strategies. To validate Pictorial Representation of Illness and Self Measure (PRISM) in psoriasis patients. An investigator initiated, prospective cohort study was performed in 108 outpatients with psoriasis to validate PRISM as an appropriate tool; Reliability was assessed in a cohort with controlled stable disease, repeated after 1 hour and after a 3-month follow-up phase; Convergent validity determined by correlation against measures of life quality (DLQI) and reported severity of psoriasis (PASI, PGA and BSA) was performed. For PRISM, we found a high reliability for short-term measurements (ICC = 0.98, P < 0.001) and for follow-up assessments at 3 months (ICC = 0.76, P < 0.001). Our investigation showed significant differences between patients with clear to minimal (PGA 0, 1), mild (PGA 2) and moderate-to-severe disease (PGA 3, 4) and significant (P < 0.001) correlation with DLQI, PGA, PASI and BSA (ρ = -0.62, -0.54, -0.44 and -0.39 respectively). PRISM is a highly reliable tool and new approach to assess perceived burden of patients with psoriasis. It is easy to use and we recommend the application as an additional outcome measure in clinical trial settings. © 2015 European Academy of Dermatology and Venereology.

Efficacy and Safety of Secukinumab in Elderly Subjects with Moderate to Severe Plaque Psoriasis: A Pooled Analysis of Phase III Studies.

PubMed

Körber, Andreas; Papavassilis, Charis; Bhosekar, Vaishali; Reinhardt, Maximilian

2018-02-01

Psoriasis is a chronic inflammatory skin disease, affecting patients of a wide age range, including elderly patients. Elderly patients can respond differently to drug treatments and can be more vulnerable to adverse reactions. There are limited data on biologic therapies for psoriasis in elderly subjects. Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has proven significant efficacy in the treatment of moderate to severe psoriasis. A post-hoc analysis of three phase III trials (ERASURE, FIXTURE and CLEAR) was performed to evaluate the efficacy and safety of secukinumab in elderly subjects. Studies were multicentre, randomized, parallel-group, double-blind, 52-week phase III trials in subjects with moderate to severe plaque psoriasis. For efficacy analyses, 67 elderly subjects (≥ 65 years) treated with secukinumab 300 mg were compared with 841 younger subjects (18-64 years). Psoriasis Area and Severity Index (PASI), Dermatological Life Quality Index (DLQI) and safety were analysed. Elderly subjects had higher baseline frequencies of cardiovascular and metabolic disorders. Secukinumab efficacy in elderly subjects was comparable to that in younger subjects throughout 52 weeks of treatment. PASI 75 response was reached by 81.8% of elderly subjects and 79.4% of younger subjects at Week 52. Similar rates of DLQI 0/1 response were observed. The total rate of adverse events was similar between elderly and younger subjects. Secukinumab at the recommended dose (300 mg) is effective and acceptably safe in subjects aged ≥ 65 years with moderate to severe psoriasis, with quality-of-life benefits, despite an increased prevalence of cardiovascular and metabolic comorbidities in this population.

Psychometric validation of the Psoriasis Symptom Diary using Phase III study data from patients with chronic plaque psoriasis.

PubMed

Strober, Bruce; Zhao, Yang; Tran, Mary Helen; Gnanasakthy, Ari; Nyirady, Judit; Papavassilis, Charis; Nelson, Lauren M; McLeod, Lori D; Mordin, Margaret; Gottlieb, Alice B; Elewski, Boni E; Lebwohl, Mark

2016-03-01

This analysis aimed to confirm the reliability, validity, and responsiveness of the Psoriasis Symptom Diary (PSD) using data from two Phase III studies in patients with moderate to severe chronic plaque psoriasis. Data from two randomized, double-blind, double-dummy, placebo-controlled, multicenter Phase III studies (n = 820) assessing the efficacy and safety of secukinumab were used. The PSD (24-h recall; 0-10 numeric rating scale) was electronically administered each evening. Test-retest reliability was determined using intraclass correlations. Construct validity hypotheses were evaluated via correlations with the Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI), EuroQoL 5-Dimension Health Status Questionnaire, and Patient Global Impression of Change (PGIC). Discriminating ability and responsiveness were evaluated by estimating mean differences and effect sizes between known groups (using the PASI and IGA). Phase II-derived, anchor-based PGIC thresholds and cumulative distribution function (CDF) plots described meaningful change. Items on the PSD yielded high intraclass coefficients (>0.90). Correlations were in the anticipated direction and by week 12 were moderate to strong (0.41-0.73) in magnitude, demonstrating construct validity. Average PSD item scores differed predictably and significantly between known groups. Responsiveness effect size estimates were moderate to large (0.6-1.5), and CDF plots showed the percentage of responders to be consistently higher in treatment than in placebo arms across the range of change in PSD scores. The PSD is reliable, valid, and responsive, and represents a valid tool to enhance treatment decisions in patients with moderate to severe plaque psoriasis. © 2015 The International Society of Dermatology.

[Comparison of blood pressure profiles with flunitrazepam/fentanyl/nitrous oxide vs cervical epidural anesthesia in surgery of the carotid artery].

PubMed

Pluskwa, F; Bonnet, F; Abhay, K; Touboul, C; Rey, B; Marcandoro, J; Becquemin, J B

1989-01-01

A study was carried out to compare the evolution of arterial blood pressure during carotid endarterectomy performed under either general anaesthesia (GA) or cervical epidural anaesthesia (CEA). 20 patients were randomly assigned to two equal groups. In the CEA group, 15 ml of 0.375% bupivacaine and 150 micrograms fentanyl were injected into the epidural space at C7-D1 level. In the GA group, patients were anaesthetized with 0.2 mg.kg-1 flunitrazepam and 5 micrograms.kg-1 fentanyl; intubation was carried out using 0.08 mg.kg-1 vecuronium, and the patients were ventilated with a mixture of nitrous oxide and oxygen (50% of each). Further injections, every 30 min, of 2 micrograms.kg-1 fentanyl were given to the patients in group GA. Blood pressure was monitored continuously, up to 4 h postoperatively, with a radial arterial catheter. Per- or postoperative hypertension was defined as a rise in systolic arterial blood pressure (Pasys) over 180 mmHg for greater than 3 min; this was treated with 20 mg nifedipine intranasally (group CEA) or 100 micrograms fentanyl with 0.5 mg flunitrazepam with or without nifedipine (group GA). Per- or postoperative hypotension was defined as a fall in Pasys below 100 mmHg and or a 30% fall in mean arterial blood pressure for greater than 3 min; this was treated, in both groups, with an intravenous bolus of 3 mg ephedrine. Patients in group CEA experienced more frequent episodes of peroperative hypertension (8/2; p less than 0.02) and postoperative hypotension (5/1) than group GA.(ABSTRACT TRUNCATED AT 250 WORDS)

G-231A and G+70C Polymorphisms of Endothelin Receptor Type-A Gene could Affect the Psoriasis Area and Severity Index Score and Endothelin 1 Levels.

PubMed

Okan, Gökhan; Yıldız, Zeynep; Gökdemir, Gonca; Yorulmaz, Eda; Vural, Pervin; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

2015-01-01

The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1) and endothelin receptor type-A (EDNRA) are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (G-231A and G + 70C) single nucleotide polymorphisms (SNPs) with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI) score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG) was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively). In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG) were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05). Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

A preliminary study for fully automated quantification of psoriasis severity using image mapping

NASA Astrophysics Data System (ADS)

Mukai, Kazuhiro; Iyatomi, Hitoshi

2014-03-01

Psoriasis is a common chronic skin disease and it detracts patients' QoL seriously. Since there is no known permanent cure so far, controlling appropriate disease condition is necessary and therefore quantification of its severity is important. In clinical, psoriasis area and severity index (PASI) is commonly used for abovementioned purpose, however it is often subjective and troublesome. A fully automatic computer-assisted area and severity index (CASI) was proposed to make an objective quantification of skin disease. It investigates the size and density of erythema based on digital image analysis, however it does not consider various inadequate effects caused by different geometrical conditions under clinical follow-up (i.e. variability in direction and distance between camera and patient). In this study, we proposed an image alignment method for clinical images and investigated to quantify the severity of psoriasis under clinical follow-up combined with the idea of CASI. The proposed method finds geometrical same points in patient's body (ROI) between images with Scale Invariant Feature Transform (SIFT) and performs the Affine transform to map the pixel value to the other. In this study, clinical images from 7 patients with psoriasis lesions on their trunk under clinical follow-up were used. In each series, our image alignment algorithm align images to the geometry of their first image. Our proposed method aligned images appropriately on visual assessment and confirmed that psoriasis areas were properly extracted using the approach of CASI. Although we cannot evaluate PASI and CASI directly due to their different definition of ROI, we confirmed that there is a large correlation between those scores with our image quantification method.

CD19+ B cell subsets in the peripheral blood and skin lesions of psoriasis patients and their correlations with disease severity

PubMed Central

Lu, J.; Ding, Y.; Yi, X.; Zheng, J.

2016-01-01

T lymphocytes are important in the pathogenesis of psoriasis, and increasing evidence indicates that B cells also play an important role. The mechanisms of action, however, remain unclear. We evaluated the ratios of CD19+ B cells in peripheral blood mononuclear cells (PBMCs) from 157 patients with psoriasis (65 patients with psoriasis vulgaris, 32 patients with erythrodermic psoriasis, 30 patients with arthropathic psoriasis, and 30 patients with pustular psoriasis) and 35 healthy controls (HCs). Ratios of CD19+ B cells in skin lesions were compared with non-lesions in 7 erythrodermic psoriasis patients. The Psoriasis Area Severity Index (PASI) was used to measure disease severity. CD19+ B cell ratios in PBMCs from psoriasis vulgaris (at both the active and stationary stage) and arthropathic psoriasis patients were higher compared with HCs (P<0.01), but ratios were lower in erythrodermic and pustular psoriasis patients (P<0.01). CD19+ B cell ratios in erythrodermic psoriasis skin lesions were higher than in non-lesion areas (P<0.001). Different subsets of CD19+CD40+, CD19+CD44+, CD19+CD80+, CD19+CD86+, CD19+CD11b+, and CD19+HLA-DR+ B cells in PBMCs were observed in different psoriasis clinical subtypes. PASI scores were positively correlated with CD19+ B cell ratios in psoriasis vulgaris and arthropathic psoriasis cases (r=0.871 and r=0.692, respectively, P<0.01), but were negatively correlated in pustular psoriasis (r=-0.569, P<0.01). The results indicated that similar to T cells, B cells activation may also play important roles in different pathological stages of psoriasis. PMID:27532281

Clinic characteristics of psoriasis in China: a nationwide survey in over 12000 patients.

PubMed

Chen, Kun; Wang, Gang; Jin, Hongzhong; Xu, Jinhua; Zhu, Xuejun; Zheng, Min; Gu, Heng

2017-07-11

Psoriasis is a worldwide chronic inflammatory disease, involving both skin and joints. In order to characterize psoriasis in Han Chinese population, we conducted this nationwide prospective and hospital based survey, in which 56 hospitals with departments of dermatology participated, located in 33 cities across China. A total of 12,031 outpatients with psoriasis were registered during 2009 to 2010, which the data was collected by standard questionnaires. The main data acquisition included demographics, family history, disease status and other comorbidities. Physical and dermatological examination, including body surface area (BSA) and psoriasis area severity index (PASI) were applied to evaluate the disease severity. Descriptive statistics, 2 tailed t-test and chi-square test were used appropriately for the statistical analysis. From the study, we found that the male and female ratio of the patients was 1.49:1. Mean age of onset was 30.2 ± 14.5 years for males and 27.1 ± 15.6 years for females (P < 0.05). Scalp was the most common onset site (52.8%), The mean PASI was 18.70 ± 10.01, indicating that most patients presenting at the hospitals had moderate-to-severe psoriasis and the majority was psoriasis vulgaris (96.5%). Among 12,031 patients, 23.1% had a family history of psoriasis,16.1% had comorbidities, and 29.9% had nail changes. The most important aggravation factor was season change (60.2%), followed by psychological stress (34.5%), and there significant differences between genders on trigger factors. In conclusion, this study characterizing psoriasis in Han Chinese population, could be used as basic data for future study.

Body Image, Self-esteem, and Quality of Life in Patients with Psoriasis.

PubMed

Nazik, Hulya; Nazik, Selcuk; Gul, Feride C

2017-01-01

Psoriasis is a chronic inflammatory disease of the skin that may affect the visible areas of body. Hence, the quality of life, self-esteem, and body image can be affected in psoriasis patients. We aimed in the present study to assess the effects of psoriasis on the quality of life, self-esteem, and body image. The study included 92 patients with psoriasis, along with 98 control participants. The sociodemographic characteristics of the patients were assessed, their Psoriasis Area Severity Index (PASI) scores were calculated to determine the clinical severity of the psoriasis, and the values were recorded. In addition, Dermatology Life Quality Index (DLQI), Body Image Scale, and Rosenberg Self-Esteem Scale results were evaluated. When the control and psoriasis groups were evaluated regarding the DLQI, self-esteem, and body image, quality of life was found to be more negatively affected in the psoriasis group than the controls, which was statistically significant ( P < 0.001), and self-esteem ( P < 0.001) and body image ( P < 0.001) were found to be significantly lower. Educational status significantly affected self-esteem ( P < 0.001) and body image ( P = 0.021), however, quality of life was not significantly affected by this parameter ( P = 0.345). PASI was positively correlated with the quality of life ( r = 0.703) and self-esteem ( r = 0.448), however, it was negatively correlated with the body image ( r = -0.423). Psoriasis may negatively affect quality of life, self-esteem, and body image, and may also cause psychosocial problems. An assessment of new approaches on this issue may contribute to developments in the treatment of and rehabilitation from this disease.

Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

PubMed

Casas, C; Ribet, V; Alvarez-Georges, S; Sibaud, V; Guerrero, D; Schmitt, A-M; Redoulès, D

2011-02-01

A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus. © 2010 The Authors. JEADV © 2010 European Academy of Dermatology and Venereology.

Effects of excimer laser irradiation on the expression of Th17, Treg, TGF-beta1, and IL-6 in patients with psoriasis vulgaris

NASA Astrophysics Data System (ADS)

Xiong, Guo-Xin; Li, Xin-Zhong

2017-11-01

The effects of laser irradiation on the expression of T helper 17 (Th17) and regulatory T (Treg) cells and their related cytokines, transforming growth factor beta 1 (TGF-β1) and interleukin-6 (IL-6), respectively, in the peripheral blood of patients with psoriasis vulgaris were investigated. 38 patients with psoriasis vulgaris in the stable state were selected as the treatment group that was treated twice a week for eight weeks. Another 38 healthy persons were chosen as the control group. Before and after treatment, the percentages of Th17 cells and Treg cells in the patients’ peripheral blood were detected using flow cytometry, the content of TGF-β1 and IL-6 in the patients’ sera were detected using enzyme-linked immunosorbent assay, and the extent and severity of lesions were determined by weighing the psoriasis area and severity index (PASI). After laser treatment, the percentage of Th17 cells, the Th17/Treg cell ratio and the level of IL-6 in the peripheral blood of patients with psoriasis in the treatment group were significantly lower than those of the same patients before the treatment (P  <  0.01), while the percentage of Treg and the content of TGF-β1 in the patients’ sera were significantly higher than before the treatment (P  <  0.01). The effective rate for laser irradiation of psoriasis vulgaris was 84.21%, and the PASI score was significantly lower (P  <  0.01). Excimer laser irradiation can positively affect the Th17/Treg cell ratio and the expression of related cytokines in the peripheral blood of patients with psoriasis vulgaris.

Impact of training on concordance among rheumatologists and dermatologists in the assessment of patients with psoriasis and psoriatic arthritis.

PubMed

Salvarani, Carlo; Girolomoni, Giampiero; Di Lernia, Vito; Gisondi, Paolo; Tripepi, Giovanni; Egan, Colin Gerard; Marchesoni, Antonio

2016-12-01

To evaluate the impact of training on the reliability among dermatologists and rheumatologists in the assessment of psoriatic arthritis (PsA) patients. Overall, 9 hospital-based rheumatologists and 8 hospital-based dermatologists met in Reggio Emilia, Italy on October 2015 to assess 17 PsA patients. After 1 month, physicians underwent a 3-h training session by 4 recognized experts and then assessed 19 different PsA patients according to a modified Latin square design. Measures included tender (TJC) and swollen joint count (SJC), dactylitis, enthesitis, Schober test, psoriasis body surface area (BSA), Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), and static physician's global assessment of PsA disease activity (sPGA). Variance components analyses were performed to estimate the intraclass correlation coefficient (ICC). TJC and enthesitis-measured pre-training by dermatologists or rheumatologists revealed moderate-substantial agreement (ICC: 0.4-0.8). In contrast, SJC and Schober test showed fair (ICC: 0.2-0.4) and moderate agreement, respectively (ICC: 0.4-0.6), while poor agreement (ICC: 0-0.2) was represented by dactylitis. Moderate-substantial (ICC: 0.4-0.8) agreement was observed for most skin measures by dermatologists and rheumatologists, apart from BSA, where fair agreement (ICC: 0.2-0.4) was observed. Agreement levels were similar before and after training for arthritis measures. In contrast, levels of agreement after training for 3 of the 4 skin measures were increased for dermatologists and all 4 skin measures were increased for rheumatologists. Substantial to excellent agreement was observed for TJC, enthesitis, PASI, and sPGA. Rheumatologists benefited from training to a greater extent. Copyright © 2016 Elsevier Inc. All rights reserved.

The Cellosaurus, a Cell-Line Knowledge Resource

PubMed Central

Bairoch, Amos

2018-01-01

The Cellosaurus is a knowledge resource on cell lines. It aims to describe all cell lines used in biomedical research. Its scope encompasses both vertebrates and invertebrates. Currently, information for >100,000 cell lines is provided. For each cell line, it provides a wealth of information, cross-references, and literature citations. The Cellosaurus is available on the ExPASy server (https://web.expasy.org/cellosaurus/) and can be downloaded in a variety of formats. Among its many uses, the Cellosaurus is a key resource to help researchers identify potentially contaminated/misidentified cell lines, thus contributing to improving the quality of research in the life sciences. PMID:29805321

Student designed experiments to learn fluids

NASA Astrophysics Data System (ADS)

Stern, Catalina

2013-11-01

Lasers and high speed cameras are a wonderful tool to visualize the very complex behavior of fluids, and to help students grasp concepts like turbulence, surface tension and vorticity. In this work we present experiments done by physics students in their senior year at the School of Science of the National University of Mexico as a final project in the continuum mechanics course. Every semester, the students make an oral presentation of their work and videos and images are kept in the web page ``Pasión por los Fluidos''. I acknowledge support from the Physics Department of Facultad de Ciencias, Universidad Nacional Autónoma de México.

The Effect of Pollution on Newly-Formed Particle Composition in Boreal Forest

NASA Astrophysics Data System (ADS)

Vaattovaara, Petri

2010-05-01

Petri Vaattovaara (1), Tuukka Petäjä (2), Jorma Joutsensaari (1), Pasi Miettinen (1), Boris Zaprudin (1,6), Aki Kortelainen (1), Juha Heijari (3,7), Pasi Yli-Pirilä (3), Pasi Aalto (2), Doug R. Worsnop (4), and Ari Laaksonen(1,5) (1) University of Eastern Finland, Finland (2) University of Helsinki, Finland (3) University of Eastern Finland, Finland (4) Aerodyne Research Inc., USA (5) Finnish Meteorological Institute, Finland (6) Currently at University of Turku, Finland (7) Currently at Maritime Research Centre, Finland Email address of the Corresponding author: Petri.Vaattovaara@uef.fi The geographical extent of the tropical, temperate and boreal forests is about 30% of the Earth's land surface. Those forests are located around the world in different climate zones effecting widely on atmospheric composition via new particle formation. The Boreal forests solely cover one third of the forests extent and are one of the largest vegetation environments, forming a circumpolar band throughout the northern hemisphere continents, with a high potential to affect climate processes [1]. In order to more fully understand the possible climatic effects of the forests, the properties of secondary organic aerosols (SOA) in varying conditions (e.g. a change in meteorological parameters or in the concentrations of biogenic and antropogenic trace gases) need to be better known. In this study, we applied the UFO-TDMA (ultrafine organic tandem differential mobility analyzer [2]) and the UFH-TDMA (ultrafine hygroscopicity tandem differential mobility analyzer [3]) methods parallel to shed light on the evolution of the nucleation and Aitken mode particle compositions (via physic-chemical properties) at a virgin boreal forest site in varying conditions. The measurements were carried out at Hyytiälä forest station in Northern Europe (Finland) during 15 spring nucleation events. We also carried out a statistical analysis using linear correlations in order to explain the variability in

Dr Michaels® product family (also branded as Soratinex®) versus Methylprednisolone aceponate - a comparative study of the effectiveness for the treatment of plaque psoriasis.

PubMed

Hercogovấ, J; Fioranelli, M; Gianfaldoni, S; Chokoeva, A A; Tchernev, G; Wollina, U; Tirant, M; Novotny, F; Roccia, M G; Maximov, G K; França, K; Lotti, T

2016-01-01

As one of the most common dermatologic chronic-recurrent disease, variable therapeutic options are available today for management of psoriasis. Although topical high potency corticosteroids, alone or in association with salicylic acid or vitamin D analogues, are still considered the best treatment, they do not seem to possess the capability for a long-term control of the disease or prevent recurrences, as their side effects are major contraindications for continuative use. The aim of this study was to investigate whether Dr. Michaels® product family is comparable to methylprednisolone aceponate (MPA) as a viable alternative treatment option for the treatment and management of stable chronic plaque psoriasis. Thirty adults (13 male, 17 female, mean age 40 years) with mild to severe stable chronic plaque psoriasis, were included in the study. Patients were advised to treat the lesions of the two sides of their body (left and right) with two different unknown modalities for 8 weeks; the pack of Dr. Michaels® products on the left side (consisting of a cleansing gel, an ointment and a skin conditioner) and a placebo pack on the right side, consisting of a cleansing gel, methylprednisolone ointment and a placebo conditioner. Assessment was done using the Psoriasis Activity Severity Index (PASI) scores before treatment and after 2, 4, 6 and 8 weeks. The results achieved with the Dr. Michaels® (Soratinex®) product family for the treatment of chronic plaque psoriasis were better than the results achieved with methylprednisolone aceponate (MPA), even though quicker resolution was achieved with the steroid with 45% of patients achieving resolution within 8-10 days in comparison to 5-6 weeks in the Dr. Michaels® (Soratinex®) group. Before therapy, the mean PASI score of the LHS in Dr. Michaels® (Soratinex®) group was 13.8±4.1 SD and 14.2±4.2 SD in the RHS methylprednisolone aceponate (MPA) group. After 8 weeks of treatment 62% of the Dr. Michaels® (Soratinex

Microwave discharge electrodeless lamps (MDEL). III. A novel tungsten-triggered MDEL device emitting VUV and UVC radiation for use in wastewater treatment.

PubMed

Horikoshi, Satoshi; Miura, Takashi; Kajitani, Masatsugu; Serpone, Nick

2008-03-01

Exposure to low doses of the xenoestrogen bisphenol A (BPA) and to the hormonal 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide, an environmental endocrine disruptor, can have serious health consequences such as the induction of mammary gland ductal hyperplasias and carcinoma (LaChapelle et al., Reprod. Toxicol., 2007, 23, 20; Murray et al., Reprod. Toxicol., 2007, 23, 383). To the extent that these toxins are present in wastewaters (Donald et al., Sci. Total Environ. 1999, 231, 173; Brotons et al., Environ. Health Perspect. 1994, 103, 608; Olea et al., Environ. Health Perspect. 1996, 104, 298; Biles et al., J. Agric. Food Chem. 1997, 45, 3541; Markey et al., J. Steroid Biochem. Mol. Biol., 2003, 83, 235), we examined their oxidative destruction in aqueous media by a novel light source. A tungsten-triggered microwave discharge electrodeless lamp (W-MDEL) was fabricated for possible use in wastewater treatment using vacuum UV-transparent quartz in which a tungsten trigger, also embedded in quartz, was attached to the MDEL to aid in the self-ignition of the lamp on irradiation at low microwave power levels. The quantity of mercury gas in the W-MDEL was optimized by monitoring the continuous radiation and peak intensities of the emitted light in the vacuum UV (VUV) and UVC regions. The usefulness of the W-MDEL device was assessed through the degradation of 2,4-D and BPA in air-equilibrated aqueous media and in oxygen-saturated aqueous media. Enhanced degradation of these two xenoestrogenic toxins was achieved by increasing the number of W-MDEL devices while keeping constant the microwave radiation feeding each W-MDEL lamp. This novel lamp provides an additional light source in the photooxidation of environmental contaminants without the need for a metal-oxide photocatalyst. Under our conditions, process dynamics using the W-MDEL light source are greater than with the more conventional photochemical methods that employ low-pressure Hg arc electrode lamps in synthetic

Investigation of dietary supplements prevalence as complementary therapy: Comparison between hospitalized psoriasis patients and non-psoriasis patients, correlation with disease severity and quality of life.

