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Sleep disturbance is one of the most frequent and clinically consequential problems in atopic dermatitis. Current evidence indicates that it is not merely a secondary symptom of pruritus but a complex disease domain associated with higher inflammatory activity, sleep fragmentation, impaired quality of life, daytime fatigue, and anxiety or depressive symptoms. The best established pathway runs from active dermatitis to impaired sleep: nocturnal itch, scratching, pain, xerosis, heat sensation, and epidermal barrier dysfunction promote repeated awakenings and difficulty maintaining sleep. However, growing mechanistic and epidemiological evidence supports a bidirectional model. Insufficient, fragmented, or circadian-misaligned sleep may impair barrier repair, increase transepidermal water loss, alter neuroimmune itch signaling, and perpetuate behavioral amplification through scratching, stress, and reduced treatment adherence. This narrative review synthesizes recent literature on the epidemiology, sleep phenotype, biological mechanisms, assessment tools, therapeutic evidence, and research gaps linking sleep disturbance with aggravation of atopic dermatitis. The clinical implication is practical: sleep should be assessed as a core treatment outcome in atopic dermatitis, and persistent sleep disruption should be interpreted as a marker of undercontrolled disease and a potential amplifier of cutaneous inflammation.

To characterise immunoglobulin A (IgA) levels in the faeces and saliva of dogs with canine atopic dermatitis (CAD) and healthy breed matched controls. Dogs with canine atopic dermatitis were recruited based on history, clinical examination and diagnostic testing where appropriate. Control dogs were over 4 years of age with no history of skin disease. Saliva samples were obtained using chewable synthetic swabs with saliva extracted by centrifugation. Faecal samples were collected from the ground before homogenisation in phosphate buffered saline and centrifugation to extract faecal supernatant. Total immunoglobulin A in saliva and faecal supernatants was measured using a commercial dog immunoglobulin A ELISA kit. Immunoglobulin A concentration was interpolated from a six-point standard curve. Mann-Whitney tests were performed to compare immunoglobulin A concentrations between cases and controls. Mean ranked faecal immunoglobulin A was significantly lower in dogs with canine atopic dermatitis than controls (difference between medians 0.803 g/L, 95% CI 0.064 to 1.721). There was no significant difference in mean ranked salivary immunoglobulin A between the groups (difference between medians 0.108 g/L). Faecal immunoglobulin A and salivary immunoglobulin A were not correlated. There were no dogs in either group with both low faecal and low salivary immunoglobulin A suggestive of selective immunoglobulin A deficiency. This study builds on existing evidence that low immunoglobulin A is associated with canine atopic dermatitis. Further work is required to determine the significance of low faecal immunoglobulin A in the development of tolerance or hypersensitivity to food and environmental allergens which may inform strategies for interventions in high-risk breeds.

The expanding use of biologic and oral targeted therapies has transformed the management of psoriasis and atopic dermatitis. These agents are increasingly prescribed to patients with current malignancy, a history of malignancy or an increased cancer risk, populations typically excluded from clinical trials. In the absence of robust long-term safety data, clinicians often rely on real-world evidence to inform treatment decisions. To review the evidence regarding malignancy risk associated with biologic and oral targeted therapies used in psoriasis and atopic dermatitis and to provide expert consensus recommendations for patients with current malignancy, previous malignancy or increased risk of malignancy. We describe the physiological roles of key immune pathways targeted in psoriasis and atopic dermatitis, as well as in cancer immunosurveillance, tumour progression and immune escape. We then summarize evidence from randomized controlled trials regarding the risk of de novo malignancy, followed by a synthesis of real-world data addressing cancer recurrence and progression in patients treated with biologic and oral targeted therapies. Available evidence suggests that the overall malignancy risk associated with most biologic and oral targeted therapies used in psoriasis and atopic dermatitis is low, although differences between therapeutic classes may exist. Real-world data remain limited for several therapeutic classes and in patients with active or previous malignancy. Based on the available evidence, we present consensus-based recommendations developed by a multidisciplinary expert panel convened by the Skin Inflammation & Psoriasis International Network-Fondation René Touraine (SPIN-FRT). These recommendations aim to support treatment decisions by balancing disease control with potential cancer-related risks while highlighting key evidence gaps.

