A dermocosmetic product containing the sap of oat plantlets and Garcinia mangostana extract improves the clinical signs of acne.

BACKGROUND: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, characterized by papules, pustules and/or nodules manifesting primarily on the face and/or upper back that can leave scars, post-inflammatory hyperpigmentation (PIH) and erythema (PIE). OBJECTIVE: To evaluate the anti-inflammatory properties of a protein-free sap extruded from Rhealba® oat plantlets and a Garcinia mangostana extract on Cutibacterium acnes-induced inflammation in vitro and assess the tolerability and efficacy of a dermocosmetic product containing these actives in subjects with mild-to-moderate acne. METHODS: Monocyte-derived dendritic cells (Mo-DCs) from acne patients were stimulated with a planktonic culture of C. acnes and cytokine production was evaluated before and after addition of the test extracts by RT-PCR and ELISA. The clinical study was conducted in subjects with mild-to-moderate acne who applied the product to their face and upper back twice-daily for 2 months. RESULTS: Cutibacterium acnes-induced IL-6, IL-12p40, IL-10 and TNFα synthesis was reduced by the addition of the Garcinia mangostana extract and oat sap in vitro. The clinical study included 54 subjects. The 2-month, twice-daily application of the test product to the whole face and acne-affected areas on the upper back was well tolerated. It led to significant decreases in the number of retentional (-21% for 69% of subjects at D57) and inflammatory (-35% for 79% of subjects at D57) acne lesions, as well as a decrease in Global Acne Evaluation severity scores (2.5 at D1, 2.2 at D29 and 2.1 at D57). The dermatologist also rated the product as effective or very effective in most subjects with PIE (82%; n = 33/40) and PIH (70%; n = 8/11) at D57. CONCLUSION: The actives demonstrated anti-inflammatory effects in vitro, and the dermocosmetic product showed good clinical efficacy and tolerability in subjects with mild-to-moderate acne, supporting the use of this product in acne management.

Characterization of the forehead skin microbiome in the early phase of acne.

BACKGROUND: The skin microbiota is known to be imbalanced in acne vulgaris, but the changes occurring during the early stages of acne onset remain poorly described. OBJECTIVES: To characterize the skin microbiome of subclinical stages of acne in adults and adolescents. METHODS: The composition and diversity of the microbiota from non-lesional skin on the forehead of subjects with mild-to-moderate acne were compared to the ones from non-acne subjects. Analyses of skin swab samples were performed using high-throughput sequencing of the V1-V3 regions of the bacterial 16S ribosomal RNA gene, the tuf gene fragment of Staphylococcus species and the internal transcribed spacer (ITS1) region of the fungal rRNA gene to determine the relative abundance, alpha-diversity and beta-diversity of bacteria and fungi. RESULTS: Compared with non-acne subjects, acne subjects had a higher abundance of Cutibacterium (72.4% vs. 57.8%) and lower abundances of Corynebacterium (2.8% vs. 4.8%) and Streptococcus (1.4% vs. 3.2%). Bacterial alpha- and beta-diversity indices also differed significantly between the two groups, reflecting differences in richness, evenness, abundance and phylogenetic distance between bacterial populations. Differences were also observed at the level of Staphylococcus species: S. capitis was predominant in skin samples from non-acne subjects (46.7%), whereas S. epidermidis was the most abundant Staphylococcus species in non-lesional forehead skin areas of acne subjects (44.2%). Conversely, no significant between-group differences were found for fungi, with Malasseziales being the predominant order in both subject groups. CONCLUSION: Dysbiosis was observed very early in subclinical acne stages of the forehead skin, with the overall abundance, richness and evenness of the bacterial population being lower in acne than in non-acne skin samples. Dysbiosis was also found at the level of Staphylococcus species. The development of acne lesions could therefore be prevented by using a skin care product that rebalances facial skin microbiota at very early stages.

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system.

PURPOSE: Over the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. MATERIAL AND METHODS: Various patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. RESULTS: A total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0-3); (B=50 patients, score 4-7); (C=33 patients, score 8-10); and (D=13 patients, score 11-16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). CONCLUSION: There exists a lack of universally acceptable 'standard-of-care' salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

Purpose To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. Methods Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. Results A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3–7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6–7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4–55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6–109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan–Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis (AU)

[EHPAD: Reintroducing relational life after the health emergency]. / Après l'urgence sanitaire, réaffirmer le droit à la vie personnelle en EHPAD avec pour horizon le respect de la dignité des anciens et de leur famille.