PubMed

Yousefzadeh, Hadis; Mahmoudi, Mahmoud; Banihashemi, Mahnaz; Rastin, Maryam; Azad, Farahzad Jabbari

2017-08-01

Psoriasis patients are often displeased with traditional medical treatments and they may self-prescribe dietary supplements as an alternative or complementary treatments. We aimed to investigate the prevalence of self-medication of dietary supplements among psoriasis and non-psoriasis cases and its impact on disease severity and quality of life. This case-control study evaluated 252 records of psoriasis patients and 245 non-psoriasis cases. Dietary supplementation over last 30days and characteristics, including age, age at onset of disease, co-morbidities, smoking and education were recorded. Psoriasis area and severity index (PASI) and dermatology quality of life index (DLQI) were calculated. P value less than 0.05 was considered as significant level. This study consisted 138 psoriasis (females; 54) and 138 non-psoriasis cases (females; 50), aged between 21 and 91 years. Among psoriasis patients, 72% reported using at least one of dietary supplements, which was different from non-psoriasis cases (25.36%, P=0.01). Multivitamin/mineral supplements (MVM) were the most frequent used dietary supplements (26.81%) and the most common reasons for the consumption of these supplements were to maintain and improve health. The consumption of folic acid (21.73%), omega-3 fatty acids or fish oil (10.14%), herbs (12.31%) and vitamin E (1.44%) had the most frequencies after MVM. No significant differences in PASI and DLQI were found among patients with consumption of different supplements (P>0.05). There was non-significant and negative correlation between education and use of supplements (P=0.21, r=-0.02). Self-medicating of MVM over last 30days was prevalent among studied psoriasis patients. They took dietary supplements in order to improve and maintain their health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial.

PubMed

Abe, Masatoshi; Nishigori, Chikako; Torii, Hideshi; Ihn, Hironobu; Ito, Kei; Nagaoka, Makoto; Isogawa, Naoki; Kawaguchi, Isao; Tomochika, Yukiko; Kobayashi, Mihoko; Tallman, Anna M; Papp, Kim A

2017-11-01

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.

PubMed

Ishibashi, Toru; Ichikawa, Miki; Sato, Bunpei; Shibata, Shinji; Hara, Yuichi; Naritomi, Yuji; Okazaki, Ken; Nakashima, Yasuharu; Iwamoto, Yukihide; Koyanagi, Samon; Hara, Hiroshi; Nagao, Tetsuhiko

2015-08-01

Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.

A smartphone application for psoriasis segmentation and classification (Conference Presentation)

NASA Astrophysics Data System (ADS)

Vasefi, Fartash; MacKinnon, Nicholas B.; Horita, Timothy; Shi, Kevin; Khan Munia, Tamanna Tabassum; Tavakolian, Kouhyar; Alhashim, Minhal; Fazel-Rezai, Reza

2017-02-01

Psoriasis is a chronic skin disease affecting approximately 125 million people worldwide. Currently, dermatologists monitor changes of psoriasis by clinical evaluation or by measuring psoriasis severity scores over time which lead to Subjective management of this condition. The goal of this paper is to develop a reliable assessment system to quantitatively assess the changes of erythema and intensity of scaling of psoriatic lesions. A smartphone deployable mobile application is presented that uses the smartphone camera and cloud-based image processing to analyze physiological characteristics of psoriasis lesions, identify the type and stage of the scaling and erythema. The application targets to automatically evaluate Psoriasis Area Severity Index (PASI) by measuring the severity and extent of psoriasis. The mobile application performs the following core functions: 1) it captures text information from user input to create a profile in a HIPAA compliant database. 2) It captures an image of the skin with psoriasis as well as image-related information entered by the user. 3) The application color correct the image based on environmental lighting condition using calibration process including calibration procedure by capturing Macbeth ColorChecker image. 4) The color-corrected image will be transmitted to a cloud-based engine for image processing. In cloud, first, the algorithm removes the non-skin background to ensure the psoriasis segmentation is only applied to the skin regions. Then, the psoriasis segmentation algorithm estimates the erythema and scaling boundary regions of lesion. We analyzed 10 images of psoriasis images captured by cellphone, determined PASI score for each subject during our pilot study, and correlated it with changes in severity scores given by dermatologists. The success of this work allows smartphone application for psoriasis severity assessment in a long-term treatment.

Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis.

PubMed

Cawson, Matthew Richard; Mitchell, Stephen Andrew; Knight, Chris; Wildey, Henry; Spurden, Dean; Bird, Alex; Orme, Michelle Elaine

2014-01-20

An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate. A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes. All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments.

[Impact of SPA therapy with sulphureous mineral water on quality of life and psychological distress in chronic plaque psoriasis].

PubMed

Costantino, M; Filippelli, A

2014-01-01

The plaque psoriasis, one of the most common form of psoriasis, is a chronic inflammatory disease. This pathology can cause devastating effects on quality of life and social relations with significant physical and psychological distress. Currently among the therapeutic agents available for the treatment of psoriasis is including SPA therapy, whose mechanism of action is only partially known, as well as very few studies examined the impact of this therapy on the quality of life. On the basis of these considerations, the research analyzed the effectiveness of SPA bath therapy (BLT) and its impact on quality of life and psychological distress in patients suffering from chronic plaque psoriasis. The study was conducted on 35 patients with chronic plaque psoriasis: 23% male and 77% female; mean age:56 ± 19 years; age range:17-85 years. The subjects were treated, for 2 weeks, with sulphureous SPA bath therapy from Terme of Telese SpA (Benevento-Italy). At the beginning and at the end of the SPA treatment considered was evaluated: the itching symptom (using NRS scale); the PASI Index; the impact on quality of life (using SF-36 and DLQI questionnaires) and on psychological distress (using ZUNG -tests). At the end of the SPA treatment, the mean values ± SD, compared to baseline, have showed a significant (p <0.01) reduction in itching symptom (1.8 ± 1.1-->1.0 ± 1.0) and PASI score (4 ± 4-->1.7 ± 2) with an improvement in quality of life and psichological distress as demonstrated by SF-36, DLQI and ZUNG tests. The data of this research show that the sulphureous SPA bath therapy can be considered very useful in patients with mild-to-moderate psoriasis for the improving of the quality of life and social relationship.

Healthcare Provider Type and Switch to Biologics in Psoriasis: Evidence from Real-World Practice.

PubMed

Calara, Paul S; Norlin, Jenny M; Althin, Rikard; Carlsson, Katarina Steen; Schmitt-Egenolf, Marcus

2016-04-01

Previous research indicates an uneven uptake of biologics in patients with moderate-to-severe psoriasis in Sweden. Therefore, it is essential to scrutinise variations in treatment patterns. The aim of this study was to evaluate the extent to which the uptake of biologics for psoriasis differs between types of healthcare provider. Three types of provider were identified within 52 units participating in the Swedish National Registry for Systemic Psoriasis Treatment (PsoReg): university hospitals, non-university hospitals and individual practices. Biologics-naïve patients (n = 3165) were included in analyses to investigate the probability of switch to biologics. The numbers of patients fulfilling the criteria for moderate-to-severe psoriasis [Psoriasis Area and Severity Index (PASI) ≥10 and Dermatology Life Quality Index (DLQI) ≥10] among patients who switched to biologics and patients who did not switch were reported. A logistic regression model was used to calculate how healthcare provider type influenced the probability of switch to biologics whilst adjusting for patient characteristics and disease severity. During registration, 16% of patients switched to biologics while 84% remained on conventional systemic treatment. In 7% of patients, the criteria PASI ≥10 and DLQI ≥10 was fulfilled at their last visit without switching to biologics, whereas in 10% of patients the criteria was not fulfilled prior to switch. After controlling for patient characteristics and disease severity, small or no difference in the probability of switch was observed between provider types. Disease severity does not explain the decision to switch or not to switch to biologics for a disproportionate number of patients. There seems to be an uneven uptake of biologics in Swedish clinical practice, but the type of healthcare provider cannot explain this variation. More research is needed on what factors influence the prescription of biologics.

Cardiogoniometry in psoriatic patients and its comparison with a control group.

PubMed

Poorzand, Hoorak; Kiafar, Bita; Asadzadeh Heravi, Fardideh; Vejdanparast, Mohammad; Saki, Azadeh; Tayebi, Mohammad; Morovatdar, Negar; Karimabadi, Neda

Cardiogoniometry (CGM), a spatiotemporal electrocardiologic method may be useful as a cardiovascular diagnostic tool. Increased incidence of coronary artery or myocardial involvement and defects in automatic setting of heart activity have been reported in psoriasis which could be related to the presence of systemic inflammation. Cardiogoniometry and the related parameters have been used in this study as a diagnostic technique in psoriasis patients. Thirty patients with psoriasis and 30 healthy, age and sex-matched individuals with no history of cardiovascular diseases or traditional coronary risk factors were enrolled. Duration and severity of the disease, using psoriasis severity and area index (PASI) score were recorded. Electrocardiography and cardiogoniometry were performed. Heart rate, QT interval and QT dispersion (QTD) were measured. SDNN (standard deviation of normal R-R interval) and myocardial ischemia score were determined by cardiogoniometry. There was significant difference between the psoriasis patients and the controls in terms of heart rate (76.37±14.41 vs 72.53±9.684, p=0.02), myocardial ischemia score (-1.53±2.63 vs -0.46±0.73, p=0.037), corrected QT interval (392.64±26.00 vs 377.26±22.34, p=0.017) and QTD (32.00±17.88 vs 6.67±15.16, p<0.001). No statistically significant difference was found in SDNN (36.37±21.01 vs 26.90±14.88, p=.29). There were moderate correlation between PASI and SDNN (r=0.427, p=0.009), heart rate (r=0.427, p=.009) and score (r=0.481, p=.004). Abnormalities in resting ECG and CGM and their correlation with disease severity raises concerns about the need for cardiovascular follow-ups of psoriatic patients, especially those with severe disease. Copyright © 2016. Published by Elsevier B.V.

New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions.

PubMed

Li, Jiang; Liu, Lei; Rui, Wenlong; Li, Xiangyu; Xuan, Dandan; Zheng, Shucong; Yu, Yiyun; Zhang, Jiong; Kong, Ning; Zhu, Xiaoxia; Zou, Hejian; Wan, Weiguo; Xue, Yu

2017-01-01

New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-κB ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis. © 2017 S. Karger AG, Basel.

Effects of mud-bath therapy in psoriatic arthritis patients treated with TNF inhibitors. Clinical evaluation and assessment of synovial inflammation by contrast-enhanced ultrasound (CEUS).

PubMed

Cozzi, Franco; Raffeiner, Bernd; Beltrame, Valeria; Ciprian, Luca; Coran, Alessandro; Botsios, Constantin; Perissinotto, Egle; Grisan, Enrico; Ramonda, Roberta; Oliviero, Francesca; Stramare, Roberto; Punzi, Leonardo

2015-03-01

Despite the efficacy of TNF inhibitors, most patients with psoriatic arthritis maintain a residual synovial inflammation. The main aim of the study was to evaluate the effects of mud-bath therapy on clinical picture of PsA patients treated with TNF inhibitors. The secondary outcome was to assess synovial inflammation in hand joints detected by contrast-enhanced ultrasound. Other aims were to verify the risk of arthritis flare and to evaluate the effects of spa treatment on functional ability and on quality of life. Thirty-six patients with psoriatic arthritis, treated in the last 6 months with TNF inhibitors, were enrolled. After 1:1 randomisation, 18 patients (group A) underwent mud-bath therapy (12 mudpacks and 12 thermal baths), maintaining treatment with TNF inhibitors; 18 patients (group B) continued pharmacological therapy alone. CRP, PASI, DAS28, swollen and tender joint count, VAS pain, HAQ and SF-36 were evaluated at baseline (T0) and after 45 days (T1). Synovial inflammation detected by contrast-enhanced ultrasound, analysed by a software system, was also assessed. A significant improvement in PASI (P<0.005), DAS28 (P<0.05), swollen joint count and tender joint count (P<0.001), and HAQ (P<0.001) between T0 and T1 was observed in group A. No patient underwent a flare-up of arthritis. Ultrasound videos demonstrated a significant appearance delay (P<0.05) and faster washout (P<0.02) of contrast dye in group A patients with respect to group B. These data suggest a decrease of residual synovial inflammation and a beneficial clinical effect of spa therapy in psoriatic arthritis patients treated with TNF inhibitors. Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis.

PubMed

Awad, S M; Attallah, D A; Salama, R H; Mahran, A M; Abu El-Hamed, E

2018-04-01

Psoriasin (S100A7) and koebnerisin (S100A15) are proinflammatory proteins upregulated in psoriasis, but their relation to atherosclerosis remains unclear. To evaluate the role of serum psoriasin and koebnerisin as possible markers for subclinical atherosclerosis in patients with psoriasis. Serum levels of psoriasin and koebnerisin were measured by ELISA in 45 patients with psoriasis and in 45 healthy controls (HCs). Intima-media thickness (IMT) of the right and left common carotid arteries was measured to detect the presence of subclinical atherosclerosis. Clinical severity of psoriasis was estimated using the Psoriasis Area and Severity Index (PASI). Compared with HCs, patients with psoriasis had significantly higher levels of psoriasin (26.61 ± 22.45 ng/mL vs. 6.31 ± 1.68 ng/mL, P < 0.001) and koebnerisin (21.2 ± 13.12 ng/mL vs. 12.2 ± 4.67 ng/mL, P = 0.001), and significantly higher IMT values (1.07 ± 0.4 mm vs. 0.61 ± 0.1 mm, P < 0.001). A positive correlation was observed between IMT and PASI (r = 0.78, P < 0.001), serum psoriasin (r = 0.48, P > 0.01) and serum koebnerisin (r = 0.48, P < 0.01). Patients with psoriasis with subclinical atherosclerosis had higher serum levels of koebnerisin compared with patients without subclinical atherosclerosis (P = 0.04), which was not observed for psoriasin (P = 0.94). Serum psoriasin and koebnerisin correlate with IMT, underlining their value as a potential link between psoriasis and atherosclerosis. In particular, koebnerisin seems to be a useful marker of subclinical atherosclerosis in patients with psoriasis. © 2018 British Association of Dermatologists.

Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice via the NF-κB pathway.

PubMed

Chen, Haiming; Lu, Chuanjian; Liu, Huazhen; Wang, Maojie; Zhao, Hui; Yan, Yuhong; Han, Ling

2017-07-01

Quercetin (QC) is a dietary flavonoid abundant in many natural plants. A series of studies have shown that it has been shown to exhibit several biological properties, including anti-inflammatory, anti-oxidant, cardio-protective, vasodilatory, liver-protective and anti-cancer activities. However, so far the possible therapeutic effect of QC on psoriasis has not been reported. The present study was undertaken to evaluate the potential beneficial effect of QC in psoriasis using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, and to further elucidate its underlying mechanisms of action. Effects of QC on PASI scores, back temperature, histopathological changes, oxidative/anti-oxidative indexes, pro-inflammatory cytokines and NF-κB pathway in IMQ-induced mice were investigated. Our results showed that QC could significantly reduce the PASI scores, decrease the temperature of the psoriasis-like lesions, and ameliorate the deteriorating histopathology in IMQ-induced mice. Moreover, QC effectively attenuated levels of TNF-α, IL-6 and IL-17 in serum, increased activities of GSH, CAT and SOD, and decreased the accumulation of MDA in skin tissue induced by IMQ in mice. The mechanism may be associated with the down-regulation of NF-κB, IKKα, NIK and RelB expression and up-regulation of TRAF3, which were critically involved in the non-canonical NF-κB pathway. In conclusion, our present study demonstrated that QC had appreciable anti-psoriasis effects in IMQ-induced mice, and the underlying mechanism may involve the improvement of antioxidant and anti-inflammatory status and inhibition on the activation of the NF-κB signaling. Hence, QC, a naturally occurring flavone with potent anti-psoriatic effects, has the potential for further development as a candidate for psoriasis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis.

PubMed

Marzo-Ortega, Helena; McGonagle, Dennis; Rhodes, Laura A; Tan, Ai Lyn; Conaghan, Philip G; O'Connor, Philip; Tanner, Steven F; Fraser, Alexander; Veale, Douglas; Emery, Paul

2007-06-01

Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. To assess the impact of infliximab on bone oedema in PsA as shown by MRI. 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.

Mental health self-assessment in patients with moderate to severe psoriasis: an observational, multicenter study of 1164 patients in Spain (the VACAP Study).

PubMed

Pujol, R M; Puig, L; Daudén, E; Sánchez-Carazo, J L; Toribio, J; Vanaclocha, F; Yébenes, M; Sabater, E; Casado, M A; Caloto, M T; Aragón, B

2013-12-01

Poor self-assessed mental health appears to be related to the severity of psoriasis. To evaluate the impact of psoriasis severity on mood and anxiety disorders. A prospective, observational, multicenter study was conducted by 123 dermatologists in Spain. Patients (n=164; mean [SD] age, 45.11 [13.92] years; 60.8% males) with moderate to severe psoriasis were evaluated at baseline and 4 months later. Psoriasis severity was measured using the Psoriasis Area and Severity Index (PASI), with a score range of 0 (mild) to 72 (severe); body surface area involvement (BSA); and physician global assessment (PGA) scores, with a range of 1 (mild) to 7 (severe). Mental health was assessed using the Hospital Anxiety and Depression Scale (HADS), with a total possible score of 0-42 (higher scores representing worse mental health). Mean first and second visit scores were compared. Mean (SD) scores improved between the first and second visit as follows: 13.24 (9.50) to 5.07 (6.03) for PASI, 12.52 (7.92) to 10.78 (7.32) for overall HADS, 7.83 (4.55) to 6.85 (4.21) for the HADS anxiety subscale, and 4.72 (4.12) to 3.95 (3.76) for the HADS depression subscale (P<.001 in all cases). Multivariate analyses showed that the main factors related to anxiety were psoriasis severity, sex, and completion of graduate studies. The independent variables included in the model for depression were psoriasis severity, sex, and psoriasis located on the head. Reductions in disease severity improve self-assessed mood and anxiety disorders in patients with moderate to severe psoriasis. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

Toxin-Antitoxin Systems Are Important for Niche-Specific Colonization and Stress Resistance of Uropathogenic Escherichia coli

PubMed Central

Norton, J. Paul; Mulvey, Matthew A.

2012-01-01

Toxin-antitoxin (TA) systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a subset is associated with strains of extraintestinal pathogenic E. coli (ExPEC). These pathogens colonize diverse niches and are a major cause of sepsis, meningitis, and urinary tract infections. Using a murine infection model, we show that two TA systems (YefM-YoeB and YbaJ-Hha) independently promote colonization of the bladder by the reference uropathogenic ExPEC isolate CFT073, while a third TA system comprised of the toxin PasT and the antitoxin PasI is critical to ExPEC survival within the kidneys. The PasTI TA system also enhances ExPEC persister cell formation in the presence of antibiotics and markedly increases pathogen resistance to nutrient limitation as well as oxidative and nitrosative stresses. On its own, low-level expression of PasT protects ExPEC from these stresses, whereas overexpression of PasT is toxic and causes bacterial stasis. PasT-induced stasis can be rescued by overexpression of PasI, indicating that PasTI is a bona fide TA system. By mutagenesis, we find that the stress resistance and toxic effects of PasT can be uncoupled and mapped to distinct domains. Toxicity was specifically linked to sequences within the N-terminus of PasT, a region that also promotes the development of persister cells. These results indicate discrete, multipurpose functions for a TA-associated toxin and demonstrate that individual TA systems can provide bacteria with pronounced fitness advantages dependent on toxin expression levels and the specific environmental niche occupied. PMID:23055930

Safety and Efficacy of Methotrexate in Psoriasis: A Meta-Analysis of Published Trials

PubMed Central

West, Jonathan; Ogston, Simon; Foerster, John

2016-01-01

Background Methotrexate (MTX) has been used to treat psoriasis for over half a century. Even so, clinical data characterising its efficacy and safety are sparse. Objective In order to enhance the available evidence, we conducted two meta-analyses, one for efficacy and one for safety outcomes, respectively, according to PRISMA checklist. (Data sources, study criteria, and study synthesis methods are detailed in Methods). Results In terms of efficacy, only eleven studies met criteria for study design and passed a Cochrane risk of bias analysis. Based on this limited dataset, 45.2% [95% confidence interval 34.1–60.0] of patients achieve PASI75 at primary endpoint (12 or 16 weeks, respectively, n = 705 patients across all studies), compared to a calculated PASI75 of 4.4 [3.5–5.6] for placebo, yielding a relative risk of 10.2 [95% C.I. 7.1–14.7]. For safety outcomes, we extended the meta-analysis to include studies employing the same dose range of MTX for other chronic inflammatory conditions, e.g. rheumatoid arthritis, in order not to maximise capture of relevant safety data. Based on 2763 patient safety years, adverse events (AEs) were found treatment limiting in 6.9 ± 1.4% (mean ± s.e.) of patients treated for six months, with an adverse effect profile largely in line with that encountered in clinical practice. Finally, in order to facilitate prospective clinical audit and to help generate long-term treatment outcomes under real world conditions, we also developed an easy to use documentation form to be completed by patients without requirement for additional staff time. Limitations Meta-analyses for efficacy and safety, respectively, employed non-identical selection criteria. Conclusions These meta-analyses summarise currently available evidence on MTX in psoriasis and should be of use to gauge whether local results broadly fall within outcomes. PMID:27168193

Turmeric tonic as a treatment in scalp psoriasis: A randomized placebo-control clinical trial.

PubMed

Bahraini, Parichehr; Rajabi, Mehdi; Mansouri, Parvin; Sarafian, Golnaz; Chalangari, Reza; Azizian, Zahra

2018-06-01

Psoriasis is an autoimmune and recurrent chronic inflammatory skin disorder with a strong genetic basis. The characteristic features are hyperproliferation of keratinocytes, leading to redness, thickening, and scaling of the epidermis followed by itching and the appearance of lesions, which in most cases can affect the patients both medically and psychologically. The scalp is one of the most common sites for psoriasis. This condition is predominantly managed with steroids, which are associated with various side effects. Turmeric (Curcuma longa L.), a spice commonly used throughout the world, has been shown to exhibit anti-inflammatory, antimicrobial, antioxidant, and antineoplastic properties. It has been reported to exhibit inhibitory activity on potassium channels in T cells and plays a key role in psoriasis. We were prompted to investigate the turmeric tonic as an immune modulation and anti-inflammatory therapy on scalp psoriasis. Forty patients with mild-to-moderate scalp psoriasis who fulfilled the inclusion criteria were randomly allocated into two groups. The case group received turmeric tonic twice a day for 9 weeks, whereas the other group received a placebo applied in the same manner. Patients were evaluated at the following points: baseline, weeks 3, 6, and 9. The dermatology life quality index (DLQI) questionnaire and PASI (psoriasis area & severity index) scores, as well as medical photos before, during and after treatment were also evaluated. The probable adverse effects were also recorded and reported. Compared to the placebo, turmeric tonic significantly reduced the erythema, scaling and induration of lesions (PASI score), and also improved the patients' quality of life (P value < .05). The clinical effects of turmeric tonic on scalp psoriasis were satisfactory overall. This formulation could be considered as a treatment for scalp psoriasis. © 2018 Wiley Periodicals, Inc.

A Review of Guselkumab, an IL-23 Inhibitor, for Moderate-to-Severe Plaque Psoriasis.

PubMed

Nawas, Z; Hatch, M; Ramos, E; Liu, M; Tong, Y; Peranteau, A; Tyring, S

2017-03-01

Psoriasis is a chronic inflammatory skin disorder that affects 2% of the population. Evidence suggests that interleukin (IL)-23 plays a pivotal role in the pathogenesis of psoriasis. Guselkumab is a subcutaneously administered, humanized anti-IL23 monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis. Data from Phase I-III trials in this patient population reveal that guselkumab has proven to be superior to placebo or adalimumab based on achieving a Psoriasis Area and Severity Index (PASI) 90% reduction, or a static Physician Global Assessment (sPGA) score of 0 or 1 from baseline. This article reviews the current status of guselkumab as a therapy for moderate-to-severe plaque psoriasis.

Members of Microvirga and Bradyrhizobium genera are native endosymbiotic bacteria nodulating Lupinus luteus in Northern Tunisian soils.

