Reducing cardiovascular risk in immune-mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies-A systematic review and meta-analysis.

Immune-mediated inflammatory disease (IMID) patients including psoriasis, inflammatory arthritides and bowel diseases have a higher risk of developing cardiovascular (CV) diseases compared to the general population. The increased CV risk may be promoted by tumour necrosis factor (TNF)-α-mediated immunological processes, which are present both in the pathomechanism of IMIDs and atherosclerosis. Our objective was to comprehensively investigate the effect of TNF inhibitors (TNFi) on CV risk compared with conventional therapies in IMIDs. The systematic literature search was conducted in three databases (MEDLINE, EMBASE, Cochrane Library) on 14 November 2022. Randomized controlled trials, cohort and case-control studies were eligible for inclusion. Outcomes consisted of the incidence of CV events, with major adverse cardiovascular events (MACE) as a main endpoint. A random-effects meta-analysis was performed by pooling fully adjusted multivariate hazard ratios (HR) and incidence rate ratios (IRR) with a 95% confidence interval (CI) comparing TNFis with conventional systemic non-biologicals (CSNBs). Of a total of 8724 search results, 56 studies were included overall, of which 29 articles were eligible for the meta-analysis, and 27 were involved in the systematic review. Including all IMIDs, the TNFi group showed a significantly reduced risk of MACE compared with the CSNB group (HR = 0.74, 95% confidence interval (CI) 0.58-0.95, p = 0.025; IRR = 0.77, 95% CI 0.67-0.88, p < 0.001). Subgroup analysis of Pso, PsA patients by pooling IRRs also confirmed the significantly decreased risk of MACE in TNFi-treated patients compared with CSNB groups (IRR = 0.79, 95% CI 0.64-0.98). The observational nature of most included studies leading to high heterogeneity represents a limitation. Based on the results, TNFis may reduce the risk of CV events compared to CSNBs. Therefore, earlier use of TNFis compared to conventional systemic agents in the therapeutic sequence may benefit CV risk in IMID patients.

DLQI-R scoring improves the discriminatory power of the Dermatology Life Quality Index in patients with psoriasis, pemphigus and morphea.

BACKGROUND: The Dermatology Life Quality Index (DLQI) rates 'not relevant' responses (NRRs) as the item on the questionnaire having no impact on the patients' lives at all. The DLQI-Relevant (DLQI-R) is a recently developed scoring that adjusts the total score of the questionnaire for the number of NRRs indicated by a patient. OBJECTIVES: To compare the discriminatory power of the original and DLQI-R scoring approaches in terms of absolute and relative informativity. METHODS: Cross-sectional data from 637 patients with morphea, pemphigus and psoriasis were used for the analyses. To assess absolute and relative informativity, Shannon's index and Shannon's evenness index were calculated for the 10 items on the questionnaire and for DLQI and DLQI-R total scores. RESULTS: Mean DLQI and DLQI-R scores of patients were 6·13 vs. 6·91. In the subset of patients with NRRs (n = 261, 41%), absolute informativity was higher with the DLQI-R scoring for all eight items with NRR options in all three conditions. The DLQI-R exhibited a better relative informativity in 8, 8 and 6 items in pemphigus, morphea and psoriasis, respectively. The DLQI-R led to an improvement in average item-level informativity in all DLQI score bands up to 20 points. Regarding total scores, the DLQI-R produced both a higher absolute and relative informativity in all three conditions. CONCLUSIONS: In patients with morphea, pemphigus and psoriasis, DLQI-R scoring improves the discriminatory power of the questionnaire by benefiting from the additional information in NRRs. DLQI-R scoring may be useful both in clinical practice and research. A scoring chart has been developed to aid physicians with scoring. What's already known about this topic? The original scoring of the Dermatology Life Quality Index (DLQI) rates 'not relevant' responses as the item of the questionnaire having no impact on the patients' lives at all. DLQI-Relevant (DLQI-R) is a new scoring developed in 2018 that adjusts the total score of the questionnaire for the number of 'not relevant' responses indicated by patients. The discriminatory power of the DLQI-R compared with the DLQI has not yet been investigated. What does this study add? In patients with psoriasis, pemphigus and morphea, DLQI-R scoring improves the discriminatory power of the questionnaire by benefiting from the additional information in 'not relevant' responses. What are the clinical implications of this work? DLQI-R scoring may help to more accurately quantify patients' health-related quality of life both in clinical practice and research. A scoring chart has been developed to aid physicians with scoring.