Atopic dermatitis is commonly associated with depressive symptoms and fatigue, which significantly impact quality of life. While clinical trials suggest beneficial effects of dupilumab on mental health, real-world evidence remains limited. This longitudinal cohort study analysed data from adult patients treated with dupilumab in the TREATgermany registry. Subgroups were defined by baseline Center for Epidemiologic Studies Depression Scale (CES D) scores ≥16 (clinically significant depressive symptoms) and Fatigue Severity Scale (FSS) scores >4 (significant fatigue). Clinical severity (Eczema Area and Severity Index [EASI], objective Scoring Atopic Dermatitis [oSCORAD]), quality of life (DLQI), psychological symptoms, treatment needs and benefits (PNQ, PBI) and drug survival were assessed over 12 months. Among 633 patients, those with elevated baseline CES-D (n=309) or FSS (n=281) scores reported greater disease burden measured by DLQI, while EASI and oSCORAD did not differ between subgroups. Both CES-D and FSS scores decreased markedly within the first 3 months. Sleep and social functioning needs were more frequently reported in high-burden subgroups and more often fulfilled after 12 months. Drug survival was comparable across subgroups. Dupilumab treatment was associated with significant improvements in depressive symptoms, fatigue and skin severity. Patients with higher baseline mental health burden showed comparable improvements in patient relevant domains, supporting the broad relevance of dupilumab in real-world atopic dermatitis care.

The purpose of study is to characterize the skin microbiome profile of breast cancer patients before and during radiation therapy, and evaluate the relationship between the microbiome profile and the severity of acute radiation dermatitis (aRD). In this observational, single-center, single-arm study, breast cancer patients received RT at Rambam Health Care Campus from November 2020 to July 2021. Skin assessments and skin microbiome samples were collected from all patients before, weekly during RT, after completion of the treatment. The outcome measures were: aRD grade, skin microbiome composition at baseline and during RT. 640 skin samples were collected from 86 patients, bacterial DNA was extracted, and 16S rDNA was amplified and sequenced.At mid-treatment, the bacterial family Clostridiaceae was unique to patients later diagnosed with moderate/severe acute dermatitis, and present in 30% of the samples (p-value = 0.002038). An unknown species of Anaerococcus, designated Anaerococcus US436, was unique to patients in the moderate/severe aRD group at mid-treatment (21.67% in this group, p-value = 0.002038).To increase sample size and reduce noise, we collected all treated samples from all time points and compared the microbiome composition between the groups of dermatitis severity. The Clostridiaceae family and Clostridium genus remained significantly enriched in the moderate/severe group (p-value = 0.002095 and 0.004269, respectively), as well as the Anaerococcus genus and its unknown species (p-value = 0.001825 and 0.007104, respectively).The treated samples for each patient were summed up, and each bacterium was examined for at least one appearance per patient during the treatment. Granulicatella elegans was enriched in the moderate/severe group (p-value = 0.000512), and Bacillus thuringiensis was enriched in the mild group (p-value = 0.000595). A bacterial composition associated with moderate/severe aRD was identified: Clostridium, Anaerococcus US436, and Granulicatella elegans.

Atopic dermatitis (AD) (also known as eczema) is a long-term skin disease affecting 13% of children in the United States. These children often have other inflammatory conditions, including asthma, hay fever (allergic rhinitis), and food allergies. Currently, little is known about the use of healthcare resources (hospital visits and admissions and emergency room/urgent care visits) and the associated healthcare costs in children with AD. In this study, we looked at the treatment received for AD, use of healthcare, and associated costs in patients with AD in the United States aged between 6 months and 6 years who were treated for their AD. Patients were split into 3 groups based on received treatments: low-potency topical treatment (LTT) used to treat mild AD, medium-to-high-potency topical treatment (MHTT) for moderate AD, and systemic treatments (ST) for severe AD. Of 23,098 patients studied, 5,452 received LTT, 6,778 received MHTT, and 10,868 received ST. The use of healthcare was similar in children treated with LTT and MHTT, but higher in children treated with ST, including hospital admissions and emergency room/urgent care visits. Healthcare costs per patient were higher in AD patients treated with MHTT and ST, compared to LTT, primarily due to medical expenses. Children had a high number of AD-related inflammatory conditions, with highest burden in the ST group The study showed that patients treated with ST had higher healthcare utilization and costs, suggesting a higher disease burden. To assess healthcare resource utilization and healthcare costs in this patient group. This retrospective, 1-year, cross-sectional, observational study (July 2016-December 2019) of US patients used data from the IQVIA PharMetrics Plus Database. Patients were assigned to cohorts based on treatments received: LTTs, MHTTs, and STs. Overall, 23,098 patients were included (LTT: 5452; MHTT: 6778; ST: 10,868). All-cause health care resource utilization was generally similar for the MHTT and LTT cohorts, but was higher in the ST cohort, including inpatient admissions (1.5% and 1.5% vs 6.5%) and emergency room/urgent care visits (22.0% and 22.0% vs 37.5%). The mean all-cause healthcare costs per patient were higher in the ST and MHTT cohorts vs LTT cohort ($9272.24 and $5671.60 vs $5249.69), with the majority being medical costs ($8135.93 and $4669.39 vs $4221.56). Possibility of selection bias and misclassification if treatments were used for conditions other than atopic dermatitis; exclusion of patients using over-the-counter treatments; neglecting out-of-pocket costs. Patients receiving ST had higher healthcare resource utilization and costs than patients receiving LTT, with medical costs being the main driver.