PubMed

Msaddak, Abdelhakim; Rejili, Mokhtar; Durán, David; Rey, Luis; Imperial, Juan; Palacios, Jose Manuel; Ruiz-Argüeso, Tomas; Mars, Mohamed

2017-06-01

The genetic diversity of bacterial populations nodulating Lupinus luteus (yellow lupine) in Northern Tunisia was examined. Phylogenetic analyses of 43 isolates based on recA and gyrB partial sequences grouped them in three clusters, two of which belong to genus Bradyrhizobium (41 isolates) and one, remarkably, to Microvirga (2 isolates), a genus never previously described as microsymbiont of this lupine species. Representatives of the three clusters were analysed in-depth by multilocus sequence analysis of five housekeeping genes (rrs, recA, glnII, gyrB and dnaK). Surprisingly, the Bradyrhizobium cluster with the two isolates LluI4 and LluTb2 may constitute a new species defined by a separate position between Bradyrhizobium manausense and B. denitrificans. A nodC-based phylogeny identified only two groups: one formed by Bradyrhizobium strains included in the symbiovar genistearum and the other by the Microvirga strains. Symbiotic behaviour of representative isolates was tested, and among the seven legumes inoculated only a difference was observed i.e. the Bradyrhizobium strains nodulated Ornithopus compressus unlike the two strains of Microvirga. On the basis of these data, we conclude that L. luteus root nodule symbionts in Northern Tunisia are mostly strains within the B. canariense/B. lupini lineages, and the remaining strains belong to two groups not previously identified as L. luteus endosymbionts: one corresponding to a new clade of Bradyrhizobium and the other to the genus Microvirga. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure

PubMed Central

Mease, P; Deodhar, A; Fleischmann, R; Wollenhaupt, J; Gladman, D; Leszczyński, P; Vitek, P; Turkiewicz, A; Khraishi, M; FitzGerald, O; Landewé, R; de Longueville, M; Hoepken, B; Peterson, L; van der Heijde, D

2015-01-01

Objective Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. Methods RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. Results Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. Conclusions CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. Trial registration number NCT01087788. PMID:26509074

Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo‐Controlled Phase III Trial

PubMed Central

Puig, Lluís; Gottlieb, Alice B.; Ritchlin, Christopher; Li, Shu; Wang, Yuhua; Mendelsohn, Alan M.; Song, Michael; Zhu, Yaowei; Rahman, Proton; McInnes, Iain B.

2015-01-01

Objective To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA). Methods A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS). Results At week 100, ACR20, DAS28‐CRP moderate/good response, and PASI75 rates ranged from 56.7–63.6%, 71.9–76.7%, and 63.9–72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups. Conclusion Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab. PMID:26097039

Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis.

PubMed

Kamata, Yayoi; Kimura, Utako; Matsuda, Hironori; Tengara, Suhandy; Kamo, Atsuko; Umehara, Yoshie; Iizumi, Kyoichi; Kawasaki, Hiroaki; Suga, Yasushi; Ogawa, Hideoki; Tominaga, Mitsutoshi; Takamori, Kenji

2016-12-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H 1 -antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. Plasma GzmB levels may reflect the degree of pruritus and dermatitis in

Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study.

PubMed

Paul, C; Stein Gold, L; Cambazard, F; Kalb, R E; Lowson, D; Bang, B; Griffiths, C E M

2017-01-01

Fixed combination calcipotriol 50 μg/g (Cal) plus betamethasone 0.5 mg/g (BD) foam has been developed as a new treatment option for patients with psoriasis. The randomized, parallel-group, investigator-blinded Phase III, 12-week PSO-ABLE study compared the efficacy and safety of Cal/BD foam with Cal/BD gel. Patients aged ≥18 years with mild-to-severe psoriasis were randomized 4:4:1:1 to once-daily Cal/BD foam, Cal/BD gel, foam vehicle or gel vehicle (NCT02132936). The primary efficacy endpoint was the proportion of patients who were clear/almost clear with a ≥ 2 grade improvement according to the physician's global assessment of disease severity (i.e. treatment success) at week 4 for Cal/BD foam vs. week 8 for Cal/BD gel. Secondary efficacy endpoints included: proportion of patients achieving at least a 75% reduction in modified psoriasis area and severity index (mPASI75), and time to treatment success (TTTS). Safety was monitored throughout. A total of 463 patients were randomized: Cal/BD foam (n = 185), Cal/BD gel (n = 188), foam vehicle (n = 47), gel vehicle (n = 43); overall completion rate was 90%. Cal/BD foam achieved higher treatment success rates (38% vs. 22%; P < 0.001) and mPASI75 (52% vs. 35%; P < 0.001) by week 4 than Cal/BD gel by week 8. Median TTTS with Cal/BD foam was 6 weeks; this could not be determined for Cal/BD gel as 50% treatment success was not achieved (P < 0.001). Adverse drug reactions were reported in 14 (7.6%) Cal/BD aerosol foam patients and 7 (3.7%) Cal/BD gel patients; all were single events except for itch with Cal/BD aerosol foam (n = 5; 2.7%) and worsening psoriasis with Cal/BD gel (n = 3; 1.6%). Cal/BD aerosol foam showed significantly greater efficacy after 4 weeks, than 8 weeks of treatment with Cal/BD gel, with similar tolerability. © 2016 European Academy of Dermatology and Venereology.

Budget impact model in moderate-to-severe psoriasis vulgaris assessing effects of calcipotriene and betamethasone dipropionate foam on per-patient standard of care costs.

PubMed

Asche, Carl V; Kim, Minchul; Feldman, Steven R; Zografos, Panagiotis; Lu, Minyi

2017-09-01

To develop a budget impact model (BIM) for estimating the financial impact of formulary adoption and uptake of calcipotriene and betamethasone dipropionate (C/BD) foam (0.005%/0.064%) on the costs of biologics for treating moderate-to-severe psoriasis vulgaris in a hypothetical US healthcare plan with 1 million members. This BIM incorporated epidemiologic data, market uptake assumptions, and drug utilization costs, simulating the treatment mix for patients who are candidates for biologics before (Scenario #1) and after (Scenario #2) the introduction of C/BD foam. Predicted outcomes were expressed in terms of the annual cost of treatment (COT) and the COT per member per month (PMPM). At year 1, C/BD foam had the lowest per-patient cost ($9,913) necessary to achieve a Psoriasis Area and Severity Index (PASI)-75 response compared with etanercept ($73,773), adalimumab ($92,871), infliximab ($34,048), ustekinumab ($83,975), secukinumab ($113,858), apremilast ($47,960), and ixekizumab ($62,707). Following addition of C/BD foam to the formulary, the annual COT for moderate-to-severe psoriasis would decrease by $36,112,572 (17.91%, from $201,621,219 to $165,508,647). The COT PMPM is expected to decrease by $3.00 (17.86%, from $16.80 to $13.80). Drug costs were based on Medi-Span reference pricing (January 21, 2016); differences in treatment costs for drug administration, laboratory monitoring, or adverse events were not accounted for. Potentially confounding were the definition of "moderate-to-severe" and the heterogeneous efficacy data. The per-patient cost for PASI-75 response at year 1 was estimated from short-term efficacy data for C/BD foam and apremilast only. The introduction of C/BD foam is expected to decrease the annual COT for moderate-to-severe psoriasis treatable with biologics by $36,112,572 for a hypothetical US healthcare plan with 1 million plan members, and to lower the COT PMPM by $3.00.

ExplorEnz: a MySQL database of the IUBMB enzyme nomenclature

PubMed Central

McDonald, Andrew G; Boyce, Sinéad; Moss, Gerard P; Dixon, Henry BF; Tipton, Keith F

2007-01-01

Background We describe the database ExplorEnz, which is the primary repository for EC numbers and enzyme data that are being curated on behalf of the IUBMB. The enzyme nomenclature is incorporated into many other resources, including the ExPASy-ENZYME, BRENDA and KEGG bioinformatics databases. Description The data, which are stored in a MySQL database, preserve the formatting of chemical and enzyme names. A simple, easy to use, web-based query interface is provided, along with an advanced search engine for more complex queries. The database is publicly available at . The data are available for download as SQL and XML files via FTP. Conclusion ExplorEnz has powerful and flexible search capabilities and provides the scientific community with the most up-to-date version of the IUBMB Enzyme List. PMID:17662133

ExplorEnz: a MySQL database of the IUBMB enzyme nomenclature.

PubMed

McDonald, Andrew G; Boyce, Sinéad; Moss, Gerard P; Dixon, Henry B F; Tipton, Keith F

2007-07-27

We describe the database ExplorEnz, which is the primary repository for EC numbers and enzyme data that are being curated on behalf of the IUBMB. The enzyme nomenclature is incorporated into many other resources, including the ExPASy-ENZYME, BRENDA and KEGG bioinformatics databases. The data, which are stored in a MySQL database, preserve the formatting of chemical and enzyme names. A simple, easy to use, web-based query interface is provided, along with an advanced search engine for more complex queries. The database is publicly available at http://www.enzyme-database.org. The data are available for download as SQL and XML files via FTP. ExplorEnz has powerful and flexible search capabilities and provides the scientific community with the most up-to-date version of the IUBMB Enzyme List.

Volcanic hazards and remote sensing in Pacific Latin America

NASA Astrophysics Data System (ADS)

Lyons, John; Rose, Bill; Escobar, Rüdiger

2011-06-01

PASI Workshop on Open Vent Volcanoes; San José, Costa Rica, 10-24 January 2011 ; Open-vent volcanoes are a class of volcano that contain a relatively open path from the subsurface to the atmosphere without a major vent obstruction. Their persistent, low-level activity, which poses little danger to communities, may be punctuated by violent activity without warning. These complex systems challenge and provide opportunity for observatories and national and international investigators. Long-lived eruptions are also laboratories for students and scientists and a locus for developing collaborations and field testing new instrumentation and methods. Pacific Latin America hosts a high density of active volcanoes, and many are under-monitored and under-researched despite the efforts of local volcano observatories and their accessibility to U.S. and European scientists.

The skin in psoriasis: assessment and challenges.

PubMed

Oji, Vinzenz; Luger, Thomas A

2015-01-01

The coexistence of psoriasis arthritis (PsA) and psoriasis vulgaris in about 20% of patients with psoriasis leads to a need for rheumatologic-dermatologic team work. We summarise the role of dermatologists in assessment of the skin in psoriasis. Chronic plaque psoriasis must be differentiated from other subtypes such as generalised pustular psoriasis (GPP) or palmoplantar pustulosis (PPP). Therapeutic management is based on the evaluation of the disease severity. Quantitative scoring of skin severity includes calculation of the Psoriasis Area and Severity Index (PASI), body surface area (BSA) as well as the Dermatology Life Quality Index (DLQI). These scoring systems do not replace the traditional dermatologic medical history and physical examination of the patient. The skin should be examined for additional skin diseases; moreover, patients should be monitored for comorbidity, most importantly PsA and cardiovascular comorbidity.

A kite-based approach for water-vapor lidar calibration and application to multi-platform intercomparison in the Western Mediterranean during ChArMEx/ADRIMED

NASA Astrophysics Data System (ADS)

Totems, Julien; Chazette, Patrick; Dulac, François; Hassanzadeh, Sahar

2015-04-01

In the framework of the ADRIMED campaign included in the ChArMEx (Chemistry Aerosol Mediterranean Experiment) research program, performed in June 2013 in the western Mediterranean, the mobile Water vapor Aerosol LIdar (WALI) developed by LSCE was deployed at Cap d'en Font on the island of Menorca (Spain). Alongside an elastic backscatter channel, it features depolarization, N2- and H2O-Raman channels, the two latter yielding profiles of atmospheric water vapor mixing ratio (WVMR). The water content thus provided by the lidar is essential to validate models or satellite water vapor products for meteorological purposes. It also proved to be very helpful in characterizing particle types and sources, especially for the multi-layer situations observed during the ChArMEx/ADRIMED special observation period. Beforehand, however, a precise calibration of the WVMR had to be done on-site. Balloon rawindsoundings performed by CNES were available about 10 km off-site on Saint-Lluis aerodrome or 100 km away on Majorca for this purpose, but strong inhomogeneities in the WVMR observed under 2 km altitude prevent an accurate calibration and the determination of the lidar overlap factor, which biases WVMR retrieval under 300 m. Instead, we propose the use of a lightweight Pressure-Temperature-Relative Humidity (PTU) sound carried under a simple kite to perform a co-localized sounding. Modern kites indeed combine the advantages of an easy deployment and the possibility of longer, more precise soundings in the low troposphere. After showing that this approach leads to calibration with less than 2% error from 80 m altitude, we validate it against rawindsounding WVMR profiles, with very good agreement at high altitude. We also present further comparisons between the lidar-derived WVMR and the one given by meteorological model reanalyses (AROME, ECMWF) or satellite inversion products (IASI).

Improvement in signs and symptoms in psoriasis patients with Pycnogenol® supplementation.

PubMed

Belcaro, G; Luzzi, R; Hu, S; Cesarone, M R; Dugall, M; Ippolito, E; Corsi, M; Caporale, S

2014-03-01

The aim of the study was the evaluation of supplementation with Pycnogenol®, French maritime pine bark extract (registered trademark of Horphag Research Ltd.) to improve the effects of the management of psoriasis and reduce the need for treatments. Patients (age range 30-45) with moderate/severe plaque psoriasis were included in a 12-week registry study that did not interfere with 'standard management'. The minimum Psoriasis Area Severity Index (PASI) score at inclusion was 10. Subjects with 10-29% (grade 2) and 30-49% (grade 3) of involved area were included. Oxidative stress (plasma free radicals) was measured. Patient-reported measures included the Dermatology Life Quality Index (DLQI). The supplement was used at a dosage of 150 mg/day (50 mg three times daily). The two registry groups (standard management and standard management+supplementation) were comparable. Dropouts were due to logistical problems. Single PASI items were evaluated: a decrease in the affected body area in boths groups was observed. The decrease in affected areas was more pronounced in the Pycnogenol group in all body regions. The severity score (erythema, induration, desquamation) improved more significantly with Pycnogenol. Considering the water content of skin in all areas, the increase was higher with Pycnogenol. The quantity of exfoliating cells (score from -5 to +5) was significantly reduced in both groups, with a better action using Pycnogenol. Skin moisture improved with treatment in all subjects, with better effects using Pycnogenol. Using a modified (12 items) DLQI indicating how much psoriasis had affected the patient's life in the previous week, Pycnogenol-supplemented subjects performed better for each single parameter in comparison with standard management. Improvement in the treatment time (-32% in comparison with standard management) and costs (decreased on average 36.4% in comparison with standard management) were observed in the supplement group. A decrease in consumption

Effect of tofacitinib withdrawal and re-treatment on patient-reported outcomes: results from a Phase 3 study in patients with moderate to severe chronic plaque psoriasis.

PubMed

Griffiths, C E M; Vender, R; Sofen, H; Kircik, L; Tan, H; Rottinghaus, S T; Bachinsky, M; Mallbris, L; Mamolo, C

2017-02-01

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. A Phase 3 withdrawal/re-treatment study (NCT01186744; OPT Retreatment) showed tofacitinib re-treatment was effective in patients with chronic plaque psoriasis. To describe the effects of tofacitinib withdrawal/re-treatment on health-related quality of life (HRQoL) and disease symptoms measured by patient-reported outcomes (PROs). The study was divided into initial treatment, treatment withdrawal, and re-treatment periods. Initial treatment: patients were randomized to receive tofacitinib 5 (n = 331) or 10 mg (n = 335) BID for 24 weeks. Treatment withdrawal: patients who achieved both ≥ 75% reduction in Psoriasis Area and Severity Index (PASI) score from baseline and Physician's Global Assessment of 'clear'/'almost clear' at Week (W)24 received placebo (withdrawal) or the previous dose (continuous treatment). Re-treatment: at relapse (> 50% loss of W24 PASI response) or at W40, patients received their initial tofacitinib dose. PROs included: Dermatology Life Quality Index (DLQI), Itch Severity Item (ISI), Short Form-36 (SF-36) and Patient's Global Assessment (PtGA). After initial treatment with tofacitinib 5 and 10 mg BID, substantial and significant improvements were reported for mean DLQI (baseline: 12.6 and 12.6; W24: 5.1 and 2.6) and ISI (baseline: 6.7 and 6.9; W24: 2.9 and 1.6). Patients continuously treated with tofacitinib 5 and 10 mg BID maintained those improvements through Week 56 (DLQI: 3.0 and 2.1; ISI: 2.3 and 1.4). By W40, patients withdrawn from tofacitinib 5 and 10 mg BID showed worsening in DLQI (5.0 and 6.2) and ISI (3.7 and 4.0) scores; improvements were regained upon re-treatment (W56, DLQI: 3.4 and 2.4; ISI: 2.2 and 1.6). Similar results were reported for PtGA and SF-36. Continuous tofacitinib treatment provided sustained improvement in HRQoL and disease symptoms. Patients randomized to treatment withdrawal lost initial improvements. Upon re-treatment, improvements

A Randomized, Investigator-Blinded Comparison of Two Topical Regimens in Fitzpatrick Skin Types III-VI With Moderate to Severe Facial Hyperpigmentation.

PubMed

Vanaman Wilson, Monique J; Jones, Isabela T; Bolton, Joanna; Larsen, Lisa; Wu, Douglas C; Goldman, Mitchel P

2017-11-01

Purpose: Though hydroquinone (HQ) remains the gold standard for treatment of hyperpigmentation, concerns about its safety have prompted the development of HQ-free topical skin lightening systems. To compare the efficacy and tolerability of a new HQ-free system and a popular HQ-based system for the improvement of facial hyperpigmentation and photoaging in darker skin types. This investigator-blinded trial randomized 30 subjects of Fitzpatrick skin types III to VI with moderate to severe hyperpigmentation to a new 7-product HQ-free system or a 7-product HQ-based system for 12 weeks. At 4, 8, and 12 week follow-up visits, a blinded investigator assessed efficacy and tolerability using standardized scales. Subjects also performed a self-assessment at each visit. Both the HQ-free and HQ-based systems produced significant improvements in Overall Hyperpigmentation that were sustained through week 12 (P=0.008, 0.0003). The HQ-based system demonstrated better improvement in overall hyperpigmentation at weeks 4, 8, 12 (P=0.01, 0.001, 0.003, respectively). Mottled Pigmentation Area Severity Index (MoPASI) scores improved with both systems (P=0.02, 0.01), with no statistically significant differences between the two treatment groups. Subject-rated hyperpigmentation was not different between groups. Subjects reported significantly more discomfort with the HQ-free system at week 8 (P=0.02); otherwise, measures of irritation were the same between groups. All irritation was described as mild to moderate. At week 12, 100% of subjects in the HQ-free group and 92.3% of subjects in the HQ-based group were satisfied with their outcome. Both a new HQ-free skincare system and a widely-available HQ-based system improved hyperpigmentation in Fitzpatrick skin types III to VI. Though the HQ-based system produced greater improvement in hyperpigmentation when compared to the HQ-free system, there was no difference in MoPASI scores between the treatment groups. Subjects were satisfied with

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study

PubMed Central

Koek, Mayke BG; Buskens, Erik; Steegmans, Paul HA; van Weelden, Huib; Bruijnzeel-Koomen, Carla AFM; Sigurdsson, Vigfús

2006-01-01

Background Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). Methods We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. Discussion In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study.

PubMed

Koek, Mayke B G; Buskens, Erik; Steegmans, Paul H A; van Weelden, Huib; Bruijnzeel-Koomen, Carla A F M; Sigurdsson, Vigfús

2006-08-01

Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as

Health economic analyses of psoriasis management: a systematic literature search.

PubMed

Gutknecht, Mandy; Krensel, Magdalene; Augustin, Matthias

2016-11-01

In the course of the chronic skin disease psoriasis, where a variety of treatment interventions is available, a strong growth of health economic studies comparing treatment costs and benefits can be noticed. The objective was to identify health economic evaluations of psoriasis treatments that have been published to date. Of particular interest were the mostly used analysis and outcome parameters, the compared treatments, and the question, if available health economic studies may be used to perform a meta-analysis of qualitative findings. A systematic literature search using PubMed Medline, Ovid Medline, and Cochrane Library was performed for articles, published and available until mid of January 2016. Among the key words were the terms "psoriasis" and "cost-effectiveness". The search resulted in 318 articles without duplicates. Thereof 60 health economic analyses in psoriasis management were identified. Most of these are cost-effectiveness evaluations (45). The clinical parameter PASI (Psoriasis Area Severity Index) is the most often used cost-effectiveness outcome (33) followed by the Dermatology Life Quality Index (DLQI) (6). In case of cost-utility analyses, QALYs (quality-adjusted life-years) were mostly generated with the help of EuroQol five dimensions questionnaire (EQ-5D) (12), which was partly based on PASI and DLQI values. The majority of health economic studies is focusing on the direct medical and non-medical costs without consideration of productivity losses. Almost 70 % of 60 publications were conducted in Europe. Overall, most considered systemic treatments were the biological agents etanercept (36), adalimumab (27), and infliximab (26) followed by ustekinumab (17) and phototherapy (incl. UV-B, PUVA/psoralen combined with UV-A) (14). Comparisons including only topical treatments mostly focused on vitamin D treatment (14), corticosteroids (13), and coal tar products (6) followed by dithranol (5) and tazarotene (4). Given the setting, compared

Local Site Characterization Using HVSR, ReMi, and SPAC, Study Case: Soccer Field At Autonomous University of Santo Domingo, Dominican Republic

NASA Astrophysics Data System (ADS)

Upegui Botero, F. M.; Rojas Mercedes, N.; Huerta-Lopez, C.; Martinez-Cruzado, J. A.; Suárez, L.; Lopez, A. M.; Huerfano Moreno, V.

2013-12-01

Earthquake effects are frequently quantified by the energy liberated at the source, and the degree of damage produced in urban areas. The damage of historic events such as the Mw=8.3, September 19, 1985 Mexico City Earthquake was dominated by the amplification of seismic waves due to local site conditions. The assessment of local site effects can be carried out with site response analyses in order to determine the properties of the subsoil such as the dominant period, and the Vs30. The evaluation of the aforementioned properties is through the analysis of ground motion. However, in locations with low seismicity, the most convenient method to assess the site effect is the analysis of ambient vibration measurements. The Spatial Auto Correlation method (SPAC) can be used to determine a Vs30 model from ambient vibration measurements using a triangular array of sensors. Refraction Microtremor (ReMi) considers the phase velocity of the Rayleigh waves can be separated of apparent velocities; the aim of the ReMI method is to obtain the Vs30 model. The HVSR technique or Nakamura's method has been adopted to obtain the resonant frequency of the site from the calculation of ratio between the Fourier amplitude spectra or PSD spectrum of the horizontal and vertical components of ambient vibration. The aim of this work is to compare the results using different techniques to assess local site conditions in the urban area of Santo Domingo, Dominican Republic. The data used was collected during the Pan-American Advance Studies Institute (PASI), Workshop held in Santo Domingo, Dominican Republic from July 14 to 25, 2013. The PASI was sponsored by IRIS Consortium, NSF and DOE. Results obtained using SPAC, and ReMi, show a comparable model of surface waves velocities. In addition to the above, the HVSR method is combined with the stiffness matrices method for layered soils to calculate a model of velocities and the predominant period on the site. As part of this work a comparison with

Brodalumab: the first anti-IL-17 receptor agent for psoriasis.

PubMed

Puig, L

2017-05-01

Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef). The U.S. Food and Drug Administration has also recently approved brodalumab (Siliq) for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Regulatory applications are under review in the E.U. and Canada. The phase III clinical trials in moderate to severe plaque psoriasis met their primary endpoints after 12 weeks' treatment, with PASI 75 (75% improvement in the Psoriasis Area and Severity Index) response rates ranging between 83% and 86% (210 mg) and PASI 100 response rates ranging between 37% and 44%, significantly higher than those achieved with ustekinumab in the head-to-head trials AMAGINE-1 and AMAGINE-2. The most frequently reported adverse events in brodalumab clinical trials consisted of nasopharyngitis, headache, upper respiratory tract infection and arthralgia. In the head-to-head trials, rates of neutropenia were higher with both active drugs than with placebo, and mild or moderate Candida infections were more frequent with brodalumab than with ustekinumab or placebo. Clinical development was terminated by Amgen after adverse events of suicidal ideation and behavior were observed ls involving several indications, but data are

Comparative evaluation of topical calcipotriol versus coal tar and salicylic acid ointment in chronic plaque psoriasis.

PubMed

Singh, Preeti; Gupta, Surabhi; Abidi, Afroz; Krishna, Arvind

2013-08-01

Calcipotriol is a newer topical treatment option available for plaque psoriasis and coal tar being one of the oldest treatment and still in use. To evaluate and compare the differences in terms of efficacy, safety and relapse with Calcipotriol 0.005% (50 mcg/gm) and 6% coal tar and 3% salicylic ointment in patients with Plaque psoriasis. SETTING and Study conducted on 60 patients of plaque psoriasis, who attended the skin OPD in our hospital. The patients with mild to moderate plaque psoriasis were selected. 60 patients were enrolled for the study after obtaining informed consent. Subjects were asked to apply Calcipotriol 0.005% (50 mcg/gm) (Heximar Win care) twice a day on the right side plaques and on left side plaques, Petroleum jelly (Vaseline) in the morning and 6% coal tar and 3% salicylic ointment (Protar® Percos) at nighttime. PASI score was used to assess the reponse to therapy at 2nd, 4th, 6th and 8th week. After treatment subjects were observed for 6 weeks for any relapse. It was done by paired t-test and independent sample t-test. The results showed that statistically significant difference was seen in the mean percentage reduction of PASI score between both the groups, at all the assessment visits, 2, 4, 6, and 8 weeks, the mean percentage reduction at 2 weeks for calcipotriol being 21±12.06 and for coal tar being 13.44±11.19 (P=0.000), at 4 weeks for calcipotriol was 40±16.71 and for coal tar 25±99 (P=0.000), at 6 weeks for calcipotriol was 53.99+-22.43 and for coal tar 41±21.23 (P=0.002), at 8 weeks for calcipotriol was 62.73±24.04 and for coal tar was 51.53±23.27 (P=0.11). Relapse was seen in 5/60 (8.3%) of patients on calcipotriol treated side and 9/60 (15%) of patients with coal tar treated side. Thus it can be concluded that calcipotriol cream is more efficacious when compared with coal tar and does have a quick response. It is well tolerated and acceptable cosmetically.

