The Patient-Oriented Scoring of Atopic Dermatitis and SCORAD in young children: New data on interpretability and clinical usefulness.

BACKGROUND: There is limited data about the clinical meaningfulness of the Scoring of Atopic Dermatitis (SCORAD) and Patient-Oriented SCORAD (PO-SCORAD), particularly in children with mild-to-moderate AD. Regular use of patient-reported outcomes, may deliver more accurate information about the overall health status of AD patients than routine but sparse physician assessments. OBJECTIVE: To confirm the correlation between SCORAD, PO-SCORAD, Patient-Oriented Eczema Measure (POEM) and Investigator's Global Assessment (IGA). To evaluate the interpretability and clinical usefulness of the SCORAD and PO-SCORAD scores in children. METHODS: Data were drawn from a 12-week randomized controlled trial in 335 children, aged 2-6 years, with mainly mild-to-moderate AD. Investigators captured SCORAD and IGA at each study visit. Parents used PO-SCORAD twice-weekly, and POEM once-weekly. RESULTS: There were strong correlations between PO-SCORAD and SCORAD (r = 0.874), PO-SCORAD and POEM (0.734) and PO-SCORAD and IGA (0.613). The best fit ('k' statistic: 0.68) between SCORAD and IGA classes was noted for the following SCORAD categories: <12 (clear/almost clear); 12-25 (mild); and ≥25 (moderate/severe). PO-SCORAD area under the curve over 8 weeks was significantly greater than that of SCORAD (p = 0.0002), giving a better estimate of disease severity between visits. Patients with a flare within the next 7 days had significantly higher PO-SCORAD scores 7 days before the flare (p < 0.0001). Moderate erythema was the most significant flare predictor (p < 0.0001). CONCLUSION: PO-SCORAD is robust and reliable and appears to warrant far greater utility in routine clinical practice than other scores. PO-SCORAD, used twice-weekly, may improve the management of patients with AD.

A battery of tandem mass spectrometry assays with stable isotope-dilution for the quantification of 15 anti-tuberculosis drugs and two metabolites in patients with susceptible-, multidrug-resistant- and extensively drug-resistant tuberculosis.

OBJECTIVE: Anti-tuberculosis (antiTB) drugs are characterized by an important inter-interindividual pharmacokinetic variability poorly predictable from individual patients' characteristics. Therapeutic drug monitoring (TDM) may therefore be beneficial for patients with Mycobacterium tuberculosis infection, especially for the management of multidrug/extensively drug resistant- (MDR/XDR)-TB. Our objective was to develop robust HPLC-MS/MS methods for plasma quantification of 15 antiTB drugs and 2 metabolites, namely rifampicin, isoniazid plus N-acetyl-isoniazid, pyrazinamide, ethambutol (the conventional quadritherapy for susceptible TB) as well as combination of agents against MDR/XDR-TB: bedaquiline, clofazimine, delamanid and its metabolite M1, levofloxacin, linezolid, moxifloxacin, pretomanid, rifabutin, rifapentine, sutezolid, and cycloserine. METHODS: Plasma protein precipitation was used for all analytes except cycloserine, which was analyzed separately after derivatization with benzoyl chloride. AntiTB quadritherapy drugs (Pool1) were separated by Hydrophilic Interaction Liquid Chromatography (column Xbridge BEH Amide, 2.1 × 150 mm, 2.5 µm, Waters®) while MDR/XDR-TB agents (Pool 2) and cycloserine (as benzoyl derivative) were analyzed by reverse phase chromatography on a column XSelect HSS T3, 2.1 × 75 mm, 3.5 µm (Waters®). All runs last <7 min. Quantification was performed by selected reaction monitoring electrospray tandem mass spectrometry, using stable isotopically labelled internal standards. RESULTS: The method covers the clinically relevant plasma levels and was extensively validated based on FDA recommendations, with intra- and inter-assay precision (CV) < 15% over the validated ranges. Application of the method is illustrated by examples of TDM for two patients treated for drug-susceptible- and MDR-TB. CONCLUSION: Such convenient extraction methods and the use of stable isotope-labelled drugs as internal standards provide an accurate and precise quantification of plasma concentrations of all major clinically-used antiTB drugs regimens and is optimally suited for clinically efficient TDM against tuberculosis.