Proposal of a new scoring formula for the Dermatology Life Quality Index in psoriasis.

BACKGROUND: 'Not relevant' responses (NRRs) on the Dermatology Life Quality Index (DLQI) may occur in up to 40% of patients with psoriasis. As these responses are scored as the item of the questionnaire having no impact on the patients' lives at all, it is more difficult for these patients to fulfil the DLQI > 10 criterion required by clinical guidelines to become candidates for systemic treatment including biologics. OBJECTIVES: We propose a new scoring system for the DLQI that corrects for the bias in the NRR option and test its construct validity in a sample of patients with psoriasis. METHODS: Data from 242 patients (104 of whom marked at least one NRR) from two earlier cross-sectional surveys were reanalysed. For each patient, the DLQI score was calculated in two ways: (i) according to the original scoring and (ii) by applying a new scoring formula (DLQI-R) that adjusts the total score for the number of NRRs. The construct validity of the DLQI-R was tested against the Psoriasis Area and Severity Index (PASI) and EQ-5D-3L. RESULTS: The mean DLQI and DLQI-R scores were 9·99 ± 7·52 and 11·0 ± 8·02, respectively. The DLQI-R allowed eight more patients (3·3%) to achieve the 'PASI > 10 and DLQI > 10' threshold. The results were robust when limiting the maximum number of NRRs allowed to two or three. Compared with the DLQI, DLQI-R correlated slightly better with PASI (rs = 0·59 vs. 0·57) and EQ-5D-3L index scores (rs = -0·58 vs. -0·54). CONCLUSIONS: The DLQI-R seems to be a valid scoring system for avoiding the bias in the NRR option and can help to improve patients' access to biologics.

A detailed analysis of 'not relevant' responses on the DLQI in psoriasis: potential biases in treatment decisions.

BACKGROUND: Dermatology Life Quality Index (DLQI) is the most common health-related quality of life measure in dermatology that is widely used in treatment guidelines for psoriasis. Eight of the 10 questions of the DLQI offer a 'not relevant' response (NRR) option that is scored as the item had no impact on patients' life at all. OBJECTIVE: To explore the occurrence of NRRs on the DLQI in psoriasis patients and to examine the effect of several socio-demographic and clinical factors on giving NRRs. METHODS: Data were obtained from two cross-sectional surveys among psoriasis patients at two academic dermatology clinics in Hungary. Health-related quality of life was measured by employing DLQI and EQ-5D-3L, while disease severity was graded by Psoriasis Area and Severity Index (PASI). Multivariate logistic regression was applied to determine the predictors of providing NRRs. RESULTS: Mean age of the 428 patients was 49 years, and 65% were males. Mean PASI, DLQI and EQ-5D-3L index scores were 8.4 ± 9.5, 6.8 ± 7.4 and 0.74 ± 0.28, respectively. Overall, 38.8% of the patients had at least one NRR: 19.6% (one), 11.5% (two), 5.1% (three) and 2.6% (more than three). Most NRRs occurred in sport, sexual difficulties and working/studying items of the DLQI (28.4%, 16.4% and 14.0%, respectively). Female gender (OR 1.65; 95% CI 1.04-2.61), older age (OR 1.05; 95% CI 1.03-1.07) and higher PASI score (OR 1.03; 95% CI 1.01-1.06) were associated with providing more NRRs, whereas highly educated patients (OR 0.34; 95% CI 0.16-0.72) and those with a full-time job (OR 0.47; 95% CI 0.29-0.77) less frequently tended to tick NRRs. CONCLUSION: The high rate of psoriasis patients with NRRs, especially among women, less educated and elderly patients, indicates a content validity problem of the measure. A reconsideration of the use of the DLQI for medical and financial decision-making in psoriasis patients is suggested.

Moderate to severe psoriasis patients' subjective future expectations regarding health-related quality of life and longevity.