Pharmacogenetics of ustekinumab in patients with moderate-to-severe plaque psoriasis.

PubMed

Prieto-Pérez, Rocío; Llamas-Velasco, Mar; Cabaleiro, Teresa; Solano-López, Guillermo; Márquez, Beatriz; Román, Manuel; Ochoa, Dolores; Talegón, María; Daudén, Esteban; Abad-Santos, Francisco

2017-01-01

Aim/Materials & methods: Few studies have evaluated the influence of pharmacogenetics in psoriatic patients treated with ustekinumab. We evaluated 121 polymorphisms to study a possible association between these SNPs and the response to ustekinumab (PASI75 at 4 months; n = 69). The adjusted results (false discovery rate) showed an association between five SNPs in TNFRSF1A, HTR2A, NFKBIA, ADAM33 and IL13 genes, and poor response to ustekinumab. Furthermore, six SNPs in CHUK, C17orf51, ZNF816A, STAT4, SLC22A4 and Corf72 genes were associated with better response to ustekinumab. However, there was no significant association between response to ustekinumab and SNPs in HLA-C as it has been recently described. Finally, a higher weight was obtained in nonresponders than responders (p = 0.018). Further studies would be necessary to be closer to personalized medicine.

Dynamics of Infection and Spread of Diseases

NASA Astrophysics Data System (ADS)

Zorzenon dos Santos, Rita Maria

2003-03-01

This text summarizes a series of four lectures presented at the PASI on Modern Challenges in Statistical Mechanics. The idea was to give to the students a flavor of the biological aspects involved in the dynamics of infection and the spread of diseases, the complexity of the systems involved, and how we can improve our modeling of such systems by using different approaches in order to get closer to experimental results. In a huge universe of publications about the subject, we restrict the list of references to the ones that may be useful to the students and will lead them to other important work. Therefore, the text should not be taken as a review of the subject, but rather as an introductory text for physicists about the dynamics of infection and spread of diseases and the role of biological physics in this interdisciplinary field.

Evaluation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in Turkish patients with chronic plaque psoriasis.

PubMed

Polat, Mualla; Bugdayci, Güler; Kaya, Hatice; Oğuzman, Hamdi

2017-12-01

This study evaluates the relationship between disease activity and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with chronic plaque psoriasis. Clinical and biochemical data were retrieved through retrospective examination of patients' and healthy subjects' medical records. NLR and PLR values were calculated from the hemogram results. This study included 46 patients (25 males, 21 females; 36.58 ± 9.82 years) diagnosed with chronic plaque psoriasis and a control group of 46 healthy volunteers (21 males, 25 females; 34.02 ± 8.41 years). NLR and PLR were significantly elevated in patients with chronic plaque psoriasis (p = 0.0001 and p = 0.003, respectively). PASI was positively correlated with NLR, PLR, and serum CRP levels (r = 0.313, p = 0.034; r = 0.394, p = 0.017; r = 0.359, p = 0.014, respectively). NLR and PLR are low-cost tests that can be used to determine the severity of current systemic inflammation in patients with chronic plaque psoriasis.

Secukinumab treatment of moderate to severe plaque psoriasis in routine clinical care: real-life data of prior and concomitant use of psoriasis treatments from the PROSPECT study.

PubMed

Körber, A; Thaçi, D; von Kiedrowski, R; Bachhuber, T; Melzer, N; Kasparek, T; Kraehn-Senftleben, G; Amon, U; Augustin, M

2018-03-01

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has demonstrated efficacy and safety in patients with moderate to severe psoriasis. However, as per study protocols, transition periods from prior psoriasis treatments of a defined minimal length were required and use of concomitant psoriasis medication was prohibited. There is therefore a lack of data on the effect of shorter transition periods and concomitant psoriasis treatment with other pharmacologically active substances on the effectiveness and safety of secukinumab in routine clinical practice. The PROSPECT study was designed to assess prior and concomitant use of psoriasis treatments in subjects receiving secukinumab and the duration of transition periods from prior treatments to secukinumab. Here, we report the baseline characteristics and the duration of transition period in an interim analysis of the first 805 subjects. PROSPECT is an ongoing 24-week, single-cohort, non-interventional study. Subjects with moderate to severe psoriasis with a decision to receive secukinumab were included. The majority of subjects were male (491/796, 61.7%), with a mean age of 47.7 years (SD 13.7). The baseline Psoriasis Area and Severity Index (PASI) was available for 92.4% (744/805) of subjects, and mean baseline PASI was 17.5 (SD 13.1); 93.4% (752/805) of subjects had signs of high disease severity. Use of concomitant treatment increased with the number of signs. Within the last 12 months prior to inclusion, 10%, 40%, and 28% of subjects had received topical, conventional systemic, or biologic treatments as their last prior psoriasis therapy, respectively, and 22% of subjects had not received any psoriasis therapy. Discontinuation of prior treatment due to adverse events was high in subjects with conventional systemic treatment (93/413, 22.5%) compared to biologic treatment (5/210, 2.4%). The median duration of the transition period was 14.0, 30.5, and 38.0 days for prior topical, conventional systemic

Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor, tofacitinib: a Phase 2b randomized clinical trial.

PubMed

Papp, Kim A; Bissonnette, Robert; Gooderham, Melinda; Feldman, Steven R; Iversen, Lars; Soung, Jennifer; Draelos, Zoe; Mamolo, Carla; Purohit, Vivek; Wang, Cunshan; Ports, William C

2016-10-03

Most psoriasis patients have mild to moderate disease, commonly treated topically. Current topical agents have limited efficacy and undesirable side effects associated with long-term use. Tofacitinib is a small molecule Janus kinase inhibitor investigated for the topical treatment of psoriasis. This was a 12-week, randomized, double-blind, parallel-group, vehicle-controlled Phase 2b study of tofacitinib ointment (2 % and 1 %) applied once (QD) or twice (BID) daily in adults with mild to moderate plaque psoriasis. Primary endpoint: proportion of patients with Calculated Physician's Global Assessment (PGA-C) clear or almost clear and ≥2 grade improvement from baseline at Weeks 8 and 12. Secondary endpoints: proportion of patients with PGA-C clear or almost clear; proportion achieving Psoriasis Area and Severity Index 75 (PASI75) response; percent change from baseline in PASI and body surface area; change from baseline in Itch Severity Item (ISI). Adverse events (AEs) were monitored and clinical laboratory parameters measured. Overall, 435 patients were randomized and 430 patients received treatment. The proportion of patients with PGA-C clear or almost clear and ≥2 grade improvement from baseline at Week 8 was 18.6 % for 2 % tofacitinib QD (80 % confidence interval [CI] for difference from vehicle: 3.8, 18.2 %) and 22.5 % for 2 % tofacitinib BID (80 % CI: 3.1, 18.5 %); this was significantly higher vs vehicle for both dosage regimens. No significant difference vs vehicle was seen at Week 12. Significantly more patients achieved PGA-C clear or almost clear with 2 % tofacitinib QD and BID and 1 % tofacitinib QD (not BID) at Week 8, and with 2 % tofacitinib BID at Week 12. Pruritus was significantly reduced vs vehicle with 2 % and 1 % tofacitinib BID (starting Day 2), and 2 % tofacitinib QD (starting Day 3). Overall, 44.2 % of patients experienced AEs, 8.1 % experienced application site AEs, and 2.3 % experienced serious AEs. The highest incidence

A Systematic Review and Meta-Analysis of the Efficacy and Safety of the Interleukin (IL)-12/23 and IL-17 Inhibitors Ustekinumab, Secukinumab, Ixekizumab, Brodalumab, Guselkumab, and Tildrakizumab for the Treatment of Moderate to Severe Plaque Psoriasis.

PubMed

Bilal, Jawad; Berlinberg, Adam; Bhattacharjee, Sandipan; Trost, Jaren; Riaz, Irbaz Bin; Kurtzman, Drew J B

2018-03-13

To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. 24 randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < 0.00001) and 14.55 (10.42-20.31, p < 0.00001) for ustekinumab 90mg, 13.75 (8.49-22.28, p < 0.00001) and 9.81 (5.70-16.89, p < 0.00001) for ustekinumab 45mg, 17.65 (12.38-25.17, p < 0.00001) and 26.13 (16.05-42.53, p < 0.00001) for secukinumab 300mg, 15.36 (10.76-21.94, p < 0.00001) and 20.91 (12.82-34.13, p < 0.00001) for secukinumab 150mg, 18.22 (10.63-31.23, p < 0.000001) and 18.82 (10.36-34.16, p < 0.00001) for ixekizumab 80mg every 4 weeks, 19.83 (11.07-35.52, p < 0.00001) and 20.41 (11.01-37.81, p < 0.00001) for ixekizumab 80mg every 2 weeks, 14.79 (9.86-22.16, p < 0.00001) and 21.93 (15.52-31.01, p < 0.00001) for brodalumab 210mg, 11.55 (7.77-17.18, p < 0.00001) and 16.59 (11.72-23.49, p < 0.00001) for brodalumab 140mg, 12.40 (8.87-17.34, p < 0.00001) and 10.84 (7.91-14.85, p < 0.00001) for guselkumab 100mg, 11.45 (7.45-17.58, p < 0.00001) and 10.97 (6.44-18.69, p < 0.00001) for tildrakizumab 200mg, 11.02 (7.17-16.93, p < 0.00001) and 10.03 (6.45-15.59, p < 0.00001) for tildrakizumab 100mg. Similar outcomes were seen for PASI-90. Safety was satisfactory for each therapy at any dose, but a slightly increased risk of withdrawal due to toxicity was observed in individuals receiving ixekizumab compared to placebo. Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.

Determination of bedrock depth at Faculty of Medicine Universitas Sebelas Maret Surakarta by using seismic refraction method

NASA Astrophysics Data System (ADS)

Pridasiwi, A. T.; Legowo, B.; Koesuma, S.

2018-03-01

The study of determination of bedrock depth has been done at Faculty of Medicine Sebelas Maret University Surakarta using seismic refraction method. The study was conducted on 3 lines using seismograph PASI type 16S24-P with spread length of 46 meters, interval between geophone 2 meters, 5 shots in each spread. Data processing is done using WinSism11.6 software and intercept time calculation method. Results of seismic data processing obtained 2 dimensions interpretation of 3 layers structure. In the first line, the P wave velocity (600-2000) m/s with the depth of 11 meters, the second line (400-2000) m/s with the depth of 11 meters and the third line (600-2000) m/s with the depth of 7 meters. Based on the P wave velocity that have been correlated with the drill data, the rock lithology of the 3 lines are consist of top soil, sand with silt and clay (massif). It was concluded that bedrock lies at depth 11 meters.

The temperature dependence of the characteristics of crystalline-silicon-based heterojunction solar cells

NASA Astrophysics Data System (ADS)

Sachenko, A. V.; Kryuchenko, Yu. V.; Kostylyov, V. P.; Korkishko, R. M.; Sokolovskyi, I. O.; Abramov, A. S.; Abolmasov, S. N.; Andronikov, D. A.; Bobyl', A. V.; Panaiotti, I. E.; Terukov, E. I.; Titov, A. S.; Shvarts, M. Z.

2016-03-01

Temperature dependences of the photovoltaic characteristics of ( p)a-Si/( i)a-Si:H/( n)c-Si singlecrystalline- silicon based heterojunction-with-intrinsic-thin-layer (HIT) solar cells have been measured in a temperature range of 80-420 K. The open-circuit voltage ( V OC), fill factor ( FF) of the current-voltage ( I-U) characteristic, and maximum output power ( P max) reach limiting values in the interval of 200-250 K on the background of monotonic growth in the short-circuit current ( I SC) in a temperature range of 80-400 K. At temperatures below this interval, the V OC, FF, and P max values exhibit a decrease. It is theoretically justified that a decrease in the photovoltaic energy conversion characteristics of solar cells observed on heating from 250 to 400 K is related to exponential growth in the intrinsic conductivity. At temperatures below 200 K, the I-U curve shape exhibits a change that is accompanied by a drop in V OC. Possible factors that account for the decrease in V OC, FF, and P max are considered.

Determinants of health-related quality of life in psoriasis patients in Malaysia.

PubMed

Nyunt, Wint Wint Thu; Low, Wah Yun; Ismail, Rokiah; Sockalingam, Sargunan; Min, Aung Ko Ko

2015-03-01

Psoriasis is a chronic dermatological disorder that has a negative impact on quality of life (QoL). This hospital-based cross-sectional study determined factors associated with health-related QoL (HRQoL) impairment in adult psoriasis patients. HRQoL was assessed using the Dermatology Life Quality Index (DLQI). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). A total of 223 patients, aged 18 to 83 years, were recruited. For 67 (30%) patients, psoriasis had very large to extremely large effect on their life (DLQI score = 11-30). The median DLQI score was 7 (interquartile range = 7). Factors significantly associated with severe impact on HRQoL (DLQI ≥ 10) were disease severity, single status, working status, sports activities, nail dystrophy, exposed area involvement, itch, disturbed sleep, stress, and infection. The factor predictive of severe impact of psoriasis on HRQoL was disease severity. A holistic approach in the management, including psychosocial issues, is absolutely crucial for the optimal care of psoriasis patients. © 2013 APJPH.

Portable handheld diffuse reflectance spectroscopy system for clinical evaluation of skin: a pilot study in psoriasis patients

PubMed Central

Tzeng, Shih-Yu; Guo, Jean-Yan; Yang, Chao-Chun; Hsu, Chao-Kai; Huang, Hung Ji; Chou, Shih-Jie; Hwang, Chi-Hung; Tseng, Sheng-Hao

2016-01-01

Diffuse reflectance spectroscopy (DRS) has been utilized to study biological tissues for a variety of applications. However, many DRS systems are not designed for handheld use and/or relatively expensive which limit the extensive clinical use of this technique. In this paper, we report a handheld, low-cost DRS system consisting of a light source, optical switch, and a spectrometer, that can precisely quantify the optical properties of tissue samples in the clinical setting. The handheld DRS system was employed to determine the skin chromophore concentrations, absorption and scattering properties of 11 patients with psoriasis. The measurement results were compared to the clinical severity of psoriasis as evaluated by dermatologist using PASI (Psoriasis Area and Severity Index) scores. Our statistical analyses indicated that the handheld DRS system could be a useful non-invasive tool for objective evaluation of the severity of psoriasis. It is expected that the handheld system can be used for the objective evaluation and monitoring of various skin diseases such as keloid and psoriasis. PMID:26977366

Characterization and quantitation of phenolic compounds in new apricot (Prunus armeniaca L.) varieties.

PubMed

Ruiz, David; Egea, José; Gil, María I; Tomás-Barberán, Francisco A

2005-11-30

Thirty-seven apricot varieties, including four new releases (Rojo Pasión, Murciana, Selene, and Dorada) obtained from different crosses between apricot varieties and three traditional Spanish cultivars (Currot, Mauricio, and Búlida), were separated according to flesh color into four groups: white, yellow, light orange, and orange (mean hue angles in flesh were 88.1, 85.0, 77.6, and 72.4, respectively). Four phenolic compound groups, procyanidins, hydroxycinnamic acid derivatives, flavonols, and anthocyanins, were identified by HPLC-MS/MS and individually quantified using HPLC-DAD. Chlorogenic and neochlorogenic acids, procyanidins B1, B2, and B4, and some procyanidin trimers, quercetin 3-rutinoside, kaempferol 3-rhamnosyl-hexoside and quercetin 3-acetyl-hexoside, cyanidin 3-rutinoside, and 3-glucoside, were detected and quantified in the skin and flesh of the different cultivars. The total phenolics content, quantified as the addition of the individual compounds quantified by HPLC, ranged between 32.6 and 160.0 mg 100 g(-1) of edible tissue. No correlation between the flesh color and the phenolic content of the different cultivars was observed.

Itch, disease coping strategies and quality of life in psoriasis patients

PubMed Central

Miniszewska, Joanna; Kępska, Anna; Zalewska-Janowska, Anna

2014-01-01

Introduction Psoriasis is a psychodermatological condition, so psychological factors can trigger and/or exacerbate skin lesions. Additionally, disease can be a source of stress and can worsen patients’ quality of life (QoL). Aim To evaluate the relationship between medical (disease severity, itch) and psychological variables (disease coping strategies, QoL) in the psoriasis patients group. Material and methods The study comprises 60 in-patients of the dermatological ward (30 females and 30 males) with the diagnosis of psoriasis. Methods used: Psoriasis Area and Severity Index (PASI), Itch Severity Evaluation Questionnaire, Coping with Skin Disease Scale-SRS-DER, SKINDEX-29 questionnaire. Results The study demonstrated significant correlations between disease coping strategies, itch and quality of life. Women presented worse QoL (generally and in physical functioning). The older patients with a longer disease duration revealed QoL impairment. Conclusions The obtained results could help in identifying patients risk groups which are in the highest danger of decreased QoL. Our data indicate the need for psychological interventions. PMID:25395926

PaLaCe: A Coarse-Grain Protein Model for Studying Mechanical Properties.

PubMed

Pasi, Marco; Lavery, Richard; Ceres, Nicoletta

2013-01-08

We present a coarse-grain protein model PaLaCe (Pasi-Lavery-Ceres) that has been developed principally to allow fast computational studies of protein mechanics and to clarify the links between mechanics and function. PaLaCe uses a two-tier protein representation with one to three pseudoatoms representing each amino acid for the main nonbonded interactions, combined with atomic-scale peptide groups and some side chain atoms to allow the explicit representation of backbone hydrogen bonds and to simplify the treatment of bonded interactions. The PaLaCe force field is composed of physics-based terms, parametrized using Boltzmann inversion of conformational probability distributions derived from a protein structure data set, and iteratively refined to reproduce the experimental distributions. PaLaCe has been implemented in the MMTK simulation package and can be used for energy minimization, normal mode calculations, and molecular or stochastic dynamics. We present simulations with PaLaCe that test its ability to maintain stable structures for folded proteins, reproduce their dynamic fluctuations, and correctly model large-scale, force-induced conformational changes.

What is clearance worth? Patients' stated risk tolerance for psoriasis treatments.

PubMed

Fairchild, Angelyn O; Reed, Shelby D; Johnson, F Reed; Anglin, Greg; Wolka, Anne M; Noel, Rebecca A

2017-12-01

The purpose of this study was to provide quantitative evidence of patients' tolerance for therapeutic risks associated with psoriasis treatments that could offer psoriasis improvements beyond the PASI 75 benchmark. We used a discrete-choice experiment in which respondents chose between competing psoriasis treatments characterized by benefits (i.e. reduced plaque severity, reduced plaque area), risks (i.e. 10-year risk of tuberculosis, 10-year risk of death from infection), and treatment regimen. We analyzed choice data using random-parameters logit models for psoriasis affecting the body, face, or hands. Of 927 eligible members of the National Psoriasis Foundation who completed the survey, 28% were unwilling to accept any greater risk of treatment-related infection mortality. Among the remaining 72%, respondents were willing to accept higher risks of infection-related mortality associated with treatment to completely remove plaques covering only 1% of the body, compared to reducing lesions from 10 to 1% of the affected area. This finding was more pronounced for lesions on the face. Most patients placed greater value on eliminating even very small plaques compared to avoiding treatment-related risks. The perceived importance of complete versus near-complete clearance was stronger than previously documented.

Identification and the molecular mechanism of a novel myosin-derived ACE inhibitory peptide.

PubMed

Yu, Zhipeng; Wu, Sijia; Zhao, Wenzhu; Ding, Long; Shiuan, David; Chen, Feng; Li, Jianrong; Liu, Jingbo

2018-01-24

The objective of this work was to identify a novel ACE inhibitory peptide from myosin using a number of in silico methods. Myosin was evaluated as a substrate for use in the generation of ACE inhibitory peptides using BIOPEP and ExPASy PeptideCutter. Then the ACE inhibitory activity prediction of peptides in silico was evaluated using the program peptide ranker, following the database search of known and unknown peptides using the program BIOPEP. In addition, the interaction mechanisms of the peptide and ACE were evaluated by DS. All of the tripeptides were predicted to be nontoxic. Results suggested that the tripeptide NCW exerted potent ACE inhibitory activity with an IC 50 value of 35.5 μM. Furthermore, the results suggested that the peptide NCW comes into contact with Zn 701, Tyr 523, His 383, Glu 384, Glu 411, and His 387. The potential molecular mechanism of the NCW/ACE interaction was investigated. Results confirmed that the higher inhibitory potency of NCW might be attributed to the formation of more hydrogen bonds with the ACE's active site. Therefore, the in silico method is effective to predict and identify novel ACE inhibitory peptides from protein hydrolysates.

Anti-IL-23 Phase II Data for Psoriasis: A Review.

PubMed

Beroukhim, Kourosh; Danesh, Melissa J; Nguyen, Catherine; Austin, Annemieke; Koo, John; Levin, Ethan

2015-10-01

Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23. We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent. By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache. The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

Effects of anti-TNF-α agents on circulating endothelial-derived and platelet-derived microparticles in psoriasis.

PubMed

Pelletier, Fabien; Garnache-Ottou, Francine; Biichlé, Sabeha; Vivot, Aurore; Humbert, Philippe; Saas, Philippe; Seillès, Estelle; Aubin, François

2014-12-01

Psoriasis involves TNF-α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti-TNF-α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti-TNF-α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti-TNF-α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti-TNF-α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Automatic segmentation of psoriasis lesions

NASA Astrophysics Data System (ADS)

Ning, Yang; Shi, Chenbo; Wang, Li; Shu, Chang

2014-10-01

The automatic segmentation of psoriatic lesions is widely researched these years. It is an important step in Computer-aid methods of calculating PASI for estimation of lesions. Currently those algorithms can only handle single erythema or only deal with scaling segmentation. In practice, scaling and erythema are often mixed together. In order to get the segmentation of lesions area - this paper proposes an algorithm based on Random forests with color and texture features. The algorithm has three steps. The first step, the polarized light is applied based on the skin's Tyndall-effect in the imaging to eliminate the reflection and Lab color space are used for fitting the human perception. The second step, sliding window and its sub windows are used to get textural feature and color feature. In this step, a feature of image roughness has been defined, so that scaling can be easily separated from normal skin. In the end, Random forests will be used to ensure the generalization ability of the algorithm. This algorithm can give reliable segmentation results even the image has different lighting conditions, skin types. In the data set offered by Union Hospital, more than 90% images can be segmented accurately.

Hierarchical feature selection for erythema severity estimation

NASA Astrophysics Data System (ADS)

Wang, Li; Shi, Chenbo; Shu, Chang

2014-10-01

At present PASI system of scoring is used for evaluating erythema severity, which can help doctors to diagnose psoriasis [1-3]. The system relies on the subjective judge of doctors, where the accuracy and stability cannot be guaranteed [4]. This paper proposes a stable and precise algorithm for erythema severity estimation. Our contributions are twofold. On one hand, in order to extract the multi-scale redness of erythema, we design the hierarchical feature. Different from traditional methods, we not only utilize the color statistical features, but also divide the detect window into small window and extract hierarchical features. Further, a feature re-ranking step is introduced, which can guarantee that extracted features are irrelevant to each other. On the other hand, an adaptive boosting classifier is applied for further feature selection. During the step of training, the classifier will seek out the most valuable feature for evaluating erythema severity, due to its strong learning ability. Experimental results demonstrate the high precision and robustness of our algorithm. The accuracy is 80.1% on the dataset which comprise 116 patients' images with various kinds of erythema. Now our system has been applied for erythema medical efficacy evaluation in Union Hosp, China.

Secukinumab in plaque psoriasis--results of two phase 3 trials.

PubMed

Langley, Richard G; Elewski, Boni E; Lebwohl, Mark; Reich, Kristian; Griffiths, Christopher E M; Papp, Kim; Puig, Lluís; Nakagawa, Hidemi; Spelman, Lynda; Sigurgeirsson, Bárður; Rivas, Enrique; Tsai, Tsen-Fang; Wasel, Norman; Tyring, Stephen; Salko, Thomas; Hampele, Isabelle; Notter, Marianne; Karpov, Alexander; Helou, Silvia; Papavassilis, Charis

2014-07-24

Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the

[Clinical and experimental study on effect of qinbal ointment in treating psoriasis in the active stage of blood-heat syndrome type].