The health emergency linked to COVID-19 has been stressful for staff working in nursing home, doubly painful for residents faced with the risk of infection and the reality of family separation. We explore in this article some psychological consequences resulting from the experience of residents and caregivers in the waning health crisis, hoping that the experience gained will allow greater efficiency in the event of a resumption of the pandemic. At the same time, we proposed to combine this point of view with the more ethical one, taking seriously a fundamental tendency towards ageism in Western societies and what they reflect from the social ethics of care. It is now important to declare a refusal to "return to the abnormal", this medical and ethical prehistory, such as suffered by many of our elders and their caregivers during confinement.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

PURPOSE: To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. METHODS: Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. RESULTS: A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3-7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6-7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4-55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6-109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. CONCLUSION: This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.

Prospective Longitudinal Assessment of Quality of Life and Activities of Daily Living as Patient-Reported Outcome Measures in Recurrent/Progressive Glioma Treated with High-dose Salvage Re-irradiation.

AIMS: To evaluate quality of life (QOL) and activities of daily living (ADL) longitudinally in patients treated with salvage re-irradiation for recurrent/progressive glioma. Secondary end points included post-re-irradiation survival. MATERIALS AND METHODS: Patients with diffuse glioma, aged 18-70 years with preserved performance status and unequivocal evidence of recurrence/progression with a minimum 2-year time interval from index radiation therapy were eligible. QOL was assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and brain cancer module (BN20). ADL was assessed using a modified Barthel's index. Assessments were carried out longitudinally, first before re-irradiation, at completion of re-irradiation and subsequently periodically on follow-up. Summary scores were calculated from raw scores as per the EORTC scoring manual; higher functional scores and lower symptom scores indicating better QOL. Summary mean scores for the modified Barthel's index were also calculated, with lower scores indicating higher disability. Differences between the summary scores at different time points were tested using the Friedman test. RESULTS: In total, 225 assessments were carried out in 60 patients accrued on the study. A significant improvement in scores was noted for physical function (P < 0.001), emotional function (P = 0.002), cognitive function (P = 0.009) and social functioning (P = 0.047) over time. Role function scores (P = 0.182) and global health status scores (P = 0.074) remained stable. Among symptom scores, fatigue showed a statistically significant improvement over time (P = 0.01), whereas other symptom scores remained largely stable. There was a significant increase in the modified Barthel's index score over time (P = 0.001), suggesting greater functional independence. At a median follow-up of 12.9 months, the 1-year Kaplan-Meier estimates with 95% confidence intervals of post-re-irradiation progression-free survival and overall survival were 45.1% (31.5-58.7%) and 62.2% (49.2-75.2%), respectively. CONCLUSIONS: High-dose salvage re-irradiation in carefully selected patients with recurrent/progressive glioma is associated with stable QOL (preserved functional domains and reduced symptom burden) and improvement in ADL (greater functional independence) over time with encouraging survival outcomes.

Additional pharmacological activity of I-modulia and generation of two newly designed extracts of Aquaphilus dolomiae culture for dermocosmetic actives.

Aquaphilus dolomiae (AD) is a unique isolate from Avène Thermal Spring Water. I-Modulia, the first biotech extract from culture of AD, was used as immune modulator in Th2 inflammatory models. In this short publication, firstly we describe generation of two AD de novo extracts specifically designed for repairing and for neuroinflammation modulation activities which will be described, respectively, in two other articles in this supplement. Finally, for I-modulia, we describe new data on inhibition of human mast cell degranulation in vitro and its effect on substance P-induced neurogenic inflammation on ex vivo human skin explants.

The work programme of NERIS in post-accident recovery.

NERIS is the European platform on preparedness for nuclear and radiological emergency response and recovery. Created in 2010 with 57 organisations from 28 different countries, the objectives of the platform are to: improve the effectiveness and coherency of current approaches to preparedness; identify further development needs; improve 'know how' and technical expertise; and establish a forum for dialogue and methodological development. The NERIS Strategic Research Agenda is now structured with three main challenges: (i) radiological impact assessments during all phases of nuclear and radiological events; (ii) countermeasures and countermeasure strategies in emergency and recovery, decision support, and disaster informatics; and (iii) setting up a multi-faceted framework for preparedness for emergency response and recovery. The Fukushima accident has highlighted some key issues for further consideration in NERIS research activities, including: the importance of transparency of decision-making processes at local, regional, and national levels; the key role of access to environmental monitoring; the importance of dealing with uncertainties in assessment and management of the different phases of the accident; the use of modern social media in the exchange of information; the role of stakeholder involvement processes in both emergency and recovery situations; considerations of societal, ethical, and economic aspects; and the reinforcement of education and training for various actors. This paper emphasises the main issues at stake for NERIS for post-accident management.

