Medical specialists' use and opinion of video consultation in Denmark: a survey study.

BACKGROUND: The COVID-19 pandemic accelerated the use of telemedicine which is seen as a possibility to reduce the pressure on healthcare systems globally. However, little research has been carried out on video as a consultation medium in medical specialists' practice. This study investigated the use of and opinion on video consultation among specialists in Denmark. METHODS: An online survey on use of video consultation, as well as relevance of and opinion on video consultation, was distributed to all 963 medical specialists in private practice in Denmark throughout May and June 2022, resulting in 499 complete answers (response rate: 51.8%). Data were analysed using descriptive and logistic regression analyses, and data from open text fields were analysed using thematic network analysis. RESULTS: Among the respondents, 62.2% had never used video consultation, while 23.4% were currently using video consultation, most particularly among psychiatrists. A total of 47.3% found video consultation medically irrelevant to their specialty, especially radiologists, plastic surgeons, ophthalmologists and otorhinolaryngologists. According to the specialists, video consultation was most suitable for follow-up consultations and simple medical issues, where the patient had an established diagnosis. In these cases, mutual trust remained present in video consultations. Better access for the patients and fewer cancellations, especially for psychiatrists, were highlighted as benefits. IT problems were reported as obstacles hindering optimal use of video consultation. CONCLUSION: The political aspiration to digitization in healthcare systems should be rooted in professionals' and patients' perceptions and experiences with video consultation which emphasize that it is not a standard tool for all consultations.

Predictors of Response to Biologics in Patients with Moderate-to-severe Psoriasis: A Danish Nationwide Cohort Study.

Identifying patient characteristics associated with achieving treatment response to biologics in patients with psoriasis could prevent expensive switching between biologics. The aim of this study was to identify patient characteristics that predict the efficacy of treatment for biologics that inhibit tumour necrosis factor-α, interleukin-12/-23, and -17A. The study investigated biologic-naïve patients from the DERMBIO registry treated with adalimumab, etanercept, infliximab, secukinumab, or ustekinumab. Multivariable logistic models were conducted to assess associations between patient characteristics and treatment response. A total of 2,384 patients were included (adalimumab n = 911; etanercept n = 327; infliximab n = 152; secukinumab n = 323; ustekinumab n = 671). Smoking (odds ratio 0.74; 95% confidence interval (CI) 0.56-0.97; p = 0.03) and higher bodyweight (odds ratio 0.989; 95% CI 0.984-0.994; p < 0.001) reduced the odds of achieving response defined as Psoriasis Area and Severity Index ≤2.0 after 6 months of treatment. In conclusion, higher bodyweight and smoking were associated with a reduced probability of treatment response for tumour necrosis factor-α inhibitors, ustekinumab, and secukinumab.

Outcomes Following a Mandatory Nonmedical Switch From Adalimumab Originator to Adalimumab Biosimilars in Patients With Psoriasis.