PubMed

Xu, Jia; Zhang, Cang; Qu, Xing

2009-07-01

To investigate and compare the efficacy and safety of two kinds of Qinbai ointment prepared conventionally and finely (C-QBO and F-QBO) in treating psoriasis in the active stage of blood-heat syndrome type, and to observe their influences on vaginal epithelial cell mitosis, also on keratinization of caudal flakes in mice. Adopting randomized, single-blinded, controlled design, 93 patients administered orally with Liangxue Huoxue Decoction were randomized into three groups treated externally with C-QBO, F-QBO and white vaseline respectively, applied twice a day for 8 weeks. The safety was checked and the changes of modified psoriasis area severity index (PASI), as well as the conditions of skin lesions (size, erythema, infiltration, squama, and itching) and symptom improving time were compared. Experimental study 1: Mice were randomized into the model group, the C-QBO group, the F-QBO group and the blank group, 7 in each group. Their vaginal epithelial cell mitosis indices were compared after 3 days of treatment with corresponding remedies. Experimental study 2: Mice were randomized into the C-QBO group, the F-QBO group and the blank group, 7 in each group. After the mice had been treated with corresponding remedies for 28 days, the granular layer formation in their caudal scales was compared. The markedly effective rate was 63.3% (25/30) in the C-QBO group, 66.7% (20/30) in the F-QBO group, and 36.7% (11/30) in the control group. No statistical difference was showen between the two QBO treated groups (P > 0.05), but that in both of them was significantly different from that in the control group (P < 0.05). PASI scores lowered after treatment in all the three groups (P < 0.01), but the improvement in the two QBO groups was better than that in the control group (P < 0.05); the conditions of skin lesion were improved in all groups, but the improvements were more significant in the two QBO groups in terms of squama, infiltration and itching (P < 0.05), in aspects of

Switching of biologics in psoriasis: Reasons and results.

PubMed

Honda, Hiromi; Umezawa, Yoshinori; Kikuchi, Sota; Yanaba, Koichi; Fukuchi, Osamu; Ito, Toshihiro; Nobeyama, Yoshimasa; Asahina, Akihiko; Nakagawa, Hidemi

2017-09-01

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second-line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis. © 2017 Japanese Dermatological Association.

Entamoeba histolytica: construction and applications of subgenomic databases.

PubMed

Hofer, Margit; Duchêne, Michael

2005-07-01

Knowledge about the influence of environmental stress such as the action of chemotherapeutic agents on gene expression in Entamoeba histolytica is limited. We plan to use oligonucleotide microarray hybridization to approach these questions. As the basis for our array, sequence data from the genome project carried out by the Institute for Genomic Research (TIGR) and the Sanger Institute were used to annotate parts of the parasite genome. Three subgenomic databases containing enzymes, cytoskeleton genes, and stress genes were compiled with the help of the ExPASy proteomics website and the BLAST servers at the two genome project sites. The known sequences from reference species, mostly human and Escherichia coli, were searched against TIGR and Sanger E. histolytica sequence contigs and the homologs were copied into a Microsoft Access database. In a similar way, two additional databases of cytoskeletal genes and stress genes were generated. Metabolic pathways could be assembled from our enzyme database, but sometimes they were incomplete as is the case for the sterol biosynthesis pathway. The raw databases contained a significant number of duplicate entries which were merged to obtain curated non-redundant databases. This procedure revealed that some E. histolytica genes may have several putative functions. Representative examples such as the case of the delta-aminolevulinate synthase/serine palmitoyltransferase are discussed.

Identification of proteinaceous binders used in artworks by MALDI-TOF mass spectrometry.

PubMed

Kuckova, Stepanka; Hynek, Radovan; Kodicek, Milan

2007-05-01

Proper identification of proteinaceous binders in artworks is essential for specification of the painting technique and thus also for selection of the restoration method; moreover, it might be helpful for the authentication of the artwork. This paper is concerned with the optimisation of analysis of the proteinaceous binders contained in the colour layers of artworks. Within this study, we worked out a method for the preparation and analysis of solid samples from artworks using tryptic cleavage and subsequent analysis of the acquired peptide mixture by matrix-assisted laser desorption/ionisation time of flight mass spectrometry. To make this approach rational and efficient, we created a database of commonly used binders (egg yolk, egg white, casein, milk, curd, whey, gelatine, and various types of animal glues); certain peaks in the mass spectra of these binders, formed by rich protein mixtures, were matched to amino acid sequences of the individual proteins that were found in the Internet database ExPASy; their cleavage was simulated by the program Mass-2.0-alpha4. The method developed was tested on model samples of ground layers prepared by an independent laboratory and then successfully applied to a real sample originating from a painting by Edvard Munch.

Dithranol in a cream preparation: disperse or dissolve?

PubMed

Prins, M; Swinkels, O Q; Bouwhuis, S; de Gast, M J; Bouwman-Boer, Y; van der Valk, P G; van de Kerkhof, P C

2000-01-01

In the search for the ideal dithranol cream preparation for short-contact treatment of psoriasis, we investigated the clinical efficacy, side effects and patient appreciation of two dithranol cream preparations (cream A and B) in a double-blind left-right comparing study. Dithranol was dissolved at preparation in cream A and dispersed in cream B. Cream A is known to have a shelf life of 1 year, while cream B has a much shorter shelf life (several months). Ten patients with chronic plaque-type psoriasis were treated during 7 weeks in a short-contact regimen. The clinical efficacy was monitored by scoring of erythema, induration, scaling and involved area (PASI); skin irritation was scored visually, and patient appreciation was evaluated by means of a multiple-choice questionnaire. Dispersion of dithranol in a cream was associated with less irritation and less discoloration of the skin, and its efficacy was comparable with that of the cream in which the dithranol was dissolved. As the dispersed dithranol formulation is easier to be manufactured, its quality will be less depending on the pharmacist's experience and equipment, and so more reliable. Besides, it will be less expensive to prepare. We advise to use this formulation for short-contact treatment. Copyright 2000 S. Karger AG, Basel.

Effective treatment of etanercept and phototherapy-resistant psoriasis using the excimer laser.

PubMed

Park, Kelly K; Swan, James; Koo, John

2012-03-15

Treatment of moderate-to-severe plaque psoriasis often requires the use of phototherapy or systemic therapy, which includes immunosuppressants, retinoids, and biologic agents. Although biologic use is becoming increasingly popular, it is not uncommon for patients to experience treatment failure. We describe a patient who had a suboptimal response to etanercept monotherapy after twelve weeks of induction dosing (50 mg twice weekly), as well as to a combination of etanercept (50 mg once weekly-maintenance dosing) and narrowband ultraviolet B (NB-UVB) phototherapy three times weekly for an additional twelve weeks. Noticeable improvement was noted after the addition of NB-UVB and the patient's promising response to phototherapy influenced further management. Etanercept and NB-UVB were discontinued and the patient was initiated on excimer laser treatments twice weekly. After 4 weeks, the patient had a 75 percent reduction in Psoriasis Area Severity Index (PASI) score and after 7 weeks had over 95 percent clearance of psoriasis. The unique properties of the excimer laser may account for its clinical efficacy in our patient as well as in other cases of recalcitrant psoriasis. We propose that the excimer laser be considered in cases of biologic or conventional phototherapy failure in addition to being a standard treatment option or adjunct for the treatment of psoriasis.

Childhood trauma and resilience in psoriatic patients: A preliminary report.

PubMed

Crosta, Maria Luigia; De Simone, Clara; Di Pietro, Salvatore; Acanfora, Mariateresa; Caldarola, Giacomo; Moccia, Lorenzo; Callea, Antonino; Panaccione, Isabella; Peris, Ketty; Rinaldi, Lucio; Janiri, Luigi; Di Nicola, Marco

2018-03-01

Psoriasis is a chronic inflammatory skin disease with a complex etiology, involving the immune system, genetic factors, and external/internal triggers, with psychosomatic aspects. The aim of the study was to investigate childhood trauma and resilience in a psoriatic sample compared with healthy controls. Correlations between childhood trauma, resilience, quality of life, clinical data and psoriatic features were also evaluated. Seventy-seven psoriatic patients and seventy-six homogeneous healthy controls were enrolled. We used the Psoriasis Area and Severity Index (PASI) to assess the severity of psoriasis and the Skindex-29 to measure health-related quality of life. The psychometric battery included the Childhood Trauma Questionnaire (CTQ) and the Connor-Davidson Resilience Scale (CD-Risc) to assess trauma exposure and resilience, respectively. Psoriatic patients showed a significant prevalence of childhood trauma and a lower resilience level compared to healthy controls. Associations between traumatic experiences, low resilience and reduced quality of life in psoriatic subjects were also observed. A multidisciplinary approach is helpful to investigate clinical aspects, trigger factors and psychophysiological stress response in psoriatic subjects. Improving resilience with an early psychological intervention focused on self-motivation and strengthening of self-efficacy could facilitate the management of psoriasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Carotenoids from new apricot (Prunus armeniaca L.) varieties and their relationship with flesh and skin color.

PubMed

Ruiz, David; Egea, José; Tomás-Barberán, Francisco A; Gil, María I

2005-08-10

Thirty-seven apricot varieties, including four new releases (Rojo Pasión, Murciana, Selene, and Dorada) obtained from different crosses between apricot varieties and three traditional Spanish cultivars (Currot, Mauricio, and Búlida), were separated according to flesh color into four groups. The L*, a*, b*, hue angle, and chroma color measurements on the skin and flesh as well as other quality indices including flesh firmness, soluble solids, titratable acidity, and pH were plotted against the total carotenoid content measured by HPLC. Among the 37 apricot varieties, the total carotenoid content ranged from 1,512 to 16,500 microg 100 g(-1) of edible portion, with beta-carotene as the main pigment followed by beta-cryptoxanthin and gamma-carotene. The wide range of variability in the provitamin A content in the apricot varieties encouraged these studies in order to select the breeding types with enhanced carotenoid levels as the varieties with a higher potential health benefit. The carotenoid content was correlated with the color measurements, and the hue angle in both flesh and peel was the parameter with the best correlation (R = 0.92 and 0.84, respectively). An estimation of the carotenoid content in apricots could be achieved by using a portable colorimeter, as a simple and easy method for field usage applications.

Optimism as a predictor of health-related quality of life in psoriatics

PubMed Central

Miniszewska, Joanna; Chodkiewicz, Jan; Zalewska-Janowska, Anna

2013-01-01

Introduction Psoriasis is a chronic and relapsing disease which significantly affects the quality of life and social functioning of the affected people. It is one of the so-called psychodermatological diseases, which means that there exists a psychological component in the image of the disease. Aim To examine the relationship between health-related quality of life (HRQoL) in psoriatics and selected demographic, medical and psychological (dispositional optimism) variables and to determine the predictors of HRQoL in the examined group. Material and methods The study consisted of 138 patients with the diagnosis of psoriasis vulgaris. Most respondents (125) had psoriasis on exposed parts of the body. Methods used: SKINDEX, Life Orientation Test, PASI. Results The gender does not differentiate patients in terms of HRQoL and optimism. Almost all of analyzed variables correlate with HRQoL and all examined variables explain the results variability for overall HRQoL but only optimism explains the highest percentage of the variability (β = –0.35). Conclusions The study demonstrated a very interesting relationship – the stronger optimism the better quality of life in psoriatics. So, a generalized expectation of positive life events is related to better assessment of HRQoL. PMID:24278054

Serum VEGFR-3 as a potential biomarker in psoriasis.

PubMed

Hong, Xia; Jiang, Shan; Marmolejo, Nancy; Vangipuram, Ramya; Ramos-Rojas, Elmira; Yuan, Yulin; Lin, Zuan-Tao; Li, Yaxi; Qiu, Jingyi; Xing, Yikun; Haley, Christopher; Tyring, Stephen K; Wu, Tianfu

2018-06-29

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that Vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N=73) were conducted which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, Receiver operating characteristic (ROC) curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: Area Under the Curve (AUC) = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index (PASI) scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Adalimumab for treating childhood plaque psoriasis: a clinical trial evaluation.

PubMed

Di Lernia, Vito

2017-12-01

Most systemic therapies have not been systematically investigated in moderate to severe childhood plaque psoriasis. Evidence on the efficacy and safety of systemic treatments is limited and therapeutic guidelines are lacking. Recently adalimumab, a fully human monoclonal antibody that binds tumor necrosis factor (TNF)- alpha, was investigated in childhood psoriasis. Adalimumab is licensed for many inflammatory conditions including chronic plaque psoriasis in adults. Areas covered: A randomized phase III study published provided favourable efficacy and safety data of adalimumab in childhood psoriasis. The active comparator was methotrexate. After 16 weeks of treatment, a PASI 75 score was achieved in 58% of patients within the adalimumab 0.8 mg/kg group compared with 32% of patients within the methotrexate group. Safety data gave no evidence of drug-related serious adverse events and no organ toxicity. This is the first randomised controlled study of either adalimumab or methotrexate in children and adolescents with psoriasis. Expert opinion: The aforementioned trial was the first to provide clinical data on adalimumab's efficacy and safety in the short term when treating children and adolescents with psoriasis. Through the use of an active comparator, this study has opened the way for the future assessment of systemic therapies in children and adolescent with this condition.

A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology.

PubMed

Moustafa, Farah; Feldman, Steven R

2014-05-16

Phosphodiesterase inhibitors are commonly used drugs. Specific phosphodiesterase inhibitors with anti-inflammatory properties are being assessed as dermatological treatments. To describe important aspects of phosphodiesterase inhibition and the safety and efficacy of 2 phosphodiesterase- 4 inhibitors being studied for the treatment of dermatologic diseases We did a non-systematic analysis of literature on phosphodiesterase inhibition followed by a review of published information on apremilast and topical AN2728 and their use for psoriasis and atopic dermatitis. Apremilast and topical AN2728 have modest efficacy in treatment of psoriasis. Apremilast achieved PASI-75 scores ranging from 24-33%. In phase 2 studies, AN2728 had modest efficacy for psoriasis (40% of patients achieved a ≥ 2 grade improvement as assessed by the Overall target Plaque Severity Score). In phase 2 studies of AN2728 use in atopic dermatitis, subjects achieved a 71% improvement from baseline Atopic Dermatitis Severity Index. In all studies, most adverse effects were minimal. The limitations of this paper are the limited number of published studies, the lack of long-term data, and the lack of head -to - head trials directly comparing phosphodiesterase inhibitors with other treatments. Phosphodiesterase inhibitors constitute a widely used class of drugs that may see growing use for inflammatory dermatologic diseases.

Dynamic thiol/disulfide homeostasis and effects of smoking on homeostasis parameters in patients with psoriasis.

PubMed

Emre, Selma; Demirseren, Duriye Deniz; Alisik, Murat; Aktas, Akin; Neselioglu, Salim; Erel, Ozcan

2017-12-01

Recently, increased reactive oxygen species (ROS), reduced antioxidant capacity, and oxidative stress have been suggested in the pathogenesis of psoriasis. The aim of this study to evaluate the thiol/disulfide homeostasis in patients with psoriasis. Ninety patients with psoriasis who did not receive any systemic treatment in the last six  months were included in the study. Seventy-six age and gender-matched healthy volunteers served as control group. Thiol/disulfide homeostasis was measured in venous blood samples obtained from patient and control groups. Native thiol and total thiol levels were significantly higher in patients than in control group. When thiol/disulfide hemostasis parameters and clinical and demographic characteristics were compared, a negative correlation was detected between native thiol and total thiol with age. The levels of total thiols had also negative correlation with PASI and duration of the disease. When we divided the patients into smokers and non-smokers, native thiol and total thiol levels were significantly higher in smokers than in controls, whereas native thiol and total thiol levels were comparable in non-smoker patients and controls. Thiol/disulfide balance shifted towards thiol in psoriasis patients and this may be responsible for increased keratinocyte proliferation in the pathogenesis of psoriasis.

A rational approach to long-term care: comparing the independent living model with agency-based care for persons with high spinal cord injuries.

PubMed

Mattson-Prince, J

1997-05-01

Two groups of individuals with high level tetraplegia (C1-4) were compared with respect to the model of personal care assistance used. The study was undertaken to determine whether a finite population with severe disability had differences in health status, costs and perceived quality of life, relative to whether they used agencies for their care, or hired, trained and reimbursed care givers independently. A survey, which included demographics as well as portions of RAND-36, LSI-A, PIP, PASI and CHART was used. Telephone interviews were held with 29 individuals who received their care through an agency and 42 who managed care independently. Chi square, 't'-tests, and multiple regression analysis were used to control for potentially confounding group differences. The self-managed group demonstrated significantly better health outcomes, with fewer re-hospitalizations for preventable complications. They experienced better life satisfaction and significantly lower costs. Although those who used an independent model of care-giving received significantly more hours of paid assistance, the average annual cost of care was significantly lower for each individual. In addition to reducing the financial burden on the individual and society, self-managed care seemed to diminish the emotional burden borne by these individuals.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.

PubMed

Griffiths, Christopher E M; Reich, Kristian; Lebwohl, Mark; van de Kerkhof, Peter; Paul, Carle; Menter, Alan; Cameron, Gregory S; Erickson, Janelle; Zhang, Lu; Secrest, Roberta J; Ball, Susan; Braun, Daniel K; Osuntokun, Olawale O; Heffernan, Michael P; Nickoloff, Brian J; Papp, Kim

2015-08-08

Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved

Wirksamkeit und Sicherheit von Fumarsäureestern in Kombination mit Phototherapie bei Patienten mit moderater bis schwerer Plaque-Psoriasis (FAST).

PubMed

Weisenseel, Peter; Reich, Kristian; Griemberg, Wiebke; Merten, Katharina; Gröschel, Christine; Gomez, Natalie Nunez; Taipale, Kirsi; Bräu, Beate; Zschocke, Ina

2017-02-01

Die Behandlung von Psoriasis-Patienten mit einer Kombination aus Fumarsäureestern (FSE, Fumaderm ® ) und Phototherapie (UV) ist verbreitet, wurde aber im Rahmen von Studien wenig untersucht. Bisher liegen lediglich Daten aus einer kleinen Pilotstudie vor. Intention dieser Studie war, eine FSE/UV-Kombinationsbehandlung an einem größeren Patientenkollektiv mit mittelschwerer bis schwerer Psoriasis zu untersuchen. In dieser prospektiven, multizentrischen, nichtinterventionellen Studie wurden Daten von Patienten mit FSE/UV-Kombinationstherapie hinsichtlich der Wirksamkeit (PGA' PASI, DLQI, EQ-5D), Sicherheit und Dosierung über einen Zeitraum von zwölf Monaten erfasst und mit Daten einer retrospektiven Studie mit FSE-Monotherapie verglichen. Es wurden Daten von 363 Patienten ausgewertet. Unter der Kombinationstherapie verbesserten sich alle Wirksamkeitsparameter deutlich. Im Vergleich zur Monotherapie mit FSE konnte durch die Kombination mit UV ein schnellerer Wirkeintritt erzielt werden, wobei nach zwölf Monaten kein Unterschied in der Wirksamkeit bestand. Die Dauer und Art der Phototherapie zeigte keinen Einfluss auf die Wirksamkeitsparameter. Allgemein wurde die Kombinationstherapie gut vertragen. Unerwünschte Ereignisse wurden bei 7 % der Patienten berichtet. Die FSE/UV Kombinationstherapie zeigt eine gute Wirksamkeit und Verträglichkeit und kann zu einem schnelleren Wirkeintritt führen. Eine Kombinationstherapie erscheint vor allem in den ersten drei Monaten der FSE Behandlung sinnvoll. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

[Clinical experiences with four newly developed, surface modified stimulation electrodes].

PubMed

Winter, U J; Fritsch, J; Liebing, J; Höpp, H W; Hilger, H H

1993-05-01

Newly developed pacing electrodes with so-called porous surfaces promise a significantly improved post-operative pacing and sensing threshold. We therefore investigated four newly developed leads (ELA-PMCF-860 n = 10; Biotronik-60/4-DNP n = 10, CPI-4010 n = 10, Intermedics-421-03-Biopore n = 6) connected to two different pacing devices (Intermedics NOVA II, Medtronic PASYS) in 36 patients (18 men, 18 women, age: 69.7 +/- 9.8 years) suffering from symptomatic bradycardia. The individual electrode maturation process was investigated by means of repeated measurements of pacing threshold, electrode impedance in acute, subacute, and chronic phase, as well as energy consumption and sensing behavior in the chronic phase. However, with the exception of the 4010, the investigated leads showed largely varying values of the pacing threshold with individual peaks occurring from the second up to the 13th week. All leads had nearly similar chronic pacing thresholds (PMCF 0.13 +/- 0.07; DNP 0.25 +/- 0.18; Biopore 0.15 +/- 0.05; 4010 0.14 +/- 0.05 ms). Impedance measurements revealed higher, but not significantly different values for the DNP (PMCF 582 +/- 112, DNP 755 +/- 88, Biopore 650 +/- 15, 4010 718 +/- 104 Ohm). Despite differing values for pacing threshold and impedance, the energy consumption in the chronic phase during threshold-adapted, but secure stimulation (3 * impulse-width at pacing threshold) were comparable.

[Self-Reported consumption of illegal psychoactive substances in a street inhabitant population from Cali, Colombia].

PubMed

Hernández-Carrillo, Mauricio; Álvarez-Claros, Katherine E; Osorio-Sabogal, Iván Alberto

2015-04-01

Objective To determine the prevalence of self-reported use of illegal psychoactive substances in a homeless population of the city of Cali. Method Descriptive study of prevalence of period. The target population was 763 homeless people registered during 2010 in the database provided by a temporary shelter facility in the city of Cali. Statistical analysis was performed using R version 3.2.0. Research safe according to the resolution 8430 of 1993. Results 76.9 % of the homeless population recognizes that they consume some type of illegal psychoactive substance (IPAS). The substances with a higher prevalence of use in this population were: marijuana (51.2 %), the crack cocaine (44.6 %) and cocaine (11.3 %). 28.6 % of homeless people were found to consume IPAS more than three times a day and that the main route of administration is smoke (54.7 %). 50% of respondents reported having been hospitalized at some time in a rehabilitation center. Discussion The results in this study show that the problem of PASI consumption significantly affects the population of homeless people, with marijuana and crack cocaine being the most commonly used, which is a complex situation if the easy access of these substances and the severe physical and mental degenerative effects the cause in those who consume them are taken into account. Therefore it is necessary to support initiatives aimed at intervening in this social phenomenon.

Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial.

PubMed

Radmanesh, Mohammad; Rafiei, Behnam; Moosavi, Zahra-Beigum; Sina, Niloofar

2011-10-01

Methotrexate (MTX) treatment for psoriasis is most often administered weekly, because the drug has been considered more hepatotoxic when taken daily. However, some patients may tolerate smaller, more frequent doses better. To study the efficacy and toxicity of daily vs. weekly MTX. In a randomized controlled trial, 101 patients with generalized plaque psoriasis received oral MTX 2.5 mg daily for weeks, 4 weeks and monthly for a total of 4 months. Changes in PASI scores were classified into three categories: >75% improvement was considered significant; 25-75% moderate; and <25% poor. Sixty Group 1 patients and 81 Group 2 patients showed a significant response (P-value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22 patients in Group 1 and six patients from Group 2 responded poorly. Forty-five patients in Group 1 and 33 in Group 2 developed transient increases in liver enzymes (P-value 0.11). Nausea, headache, fatigue, and gastrointestinal upset were noted in four Group 1 patients and 30 Group 2 patients (P-value 0.0001). Nausea, vomiting, headache, and fatigue were significantly less common side effects in our patients who received MTX daily, but liver enzyme abnormalities were less common, and clinical efficacy was greater in the patients who received MTX weekly. © 2011 The International Society of Dermatology.

Treatment patterns in moderate-to-severe plaque psoriasis: results from a Belgian cross-sectional study (DISCOVER).

PubMed

Lambert, Julien; Ghislain, Pierre-Dominique; Lambert, Jo; Cauwe, Bénédicte; Van den Enden, Maria

2017-08-01

The present study aimed to evaluate current treatment patterns and achievement of treatment goals in Belgian patients with moderate-to-severe plaque psoriasis. This cross-sectional observational study (DISCOVER) was conducted in 2011 - 2012 in Belgian dermatology centers. Patient data were collected during a single visit and included information on psoriasis management and severity (PASI and DLQI). Treatment success was defined according to the current European consensus treatment goal algorithm. Of the 556 patients included in the study, 38.1% reported no current treatment or only topicals, 34.2% were being treated with traditional systemics and/or phototherapy, and 29.5% with biologics. Methotrexate (11.7%) was the most commonly prescribed traditional systemic and adalimumab (14.2%) was the most commonly prescribed biologic agent at the time of the study. The percentage of patients achieving treatment goals was significantly higher in biologic-treated patients (73.1%) compared to those using traditional systemics (50.6%), phototherapy (41.1%), or no treatment/only topicals (20.9%; p < .001). Nearly 40% of Belgian patients with moderate-to-severe psoriasis in the DISCOVER study were undertreated despite the severity of their disease. Undertreatment of psoriasis remains a problem in Belgium and more effective educational strategies are needed to ensure the best treatment outcome for these patients. [Formula: see text].

Apremilast for the Treatment of Moderate to Severe Plaque Psoriasis: A Critique of the Evidence.