Position statement on the role of nurses in therapeutic patient education in atopic dermatitis.

In chronic skin diseases such as atopic dermatitis (AD), therapeutic failure due to poor patient adherence to treatment is commonly reported. Therapeutic patient education (TPE) is an approach to improve self-management and adherence. Several studies demonstrated that TPE programmes have positive effects on disease management resulting in decreased disease severity and improved quality of life in AD patients. Various healthcare professionals (dermatologists, nurses, psychologists, dieticians) have been involved. TPE performed by trained dermatology nurses are highly efficient and improve various health-related outcomes. The aim of this position paper is to analyse the aims, modalities and efficacy of TPE in AD, to identify specific roles of dermatology nurses, to assess qualification requirements, and to propose practical recommendations. Potential activities of nurses in ongoing and future TPE programmes for AD patients will be discussed.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

A position paper on the management of itch and pain in atopic dermatitis from the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force.

Atopic dermatitis (AD) is a disease that can have a high impact on quality of life, especially due to itch and skin pain. This paper utilizes expertise from members of the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force to review the epidemiology, pathophysiology and exacerbating factors of itch and pain in atopic dermatitis. General principles of treatment are provided, as well as a more detailed evaluation of topical and systemic therapies. Educational and psychological approaches to itch and pain in atopic dermatitis are proposed, along with expert recommendations for the management of itch and pain in atopic dermatitis.

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children.

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Whole-genome sequencing for rapid, reliable and routine investigation of Mycobacterium tuberculosis transmission in local communities.

Contact investigations following the diagnosis of active tuberculosis (TB) are paramount for the control of the disease. Epidemiological data are very powerful for contact tracing but might be delayed and/or difficult to integrate, especially in the setting of multiple contact-tracing investigations. The aim of this study was to address the added-value of whole-genome sequencing (WGS) to routine local TB surveillance systems. From November 2016 to July 2017, the local TB surveillance system identified three clusters that could constitute a unique larger outbreak. Epidemiological and clinical information were integrated with WGS genotyping data of Mycobacterium tuberculosis strains obtained using a simple DNA extraction method coupled with sequencing using an Illumina MiSeq platform and an in-house bioinformatics pipeline for single nucleotide polymorphism (SNP) analysis. Epidemiological investigations identified three putative TB clusters potentially interrelated including eight patients with active TB. Seven M. tuberculosis isolates were available and analysed by WGS. Using a 5-SNP threshold to define recent transmission, WGS-based genotyping supported the occurrence of the three clusters as well as a link between clusters 1 and 2 (SNP ≤1), constituting a larger outbreak. This outbreak was clearly delineated by refuting a potential link with the third cluster (SNP >500). Genotyping data did not support the belonging of patient 7 to any studied cluster. This study illustrates the usefulness of WGS genotyping for routine TB surveillance systems in local communities to rapidly confirm or disprove epidemiological hypotheses and delineate TB clusters, especially in the context of multiple contact-tracing investigations.

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period.

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

The rapid molecular test Xpert MTB/RIF ultra: towards improved tuberculosis diagnosis and rifampicin resistance detection.