Atopic dermatitis (AD) features impaired skin barrier, elevated cutaneous pH, and Staphylococcus aureus overcolonization. Restoring acidic skin pH while suppressing microbial overgrowth represents a promising non-steroidal strategy. To develop a copper-based acidic hydrogel and evaluate its properties, antimicrobial activity, efficacy, and safety. A hydrogel with 0.115% copper ions was prepared from basic copper carbonate, acetic acid (6% w/w), and xanthan gum, formulated at a final pH of ∼3.2, and characterized by rheology and stability testing. Antimicrobial activity was evaluated by a quantitative carrier test against S. aureus, E. coli, and C. albicans. Efficacy was assessed in DNFB-induced AD-like BALB/c mice. Dermal safety was examined in a 14-day study in rabbits. The hydrogel showed gel-like behavior (G' > G″) with 94.6% structural recovery and remained stable over 23 months. It achieved >98% killing of all pathogens within 5 min and >99.6% within 10 min. In mice, treatment dose-dependently reduced ear swelling and dermatitis scores, attenuated epidermal hyperplasia, and decreased mast cell infiltration. In rabbits, only mild, reversible local irritation occurred, without systemic toxicity. This copper-based acidic hydrogel exhibits potent broad-spectrum antimicrobial activity, ameliorates AD-like lesions, and shows a favorable short-term dermal safety profile, supporting further development as a non-steroidal topical option for AD.

A 49-year-old female presented with redness and scaling of scalp of 2 years duration. It was associated with photosensitivity and difficulty getting up from squatting position since 4 months. Written informed consent was obtained from the patient who agreed to take part in the study. Clinical examination revealed diffuse uniform erythema affecting scalp and its margins at forehead, temples and posterior aspect of neck. Cite this article as: Das P., Bhatnagar A, Sharma S, et al. Seborrheic dermatitis-like presentation of dermatomyositis. Eur J Rheumatol. 13(1), 0009, doi: 10.5152/eurjrheum.2026.25009.

Dupilumab is effective for moderate-to-severe atopic dermatitis (AD), but sustained disease control after treatment discontinuation remains challenging. House dust mite allergen immunotherapy (HDM-AIT) may provide disease-modifying effects in sensitized patients, but the added value of combining HDM-AIT with dupilumab remains unclear. To evaluate the efficacy and safety of dupilumab combined with HDM-AIT versus dupilumab monotherapy in patients with AD. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to April 21, 2026. Randomized controlled trials and comparative observational studies evaluating dupilumab plus HDM-AIT versus dupilumab alone were included. Disease severity assessed by EASI or SCORAD was pooled using standardized mean differences (SMDs), Dermatology Life Quality Index (DLQI) using mean differences, and adverse events using risk ratios. Random-effects models were applied. The certainty of evidence was assessed using the GRADE approach. Four studies involving 138 patients were included, comprising one randomized controlled trial and three comparative observational studies. Combination therapy showed no significant improvement in disease severity at 6 months (SMD = -0.02, 95% CI -0.41 to 0.36; I2 = 0%) or 12 months (SMD = 0.53, 95% CI -1.10 to 2.16; I2 = 93%). At 18 months, the pooled estimate suggested a possible benefit of combination therapy for disease severity, although the certainty of evidence was very low (SMD = -0.96, 95% CI -1.76 to -0.17; I2 = 61%), although evidence was limited. At the follow-up closest to 30 months, the effect favored combination therapy but was not significant (SMD = -1.16, 95% CI -2.56 to 0.24; I2 = 87%). No significant differences were observed in DLQI, overall adverse events, or ocular adverse events. Current evidence regarding dupilumab combined with HDM-AIT for AD remains limited and inconclusive. Although an exploratory signal of improved disease severity was observed at 18 months, the available data did not demonstrate a statistically significant difference in adverse events, and the certainty of evidence was very low for all evaluated outcomes. Further adequately powered randomized controlled trials with standardized protocols, outcome definitions, and long-term follow-up are needed.