PubMed

Hinde, Sebastian; Wade, Ros; Palmer, Stephen; Woolacott, Nerys; Spackman, Eldon

2016-06-01

As part of the National Institute for Health and Care Excellence's (NICE) single technology appraisal (STA) process, apremilast was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate to severe plaque psoriasis in two patient populations, differentiated by the severity of the patient's Psoriasis Area Severity Index (PASI) score. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) Technology Appraisal Group at the University of York was commissioned to act as the evidence review group (ERG). This article provides a summary of the company's submission, the ERG report and NICE's subsequent guidance. In the company's initial submission, a sequence of treatments including apremilast was found to be both more effective and cheaper than a comparator sequence without it in both populations considered. However, this result was found to be highly sensitive to a series of assumptions made by the company, primarily reflecting the costs of best supportive care once no further treatments are available, and the source of utility estimates. A re-estimation of the cost effectiveness of apremilast by the ERG suggested that the apremilast sequence in the two populations was more effective, but due to high additional costs was not indicative of a cost-effective use of NHS resources. As such, in the final appraisal decision NICE concluded that apremilast was not cost effective in either population.

Analyzing the subsurface structure using seismic refraction method: Case study STMKG campus

NASA Astrophysics Data System (ADS)

Wibowo, Bagus Adi; Ngadmanto, Drajat; Daryono

2015-04-01

A geophysic survey is performed to detect subsurface structure under STMKG Campus in Pondok Betung, South Tangerang, Indonesia, using seismic refraction method. The survey used PASI 16S24-U24. The waveform data is acquired from 3 different tracks on the research location with a close range from each track. On each track we expanded 24 geofons with spacing between receiver 2 meters and the total length of each track about 48 meters. The waveform data analysed using 2 different ways. First, used a seismic refractionapplication WINSISIM 12 and second, used a Hagiwara Method. From both analysis, we known the velocity of P-wave in the first and second layer and the thickness of the first layer. From the velocity and the thickness informations we made 2-D vertical subsurface profiles. In this research, we only detect 2 layers in each tracks. The P-wave velocity of first layer is about 200-500 m/s with the thickness of this layer about 3-6 m/s. The P-wave velocity of second layer is about 400-900 m/s. From the P-wave velocity data we interpreted that both layer consisted by similar materials such as top soil, soil, sand, unsaturated gravel, alluvium and clay. But, the P-wave velocity difference between those 2 layers assumed happening because the first layer is soil embankment layer, having younger age than the layer below.

Analyzing the subsurface structure using seismic refraction method: Case study STMKG campus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wibowo, Bagus Adi, E-mail: bagusadiwibowo1993@gmail.com; Ngadmanto, Drajat; Daryono

2015-04-24

A geophysic survey is performed to detect subsurface structure under STMKG Campus in Pondok Betung, South Tangerang, Indonesia, using seismic refraction method. The survey used PASI 16S24-U24. The waveform data is acquired from 3 different tracks on the research location with a close range from each track. On each track we expanded 24 geofons with spacing between receiver 2 meters and the total length of each track about 48 meters. The waveform data analysed using 2 different ways. First, used a seismic refractionapplication WINSISIM 12 and second, used a Hagiwara Method. From both analysis, we known the velocity of P-wavemore » in the first and second layer and the thickness of the first layer. From the velocity and the thickness informations we made 2-D vertical subsurface profiles. In this research, we only detect 2 layers in each tracks. The P-wave velocity of first layer is about 200-500 m/s with the thickness of this layer about 3-6 m/s. The P-wave velocity of second layer is about 400-900 m/s. From the P-wave velocity data we interpreted that both layer consisted by similar materials such as top soil, soil, sand, unsaturated gravel, alluvium and clay. But, the P-wave velocity difference between those 2 layers assumed happening because the first layer is soil embankment layer, having younger age than the layer below.« less

Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients.

PubMed

D'Amico, F; Granata, M; Skarmoutsou, E; Trovato, C; Lovero, G; Gangemi, P; Longo, V; Pettinato, M; Mazzarino, M C

2018-03-31

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

PubMed

Zhou, Zhen-Xing; Chen, Jian-Kui; Hong, Yan-Ying; Zhou, Ru; Zhou, Dong-Mei; Sun, Li-Yun; Qin, Wen-Li; Wang, Tian-Cheng

2016-09-01

Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response. © 2016 Wiley Periodicals, Inc.

An extensive library of surrogate peptides for all human proteins.

PubMed

Mohammed, Yassene; Borchers, Christoph H

2015-11-03

Selecting the most appropriate surrogate peptides to represent a target protein is a major component of experimental design in Multiple Reaction Monitoring (MRM). Our software PeptidePicker with its v-score remains distinctive in its approach of integrating information about the proteins, their tryptic peptides, and the suitability of these peptides for MRM that is available online in UniProtKB, NCBI's dbSNP, ExPASy, PeptideAtlas, PRIDE, and GPMDB. The scoring algorithm reflects our "best knowledge" for selecting candidate peptides for MRM, based on the uniqueness of the peptide in the targeted proteome, its physiochemical properties, and whether it has previously been observed. Here we present an updated approach where we have already compiled a list of all possible surrogate peptides of the human proteome. Using our stringent selection criteria, the list includes 165k suitable MRM peptides covering 17k proteins of the human reviewed proteins in UniProtKB. Compared to average of 2-4min per protein for retrieving and integrating the information, the precompiled list includes all peptides available instantly. This allows a more cohesive and faster design of a multiplexed MRM experiment and provides insights into evidence for a protein's existence. We will keep this list up-to-date as proteomics data repositories continue to grow. This article is part of a Special Issue entitled: Computational Proteomics. Copyright © 2015 Elsevier B.V. All rights reserved.

Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

PubMed

Ma, Lei; Xue, HaiBo; Gao, Tianqin; Gao, MeiLan; Zhang, YuJie

2018-01-01

To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 + T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 + T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and ROR γ t/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 + T cells, ROR γ t and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 + T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate-to-Severe Plaque Psoriasis.

PubMed

Reich, Kristian; Jackson, Kimberley; Ball, Susan; Garces, Sandra; Kerr, Lisa; Chua, Laiyi; Muram, Talia M; Blauvelt, Andrew

2018-05-08

Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is efficacious for moderate-to-severe plaque psoriasis. We examined relationships between serum ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADA), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks. During the long-term extension period dosing at 80 mg every 4 weeks, stable serum trough concentrations maintained high clinical responses through week 60. Most (82.6%, 308/373) patients never developed TE-ADA. In TE-ADA-positive patients (17.4%, n=65), variations in ADA titers, neutralizing capacity, and persistence were observed. Fifty-six patients (15%) developed low or moderate maximum titers, with serum concentrations and efficacy comparable to TE-ADA-negative patients. Nine patients (2.4%) developed high titers with variable individual clinical responses; four of these nine patients achieved at least PASI 75 at week 60. Median serum concentrations in the TE-ADA-high titer group were generally comparable to the median serum concentrations in the lower titer groups. For most patients, TE-ADA had a negligible impact on ixekizumab serum concentrations and efficacy. Clinicaltrials.gov: NCT01646177. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

NASA Astrophysics Data System (ADS)

Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

2008-01-01

Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

Effect of steroid eluting versus conventional electrodes on propafenone induced rise in chronic ventricular pacing threshold.

PubMed

Cornacchia, D; Fabbri, M; Maresta, A; Nigro, P; Sorrentino, F; Puglisi, A; Ricci, R; Peraldo, C; Fazzari, M; Pistis, G

1993-12-01

The aim of this study was to evaluate chronic ventricular pacing threshold increase after oral propafenone therapy. Eighty-three patients affected by advanced atrioventricular block and sick sinus syndrome were studied at least 3 months after pacemaker implantation, before and after oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdivided into three groups according to the type of unipolar electrode that was implanted: group I (41 patients) Medtronic CapSure 4003, group II (30 patients) Medtronic Target Tip 4011, and group III (12 patients) Osypka Vy screw-in lead. In all cases a Medtronic unipolar pacemaker was implanted: 30 Minix, 23 Activitrax, 14 Elite, 12 Legend, and 4 Pasys. Propafenone blood level was measured in 75 patients 3-5 hours after propafenone administration. The pacing autothreshold was measured at 0.8 V, 1.6 V, and 2.5 V by reducing pulse width. At the three different outputs before and after propafenone, threshold increments were significantly lower in group I in comparison with group II and group III (propafenone ranging from < 0.001 to < 0.05). No significant difference was found in pacing impedance or in propafenone plasma concentration in the three groups. Strength-duration curves were drawn for each group at baseline and after propafenone administration. Before propafenone, in group I, the knee was markedly shifted to the left and downward as compared to the classic curve, so that the steep part was predominant; in group II and group III this shift was progressively less evident.(ABSTRACT TRUNCATED AT 250 WORDS)

MAD ointment ameliorates Imiquimod-induced psoriasiform dermatitis by inhibiting the IL-23/IL-17 axis in mice.

PubMed

OuYang, Qiong; Pan, YaQian; Luo, HanQiong; Xuan, ChunXiao; Liu, JinE; Liu, Jun

2016-10-01

Psoriasis is a chronic auto-immune inflammation disease with skin lesions and abnormal keratinocyte proliferation. The IL-23/IL-17 axis plays an important role in the pathogenesis of psoriasis. Madecassoside (MAD) was the most important constituents isolated from Centella asiatica, which has long been used in dermatology, and it is supposed that MAD may have effects on psoriasis. In the present study, the BALB/c mice ear and back skin received IMQ for 6 consecutive days to induce psoriasis-like dermatitis. MAD ointment was applied 6h later after IMQ treatment, and the IL-23/IL-17 pathway was investigated. The HE staining, BrdU and Psoriasis Area and Severity Index (PASI) were used to score the severity of keratinocyte proliferation and inflammation of the skin. Real-time PCR and Western Blot were used to detect the IL-23/IL-17 related cytokines. Flow Cytometry were applied to observe the numbers of Th17 cells. Daily application of IMQ for 6days on mouse ear skin and back skin induced psoriasis-like dermatitis. Real-time PCR showed that mRNA level of IL-23, IL-22, IL-17A were significantly decreased by MAD ointment treatment in ear skin. HE staining and BrdU incorporation implied that MAD ointment reduced keratinocyte proliferation. Flow Cytometry results showed MAD ointment decreased the numbers of Th17 cells. Thus, MAD ointment ameliorates Imiquimod-induced skin inflammation and abnormal keratinocyte through regulate the IL-23/IL-17 axis. Copyright © 2016 Elsevier B.V. All rights reserved.

Concentration of selenium, zinc, copper, Cu/Zn ratio, total antioxidant status and c-reactive protein in the serum of patients with psoriasis treated by narrow-band ultraviolet B phototherapy: A case-control study.

PubMed

Wacewicz, Marta; Socha, Katarzyna; Soroczyńska, Jolanta; Niczyporuk, Marek; Aleksiejczuk, Piotr; Ostrowska, Jolanta; Borawska, Maria H

2017-12-01

Psoriasis is a common, an inflammatory skin disease. Trace elements may play an active role in the pathogenesis of psoriasis. The aim of this study was to estimate the concentration of selenium (Se), zinc (Zn), copper (Cu) and Cu/Zn ratio as well as total antioxidant status (TAS) and c-reactive protein (CRP) in the serum of patients with psoriasis. In this case-control study sixty patients with psoriasis and fifty-eight healthy people were examined. Serum levels of Se, Zn and Cu were determined by atomic absorption spectrometry. Cu/Zn ratio was calculated. TAS was measured spectrophotometrically. CRP was analyzed by immunoturbidimetric method. Clinical activity of psoriasis was evaluated using Psoriasis Area and Severity Index (PASI). Serum concentration of Se in patients with psoriasis (71.89±16.90μg/L) was lower as compared to the control group (79.42±18.97μg/L) and after NB-UVB. Cu level of patients was higher (1.151±0.320mg/L) as compared to controls (1.038±0.336mg/L), but Zn level did not differ. We observed higher Cu/Zn ratio (p<0.05) in examined patients than in the control group and after NB-UVB. We found decrease TAS before and after NB-UVB. CRP levels was found to be normal range. A significant correlation coefficient between CRP and Cu/Zn was observed. The study showed some disturbances in the serum levels of trace elements and TAS in psoriatic patients. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris.

PubMed

Ozlu, Emin; Karadag, Ayse Serap; Ozkanli, Seyma; Oguztuzun, Serpil; Akbulak, Ozge; Uzuncakmak, Tugba Kevser; Demirkan, Serkan; Akdeniz, Necmettin

2017-12-01

Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls. Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls. The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2-27.7) before the treatment whereas; 3.05 (1-23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before-after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05). These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

2940-nm Er:YAG fractional laser enhanced the effect of topical drug for psoriasis.

PubMed

Li, Ruilian; Zhou, Jun; Su, Hui; Wang, Mei; Wang, Yongxian; Xiao, Shengxiang; Ma, Huiqun

2017-08-01

We observed the promoting effects of the 2940-nm erbium:YAG (Er:YAG) fractional laser in topical drug delivery for psoriasis. A total of five (four males and one female) recalcitrant psoriasis patients were given laser treatment eight times at 1-week intervals with the following parameters: 5-11% spot density and 100-μm energy depth. The psoriatic skin lesions on the left knee and the corresponding lesions at the right ones of each psoriasis patient were randomly divided into two groups: laser + topical drug group (L) and drug alone group (D). The psoriatic lesions in both groups were treated with the same topical treatment (calcipotriol ointment). The corresponding psoriatic lesions in the L group received extra 2940-nm Er:YAG laser irradiation before topical treatment. The photos of psoriatic lesions were taken before each treatment. The final photos were obtained from the patients at the seventh day after the final treatment. Drug alone or in combination with laser Er:YAG both reduced psoriatic lesions. However, with the increase in the number of treatments, increasing differences were observed between the treatment and the control sides. The therapeutic outcomes in the L groups were better than those in the D groups. Psoriasis area and severity index (PASI) scores for five cases of both groups were decreased. However, the scores in the L groups were lower than those in the D groups. The use of 2940 nm Er:YAG promoted the absorption of topical drugs for psoriasis, improving the therapeutic effect.

β-Defensin-2 Protein Is a Serum Biomarker for Disease Activity in Psoriasis and Reaches Biologically Relevant Concentrations in Lesional Skin

PubMed Central

Jansen, Patrick A. M.; Rodijk-Olthuis, Diana; Hollox, Edward J.; Kamsteeg, Marijke; Tjabringa, Geuranne S.; de Jongh, Gys J.; van Vlijmen-Willems, Ivonne M. J. J.; Bergboer, Judith G. M.; van Rossum, Michelle M.; de Jong, Elke M. G. J.; den Heijer, Martin; Evers, Andrea W. M.; Bergers, Mieke; Armour, John A. L.

2009-01-01

Background Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2) is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. Methodology/Principal Findings We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. Conclusions/Significance Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases. PMID:19266104

Effects of Curcuma extract and visible light on adults with plaque psoriasis.

PubMed

Carrion-Gutierrez, Miguel; Ramirez-Bosca, Ana; Navarro-Lopez, Vicente; Martinez-Andres, Asunción; Asín-Llorca, Manuel; Bernd, August; Horga de la Parte, José Francisco

2015-01-01

We conducted a phase IV randomized, double-blind, placebo-controlled, pilot clinical trial to investigate the safety and efficacy of oral curcumin together with local phototherapy in patients with plaque psoriasis. Patients with moderate to severe psoriasis received Curcuma extract orally with real visible light phototherapy (VLRT) or simulated visible light phototherapy (VLST) in the experimental area, while the rest of the body surface was treated with ultraviolet A (UVA) radiation. The endpoints were the number of responders and the temporal course of the response. The secondary outcomes were related to safety and adverse events. Twenty-one patients were included in the study. In the intention-to-treat analysis, no patients included in the VLRT group showed "moderate" or "severe" plaques after the treatment, in contrast to the patients included in the VSLT group (p<0.01). Parallelisms in the evolution of PGA, BSA, and PASI scores were observed in the two groups following the treatment. At the end of the study period, 76% of all patients showed a response in the BSA exposed to UVA. Lesions on the experimental area showed a response in 81% of the patients in the VLRT group and 30% of the patients in the VLST group. There were no study-related adverse events that necessitated participant withdrawal. The results suggested that moderate to severe plaque psoriasis should show a therapeutic response to orally administered Curcuma if activated with visible light phototherapy, a new therapeutic method that would be safer for patients than existing treatments.

Health-related quality of life in psoriasis: an analysis of Psocare project patients.

PubMed

Spandonaro, F; Altomare, G; Berardesca, E; Calzavara-Pinton, P; Chimenti, S; Girolomoni, G; Peserico, A; Guerra, A Puglisi; Vena, G A; Polistena, B; Ayala, F

2011-06-01

Psoriasis is a common, chronic, immune-mediated skin disorder that may be complicated by psoriatic arthritis in up to one-third of patients. Psoriasis treatments are increasingly effective, yet more expensive, thus requiring rational decision-making on interventional priorities. The ability to perform cost-utility analyses is hindered by the lack of algorithms that allow the inference of utility measures, like QALY, from specific dermatological health-related quality-of-life (HR-QoL) measures (e.g. Dermatology Life Quality Index [DLQI]). This study aimed to assess whether psoriasis-related HR-QoL data (DLQI) could be used to obtain utility measures for use in economic analyses. Psoriasis patients attending 11 Italian Psocare project treatment centers over a 19-day period were enrolled and completed a questionnaire, including several HR-QoL scales and sociodemographic/clinical data, and underwent a clinical examination. Data were subjected to a Multiple Correspondence Analysis and multiple regression analysis to determine the contribution of single items to the HR-QoL. DLQI and Psychological General Well-Being Index (PGWBI) scores were most closely correlated with the EuroQol health status index. Age and gender were considered confounding factors, while pain and arthritis contributed significantly to HR-QoL deterioration. For disease severity, the need for hospitalization and the number of examinations, but not the Psoriasis Area Severity Index (PASI), contributed to HR-QoL deterioration. Recent historical clinical and HR-QoL data from psoriasis patients can reproducibly define a health status index, such as the EuroQol SD-5Q, that could be used reliably to estimate QALYs for use in cost-utility analyses to compare the cost-benefit profiles of competing therapies.

Frequency of undiagnosed psoriatic arthritis among psoriasis patients in Australian dermatology practice.

PubMed

Spelman, L; Su, J C; Fernandez-Peñas, P; Varigos, G A; Cooper, A J; Baker, C S; Lee, M; Ring, J M; Thirunavukkarasu, K

2015-11-01

Psoriatic arthritis commonly develops in psoriasis patients and, if undiagnosed, can lead to potentially avoidable joint damage and an increased risk of comorbidity and mortality. Increased awareness of PsA symptoms among dermatologists provides an opportunity for earlier diagnosis, more timely therapy and prevention of disability. To provide Australian epidemiological data on the frequency of undiagnosed PsA among psoriasis patients in dermatology practice, and to investigate the impact of psoriasis on quality of life and work productivity. Nine tertiary centre dermatology practices enrolled patients presenting with plaque psoriasis and no prior rheumatologist-confirmed PsA diagnosis. Patients were screened using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire and were referred to a rheumatologist for assessment of PsA status using CASPAR criteria if they had a PASE score ≥44. Based on the composite and sequential application of PASE and CASPAR criteria, undiagnosed PsA among psoriasis patients in this study is 9% [95% CI: 6, 12]. The PPV of PASE in this setting is 26% [95% CI: 19, 34]. Nail involvement and chronic large plaque psoriasis were identified as independent positive predictors of PsA, whereas scalp psoriasis was an independent negative predictor of PsA. Patients with moderate-to-severe psoriasis (PASI ≥15) had lower quality of life scores than patients with less severe psoriasis. In this study, the frequency of undiagnosed PsA in Australian dermatology practice was 9% among plaque psoriasis patients with no prior PsA diagnosis. Compared with psoriasis alone, the impact of undiagnosed PsA on health-related quality of life of psoriasis patients is substantial. © 2015 European Academy of Dermatology and Venereology.

Capacity Building for Sustainable Seismological Networks in the Americas: A Pan-American Advanced Studies Institute on New Frontiers in Seismological Research

NASA Astrophysics Data System (ADS)

Cabello, O. A.; Meltzer, A.; Sandvol, E. A.; Yepes, H.; Ruiz, M. C.; Barrientos, S. E.; Willemann, R. J.

2011-12-01

During July 2011, a Pan-American Advanced Studies Institute, "New Frontiers in Seismological Research: Sustainable Networks, Earthquake Source Parameters, and Earth Structure" was conducted in Quito Ecuador with participants from the US, Central, and South America, and the Caribbean at early stages in their scientific careers. This advanced studies institute was imparted by fifteen volunteer senior faculty and investigators from the U.S. and the Americas. The curriculum addressed the importance of developing and maintaining modern seismological observatories, reviewed the principles of sustainable network operations, and explored recent advances in the analysis of seismological data in support of basic research, education, and hazard mitigation. An additional goal was to develop future international research collaborations. The Institute engaged graduate students, post-doctoral students, and new faculty from across the Americas in an interactive collaborative learning environment including modules on double-difference earthquake location and tomography, regional centroid-moment tensors, and event-based and ambient noise surface wave dispersion and tomography. Under the faculty guidance, participants started promising research projects about surface wave tomography in southeastern Brazil, near the Chilean triple junction, in central Chilean Andes, at the Peru-Chile border, within Peru, at a volcano in Ecuador, in the Caribbean Sea region, and near the Mendocino triple junction. Other participants started projects about moment tensors of earthquakes in or near Brazil, Chile and Argentina, Costa Rica, Ecuador, Puerto Rico, western Mexico, and northern Mexico. In order to track the progress of the participants and measure the overall effectiveness of the Institute a reunion is planned where the PASI alumni will present the result of their research that was initiated in Quito

Sleep disturbance in psoriasis - a case-controlled study.

PubMed

Jensen, P; Zachariae, C; Skov, L; Zachariae, R

2018-04-28

Sleep is essential for daytime functioning and health. Given the physical symptoms of psoriasis, a higher prevalence of sleep disorders could be expected. So far, the studies examining sleep disturbance in psoriasis have been of less-than-optimal methodological quality and with mixed results. We aimed to: 1) examine the prevalence of sleep disturbance in patients with plaque psoriasis compared to controls, 2) evaluate associations with health-related quality of life (HRQoL), and 3) examine possible disease-related predictors of disturbed sleep. We used a cross-sectional, case-controlled design. Participants included 179 consecutively recruited patients with plaque psoriasis and 105 controls. Measures included psoriasis severity (Psoriasis Area and Severity index [PASI]); HRQoL (Dermatology Life Quality Index [DLQI]); insomnia severity (Insomnia Severity Index [ISI]); sleep quality (Pittsburgh Sleep Quality Index [PSQI]); stress (Perceived Stress Scale [PSS]); Itch (Itch Severity Scale [ISS]); and depressive symptoms (Beck Depression Inventory [BDI]). Analyses included group comparisons and regression analyses to identify predictors of sleep disturbance. Twenty-five per cent of patients with psoriasis reported clinical insomnia (ISI > 15), compared with 10.5% of controls. In all, 53.9% of patients with psoriasis were poor sleepers (PSQI > 5), compared with 21.9% of controls. Itch was statistically significantly associated with all sleep-related outcomes. A higher proportion of patients with psoriasis suffer from poor sleep than controls from the general population. Itch was the main predictor of impaired sleep. Improved control of psoriasis with decreased itch may improve sleep disturbance in psoriasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Childhood and adulthood traumatic experiences in patients with psoriasis.

PubMed

Simonić, Edita; Kaštelan, Marija; Peternel, Sandra; Pernar, Mirjana; Brajac, Ines; Rončević-Gržeta, Ika; Kardum, Igor

2010-09-01

It is well known that several psychiatric disorders may be related to childhood psychological trauma. Recent studies have associated childhood exposure to trauma to some skin diseases. Our study aimed at exploring whether psoriasis is related to the reported positive and negative traumatic life events in different age intervals beginning from early childhood to adulthood. Furthermore, we investigated differences between psoriatics with early and late onset according to traumatic experiences in different age intervals. Also, we investigated the possible correlation of traumatic experiences with the disease severity. One hundred patients with psoriasis and 101 controls (patients with skin conditions considered to be "non-psychosomatic") were enrolled in the study. All participants completed a specific questionnaire measuring traumatic life experiences (Traumatic Antecedents Questionnaire, TAQ). The TAQ assesses positive personal experiences (competence and safety) and negative personal experiences (neglect, separation, secrets, emotional, physical and sexual abuse, trauma witnessing, other traumas and exposure to alcohol/drugs) from early childhood to adulthood. The severity of psoriasis was estimated according to the Psoriasis Area and Severity Index (PASI), a standardized measuring instrument. The amount of positive experiences did not differ significantly among groups, except for safety scores that were higher in controls compared with both psoriatic groups (early and late onset). On the other side, negative traumatic experiences appeared more frequently in patients with psoriasis during all developmental periods. We found no correlation between severity of psoriasis and traumatic experiences. The present study demonstrates an increased history of childhood and adulthood negative traumatic experiences in patients with psoriasis compared to the control group. Our findings suggest a relationship between retrospectively reported negative traumatic experiences and

Gene Expression Analysis of Plum pox virus (Sharka) Susceptibility/Resistance in Apricot (Prunus armeniaca L.).