BACKGROUND: Tuberculosis diagnosis has dramatically improved since the introduction of the rapid molecular test Xpert MTB/RIF (Xpert) detecting M. tuberculosis and rifampicin resistance directly from clinical specimens, therefore shortening the turnaround time, reducing patient's isolation period and decreasing the time to start anti-TB drugs. The new version, Xpert MTB/RIF Ultra (Ultra), displays a higher sensitivity and an improved rifampicin resistance detection. Both tests have been endorsed by the World Health Organisation. AIMS: Xpert and Ultra rapidly became widespread and paved the way for new approaches and new paradigms as well as for the development of molecular point-of-care tests (POCTs). In this narrative review, we aimed to address their performance in the diagnosis of tuberculosis and to discuss the expectations of these tests as well as their limits and the unmet needs. SOURCES: Peer-reviewed publications addressing the diagnostic performance of Ultra and Xpert. CONTENT: We focused on publications that evaluated the performance of Ultra and Xpert on the same group of patients or the same set of specimens in different tuberculosis-burden settings. IMPLICATIONS: The studies published so far reported an increased sensitivity of Ultra when compared to Xpert, which represents a benefit for tuberculosis diagnosis. The fact that such a sensitive assay cannot distinguish between alive and dead bacilli emphasizes that caution should be exercised regarding indications and interpretation of results. Additional studies are needed to determine the true performance for the diagnosis of extrapulmonary tuberculosis because of the great diversity of the specimens.

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Topical corticosteroid phobia in atopic dermatitis: International feasibility study of the TOPICOP score.

BACKGROUND: Adherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries. METHODS: This was a prospective multicentre feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire. RESULTS: A total of 1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear, and 79% reported that it took less than 5 minutes to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7%±20.5. Mean TOPICOP subscores were 37.0±22.8% for knowledge and beliefs, 54.7±27.8% for fears and 50.1±29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country. CONCLUSIONS: The TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.

Added value of molecular assay Xpert MTB/RIF compared to sputum smear microscopy to assess the risk of tuberculosis transmission in a low-prevalence country.

Airborne precautions are required at hospital admission for patients with suspected pulmonary tuberculosis. The isolation is maintained until 3 serially collected sputum smears are acid-fast bacilli negative, a time- and labor-intensive method with limited sensitivity and specificity, which has a great impact on patient flow management. We evaluated the possibility of replacing the result of microscopy by the semiquantitative result of the molecular point-of-care test Xpert MTB/RIF to assess patients' transmission risk to quickly guide airborne isolation decisions in low-endemic countries. The performance of the Xpert MTB/RIF, used as a first-line test, was compared to the results of microscopy for specimens (n=242) collected from May 2010 to December 2014 in Lausanne, Switzerland. The sensitivity and specificity of Xpert MTB/RIF were 91.5% (65/71) and 99.6% (170/171), respectively, vs. 64.8% (46/71) and 94.2% (161/171) for microscopy. Samples with negative Xpert MTB/RIF were all smear negative for Mycobacterium tuberculosis (negative predictive value, 100%). The semiquantitative results of Xpert MTB/RIF-high, medium, low or very low-were found to correlate with acid-fast bacilli detection: positive predictive value of 100% (6/6), 96.5% (27/28), 52.2% (12/23) and 11.1% (1/9) respectively. Finally, when including clinical criteria, we identified 11 smear-negative but Xpert MTB/RIF-positive patients with a significant transmission potential. In conclusion, our data support the introduction of an Xpert MTB/RIF-based strategy as a replacement of smear microscopy for a faster and more accurate management of tuberculosis patients' transmission risk in a low-prevalence country.

Influence of meteorological data on sun tolerance in patients with erythropoietic protoporphyria in France.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare metabolic disorder, characterized by photosensitivity, caused by errors of the haem biosynthetic pathway. Avoidance of sun exposure is recommended; however, some patients suggested a paradoxical improvement of symptoms when they move to sunny areas. OBJECTIVES: In a national French study, we sought to investigate the influence of sun exposure on EPP symptoms. MATERIALS AND METHODS: We used a national transversal observational study by questionnaire. Patients were selected from the national record of the Centre Français des Porphyries (French Porphyrias referral centre). Sun exposure level by geographic area was assessed using climate data provided by the French national meteorological service (Météo France). RESULTS: Eighty-nine patients were included. We notably observed that 40% of patients declared an improvement in their tolerance of sun exposure after repeated sun exposures. In the more sunny areas, the intensity of the pain was lower (r = -0·26) and the duration of the sun exposure responsible for flares was longer (r = 0·39) than in the areas that were less sunny (P < 0·05). CONCLUSIONS: This study proposes a benefit of natural progressive sun exposure for patients with EPP.