Infective endocarditis (IE) is a rare, life-threatening infection of the cardiac endocardium caused by bacterial seeding. On the other hand, atopic dermatitis (AD) is a common inflammatory skin condition that disrupts the epidermal barrier, increasing susceptibility to Staphylococcus aureus colonisation and recurrent bacteraemia. This provides a biologically plausible bridge to IE, which we explore in this current literature review. MEDLINE, Embase and CENTRAL were searched from inception to 7 April 2025. Sixteen studies were included - 15 case reports and one retrospective cohort study - which were grouped into three categories: well-controlled AD with no predisposing risk factors, AD with predisposing risk factors, and uncontrolled AD or alternative AD management. This review is made up of 24 patients with IE secondary to AD. Of the 16 studies, nine originated from Japan. Mean age was 29.6 years (range 15-42 years), which is significantly younger than classic IE cohorts (mean 60.0 years). Staph. aureus accounted for 23/24 patients, and the mitral valve was affected in 18/24 cases. In terms of patient outcomes, all but one patient survived, but valve surgery was necessary in 20/24 patients. In conclusion, AD-related IE shows a distinct pattern: younger patients, Staph. aureus dominance and mitral valve involvement requiring mitral valve surgery in the majority. This potential link appears to be under-recognised, hence, greater cross-speciality awareness and rigorous AD control for those at high risk is recommended. The heavy Japanese skew in the literature highlights the need for broader case documentation in other regions to confirm this link across different patient demographics.

Atopic dermatitis (AD) is characterized by substantial clinical heterogeneity. Global severity is typically assessed using scores such as the POEM; however, lesion localization -- particularly on the face -- may generate psychosocial consequences partly independent of overall disease severity. This cross-sectional observational study (VISEABLE) included 1,400 French adults with physician-confirmed AD. Severity was measured using the POEM (Clear/Almost Clear: 0-7 vs. Moderate-severe: &#x2265;8) and facial involvement using the BoFA (0-109; threshold=36, population median). Six phenotypes were defined through a 2&#xd7;3 combination. The POEM and BoFA correlation was moderate (r=0.365; &#x3c1;=0.389; p<0.001). Phenotype Ph3 (Clear/Almost Clear POEM / Severe facial involvement, n=58) exhibited stigmatization scores (PUSH-d=21.93) and life trajectory impact (DLLIM=14.76) not significantly different from Ph4 (Moderate-severe POEM / No facial involvement, n=527; p>0.25 for all comparisons). In multiple regression analysis restricted to patients with facial involvement, BoFA was the dominant independent predictor of stigmatization (&#x3b2;=11.44, p<0.001; partial R&#xb2;=46.2 %; overall R&#xb2;=0.532), superseding POEM (p=0.076, ns; partial R&#xb2;=0.6%). Mild eczema with severe facial involvement generates a psychosocial burden comparable to that of moderate-to-severe eczema without facial involvement. Systematic BoFA assessment is essential in all patients with AD.