BACKGROUND: Unrealistic expectations regarding treatments and clinical outcomes may lead to disappointment about therapy and sub-optimal compliance; nonetheless, these expectations have not been studied in psoriasis patients yet. OBJECTIVE: To evaluate psoriasis patients' subjective future expectations regarding health-related quality of life (HRQOL) and life expectancy, and to explore clinical features associated with under- or overestimating behaviour. METHODS: A cross-sectional questionnaire survey of consecutive adult patients with moderate to severe psoriasis was conducted. HRQOL expectations were recorded by applying the EQ-5D descriptive system for 6 months ahead and for future ages of 60, 70, 80 and 90 respectively. RESULTS: In total, 167 patients (71% males) were included in the analysis with mean age of 50.4 ± 12.4 years and mean EQ-5D score of 0.71 ± 0.30. Overall 65% had chronic plaque psoriasis, 35% nail psoriasis, 35% scalp involvement, 29% psoriatic arthritis, 9% inverse psoriasis and 5% palmoplantar psoriasis respectively (combinations occurred). Participants expected 0.1 ± 0.23 mean improvement in EQ-5D within 6 months (P < 0.001) that achieves the minimum clinically important difference. Overall 37% expected improvement and 13% decline; however, 49% expected no changes in any of the five dimensions of EQ-5D within 6 months. Female gender, inverse or palmoplantar involvement and more severe psoriasis were likely associated with higher expectations. Patients at the initiation of their first biological at the time of the survey expected 0.18 ± 0.24 increase that seems to be realistic compared to the EQ-5D utility gain achieved in randomized controlled trials. Males expected by 2.7 ± 11.1 more, while females expected by 5.2 ± 9.3 less life years compared to the average statistical gender- and age-matched life expectancy (P < 0.05). Patients who expected to be alive at ages of 60, 70, 80 and 90 scored their future EQ-5D at ages of 60 to 90: 0.59 ± 0.46, 0.48 ± 0.41, 0.42 ± 0.41 and 0.22 ± 0.47 respectively. CONCLUSION: Our findings highlight the importance of exploring expectations that might help to increase patients' compliance.

Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Patients with severe chronic hand eczema (CHE) refractory to topical corticosteroids currently have limited treatment options suited for chronic use, and few controlled clinical studies have investigated new therapies in this setting. OBJECTIVES: To assess the efficacy and safety of oral alitretinoin (9-cis retinoic acid) taken at 10 mg or 30 mg once daily for up to 24 weeks, compared with placebo control, in the treatment of severe CHE refractory to topical corticosteroids. METHODS: A randomized, double-blind, placebo-controlled, prospective, multicentre trial was conducted in 111 dermatology outpatient clinics in Europe and Canada. A total of 1032 patients with severe refractory CHE were randomized in a 1 : 2 : 2 ratio to placebo, or 10 mg or 30 mg of oral alitretinoin once daily for up to 24 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for relapse for 24 weeks after the end of therapy. The primary efficacy parameter was Physician Global Assessment of overall CHE severity, with response defined as clear or almost clear hands. RESULTS: Responses, defined as clear or almost clear hands, were achieved in up to 48% of patients treated with alitretinoin, compared with 17% for placebo (P < 0.001), with up to 75% median reduction in disease signs and symptoms. Treatment was well tolerated, with dose-dependent adverse effects comprising headache, mucocutaneous events, hyperlipidaemia, and decreased free thyroxine and thyroid-stimulating hormone. The median time to relapse, defined as recurrence of 75% of initial signs and symptoms, was 5.5-6.2 months in the absence of anti-eczema medication. CONCLUSIONS: Alitretinoin given at well-tolerated doses induced clearing of CHE in a substantial proportion of patients with severe disease refractory to standard therapy.

Synchronous balneophototherapy is effective for the different clinical types of psoriasis.

BACKGROUND: The efficacy of synchronous balneophototherapy in clearing psoriasis is based on the multiple-targeted effects of UVB light and Dead Sea salt. Their synchronous application produces a synergic effect. OBJECTIVE: The purpose of this retrospective study is: 1) to evaluate the efficacy of synchronous balneophototherapy for treating different clinical types of psoriasis; 2) to determine whether there is any difference between response to treatment, and 3) to gain more data in order to predict the effect of treatment in different clinical types, and thus to support the selection of patients for treatment. METHODS: Patients received a basic course of synchronous balneophototherapy according to the Regensburg scheme, consisting of 35 treatment sessions, followed by a maintenance course of a further 25 treatments. The patients' skin status was monitored by weekly assessment using the PASI score throughout the course. The efficacy of the treatment was evaluated through the results of 373 patients treated according to protocol during the basic course, and the results of 78 of these patients during the maintenance course. One hundred and eighty-six patients were enrolled into the study comparing the efficacy of the basic course for the different clinical types of psoriasis: data of patients with large plaques, small plaques, guttate and confluating type of skin signs were summarized and compared. RESULTS: During the basic course of treatment 70.7% improvement of the average PASI index was observed; the average PASI index decreased from 16.14 to 4.73. A further improvement from 4.58 to 4.27 of the average PASI was found during the maintenance therapy. Small plaque-type skin signs showed the best response with a PASI decrease of 76.1%; Guttate type had a PASI decrease of 73.7%, large plaque type, 67.1% and confluating type, 62%. Comparing data with the average PASI decrease, a statistically significant lower decrease was found in confluating type cases. CONCLUSIONS: These results confirm that synchronous balneophototherapy is an effective treatment modality for different clinical types of psoriasis. Patients with small plaques have the greatest chance of the most marked clinical clearing; guttate and large plaque types of psoriasis also respond well to the treatment.