PubMed

Rubio, Manuel; Ballester, Ana Rosa; Olivares, Pedro Manuel; Castro de Moura, Manuel; Dicenta, Federico; Martínez-Gómez, Pedro

2015-01-01

RNA-Seq has proven to be a very powerful tool in the analysis of the Plum pox virus (PPV, sharka disease)/Prunus interaction. This technique is an important complementary tool to other means of studying genomics. In this work an analysis of gene expression of resistance/susceptibility to PPV in apricot is performed. RNA-Seq has been applied to analyse the gene expression changes induced by PPV infection in leaves from two full-sib apricot genotypes, "Rojo Pasión" and "Z506-7", resistant and susceptible to PPV, respectively. Transcriptomic analyses revealed the existence of more than 2,000 genes related to the pathogen response and resistance to PPV in apricot. These results showed that the response to infection by the virus in the susceptible genotype is associated with an induction of genes involved in pathogen resistance such as the allene oxide synthase, S-adenosylmethionine synthetase 2 and the major MLP-like protein 423. Over-expression of the Dicer protein 2a may indicate the suppression of a gene silencing mechanism of the plant by PPV HCPro and P1 PPV proteins. On the other hand, there were 164 genes involved in resistance mechanisms that have been identified in apricot, 49 of which are located in the PPVres region (scaffold 1 positions from 8,050,804 to 8,244,925), which is responsible for PPV resistance in apricot. Among these genes in apricot there are several MATH domain-containing genes, although other genes inside (Pleiotropic drug resistance 9 gene) or outside (CAP, Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related 1 protein; and LEA, Late embryogenesis abundant protein) PPVres region could also be involved in the resistance.

Description of Patients Treated with Biologic Drugs as First-Line Systemic Therapy in the BIOBADADERM Registry Between 2008 and 2016.

PubMed

Carretero Hernández, G; Ferrándiz, C; Rivera Díaz, R; Daudén Tello, E; de la Cueva-Dobao, P; Gómez-García, F J; Herrera-Ceballos, E; Belinchón Romero, I; López-Estebaranz, J L; Alsina Gibert, M; Sánchez-Carazo, J L; Ferrán Farrés, M; González Quesada, A; Carrascosa Carrillo, J M; Llamas-Velasco, M; Mendiola Fernández, M V; Ruiz Genao, D; Muñoz Santos, C; García-Doval, I; Descalzo, M A

2018-06-07

Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis. Publicado por Elsevier España, S.L.U.

Differentiation-dependent expression of hypothetical proteins in the neuroblastoma cell line N1E-115.

PubMed

Oh, Ji-eun; Karlmark, Karlin Raja; Shin, Jooho; Hengstschläger, Markus; Lubec, Gert

2006-05-15

Several protein cascades, including signaling, cytoskeletal, chaperones, metabolic, and antioxidant proteins, have been shown to be involved in the process of neuronal differentiation (ND) of neuroblastoma cell lines. No systematic approach to detect hitherto unknown and unnamed proteins or structures that have been predicted upon nucleic acid sequences in ND has been published so far. We therefore decided to screen hypothetical protein (HP) expression by protein profiling. Two-dimensional gel electrophoresis with subsequent matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/TOF) identification was used for expression analysis of undifferentiated and dimethylsulfoxide-induced neuronally differentiated N1E-115 cells. We unambiguously identified six HPs: Q8C520, Q99LF4, Q9CXS1, Q9DAF8, Q91WT0, and Q8C5G2. A prefoldin domain in Q91WT0, a t-SNARE domain in Q9CXS1, and a bromodomain were observed in Q8C5G2. For the three remaining proteins, no putative function using Pfam, BLOCKS, PROSITE, PRINTS, InterPro, Superfamily, CoPS, and ExPASy could be assigned. While two proteins were present in both cell lines, Q9CXS1 was switched off (i.e., undetectably low) in differentiated cells only, and Q9DAF8, Q91WT0, and Q8C5G2 were switched on in differentiated cells exclusively. Herein, using a proteomic approach suitable for screening and identification of HP, we present HP structures that have been only predicted so far based upon nucleic acid sequences. The four differentially regulated HPs may play a putative role in the process of ND. (c) 2006 Wiley-Liss, Inc.

Gene Expression Analysis of Plum pox virus (Sharka) Susceptibility/Resistance in Apricot (Prunus armeniaca L.)

PubMed Central

Rubio, Manuel; Ballester, Ana Rosa; Olivares, Pedro Manuel; Castro de Moura, Manuel; Dicenta, Federico; Martínez-Gómez, Pedro

2015-01-01

RNA-Seq has proven to be a very powerful tool in the analysis of the Plum pox virus (PPV, sharka disease)/Prunus interaction. This technique is an important complementary tool to other means of studying genomics. In this work an analysis of gene expression of resistance/susceptibility to PPV in apricot is performed. RNA-Seq has been applied to analyse the gene expression changes induced by PPV infection in leaves from two full-sib apricot genotypes, “Rojo Pasión” and “Z506-7”, resistant and susceptible to PPV, respectively. Transcriptomic analyses revealed the existence of more than 2,000 genes related to the pathogen response and resistance to PPV in apricot. These results showed that the response to infection by the virus in the susceptible genotype is associated with an induction of genes involved in pathogen resistance such as the allene oxide synthase, S-adenosylmethionine synthetase 2 and the major MLP-like protein 423. Over-expression of the Dicer protein 2a may indicate the suppression of a gene silencing mechanism of the plant by PPV HCPro and P1 PPV proteins. On the other hand, there were 164 genes involved in resistance mechanisms that have been identified in apricot, 49 of which are located in the PPVres region (scaffold 1 positions from 8,050,804 to 8,244,925), which is responsible for PPV resistance in apricot. Among these genes in apricot there are several MATH domain-containing genes, although other genes inside (Pleiotropic drug resistance 9 gene) or outside (CAP, Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related 1 protein; and LEA, Late embryogenesis abundant protein) PPVres region could also be involved in the resistance. PMID:26658051

Abnormal levels of expression of plasma microRNA-33 in patients with psoriasis.

PubMed

García-Rodríguez, S; Arias-Santiago, S; Orgaz-Molina, J; Magro-Checa, C; Valenzuela, I; Navarro, P; Naranjo-Sintes, R; Sancho, J; Zubiaur, M

2014-06-01

Circulating microRNAs (miRNA) are involved in the posttranscriptional regulation of genes associated with lipid metabolism (miRNA-33) and vascular function and angiogenesis (miRNA-126). The objective of this exploratory study was to measure plasma levels of miRNA-33 and miRNA-126 in patients with plaque psoriasis and evaluate their association with clinical parameters. We studied 11 patients with plaque psoriasis. The median Psoriasis Area Severity Index (PASI) was 13 (interquartile range [IQR], 9-14) and body surface area involvement was 12 (IQR, 11-15). Eleven healthy controls matched for age and sex were also included. We analyzed cardiovascular risk factors and subclinical carotid atheromatosis. Plasma miRNAs were evaluated using quantitative real-time polymerase chain reaction. Carotid intima-media thickness was greater in patients (0.57mm; IQR, 0.54-0.61; n=11) than in controls (0.50mm; IQR, 0.48-0.54; data available for 9 controls) (P=.0055, Mann-Whitney). Expression of miRNA-33 in patients (5.34; IQR, 3.12-7.96; n=11) was significantly higher than in controls (2.33; IQR, 1.71-2.84; only detected in 7 of 11 controls) (P=.0049, Wilcoxon signed rank). No differences in miRNA-126 levels were observed between patients and controls. In patients (n=11), we observed a positive correlation between miRNA-33 and insulin levels (r=0.7289, P=.0109) and a negative correlation between miRNA-126 and carotid intima-media thickness (r=-0.6181, P=.0426). In psoriasis patients plasma levels of lipid and glucose metabolism-related miRNA-33 are increased and correlated with insulin. The study of circulating miRNA-33 in psoriasis may provide new insights about the associated systemic inflammatory abnormalities. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

Secukinumab in the Treatment of Psoriasis and Psoriatic Arthritis: A Review of the Literature.

PubMed

Abrouk, M; Gandy, J; Nakamura, M; Lee, K; Brodsky, M; Singh, R; Zhu, H; Farahnik, B; Bhutani, T; Koo, J

2017-07-01

While there are several commercially available treatment options for psoriasis and psoriatic arthritis, there remains a large number of individuals who are refractory to current modalities. In the recent past, there has been increasing evidence that interleukin (IL)-17 plays a vital role in the pathophysiology of psoriasis. Preclinical, phase II, and phase III studies of secukinumab (Cosentyx®) targeting IL-17 and its receptor have thus far proved to be promising. We reviewed the results of phase II and phase III clinical trials for secukinumab in the treatment of psoriasis and psoriatic arthritis. Only published studies were considered in the present review. We also performed an English language literature search from January 2003 to September 2015 using PubMed with any of the following key words: (secukinumab OR AIN457) AND (psoriasis OR psoriatic arthritis). In our review of the literature, seven phase III and five phase II clinical trials, as well as open-label extension studies with unpublished findings were found. Results from phase III clinical trials indicated secukinumab to be efficacious and safe for the treatment of psoriasis and psoriatic arthritis according to Psoriasis Area and Severity Index (PASI) and American College of Rheumatology (ACR) scores. The safety profile of this agent was similar across all studies, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, headache, and injection site reaction. Secukinumab demonstrates rapid and robust clinical improvement accompanied by a favorable short- term safety profile. The results of the phase III trials continue to reinforce the theory that the IL-17 pathway is an essential target in psoriasis and psoriatic arthritis treatment. Additional extension studies of lower level evidence are needed to further understand the safety profile of the drug.

Medical nutrition therapy as a potential complementary treatment for psoriasis--five case reports.

PubMed

Brown, Amy C; Hairfield, Michelle; Richards, Douglas G; McMillin, David L; Mein, Eric A; Nelson, Carl D

2004-09-01

This research evaluated five case studies of patients with psoriasis following a dietary regimen. There is no cure for psoriasis and the multiple treatments currently available only attempt to reduce the severity of symptoms. Treatments range from topical applications, systemic therapies, and phototherapy; while some are effective, many are associated with significant adverse effects. There is a need for effective, affordable therapies with fewer side effects that address the causes of the disorder. Evaluation consisted of a study group of five patients diagnosed with chronic plaque psoriasis (two men and three women, average age 52 years; range 40-68 years) attending a 10-day, live-in program during which a physician assessed psoriasis symptoms and bowel permeability. Subjects were then instructed on continuing the therapy protocol at home for six months. The dietary protocol, based on Edgar Cayce readings, included a diet of fresh fruits and vegetables, small amounts of protein from fish and fowl, fiber supplements, olive oil, and avoidance of red meat, processed foods, and refined carbohydrates. Saffron tea and slippery elm bark water were consumed daily. The five psoriasis cases, ranging from mild to severe at the study onset, improved on all measured outcomes over a six-month period when measured by the Psoriasis Area and Severity Index (PASI) (average pre- and post-test scores were 18.2 and 8.7, respectively), the Psoriasis Severity Scale (PSS) (average pre- and post-test scores were 14.6 and 5.4, respectively), and the lactulose/mannitol test of intestinal permeability (average pre- and post-test scores were 0.066 to 0.026, respectively). These results suggest a dietary regimen based on Edgar Cayce's readings may be an effective medical nutrition therapy for the complementary treatment of psoriasis; however, further research is warranted to confirm these results.

The relationship between oxidative stress, smoking and the clinical severity of psoriasis.

PubMed

Emre, S; Metin, A; Demirseren, D D; Kilic, S; Isikoglu, S; Erel, O

2013-03-01

Recent studies suggested that increased oxidant products and decreased antioxidant system functions may be involved in the pathogenesis of psoriasis. In this study, we investigated total oxidative status, Paraoxonase (PON)1/arylesterase enzyme activities and severity of the disease in smoker and non-smoker psoriatic patients. Fifty-four patients with plaque type psoriasis (28 smokers and 26 non-smokers) and 62 healthy volunteers (16 smokers and 46 non-smokers) were enrolled in the study. Serum total oxidant status (TOS), total antioxidant capacity (TAC) and arylesterase levels were measured, and oxidative stress index (OSI) was calculated in all participants. Psoriasis Area and Severity Index scores were significantly higher in smoker patients than in non-smoker patients (P = 0.014). Both smoker and non-smoker patients had significantly increased TOS levels and OSI values and decreased TAC levels than healthy subjects (all P values = 0.000). The TAC and TOS levels, OSI values and arylesterase activities were similar between smoker and non-smoker patients. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were not significantly different between smoker and non-smoker psoriasis patients. When compared with non-smoking controls, only smoking psoriasis patients had significantly higher TG (P = 0.005), lower HDL (P = 0.022) and lower arylesterase levels (P = 0.015). There were no significant correlations with Psoriasis Area and Severity Index (PASI) scores and TAC, TOS, OSI, TG, TC, HDL and LDL levels in all psoriasis patients. Oxidative stress is increased in psoriasis patients regardless of their smoking status. The decreased arylesterase activity in smoker psoriasis patients suggested that smoking may be a considerable risk factor that increases the severity of psoriasis by increasing oxidative stress in these patients. © 2012 The Authors. Journal of the European Academy of Dermatology and

The association of clinical parameters and ultrasound verified inflammation with patients' and physicians' global assessments in psoriatic arthritis.

PubMed

Lackner, Angelika; Duftner, Christina; Ficjan, Anja; Gretler, Judith; Hermann, Josef; Husic, Rusmir; Graninger, Winfried B; Dejaco, Christian

2016-10-01

To study the association of clinical and/or ultrasound variables with patients' (PGA) and physicians' (EGA) global assessment of disease activity in psoriatic arthritis (PsA). The correlation of these parameters with the discordance between PGA and EGA, as well as with PGA/EGA changes over 6 months was also investigated. Prospective study of 83 consecutive PsA patients with 2 visits scheduled 6 months apart. All patients underwent the following assessments: tender (TJC) and swollen joint count (SJC), PASI, dactylitis and Leeds enthesitis index. PGA, patients' level of pain (pain VAS), EGA, and HAQ were also recorded. Grey scale (GS) and power Doppler (PD) ultrasound were performed at 68 joints (evaluating synovia and tendons) and 14 entheses. Regression analyses were performed to assess the association of these variables with PGA and EGA. Two new variables "PGAminusEGA" and "PGAchange - EGAchange" were developed to explore the discrepancy between PGA and EGA and the consistency of PGA/EGA changes over time, respectively. The parameters explaining most of PGA and EGA variability were pain VAS (30.5%) and SJC (48.5%), respectively. The correlation between EGA and joint counts was stronger in patients with high vs. low levels of ultrasound verified inflammation. PGAminusEGA was mainly explained by pain and SJC. Pain was the most important predictor of PGA change whereas TJC and HAQ were more closely associated with EGA changes. "PGAchange-EGAchange" was linked to pain and SJC. Ultrasound scores were not linked with either of these variables. Pain VAS and joint counts are the most important clinical parameters explaining patients' and physicians' perception of disease activity, whereas the correlation of active inflammation as verified by sonography with these factors is limited. Copyright © 2016 Elsevier Inc. All rights reserved.

Immune-mediated inflammatory diseases and other comorbidities in patients with psoriasis: baseline characteristics of patients in the AQUILES study.

PubMed

Vanaclocha, F; Crespo-Erchiga, V; Jiménez-Puya, R; Puig, L; Sánchez-Carazo, J L; Ferrán, M; Sancho, C; Juliá, B; Cea-Calvo, L; Marín-Jiménez, I; García-Vicuña, R

2015-01-01

Patients with psoriasis often have comorbidities, including other immune-mediated inflammatory diseases (IMIDs), and cardiovascular risk factors. In this article we describe the baseline prevalence of comorbidities-including other IMIDs-in a cohort of patients with psoriasis. AQUILES was a prospective observational multicenter study of 3 patient cohorts (patients with psoriasis, spondyloarthritis, or inflammatory bowel disease) undertaken to investigate the prevalence of comorbidities, including other IMIDs, in these settings. The psoriasis cohort comprised patients aged at least 18 years who were seen in hospital dermatology clinics. A predefined protocol was used to collect demographic and clinical data. The study enrolled 528 patients with psoriasis (60.2% men and 39.8% women). Mean age was 46.7 years; 89.8% of the participants had plaque psoriasis, and the median Psoriasis Area Severity Index score (PASI) was 3.2 (1.5-7.4). Comorbid IMIDs were present in 82 (15.5%) of the patients (CI 95%, 12.7%-18.9%). Spondyloarthritis was observed in 14% of patients (95% CI, 11.3%-17.2%), mostly in the form of psoriatic arthritis, for which the overall prevalence was 13.1% (95% CI, 10.5%-16.2%). Inflammatory bowel disease was present in 1.3% (95% CI, 0.6%-2.7%) and uveitis in .2% (95% CI, 0.1%-1.4%). Psoriatic arthritis was associated with male sex (odds ratio, 1.75 [.98-2.98]) and a disease duration of over 8 years (OR, 4.17 [1.84-9.44] vs a duration of < 4 years). In 73.1%, at least 1 cardiovascular risk factor was identified: smoking (40.5%), obesity (26.0%), dyslipidemia (24.8%), hypertension (24.3%), and diabetes mellitus (12.3%). In patients with psoriasis the prevalence of other IMIDs was 15.5%, a level slightly higher than that found in the general population. Nearly three-quarters of these patients had at least 1 cardiovascular risk factor. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Cost-effectiveness analysis of secukinumab for the treatment of active psoriatic arthritis: a Canadian perspective.

PubMed

Goeree, Ron; Chiva-Razavi, Sima; Gunda, Praveen; Graham, Christopher N; Miles, LaStella; Nikoglou, Efthalia; Jugl, Steffen M; Gladman, Dafna D

2018-02-01

The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective. A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150 mg and 300 mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses. Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses

PeptidePicker: a scientific workflow with web interface for selecting appropriate peptides for targeted proteomics experiments.

PubMed

Mohammed, Yassene; Domański, Dominik; Jackson, Angela M; Smith, Derek S; Deelder, André M; Palmblad, Magnus; Borchers, Christoph H

2014-06-25

One challenge in Multiple Reaction Monitoring (MRM)-based proteomics is to select the most appropriate surrogate peptides to represent a target protein. We present here a software package to automatically generate these most appropriate surrogate peptides for an LC/MRM-MS analysis. Our method integrates information about the proteins, their tryptic peptides, and the suitability of these peptides for MRM which is available online in UniProtKB, NCBI's dbSNP, ExPASy, PeptideAtlas, PRIDE, and GPMDB. The scoring algorithm reflects our knowledge in choosing the best candidate peptides for MRM, based on the uniqueness of the peptide in the targeted proteome, its physiochemical properties, and whether it previously has been observed. The modularity of the workflow allows further extension and additional selection criteria to be incorporated. We have developed a simple Web interface where the researcher provides the protein accession number, the subject organism, and peptide-specific options. Currently, the software is designed for human and mouse proteomes, but additional species can be easily be added. Our software improved the peptide selection by eliminating human error, considering multiple data sources and all of the isoforms of the protein, and resulted in faster peptide selection - approximately 50 proteins per hour compared to 8 per day. Compiling a list of optimal surrogate peptides for target proteins to be analyzed by LC/MRM-MS has been a cumbersome process, in which expert researchers retrieved information from different online repositories and used their own reasoning to find the most appropriate peptides. Our scientific workflow automates this process by integrating information from different data sources including UniProt, Global Proteome Machine, NCBI's dbSNP, and PeptideAtlas, simulating the researchers' reasoning, and incorporating their knowledge of how to select the best proteotypic peptides for an MRM analysis. The developed software can help to

Hypomethylation of HLA-DRB1 and its clinical significance in psoriasis

PubMed Central

Yang, Xueyuan; Li, Qi; Chen, Min

2017-01-01

Increasing evidences indicate that the abnormal DNA methylation is involved in the pathogenesis of psoriasis. A number of SNPs in HLA-DRB1 have been found being associated with the risk of psoriasis, however it is unclear that metylation status within HLA-DRB1 in psoriasis. Here, DNA and RNA were obtained from epidermis of 56 patients with plaque psoriasis and 28 healthy volunteers served as the control group. For the first time, we discovered mean methylation rate for HLA-DRB1 is 52.2%, 64.3% and 68.1% in epidermis from psoriatic lesions, psoriatic non-lesions and healthy controls, respectively. HLA-DRB1 methylation in psoriatic lesions is significantly lower than in psoriatic non-lesions (t = 13.077, p < 0.001). However, there is no significant difference for HLA-DRB1 methylation between in psoriatic non-lesions and in healthy controls (t = 1.046, p = 0.299). HLA-DRB1 methylation in psoriatic lesions is negatively correlated to PASI score (r = -0.431, p = 0.001). HLA-DRB1 methylation in psoriatic lesions of the patients with onset age=18 years is significantly lower than the other patients (t = 3.968, p < 0.001). Meanwhile, HLA-DRB1 mRNA expression is significantly increased in psoriatic lesions comparing to psoriatic non-lesions (t = 12.119, p < 0.001). There are no significant difference for HLA-DRB1 mRNA expression between in psoriatic non-lesions and in healthy controls (t = 1.172, p = 0,245). Moreover, HLA-DRB1 mRNA expression is negatively associated with HLA-DRB1 methylation in psoriatic lesions (r = 0.932, p < 0.001). In conclusions, our results showed hypomethylation of HLA-DRB1 is associated with HLA-DRB1 mRNA expression and severity of the disease, indicating that hypomethylation of HLA-DRB1 may play roles in the pathogenesis of psoriasis. PMID:27713139

Evaluation of inhomogeneities of repolarization in patients with psoriasis vulgaris

PubMed Central

İnci, Sinan; Aksan, Gökhan; Nar, Gökay; Yüksel, Esra Pancar; Ocal, Hande Serra; Çapraz, Mustafa; Yüksel, Serkan; Şahin, Mahmut

2016-01-01

Introduction The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. Material and methods Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring. The QTd was defined as the difference between the maximum and minimum QT intervals. The Tp-e interval was defined as the interval from the peak of the T wave to the end of the T wave. The Tp-e interval was corrected for heart rate. The Tp-e/QT ratio was calculated using these measurements. Results There were no significant differences between the groups with respect to basal clinical and laboratory characteristics (p > 0.05). The Tp-e interval, the corrected Tp-e interval (cTp-e) and the Tp-e/QT ratio were also significantly higher in psoriasis patients compared to the control group (78.5 ±8.0 ms vs. 71.4 ±7.6 ms, p < 0.001, 86.3 ±13.2 ms vs. 77.6 ±9.0 ms, p < 0.001 and 0.21 ±0.02 vs. 0.19 ±0.02, p < 0.001 respectively). A significant correlation was detected between the cTp-e time and the Tp-e/QT ratio and the PASI score in the group of psoriatic patients (r = 0.51, p < 0.001; r = 0.59, p < 0.001, respectively). Conclusions In our study, we detected a significant increase in the Tp-e interval and the Tp-e/QT ratio in patients with psoriasis vulgaris. The Tp-e interval and the Tp-e/QT ratio may be predictors for ventricular arrhythmias in patients with psoriasis vulgaris. PMID:27904512

Proteins associated with EGFR-TKIs resistance in patients with non-small cell lung cancer revealed by mass spectrometry.

PubMed

Yang, Shaoyu; Chen, Xueqin; Pan, Yuelong; Yu, Jiekai; Li, Xin; Ma, Shenglin

2016-11-01

The present study aimed to identify potential serum biomarkers for predicting the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs). A total of 61 samples were collected and analyzed using the integrated approach of magnetic bead‑based weak cation exchange chromatography and matrix‑assisted laser desorption/ionization‑time of flight‑mass spectrometry. The Zhejiang University Protein Chip Data Analysis system was used to identify the protein spectra of patients that are resistant and sensitive to EGFR‑TKIs. Furthermore, a support vector machine was used to construct a predictive model with high accuracy. The model was trained using 46 samples and tested with the remaining 15 samples. In addition, the ExPASy Bioinformatics Resource Portal was used to search potential candidate proteins for peaks in the predictive model. Seven mass/charge (m/z) peaks at 3,264, 9,156, 9,172, 3,964, 9,451, 4,295 and 3,983 Da, were identified as significantly different peaks between the EGFR‑TKIs sensitive and resistant groups. A predictive model was generated with three protein peaks at 3,264, 9,451 and 4,295 Da (m/z). This three‑peak model was capable of distinguishing EGFR‑TKIs resistant patients from sensitive patients with a specificity of 80% and a sensitivity of 80.77%. Furthermore, in a blind test, this model exhibited a high specificity (80%) and a high sensitivity (90%). Apelin, TYRO protein tyrosine kinase‑binding protein and big endothelin‑1 may be potential candidates for the proteins identified with an m/z of 3,264, 9,451 and 4,295 Da, respectively. The predictive model used in the present study may provide an improved understanding of the pathogenesis of NSCLC, and may provide insights for the development of TKI treatment plans tailored to specific patients.

[Psoriatic patients: Analysis of patients dissatisfied with their management].