Early-stage mycosis fungoides (MF) often presents diagnostic challenges because of its clinical overlap with atopic dermatitis (AD). In clinical practice, we encountered a subset of patients with severe AD who fulfilled the MF diagnostic criteria yet remained clinically indistinguishable from AD and presented refractoriness to advanced therapies. We termed this ambiguous entity "mycosis fungoides-like AD" (mfAD) and sought to determine whether it represents malignant transformation or a distinct inflammatory endotype of AD. Skin biopsies were obtained from 7 patients with AD and 11 patients with mfAD. We performed paired single-cell RNA sequencing and single-cell T-cell receptor sequencing analyses. Publicly available MF and AD datasets were integrated for comparative analysis. Spatial transcriptomic profiling was used to contextualize single-cell findings within the tissue architecture. Comparative transcriptomic analysis revealed that T cells in mfAD were aligned with those in AD and lacked genomic instability. High-resolution profiling showed that mfAD was characterized by oligoclonal Th22 expansion rather than a single dominant malignant clone. Notably, all patients with mfAD achieved rapid clinical remission with selective JAK1 inhibition, indicating the therapeutic response characteristics of inflammatory dermatoses. Our findings demonstrate that mfAD is not a true malignancy, but rather a Th22-driven inflammatory endotype of AD. These results redefine mfAD as an inflammatory subtype within the AD spectrum, providing a mechanistic explanation for both the "pseudo-monoclonality" that leads to MF misdiagnosis and the failure of dupilumab. This study establishes a rationale for the use of JAK inhibitors in precision medicine for this patient population.

Psoriasis (PsO) is a chronic, relapsing inflammatory skin disease. While targeted biologics have improved outcomes, limitations in long-term remission and safety concerns underscore the urgent need for cost-effective, safe, and potent topical therapies. Here, we investigated the therapeutic potential of Ginkgolide A (GA) for mild-to-moderate PsO. To maximize local efficacy and circumvent first-pass metabolism, we formulated a GA oily solution for topical administration. This administration of GA effectively alleviated IMQ-induced psoriasis-like dermatitis in mice. Furthermore, safety assessments confirmed that this topical approach is well-tolerated with no obvious toxicity under the tested conditions. Mechanistically, GA directly suppressed M1 macrophage polarization, as evidenced by reduced pro-inflammatory cytokine production (TNF-&#x3b1;, IL-6, IL-1&#x3b2;). Time-course signaling analysis revealed that GA concurrently inhibits the PI3K-AKT axis, with mTOR, JNK and ERK being unaffected. In conclusion, our findings position the GA oily solution as a promising, cost-effective, and potent topical candidate for psoriasis, addressing a persistent clinical gap while offering translational implications for other related immune-mediated diseases.

"Special," "sensitive," and "difficult-to-treat" areas are frequently used interchangeably in atopic dermatitis despite describing distinct clinical constructs. Sensitive sites reflect disproportionate psychosocial and functional vulnerability, whereas difficult-to-treat areas denote therapeutic refractoriness. This distinction is clinically relevant because involvement of these locations may support consideration of systemic therapy independently of the Eczema Area and Severity Index (EASI) score or body surface area. Precise terminology should guide, rather than obscure, therapeutic decision-making.

Atopic dermatitis (AD) is a self-reinforcing epithelial-immune disorder in which barrier failure, alarmin release, type 2 cytokines, oxidative stress and dysbiosis converge on interconnected signaling circuits. This review critically evaluates natural products by mode of action rather than by pathway name alone. The available evidence supports coordinated suppression of NF-kB/MAPK-driven inflammatory cascades, indirect attenuation of JAK/STAT amplification, activation of Nrf2/HO-1 and AHR-dependent barrier programs, and upstream modulation of microbiota-metabolite-immune signaling. We distinguish system-level upstream processes (barrier injury, dysbiosis and epithelial alarmins), inflammatory convergence hubs (NF-kB/MAPKs), cytokine amplifiers (JAK/STAT), and counter-regulatory nodes (Nrf2/AHR). Importantly, most natural-product studies rely on endpoint assays in immortalized keratinocytes or hapten-induced murine models; direct target engagement, kinetic selectivity and achievable skin exposure are rarely established. Translation therefore requires chemical standardization, human-relevant models, pharmacokinetic-pharmacodynamic analysis, sensitization testing, and evaluation under the altered pH and microbial conditions of AD skin. Rational adjunctive use with biologics or JAK inhibitors also demands formal assessment of CYP-mediated interactions and combined safety rather than an assumption that natural origin confers tolerability.