No significant change of plasma beta-endorphin levels of psoriasis patients after synchronous balneophototherapy.

BACKGROUND/PURPOSE: Previous studies suggested that beta-endorphin has a pathogenic role in psoriasis: its increased plasma concentration may play a role in the neuroimmunological processes in the pathomechanism of the disease, and plasma beta-endorphin levels should reflect the changes in the patients' skin status. The purpose of this study was to investigate the changes of peripheral blood beta-endorphin levels in psoriatic patients in conjunction with changes in their skin symptoms after synchronous balneophototherapy. METHODS: With synchronous balneophototherapy, 12 patients with extended skin symptoms of psoriasis were treated. The therapy followed the Regensburg protocol, consisting of a basic course of 35 sessions. Patients' skin status was characterized by evaluating the Psoriasis Area and Severity Index score before and after the therapy course. Blood samples were taken before treatment, and 1 day after the last session, with symptom-free skin. Plasma beta-endorphin levels were measured by a specific radioimmunoassay developed by the authors. RESULTS: There was no significant change in plasma levels of beta-endorphin after clinical clearance of psoriatic skin symptoms. CONCLUSION: In this non-randomized, uncontrolled study no significant difference could be detected between plasma beta-endorphin levels before and after a basic course of synchronous balneophototherapy in patients with psoriasis. Although beta-endorphin has many neuroimmunological effects, the changes of its plasma level do not consistently reflect the skin status. Inflammation in psoriatic skin lesions is probably not mediated directly by circulating beta-endorphin.

[Use of interferon-alpha (IFN-alpha) in the treatment of keratoacanthoma]. / Die Anwendung von Interferon alpha (IFN alpha) in der Keratoakanthombehandlung.

BACKGROUND AND OBJECTIVE: Keratoacanthoma are benign epithelial tumors. The aim of this study was to determine the effects of interferon alpha on keratoacanthoma. PATIENTS/METHODS: Six patients presented with histologically proven keratoacanthoma which were large or otherwise difficult to excise. Intra and perilesional interferon-alpha treatment with 3 million IU weekly was started. RESULTS: In 6-15 weeks all tumors were cured. CONCLUSIONS: Treatment with intralesional interferon-alpha offers a new possibility in cases of large keratoacanthomas, or those which are not surgically excisable.

Changes in the legislation on the use of daytime running lights by motor vehicles and their effect on road safety in Hungary.

As of 1 March 1993, a partial (relating only to semi-motorways and main roads), and as of 1 June 1994, a total (relating to all roads) legal obligation to use DRL came into force outside built-up areas in Hungary. This paper examines the effectiveness of this regulation as an accident countermeasure. In view of the fact that it became possible to use one part of the road network as a comparison group during the period of partial obligation, a comparison group investigation has been carried out in addition to the analysis based on the odds ratio method familiar from earlier studies. The different methods provided different results, the probable causes of which are discussed in the present study. The result of the comparison group analysis are consistent not only with the hypothesis that DRL reduces certain types of collisions, but also with the results of a meta-analysis of 17 studies that have evaluated the effects on accidents of using DRL on cars. By using this method, it was possible to detect in the experimental group a 13.0% reduction in the number of frontal and 'crossing' vehicle collisions in daylight, in good visibility conditions, during the after period. The number of frontal and crossing collisions decreased without a simultaneous increase in rear-end collisions: the number of the latter has not significantly changed. Thus, the hypothesis that it is more reliable to estimate the collision-reducing effect of DRL on the basis of accidents only occurring in good visibility conditions, rather than on the basis of the total number of daylight accidents, has been justified by this study. The causes of this, as well as the difficulties and confounding factors arising when the odds ratio method is used, are dealt with in this work. By analyzing over a longer time series, it was possible to verify that the positive road safety effect is not a mere novelty effect, and is not simply due to the 'regression to the mean'.