Extent of misconceptions, negative prejudices and discriminatory behaviour to psoriasis patients in France.

BACKGROUND: The perception of stigmatization of patients with psoriasis is largely due to misconceptions and negative prejudice about this skin disease. 'Uneducated' judgments can give rise to discriminatory behaviours. OBJECTIVE: Evaluate the prevalence, in France, of misconceptions, negative prejudice and discriminatory behaviour towards psoriasis patients. METHODS: Online survey conducted in June 2011, aimed at 1005 persons aged 16-64 years, representative of the French population. The representativeness of the sample was ensured by quota methodology (gender, age, occupation of the interviewed person) after stratification by region and location category. The respondents were asked to respond to a questionnaire on their knowledge of psoriasis, their attitude and main feelings/perceptions towards psoriasis patients. RESULTS: About 62.4% of respondents recognize a lack of information about psoriasis and 19.7% have misconceptions about this disease. About 16.5% believe that psoriasis is contagious, 6.8% believe this skin disease is related to personal hygiene and 3.2% believe that it affects more people with low personal hygiene. About 50.0% of respondents show discriminatory behaviour towards psoriasis patients, reflected by reluctance to maintain friendship ties/a relationship of friendliness (7.6%), to have lunch or dinner with a person with visible manifestations (17.9%), to give a kiss on the cheek in greeting (29.7%), to shake hands (28.8%) and to have sexual relations/intercourse (44.1%). Patients with negative prejudice about the psoriasis frequently have misconceptions towards psoriasis patients. About 52.8% of respondents do not know anyone with psoriasis. Socio-demographic indicators such as gender, education level and rural or urban way of life are not associated with an increased prevalence of misconceptions and/or discriminatory behaviour. CONCLUSION: The lack of knowledge about psoriasis in France is important. There is an urgent need to strengthen information campaigns about psoriasis intended for the General Public.

Early symptoms and long-term clinical outcomes of distal limb's cutaneous arterio-venous malformations: a retrospective multicentre study of 19 adult patients.

INTRODUCTION: Cutaneous arterio-venous malformations (AVM) are high-flow vascular malformations made up of a direct link between arteries and veins without intermediary capillary space. 'Distal limb's AVM', which mean involving hands or feet, are rare and their functional prognosis is often poor. Little is known about their early clinical symptoms. The objectives of this study were to identify early clinical symptoms of distal limb's cutaneous AVMs and to determine their long-term clinical outcome. METHODS: A retrospective study was carried out including adult patients who had distal limb's AVM, who were followed up between January 2000 and November 2013 in two regional tertiary care centres. The information was collected from patients' clinical records and completed by a structured telephone questionnaire. RESULTS: Nineteen patients were included in the study: four (21%) with foot AVM and 15 (79%) with hand AVM. The first clinical symptoms were as follows: swelling (47%), pain (47%), one or several venous dilatations (37%) and rarely abnormal skin colour, hyperthermia and pulsating sensation. The median diagnosis delay was 9 years after the onset of first manifestations. Amongst the 17 patients who underwent a treatment, 53% had embolotherapy session(s), 12% surgery and 35% had both. After an average follow-up of 57.6 months, 31% of the 13 patients contacted who were receiving treatment were in complete remission; 31% had partial remission; 15% had relapse after initial improvement and 23% had treatment failure. Overall, 74% of patients had a serious development of the AVM: 37% had digital or hand amputation, and 42% remained symptomatic and/or unstable. CONCLUSION: This study suggests that initial manifestations of distal limb's AVMs are discreet and non-specific, leading to a diagnosis delay of about 10 years, with poor prognosis. Doctors should evoke the diagnosis earlier, when these symptoms are shown: pain and/or swelling, sometimes with a large vein.