IMPORTANCE: The efficacy of adalimumab biosimilars is similar to that of brand-name adalimumab (Humira, hereinafter originator) in clinical trials. However, limited knowledge about real-world data exists for adalimumab biosimilars. OBJECTIVE: To assess the outcomes following a mandatory nonmedical switch from adalimumab originator to adalimumab biosimilars in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: This cohort study assesses the outcomes following a switch from adalimumab originator to an adalimumab biosimilar. Patients in the Biological Treatment in Danish Dermatology (DERMBIO) registry, a Danish nationwide registry of all patients treated with biologics (including biosimilars) for psoriasis since 2007, were assessed for eligibility. All patients who switched from adalimumab originator to an adalimumab biosimilar between November 1, 2018, and May 1, 2019, were included in the adalimumab biosimilar cohort. All patients with a visit between May 1, 2017, and November 1, 2017, treated with adalimumab originator were included in the adalimumab originator cohort. Data were analyzed from June 1, 2020, to October 10, 2021. EXPOSURE: Switch from adalimumab originator to an adalimumab biosimilar. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year drug retention in patients switching to adalimumab biosimilars compared with patients treated with adalimumab originator. Crude and adjusted retention rates for the adalimumab biosimilar cohort were compared with the adalimumab originator cohort with Cox proportional hazards regression using robust variance. RESULTS: A total of 348 patients were included in the adalimumab biosimilar cohort (mean [SD] age, 52.2 [13.6] years; 251 [72.1%] male) and 378 patients in the adalimumab originator cohort (mean [SD] age, 51.1 [14.1] years; 272 [72.0%] male). The 1-year drug retention rates were 92.0% (95% CI, 89.0%-94.9%) for the adalimumab biosimilar cohort and 92.1% (95% CI, 89.4%-94.8%) for the adalimumab originator cohort. Similar hazard ratios were observed between the 2 cohorts. The crude hazard ratios were 1.02 (95% CI, 0.61-1.70; P = .94) for all causes of drug discontinuation, 0.82 (95% CI, 0.39-1.73; P = .60) for insufficient effect, and 1.41 (95% CI, 0.52-3.77; P = .50) for adverse events for the adalimumab biosimilar cohort when compared with the adalimumab originator cohort. CONCLUSIONS AND RELEVANCE: In this cohort study from Denmark, a nonmedical switch from adalimumab originator to adalimumab biosimilars was not associated with drug retention.

Response to Biologics During the First Six Months of Therapy in Biologic-naïve Patients with Psoriasis Predicts Risk of Disease Flares: A Danish Nationwide Study.

Early response to treatment with biologics might be important for the stability of psoriasis and long-term outcome. The aim of this study was therefore to assess whether risk of flares and drug survival are associated with disease activity in the first 6 months of treatment of psoriasis with biologics. Biologic-naïve patients from the Danish nationwide registry, DERMBIO, were grouped based on absolute Psoriasis Area and Severity Index (PASI) during the first 6 months of treatment, as: PASI = 0, PASI > 0-≤2, PASI > 2-≤ 4, and PASI > 4. Among 1,684 patients, 746 achieved PASI= 0, 485 PASI > 0-≤2, 246 PASI > 2-≤4, and 207 PASI > 4. Longer flare-free period and drug survival were observed for patients with lower PASI in the first 6 months of treatment (adjusted hazard ratios for flares (95% confidence interval) with PASI= 0 as reference: PASI > 0-≤2 (1.35 (1.11-1.72]), PASI > 2-≤ 4 (2.32 [1.80-2.99]), and PASI > 4 (2.38 [1.80-3.15])). In conclusion, a low PASI in the first 6 months of treatment with biologics in biologic-naïve patients with psoriasis was associated with a more stable disease course, lower risk of flares, and longer drug survival.

Patient-reported Outcomes During Treatment in Patients with Moderate-to-severe Psoriasis: A Danish Nationwide Study.

The initiation and evaluation of treatment with biologics for psoriasis is based on the Psoriasis Area Severity Index (PASI) and/or Dermatological Life Quality Index (DLQI). However, these indices do not always correlate well, and changes in the DLQI do not always follow changes in the PASI. Based on data from the Danish national registry (DERMBIO), this study investigated the correlation between changes in PASI and DLQI in a cohort of patients with moderate-to-severe psoriasis treated with biologics or apremilast using Spearman's rank correlation analyses. The correlation analysis of 1,677 patients, of whom 276 had available data after 5 years, showed weak-to-moderate correlation between PASI and DLQI during a 5-year period and between changes in PASI and DLQI: 0.58 (p < 0.0001) for baseline to 3 months and 0.42 (p < 0.0001) for 3 to 12 months. The first question on "Symptoms and feelings" made up the largest proportion of the overall DLQI. The correlation between PASI and DLQI is weak-to-moderate and varies over time. Changes in PASI correlate weak-to-moderately with changes in DLQI during the first 12 months of treatment, with symptoms being the most important factor contributing to impaired quality of life.

Genetic polymorphisms associated with psoriasis and development of psoriatic arthritis in patients with psoriasis.