JADE REAL was a global, prospective, multicenter, open-label expanded access protocol study that integrated the rigorous follow-up, safety, and efficacy assessments of a clinical trial with dosing flexibility and ability to use concomitant topical therapies to simulate real-world management of atopic dermatitis (AD). The study aimed to provide access to abrocitinib for patients with moderate-to-severe AD without adequate treatments available. Eligible patients received abrocitinib 100&#x2009;mg or 200&#x2009;mg once daily per investigator's discretion. Dose could be adjusted during treatment. Safety and exploratory efficacy endpoints were assessed. Of 312 patients, 120 (38.5%) and 192 (61.5%) received an initial dose of abrocitinib 100&#x2009;mg and 200&#x2009;mg, respectively. TEAEs were reported in 78.2% of patients. TEAEs led to dose change in 39 patients (12.5%); 12 (3.8%) had a dose escalation and 27 (8.7%) had a dose reduction. Rapid improvements in AD severity progressed up to 72&#x2009;weeks among observed patients. Most patients continued their initial dose of abrocitinib. TEAEs accounted for a minority of documented dose reductions; instead, investigators may have determined that the patients' disease could be maintained at a lower dose. These findings support clinical decision-making around dose selection and modification. NCT04564755.

Tapinarof cream 1%, a non-steroidal topical aryl hydrocarbon receptor-modulating agent, is approved in Japan for atopic dermatitis (AD) and plaque psoriasis. Real-world data on longitudinal outcomes, treatment continuation, interruption and restart, and adverse-event timing are limited. This single-center retrospective study included patients newly prescribed tapinarof cream 1% from November 2024 to July 24, 2025. The full analysis set comprised 37&#x2009;AD and 58 plaque psoriasis patients. Primary endpoints were Eczema Area and Severity Index 50% improvement (EASI50) at week 8 for AD and Psoriasis Area and Severity Index 75% improvement (PASI75) at week 12 for psoriasis. Observed-case and non-responder imputation (NRI) analyses were reported. In AD, week-8 EASI50 was achieved by 12/24 evaluable patients (50.0%) and 12/37 under NRI (32.4%). Mean EASI decreased from 5.94 at baseline to 2.56 at week 8 and 0.83 at week 52. Week-52 EASI was available for 13/37 overall (13/27 with ascertainable status at the data cutoff). In psoriasis, week-12 PASI75 was achieved by 15/33 evaluable patients (45.5%) and 15/58 under NRI (25.9%). Mean PASI decreased from 2.95 at baseline to 1.18 at week 12 and 0.43 at week 52. Week-52 PASI was available for 25/58 overall (25/49 with ascertainable status at the data cutoff); long-term summaries were observed-case and potentially responder-enriched. Any adverse event was recorded in 11/37&#x2009;AD patients and 12/58 psoriasis patients. Median headache onset was 8&#x2009;h in AD and 1.8&#x2009;days in psoriasis. No serious drug-related adverse event was recorded. No pigmentary change was documented; however, without standardized colorimetry or photography, its absence cannot be confirmed. Tapinarof-containing treatment was associated with clinically meaningful improvement in AD and plaque psoriasis in routine practice, although frequent concomitant therapy, observed-case long-term analyses, and retrospective ascertainment limit causal and safety inferences.

For patients with stable psoriasis or atopic dermatitis (AD) receiving systemic treatment, telemedicine may offer a viable alternative to in-person consultations. However, perspectives of these patients and dermatological care providers (DCPs) regarding telemedicine are underexplored, yet essential for successful implementation. To explore experiences, preferences, and perspectives of patients and DCPs regarding telemedicine for patients with psoriasis or AD on systemic treatment. A mixed-methods study was conducted using surveys and semi-structured interviews with patients and DCPs. Surveys were completed by 162 patients and 152 DCPs, and interviews by 12 patients and 5 DCPs. Both groups expressed positive attitudes toward telemedicine, provided stable disease. Patients valued telemedicine for practical benefits, including time/cost savings, but emphasized the importance of an established relationship with DCPs before its initiation. DCPs identified key enablers including improved ICT-support, user-friendly systems, and adequate reimbursement. The majority of patients and DCPs supported telemedicine implementation, with telephonic consultations as preferred method. Many DCPs believed &#x2265;50% of consultations could be conducted through telemedicine. Additionally, telemedicine leads to substantial CO2-equivalent emission reduction. Patients and DCPs supported further implementation of telemedicine in patients with stable psoriasis or AD on systemic treatment and identified practical, financial and societal facilitators.

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