PubMed

Mahé, E; Maccari, F; Beauchet, A; Quiles-Tsimaratos, N; Beneton, N; Parier, J; Barthelemy, H; Goujon-Henry, C; Chaby, G; Thomas-Beaulieu, D; Géner, G; Wagner, L; Pallure, V; Devaux, S; Vermersch-Langlin, A; Pfister, P; Jégou, J; Livideanu, C; Sigal, M-L

The French are frequently regarded as grouchy. In a recent study, we observed a high proportion of patients initially consulting for psoriasis because they were dissatisfied with their previous therapy. We analyzed the characteristics of these patients. This was a cross-sectional multicenter study in 40 centers belonging to the ResoPso (psoriasis treatment network) multicenter study group, with consecutive inclusions over a period of 11months in 2014. All adults (age>18 years) consulting for the first time for psoriasis at a center were included in the study. Among patients, 1205 were included, of whom 249 (20.3%) were consulting because of their dissatisfaction with treatment. In the univariate analysis, these patients were younger (P=0.02) and presented psoriasis that had begun earlier in life (P<0.0001). It consisted mostly of generalized plaque psoriasis (P=0.047) and more severe forms of psoriasis (PASI and/or DLQI score>10, P<0.02). There were fewer cases of psoriatic arthritis (P=0.01). The "dissatisfied" patients reported significantly more frequent use of topical treatments (P<0.0001) and alternative medicines (P=0.02), and more infrequent use of biologics (P=0.006) as well as longer treatment periods (P=0.0005). They consulted at hospitals (P=0.01) and had previously seen more GPs and dermatologists (P≤0.0008). There was no impact of gender on the dissatisfaction profile by either comorbidities (metabolic, blood pressure, alcohol and tobacco consumption, and depression), or socio-economic data. In the multivariate analysis, DLQI>10 (P=0.01; 95% CI: 1.01-1.07) and longer duration of care (P=0.004; 95% CI: 1.23-2.99) were associated with dissatisfaction. Twenty percent of our psoriatic patients seem dissatisfied with their treatment. It is difficult to draw a specific demographic and socioeconomic profile of dissatisfied patients. Only disease severity and possibly inadequate treatment at the initial consultation are associated with patient

Computer aided identification of a Hevein-like antimicrobial peptide of bell pepper leaves for biotechnological use.

PubMed

Games, Patrícia Dias; daSilva, Elói Quintas Gonçalves; Barbosa, Meire de Oliveira; Almeida-Souza, Hebréia Oliveira; Fontes, Patrícia Pereira; deMagalhães, Marcos Jorge; Pereira, Paulo Roberto Gomes; Prates, Maura Vianna; Franco, Gloria Regina; Faria-Campos, Alessandra; Campos, Sérgio Vale Aguiar; Baracat-Pereira, Maria Cristina

2016-12-15

Antimicrobial peptides from plants present mechanisms of action that are different from those of conventional defense agents. They are under-explored but have a potential as commercial antimicrobials. Bell pepper leaves ('Magali R') are discarded after harvesting the fruit and are sources of bioactive peptides. This work reports the isolation by peptidomics tools, and the identification and partially characterization by computational tools of an antimicrobial peptide from bell pepper leaves, and evidences the usefulness of records and the in silico analysis for the study of plant peptides aiming biotechnological uses. Aqueous extracts from leaves were enriched in peptide by salt fractionation and ultrafiltration. An antimicrobial peptide was isolated by tandem chromatographic procedures. Mass spectrometry, automated peptide sequencing and bioinformatics tools were used alternately for identification and partial characterization of the Hevein-like peptide, named HEV-CANN. The computational tools that assisted to the identification of the peptide included BlastP, PSI-Blast, ClustalOmega, PeptideCutter, and ProtParam; conventional protein databases (DB) as Mascot, Protein-DB, GenBank-DB, RefSeq, Swiss-Prot, and UniProtKB; specific for peptides DB as Amper, APD2, CAMP, LAMPs, and PhytAMP; other tools included in ExPASy for Proteomics; The Bioactive Peptide Databases, and The Pepper Genome Database. The HEV-CANN sequence presented 40 amino acid residues, 4258.8 Da, theoretical pI-value of 8.78, and four disulfide bonds. It was stable, and it has inhibited the growth of phytopathogenic bacteria and a fungus. HEV-CANN presented a chitin-binding domain in their sequence. There was a high identity and a positive alignment of HEV-CANN sequence in various databases, but there was not a complete identity, suggesting that HEV-CANN may be produced by ribosomal synthesis, which is in accordance with its constitutive nature. Computational tools for proteomics and databases are

Comprehensive comparison of two protein family of P-ATPases (13A1 and 13A3) in insects.

PubMed

Seddigh, Samin

2017-06-01

The P-type ATPases (P-ATPases) are present in all living cells where they mediate ion transport across membranes on the expense of ATP hydrolysis. Different ions which are transported by these pumps are protons like calcium, sodium, potassium, and heavy metals such as manganese, iron, copper, and zinc. Maintenance of the proper gradients for essential ions across cellular membranes makes P-ATPases crucial for cell survival. In this study, characterization of two families of P-ATPases including P-ATPase 13A1 and P-ATPase 13A3 protein was compared in two different insect species from different orders. According to the conserved motifs found with MEME, nine motifs were shared by insects of 13A1 family but eight in 13A3 family. Seven different insect species from 13A1 and five samples from 13A3 family were selected as the representative samples for functional and structural analyses. The structural and functional analyses were performed with ProtParam, SOPMA, SignalP 4.1, TMHMM 2.0, ProtScale and ProDom tools in the ExPASy database. The tertiary structure of Bombus terrestris as a sample of each family of insects were predicted by the Phyre2 and TM-score servers and their similarities were verified by SuperPose server. The tertiary structures were predicted via the "c3b9bA" model (PDB Accession Code: 3B9B) in P-ATPase 13A1 family and "c2zxeA" model (PDB Accession Code: 2ZXE) in P-ATPase 13A3 family. A phylogenetic tree was constructed with MEGA 6.06 software using the Neighbor-joining method. According to the results, there was a high identity of P-ATPase families so that they should be derived from a common ancestor however they belonged to separate groups. In protein-protein interaction analysis by STRING 10.0, six common enriched pathways of KEGG were identified in B. terrestris in both families. The obtained data provide a background for bioinformatic studies of the function and evolution of other insects and organisms. Copyright © 2017 Elsevier Ltd. All rights

Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

PubMed

Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

2017-07-01

To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6PASI)=0 for at least 6 months) achieved by MTX+anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68 + , CD20 + , CD3 + cells and CD31 + vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68 + , CD20 + , CD3 + , CD31 + cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68 + (p=0.02) and CD3 + cells (p=0.04) as well as CD31 + vessels (p<0.001) than PDUS-negative patients with RA in remission. PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. Published by the BMJ

Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

PubMed Central

Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

2017-01-01

Objective To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Methods Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6PASI)=0 for at least 6 months) achieved by MTX+anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. Results PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68+, CD20+, CD3+ cells and CD31+ vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68+, CD20+, CD3+, CD31+ cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68+ (p=0.02) and CD3+ cells (p=0.04) as well as CD31+ vessels (p<0.001) than PDUS-negative patients with RA in remission. Conclusions PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. PMID

Water, soil and soccer: an experience of two years promoting humanistic competences and standardization of curricula

NASA Astrophysics Data System (ADS)

Licciardello, Feliciana; Consoli, Simona; Izquierdo, Guillermo; Parraguirre, Sebastián; Pérez-Palazón, María J.; Pimentel, Rafael; Polo, María J.; Taguas, Encarnación V.

2015-04-01

: Proyecto de Innovación Docente -Teaching Innovation Projects of University of Cordoba (2014): "Adquisición de competencias técnicas y humanísticas y estandarización internacional de currículos en la enseñanza de proyectos de ingeniería rural: llevando la pasión por el fútbol a casos prácticos de Hidrología".

Skin Microbiome in Patients With Psoriasis Before and After Balneotherapy at the Thermal Care Center of La Roche-Posay.

PubMed

Martin, Richard; Henley, Jessica B; Sarrazin, Patrick; Seité, Sophie

2015-12-01

Changes in the composition of microbial communities that colonize skin have been linked to several diseases including psoriasis. Nevertheless, the intra-individual dynamics and how these communities respond to balneotherapy remain poorly understood. This open label study was conducted between July and September 2012. Microbial communities of patients with psoriasis vulgaris were characterized prior and post a 3-week selenium-rich water balneotherapy treatment at the thermal care center La Roche-Posay (La Roche-Posay, France). Balneotherapy consisted of high-pressure filiform showers, baths, facial, and body spray treatments as well as La Roche-Posay thermal spring water (LRP-TSW) consumption. Swabs were taken from affected and proximal unaffected skin and the 16S rRNA bacterial gene was used to analyze the composition of bacterial communities. Using the same 16S rRNA gene tool, we tried to describe the LRP-TSW bacterial landscape. This study included 54 patients diagnosed with moderate to severe forms of psoriasis vulgaris. After eliminating individuals lacking paired samples from both visits, 29 individuals were analyzed for their microbiome profile. Shannon Diversity Index and global bacterial landscape indicate similar microbial communities on both unaffected and adjacent affected skin. PASI values decreased post-balneotherapy implying improvement of disease severity. No significant change in the Shannon Diversity Index was noticed at the end of the third week. The average taxonomic composition of skin microbial communities associated with unaffected and affected skin of psoriatic patients post-balneotherapy shows that treatment with LRP-TSW significantly increased the level of Xanthomonas genus and, to a lesser extent, Corynebacterium genus. The Xanthomonas genus belongs to the main Xanthomonadaceae family found in LRP-TSW and also on healthy skin. In psoriatic patients, a poor bacterial biodiversity was noticed and the bacterial communities were similar on

Elektroninės cigaretės: naujas būdas mesti rūkyti ar nauja grėsmė?

PubMed Central

Aleknaitė, Aistė; Andrijauskaitė, Monika; Latauskienė, Justė; Andrejevaitė, Viktorija

2016-01-01

Nuo 2010 m. tarp suaugusiųjų ir paauglių išaugo elektroninių cigarečių vartojimas. Dauguma el. cigarečių vartotojų anksčiau yra rūkę tradicinius tabako gaminius. Didžioji dalis žmonių el. cigaretes suvokia kaip priemonę, padėsiančią mesti rūkyti ar sumažinti surūkomų įprastinių cigarečių kiekį. Elektroninės cigaretės yra prietaisas, susidedantis iš skysčiu užpildytos kasetės, kaitiklio bei baterijos. Nuspaudus mygtuką įjungiamas kaitiklis, kuris šildo skystį, o, šiam tapus garais, jie įkvepiami. Visų rūšių el. skysčių pagrindinės sudedamosios dalys yra glicerolis arba propileno glikolis, papildomai gali būti pridedama nikotino ir / ar aromatų. Skysčiuose taip pat nustatyta įvairių kitų cheminių medžiagų. Ilgalaikio el. cigarečių vartojimo pasekmės sveikatai nėra išaiškintos, manoma, kad jos turėtų būti saugesnės nei rūkyti įprastines cigaretes. Nėra pakankamai ištirtas el. cigarečių skysčiuose esančių medžiagų toksiškumas. Trūksta duomenų apie el. cigarečių, kaip pagalbinės priemonės norint mesti rūkyti, veiksmingumą ir saugumą. Gydytojas norinčiam mesti rūkyti pacientui pirmiausia turėtų pasiūlyti patvirtintas pakaitinės nikotino terapijos ar kitas pagalbines priemones ir užtikrinti, kad pacientas gautų informaciją apie naujausius medikamentus, galinčius jam padėti. Jei pacientas atsisako šių priemonių ir renkasi el. cigaretes, gydytojas turėtų informuoti apie abejotiną jų saugumą ir veiksmingumą. Visuomenėje kyla susirūpinimas, kad el. cigarečių rūkymas gali paskatinti priklausomybę nikotinui ir padidinti norą išbandyti įprastines cigaretes. Nerimą kelia ir neapribotas el. cigarečių vartojimas viešosiose vietose. Nėra žinoma, kokią įtaką aplinkinių sveikatai gali turėti pasyvus garinimas. El. cigarečių reglamentavimas visame pasaulyje skiriasi ir laikui bėgant kinta. PMID:28356791

Stability and Load Bearing Capacity of a Bars with Built up Cross Section and Elastic Supports / Badania Stateczności I Nosności Prętów Złożonych Z Podporami Sprężystymi

NASA Astrophysics Data System (ADS)

Krajewski, Marcin

2015-03-01

The present paper is devoted to the numerical analysis and experimental tests of compressed bars with built-up cross section which are commonly used as a top chord of the roof trusses. The significant impact on carrying capacity for that kind of elements in case of out-of-plane buckling is appropriate choice of battens which are used to provide interaction between separate members. Linear buckling analysis results and nonlinear static analysis results, with material and geometrical nonlinearity, are presented for the bar with built-up cross section which was used as the top chord of the truss made in reality. Diagonals and verticals which are supports for the top chord between marginal joints were replaced by the elastic supports. The threshold stiffness (minimum stiffness) for the intermediate elastic supports which ensures maximum buckling load was appointed for the beam and shell model of the structure. The magnitude of limit load depended on length of the battens was calculated for models with initial geometric imperfections. The experimental tests results for the axially compressed bars with builtup cross section and elastic support are presented. Niniejsza praca poświecona jest analizom numerycznym i badaniom doświadczalnym ściskanych prętów złożonych, które są często stosowane, jako pasy górne kratownic dachowych. Istotny wpływ na nośność tego typu elementów, przy założeniu wyboczenia z płaszczyzny układu, ma odpowiedni dobór przewiązek zapewniający współpracę poszczególnych gałęzi. W pracy przedstawiono rezultaty liniowych analiz stateczności oraz fizycznie i geometrycznie nieliniowych analiz statycznych dla pręta złożonego, z którego zbudowany jest pas górny kratownicy wykonanej w rzeczywistości. Słupki i krzyżulce podpierające pas między węzłami skrajnymi zastąpiono podporami sprężystymi. Wyznaczono graniczną (minimalna) sztywność sprężystych podpór pośrednich zapewniającą maksymalną wartość obci

Quality of life and cost of illness in patients with psoriasis in Malaysia: a multicenter study.

PubMed

Tang, Min Moon; Chang, Choong Chor; Chan, Lee Chin; Heng, Agnes

2013-03-01

Psoriasis is an immune-mediated, chronic, inflammatory skin disease which affects approximately 2% of the world's population. It has a major impact on the patient's quality of life (QoL), influencing career, social activities, family relationships, and all other aspects of life. Many studies have described the various ways in which psoriasis can affect a patient's life. Very little is known, however, about the impact of psoriasis on the QoL of patients treated in Malaysia and the cost of illness in this region. This study aims to describe the extent to which psoriasis affects the QoL of patients treated in government-run dermatology clinics in Malaysia and to estimate the cost of illness. A total of 250 psoriasis patients treated at eight dermatology clinics in government-run hospitals in Malaysia were studied. The severity of psoriasis was assessed by dermatologists. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI) and Version 2 of the 12-Item Short-Form Health Survey (SF-12v2). Scores on the SF-12v2 of healthy subjects and of patients with other medical conditions, such as depression, diabetes mellitus, hypertension, and ischemic heart disease, were also assessed for comparison. The costs of dermatology outpatient consultant fees, medications, investigations, procedures, transportation, over-the-counter medications, and hospitalization were retrospectively estimated using questionnaires. The cohort studied had a median Psoriasis Area Severity Index (PASI) score of 9.9 and a median DLQI score of 10.0. The average SF-12v2 scores were 43.68 (standard deviation [SD] 9.23) and 42.25 (SD 10.7) on the Physical Health Summary and Mental Health Summary, respectively. The impact of disease on QoL was found to be greater in those with more extensive psoriatic lesion involvement, in younger patients, and in those with psoriatic arthropathy. Psoriasis was found to affect QoL in both genders equally. Body mass index had no effect on the severity of

Diastolic function of the nonfilling human left ventricle.

PubMed

Paulus, W J; Vantrimpont, P J; Rousseau, M F

1992-12-01

To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a

Satellite Sensornet Gateway Technology Infusion Through Rapid Deployments for Environmental Sensing

NASA Astrophysics Data System (ADS)

Benzel, T.; Silva, F.; Deschon, A.; Ye, W.; Cho, Y.

2008-12-01

impact on deep and shallow rooted plants. Our system was deployed in December 2007 and monitors sap flow on various plant species, while using a satellite link for real-time data access. In April 2008, in a joint deployment with UCLA, UC Merced, and GLEON, our SSG technology was used to study the impact of agricultural run off in a series of salt lakes near Bahia Blanca, Argentina. Our system collected meteorological data that were combined with water quality measurements taken from boats and buoys. Our SSG technology was used at the PASI workshop in June 2008 at the La Selva Biological Research Station in Costa Rica. As part of a two-week curriculum, students from throughout the americas used our system to collect measurements in the rain forest and later analyzed the data. La Selva plans to install several SSG nodes throughout the reserve and make mobile nodes available for visiting researchers to use in their research. We are currently planning a deployment with environmental engineer Tom Harmon from UC Merced to build an autonomous water quality flow path and reactive transport observation system near Merced, CA. SSG technology will be deployed to monitor soil, groundwater, and surface water parameters. In China's Guizhou Province, we are collaborating with researcher Sarah Rothenberg, who is studying mercury cycling in rice paddies. Our SSG system will collect soil parameters such as pH and ORP, in addition to environmental measurements such as PAR, and UV. This presentation will describe the SSG project, the SPAN prototype and our experience with technology infusion from the deployments. class="ab'>

NASA Sees Orbiting Stars Flooding Space with Gravitational Waves

NASA Astrophysics Data System (ADS)

2005-05-01

period of 321.5 seconds - barely more than five minutes. The observed five-minute period in J0806 is most likely the orbital period of the white dwarf system. However the possibility that it represents the spin of one of its white dwarfs cannot yet be completely ruled out. "It's either the most compact binary known or one of the most unusual systems we've ever seen," said Strohmayer. "Either way it's got a great story to tell." Strohmayer's Chandra X-ray observations, which will be published in an upcoming issue of The Astrophysical Journal, tighten orbital decay estimates made through optical observations in recent years independently by teams led by GianLuca Israel of the Astronomical Observatory of Rome and by Pasi Hakala of the University of Helsinki. NASA's Marshall Space Flight Center, Huntsville, Ala., manages the Chandra program for NASA's Science Mission Directorate, Washington. Northrop Grumman of Redondo Beach, Calif., was the prime development contractor for the observatory. The Smithsonian Astrophysical Observatory controls science and flight operations from the Chandra X-ray Center in Cambridge, Mass. Additional information and images are available at: http://chandra.harvard.edu and http://chandra.nasa.gov

EDITORIAL: 19th International Conference on General Relativity and Gravitation (GR19), México, 4-9 July 2010 19th International Conference on General Relativity and Gravitation (GR19), México City, México, 4-9 July 2010

NASA Astrophysics Data System (ADS)

Marolf, Don; Sudarsky, Daniel

2011-06-01

subject: Carlo Rovelli, and an interesting update on one the recent developments in the ADF/CFT correspondence 'the condensed matter-gravity connection' presented by Gary Horowitz, among other excellent contributions. The material presented by other plenary speakers, which is not represented in this issue, has already been widely reported either by themselves or by others. The parallel sessions covered a wide range of topics currently under investigation by the worldwide gravity community, and were enthusiastically attended by the conference participants. In the past, it has been traditional to ask session chairs to write a brief summary of the talks presented. This time, however, we asked the parallel session chairs to nominate a small number of individual speakers to contribute to this issue. By focusing on a smaller number of topics, we were able to allocate more space to each, which we hope will provide a more useful overview of at least some of the most exciting physics at GR19. We hope that this novel approach will become a standard feature of future proceedings of the GR meetings. Anther aspect we should mention is the satellite meeting on Quantum Gravity and its preceding PASI Quantum Gravity Summer School held at the Institute for Mathematics, National Autonomous University of México (UNAM), Campus Morelia, Morelia México, from 23 June to 3 July, 2010 which was attended by many students from Mexican institutions, as well as by several participants who came from abroad to learn about this fascinating subject. The organizers want to thank the generous support of the following institutions: the Mexican National Council for Science and Technology (CONACYT), the National Autonomous University of México (UNAM), the Autonomous Metropolitan University of México UAM, the Center for Research and Advanced Studies CINVESTAV, the Mexican Physical Society (SMF), The Mexican Academy of Sciences AMC, The Institute for Nuclear Sciences of UNAM (ICN), the International Union

Final work plan : phase I investigation of potential contamination at the former CCC/USDA grain storage facility in Montgomery City, Missouri.

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaFreniere, L. M.; Environmental Science Division

From September 1949 until September 1966, the Commodity Credit Corporation of the U.S. Department of Agriculture (CCC/USDA) leased property at the southeastern end of Montgomery City, Missouri, for the operation of a grain storage facility. During this time, commercial grain fumigants containing carbon tetrachloride were commonly used by the CCC/USDA and the private grain storage industry to preserve grain in their facilities. In January 2000, carbon tetrachloride was detected in a soil sample (220 {micro}g/kg) and two soil gas samples (58 {micro}g/m{sup 3} and 550 {micro}g/m{sup 3}) collected at the former CCC/USDA facility, as a result of a pre-CERCLIS sitemore » screening investigation (SSI) performed by TN & Associates, Inc., on behalf of the U.S. Environmental Protection Agency (EPA), Region VII (MoDNR 2001). In June 2001, the Missouri Department of Natural Resources (MoDNR) conducted further sampling of the soils and groundwater at the former CCC/USDA facility as part of a preliminary assessment/site inspection (PA/SI). The MoDNR confirmed the presence of carbon tetrachloride (at a maximum identified concentration of 2,810 {micro}g/kg) and chloroform (maximum 82 {micro}g/kg) in the soils and also detected carbon tetrachloride and chloroform (42.2 {micro}g/L and 58.4 {micro}g/L, respectively) in a groundwater sample collected at the former facility (MoDNR 2001). The carbon tetrachloride levels identified in the soils and groundwater are above the default target level (DTL) values established by the MoDNR for this contaminant in soils of all types (79.6 {micro}g/kg) and in groundwater (5.0 {micro}g/L), as outlined in Missouri Risk-Based Corrective Action (MRBCA): Departmental Technical Guidance (MoDNR 2006a). The corresponding MRBCA DTL values for chloroform are 76.6 {micro}g/kg in soils of all types and 80 {micro}g/L in groundwater. Because the observed contamination at Montgomery City might be linked to the past use of carbon tetrachloride-based fumigants

Golimumab for the treatment of psoriatic arthritis: a NICE single technology appraisal.

PubMed

Yang, Huiqin; Craig, Dawn; Epstein, David; Bojke, Laura; Light, Kate; Bruce, Ian N; Sculpher, Mark; Woolacott, Nerys

2012-04-01

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of golimumab (Schering-Plough/Centocor) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of active and progressive psoriatic arthritis (PsA) in patients who have responded inadequately to previous disease-modifying anti-rheumatic drugs (DMARDs). The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG) to critically appraise the evidence presented by the manufacturer. This article provides a description of the company submission, the ERG review and the resulting NICE guidance. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The main clinical effectiveness data were derived from a single phase III randomized controlled trial (GO-REVEAL) that compared golimumab with placebo for the treatment of active and progressive patients who were symptomatic despite the use of previous DMARDs or NSAIDs. The 14-week data showed that, compared with placebo, golimumab 50 mg significantly improved joint disease response as measured by American College of Rheumatology (ACR) 20 (relative risk [RR] 5.73, 95% CI 3.24, 10.56) and Psoriatic Arthritis Response Criteria (PsARC) [RR 3.45, 95% CI 2.49, 4.87], and significantly improved skin disease response as measured by Psoriasis Area and Severity Index (PASI) 75 (RR 15.95, 95% CI 4.62, 59.11). The 24-week absolute data showed that these treatment benefits were maintained. There was a significant improvement in patients' functional status as measured by Health Assessment Questionnaire change from baseline at 24 weeks (-0.33; p < 0.001). The open-label extension data showed that these beneficial effects were also maintained at 52 and 104 weeks. The ERG identified

The First 24 Years of Reverse Monte Carlo Modelling, Budapest, Hungary, 20-22 September 2012

NASA Astrophysics Data System (ADS)

Keen, David A.; Pusztai, László

2013-11-01

structure of the plastic crystalline and liquid phases of CBr2Cl2: neutron diffraction and reverse Monte Carlo modellingSzilvia Pothoczki1, László Temleitner, Luis Carlos Pardo, Gabriel Julio Cuello, Muriel Rovira-Esteva and Josep Lluis Tamarit Insights into the determination of molecular structure from diffraction data using a Bayesian algorithmA Henao, M Rovira-Esteva, A Vispa, J Ll Tamarit, E Guardia and L C Pardo Nanostructure determination from the pair distribution function: a parametric study of the INVERT approachMatthew J Cliffe and Andrew L Goodwin Empirical potential structure refinement of semi-crystalline polymer systems: polytetrafluoroethylene and polychlorotrifluoroethyleneA K Soper, K Page and A Llobet spinvert: a program for refinement of paramagnetic diffuse scattering dataJoseph A M Paddison, J Ross Stewart and Andrew L Goodwin Inter-molecular correlations in liquid Se2Br2Hironori Shimakura, Yukinobu Kawakita, Koji Ohara, László Pusztai, Yuiko Wakisaka and Shin'ichi Takeda RMCgui: a new interface for the workflow associated with running Reverse Monte Carlo simulationsMartin T Dove and Gary Rigg