Current perspectives in the interpretation of gunshot residues in forensic science: A review.

The traces produced when a firearm is discharged can provide important information in cases when questions regarding a possible association of the firearm with a person of interest (POI), time since discharge or shooting distance are raised. With advances in technology, the forensic challenges presented by these traces, known as gunshot residues (GSR), are moving from the analytical domain to the interpretation of the analytical results. Different interpretation frameworks are currently competing. Formal classification of particles, using standards such as that produced by ASTM, focusses only on evaluation of evidence at the sub-source level. Another approach, based on the application of Bayesian reasoning - namely the case-by-case approach - has been proposed that allows evaluation of evidence in regards to activity-related questions. This alternative approach allows an evaluation of the evidence that is more closely aligned to judicial and investigative aims. This paper critically presents the state of the art in regards to GSR interpretation in a holistic manner.

Development and psychometric validation of the REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) questionnaire: a common measure of plaque-type psoriasis severity and treatment efficacy for patients and clinicians.

BACKGROUND: To date, there is no global consensus on the definition of the severity of psoriasis. The REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) questionnaire has recently been developed to provide a better understanding of plaque-type psoriasis severity and treatment efficacy from both patient and clinician perspectives. OBJECTIVE: This study aimed to develop and psychometrically validate the new REFLETS questionnaire to evaluate patient and clinician perceptions of plaque-type psoriasis severity and treatment efficacy. METHODS: Two similar versions of the REFLETS questionnaire were developed following a rigorous methodology for clinicians and patients, referring to 'the psoriasis of your patient' or to 'your psoriasis', respectively. An observational, longitudinal, multicentre study was conducted in France with 34 dermatologists and 430 mild to severe plaque-type psoriasis patients to finalize the questionnaire and evaluate its psychometric properties. RESULTS: Two dimensions were defined--severity and treatment efficacy--with three subdimensions within severity (impact of psoriasis, symptoms and disease course), and two individual items on joint pain. The questionnaire was well accepted by clinicians and patients. Excellent internal consistency (Cronbach's alpha = 0.66-0.98) and test-retest reliability (intraclass correlation coefficients = 0.83-0.94) were demonstrated. REFLETS scores were moderately to highly correlated to Psoriasis Area and Severity Index (r = 0.35-0.70), Skindex-29 (r = 0.46-0.82) and DLQI scores (r = 0.36-0.82). Patients with decreased psoriasis severity and those with increased treatment efficacy, according to patient global evaluations, had lower severity and higher treatment efficacy REFLETS scores, respectively. CONCLUSION: REFlective evaLuation of psoriasis Efficacy of Treatment and Severity is a promising tool for assessing plaque-type psoriasis severity and treatment efficacy from patient and clinician perspectives. It may help to improve patient and clinician communication in treatment decision making.

Evidence-based recommendations on the role of dermatologists in the diagnosis and management of psoriatic arthritis: systematic review and expert opinion.

BACKGROUND: Psoriatic arthritis (PsA) can develop at any time during the course of psoriasis. AIMS: The aims of these practical recommendations are to help dermatologists identify patients at risk of PsA, to diagnose PsA in collaboration with rheumatologists and to gain a better understanding of initial PsA management. MATERIALS AND METHODS: A scientific committee consisting of 10 dermatologists and a rheumatologist selected clinically relevant questions to be addressed by evidence-based recommendations using the DELPHI method. For each question, a systematic literature review was performed in Medline, Embase and the Cochrane Library databases. The levels of evidence of all selected and reviewed articles were appraised according to the Oxford levels of evidence. RESULTS: An expert board of 30 dermatologists reviewed and analysed the evidence and developed recommendations for the selected questions. Agreement among participants was assessed on a 10-point scale, and the potential impact of the recommendations on clinical practice was evaluated. Among the 6960 references identified, 190 relevant articles were included in the reviews. Three recommendations regarding risk factors for PsA and one regarding PsA prevalence were issued. The mean agreement score between participants varied from 7.8 to 9.6. Three recommendations on PsA screening tools that can be used by dermatologists were issued. The mean agreement score between participants varied from 7.7 to 9.4. Initial PsA treatment options according to published guidelines were critically appraised for axial and peripheral involvement and enthesitis/dactylitis. Three recommendations were issued. The mean agreement score between participants varied from 7.6 to 8.7. DISCUSSION: The systematic literature research and meta-analyses did not provide high-quality evidence to support recommendations regarding PsA screening. Conversely, PsA treatment options were supported by strong evidence. CONCLUSION: Cooperation between dermatologists and rheumatologists should be emphasized to better identify and manage PsA patients.

Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion.

BACKGROUND: Palmoplantar pustular psoriasis (PPPP) is a variant of psoriasis whose the association with psoriatic arthritis (PsA) has been recently described. There is limited evidence regarding how to best reduce palmoplantar pustular psoriasis severity and to maintain remission once achieved. OBJECTIVE: The aim of this study was to elaborate evidence-based recommendations for PPPP treatment supported by a systematic literature review. METHODS: A systematic literature search was carried out in Embase, Medline and Cochrane Library databases from 1980 to February 2013 searching for any trial in patients with PPPP assessing therapeutic interventions not including a systemic biotherapy. The selection of articles was limited to human subjects and English or French languages. RESULTS: Among the 675 articles identified, 29 including one Cochrane review were analysed. The Cochrane review summarised 23 randomised controlled trials (RCTs) in chronic PPPP until February 2003, including 724 patients. The authors concluded that oral retinoid therapy (acitretin), photochemotherapy or combination of both, low dose of ciclosporin or topical corticosteroids under occlusion appeared to be helpful in relieving symptoms of PPPP. Since the publication of this review, 9 open studies on PPPP treatment have been published. Three new studies evaluated the benefits of PUVA on PPPP. They all showed a better efficacy of PUVA compared to UVB therapy. One open study concluded that a retinoid treatment with an arotinoid ethylesther showed a good efficacy. Five prospective studies (level of evidence of 3) assessed Laser Excimer UVB-NB (Excimer 308 nm) in PPPP. The combined analysis of these studies showed that 64% of patients experienced an improvement of 70% at the end of treatment. CONCLUSION: Phototherapy, ciclosporin and topical corticosteroids seem to be able to control PPPP. However, the standard of care for PPPP remains an issue and there is a strong need for reliable RCTs to better define treatment strategies for PPPP.

Is there a psoriasis skin phenotype associated with psoriatic arthritis? Systematic literature review.

Psoriatic arthritis (PsA) is associated with psoriasis with a prevalence varying from 5.94% to 23.9%. The aim of this study was to assess if some psoriatic skin features are associated with a higher risk of PsA. A systematic literature search was carried out from 1980 to January 2013, in the Embase and Pubmed databases, using a combination of keywords including (Psoriasis) AND (PsA). Of the 2746 articles retrieved, 25 references were selected. Meta-analysis was performed when possible. Mean age at psoriasis onset appeared to be similar among patients with skin disease alone and in those with PsA. There was no clinical type of psoriasis specifically associated with PsA, including pustular psoriasis of palms and soles. Nonetheless specific psoriasis localizations were significantly associated with an increased risk of developing PsA in one cohort study: scalp lesions [Hazard Ratio (HR) 3.89 (95% confidence interval (CI):2.18-6.94)] and intergluteal/perianal lesions [HR 2.35 (95%CI:1.32-4.19)]. A similar association was found in two cross-sectional studies. Nail involvement was significantly associated with PsA in the meta-analysis [Odds Ratio (OR) 2.92 (95% CI 2.34-3.64)], particularly onycholysis [OR 2.38 (95% CI 1.74-3.26)]. Moreover, nail psoriasis was also associated with distal interphalangeal joint arthritis. The extent of psoriasis appeared to be associated with PsA in one cohort study [≥3 sites: HR 2.24 (95% CI 1.23-4.08)], one case-control study [body surface area >75%: OR 2.52 (95% CI 1.33-4.75)] and three cross-sectional studies. The meta-analysis suggested a trend for an association between high PASI and PsA risk [mean difference 3.39 (95% CI 0.94-5.83)]. Therefore, psoriasis patients with such clinical features may require a particular attention for early and close detection of PsA during the course of the cutaneous disease.

Symptoms dermatologists should look for in daily practice to improve detection of psoriatic arthritis in psoriasis patients: an expert group consensus.

BACKGROUND: Up to 29% of patients with psoriasis seen by dermatologists have undiagnosed psoriatic arthritis (PsA). As early detection of PsA may be associated with improved joint and skin outcomes, it is essential for dermatologists to improve their ability to diagnose PsA. Skin and nail features of psoriasis associated with PsA are well known to dermatologists but they may feel less confortable assessing other symptoms and they rarely use PsA screening questionnaires. OBJECTIVE: To develop a limited list of clinical signs and symptoms that a dermatologist should be looking for in a psoriasis patient in addition to specific skin features and nail involvement, to improve PsA detection. METHODS: A systematic search was performed in Pubmed, Cochrane and Embase databases to identify clinical key symptoms associated with PsA. It yielded 27 studies in which we extracted a list of clinical signs and symptoms observed in PsA and submitted it to a panel of dermatology experts through a DELPHI selection process. The experts had to determine which minimal set of signs and symptoms dermatologists should look for in daily practice to improve detection of PsA in patients with psoriasis. RESULTS: The four items that received a score higher than 90% in the DELPHI process were finally selected. Those items were as follows: peripheral inflammatory pain (100%), axial inflammatory pain (95.3%), dactylitis (93%), buttock and sciatic pain (90.7%). The remaining items: distal interphalangeal joints (DIPs) involvement (83.7%), Talalgia (79.1%), swollen Achille's tendon (41.9%), costo-chondral involvement (32.6%), uveitis (7%), mouth ulcerations (2.3%), were not retained. CONCLUSION: We propose a set of four items to screen psoriasis patients for psoriatic arthritis for routine clinical use by dermatologists.

Treatment (biotherapy excluded) of psoriatic arthritis: an appraisal of methodological quality of international guidelines.

BACKGROUND: Some international guidelines have been published to provide the best care for patients with psoriatic arthritis (PsA) but little is known about their quality. OBJECTIVE: The primary aim of this study was to examine the quality of guidelines that concern treatment (biotherapy exluded) of PsA. The secondary aim was to review studies published since the publication of the most recent guideline. METHODS: A systematic literature search was carried out from 2007 to February 2013, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including 'Arthritis, Psoriatic/therapy' NOT 'Biological Therapy' OR 'Antibodies, Monoclonal' OR 'Recombinant Fusion Proteins' OR 'tumour necrosis factor-alpha'. The AGREE instrument (Appraisal of Guidelines Research and Evaluation) was used by four reviewers to evaluate the quality of selected guidelines according to the proposed methodology. RESULTS: Of the 518 identified references, six guidelines and two studies were selected. There was considerable variation in the quality of clinical guidelines across the AGREE domains. The least well-addressed domains were 'applicability', 'stakeholder involvement', 'scope and purpose' and 'quality of development', whereas 'editorial independence' and 'clarity and presentation' were less problematic. CONCLUSION: Although guidelines development was of good quality, many of the studies that they included are of poorer quality. This work indicates that the current guidelines can be improved, particularly the stakeholder domain and the applicability domain. The prospective use of the AGREE instrument should improve the guideline quality. More controlled trials should be required but are unlikely to be conducted, given the lack of interest in studying old drugs.

Psoriasis, cardiovascular events, cancer risk and alcohol use: evidence-based recommendations based on systematic review and expert opinion.

The relationship between psoriasis, chronic inflammation, cardiovascular risk and risk of cancer has long been debated. In addition, it has been suggested that alcohol consumption may be a risk factor for psoriasis onset and severity. The aim of this study was to develop evidence-based recommendations on the risk of comorbidities and its management for daily clinical use, focusing on cardiovascular risk, risk of cancer and alcohol use in psoriasis. A scientific committee identified and selected through the Delphi method clinically relevant questions about cardiovascular risk, risk of cancer and alcohol use in psoriasis. To address these questions, a systematic literature search was performed in Medline, Embase and the Cochrane Library databases. Systematic literature reviews including meta-analysis whenever possible were performed. Subsequently, an Expert board meeting involving 39 dermatologists took place to analyse the evidence and to elaborate recommendations on the selected questions. Recommendations were graded according to the Oxford level of evidence grading system. The degree of agreement of these recommendations was assessed on a 10-point scale, as well as their potential impact on daily clinical practice. A total of 3242 articles were identified through the systematic literature searches, among which 110 were included in the systematic reviews. Overall, 12 recommendations were elaborated regarding comorbidities management in psoriasis patients. A moderate increased risk of cardiovascular diseases (CVD), mainly myocardial infarction (MI) [meta-analysis of cohort studies: OR = 1.25 (95% CI 1.03-1.52) and of cross-sectional studies: OR = 1.57 (95% CI 1.08-2.27)], and coronary artery disease (CAD) [meta-analysis of cross-sectional: OR = 1.19 (95% CI 1.14-1.24), of cohort studies: OR = 1.20 (95% CI 1.13-1.27) and of case-control studies: OR = 1.84 (95% CI 1.09-3.09)] was acknowledged. This increased cardiovascular risk requires appropriate prevention measures. There was a lack of substantial evidence that conventional systemic treatment has any effect on cardiovascular risk although methotrexate might be cardioprotective. An increased risk of solid cancer potentially associated with smoking and alcohol use was identified. The role of systemic treatment on cancer risk could not be assessed thoroughly due to limited long-term follow-up data. A higher risk of non-melanoma skin cancers especially squamous cell carcinoma was shown, mainly due to previous exposure to oral 8-methoxypsoralen-ultraviolet-A (PUVA), ciclosporin and possibly methotrexate. No firm conclusion could be drawn regarding alcohol and psoriasis due to high variability in alcohol usage assessment in studies. Clinical experience suggests higher alcohol consumption among psoriasis patients compared to the general population. The mean expert participants' level of agreement on these recommendations varied from 6.8 to 9.4. These 12 recommendations are evidence based and supported by a panel of expert dermatologists. The next step is now to disseminate these recommendations to dermatologists who did not participate in the Expert board meeting and to assess their opinion about the recommendations.

Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.

UNLABELLED: Previous epidemiological studies have demonstrated a high prevalence of cardiovascular (CV) risk factors in psoriasis patients, including metabolic syndrome, cigarette smoking, obesity, hypertension, diabetes mellitus, insulin resistance and dyslipidaemia. An increase in CV morbidity and mortality attributable to psoriasis is still under question. PRIMARY OBJECTIVE: to assess CV morbidity and mortality in psoriasis and psoriatic arthritis (PsA) including stroke, coronary artery disease, myocardial infarction (MI) and peripheral artery disease. SECONDARY OBJECTIVES: to assess if psoriasis per se is an independent CV risk factor and if psoriasis severity is a predictor of CV risk. We also evaluated the effect of conventional systemic treatments for psoriasis on CV mortality. A systematic literature search was carried out from 1980 to December 2011, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including (Psoriasis) OR (Psoriatic arthritis) AND (Myocardial infarction) OR (Coronaropathy) OR (Stroke) OR (Cardiovascular) AND (Methotrexate) AND (Ciclosporin) AND (Retinoids). Of the 929 identified references, 33 observational studies evaluating the rates of cardiovascular events (CVE) in patients with psoriasis and PsA compared with controls were selected. Meta-analysis of both cohort and cross-sectional studies showed an increased risk of MI with Odds Ratio (OR) of 1.25 (95% CI 1.03-1.52) and 1.57 (95% CI 1.08-2.27) in psoriasis and PsA, respectively, compared with the general population. The risk of MI was more pronounced for patients having severe psoriasis and for patients with psoriasis of early onset. It remained significantly elevated after controlling for major CV risk factors. The meta-analysis identified a small, but significant association between psoriasis, PsA and coronary artery disease with an OR between 1.19 (95% CI 1.14-1.24) for cross-sectional studies, 1.20 (95% CI 1.13-1.27) for cohort studies and 1.84 (95% CI 1.09-3.09) for case-control studies. The risk of coronary artery disease seemed to be more pronounced in patients with severe psoriasis and in patients with psoriasis of early onset. The meta-analysis assessing the risk of stroke gave inconclusive results: analysis of cross-sectional studies suggested that psoriasis patients had a slightly higher risk of stroke with an OR of 1.14 (95% CI 1.08-1.99), whereas the meta-analysis of cohort studies failed to show an association. There was also an increased risk of peripheral artery disease in psoriasis. No significant increased risk of CV mortality could be shown for both psoriasis and PsA patients. The use of methotrexate was associated with a reduced incidence of cardiovascular disease in two studies. The use of etretinate was associated with a reduction of CV mortality in one study. Potential selection bias such as the 'healthy user effect' prevents from drawing definite conclusions. There may be a small, but significant increased risk of CVE, but not of CV mortality in psoriasis and PsA patients. The psoriasis attributable risk remains difficult to assess due to confounding factors. The moderate quality of CV risk factors reporting in studies should be acknowledged. In addition, heterogeneity in study design, outcome definition and assessment represent major limitations. Nevertheless, screening and management of CV risk factors are important in psoriasis.