BACKGROUND: Psoriasis (PsO) is a chronic inflammatory disease with predominantly cutaneous manifestations. Approximately one third of patients with PsO develop psoriatic arthritis (PsA), whereas the remaining proportion of patients has isolated cutaneous psoriasis (PsC). These two phenotypes share common immunology, but with different heredity that might in part be explained by genetic variables. METHODS: Using a candidate gene approach, we studied 53 single nucleotide polymorphisms (SNPs) in 37 genes that regulate inflammation. In total, we assessed 480 patients with PsO from DERMBIO, of whom 151 had PsC for 10 years or more (PsC10), 459 patients with PsA from DANBIO, and 795 healthy controls. Using logistic regression analysis, crude and adjusted for age and gender, we assessed associations between genetic variants and PsO, PsC10, and PsA, as well as associations between genetic variants and development of PsA in PsO. RESULTS: Eleven polymorphisms in 10 genes were nominally associated with PsO and/or PsC and/or PsA (P < 0.05). After correction for multiple testing with a false discovery rate of 5%, two SNPs remained significant: TNF (rs361525) was associated with PsO, PsC10, and PsA; and IL12B (rs6887695) was associated with PsO. CONCLUSION: Among a cohort of Danish patients with moderate-to-severe psoriasis, two SNPs in the IL12B and TNF genes were associated with susceptibility of psoriasis. None of the SNPs were specifically associated with isolated cutaneous psoriasis or psoriatic arthritis.

The Danish Nonmelanoma Skin Cancer Dermatology Database.

AIM OF DATABASE: The Danish Nonmelanoma Skin Cancer Dermatology Database was established in 2008. The aim of this database was to collect data on nonmelanoma skin cancer (NMSC) treatment and improve its treatment in Denmark. NMSC is the most common malignancy in the western countries and represents a significant challenge in terms of public health management and health care costs. However, high-quality epidemiological and treatment data on NMSC are sparse. STUDY POPULATION: The NMSC database includes patients with the following skin tumors: basal cell carcinoma (BCC), squamous cell carcinoma, Bowen's disease, and keratoacanthoma diagnosed by the participating office-based dermatologists in Denmark. MAIN VARIABLES: Clinical and histological diagnoses, BCC subtype, localization, size, skin cancer history, skin phototype, and evidence of metastases and treatment modality are the main variables in the NMSC database. Information on recurrence, cosmetic results, and complications are registered at two follow-up visits at 3 months (between 0 and 6 months) and 12 months (between 6 and 15 months) after treatment. DESCRIPTIVE DATA: In 2014, 11,522 patients with 17,575 tumors were registered in the database. Of tumors with a histological diagnosis, 13,571 were BCCs, 840 squamous cell carcinomas, 504 Bowen's disease, and 173 keratoakanthomas. CONCLUSION: The NMSC database encompasses detailed information on the type of tumor, a variety of prognostic factors, treatment modalities, and outcomes after treatment. The database has revealed that overall, the quality of care of NMSC in Danish dermatological clinics is high, and the database provides the necessary data for continuous quality assurance.

Debio 0932, a new oral Hsp90 inhibitor, alleviates psoriasis in a xenograft transplantation model.

Debio 0932 is a novel oral heat shock protein 90 (Hsp90) inhibitor developed for anti-cancer therapy. Surprising-ly, during the first clinical trial, one psoriasis patient experienced complete remission of his skin manifestation. However, a possible therapeutic utility of Hsp90 in psoriasis has not previously been reported. The objective of the present study was to explore the ability of Debio 0932 to alleviate psoriasis in a preclinical model. A psoriasis xenograft transplantation model was employed where skin from 5 psoriasis patients was transplanted onto immunodeficient mice (8 xenografts per donor). Debio 0932 was administered perorally daily for 3 weeks and resulted in significant clinical alleviation of psoriasis by day 11 and reduced epidermal thickness evaluated post-treatment. Alleviation of psoriasis in the psoriasis xenograft transplantation model, which may be due to Hsp90's involvement in signalling pathways that are up-regulated in psoriasis, substantiates a potential role of Debio 0932 in psoriasis treatment.

Valrubicin activates PKCa in keratinocytes: a conceivable mode of action in treating hyper-proliferative skin diseases.

BACKGROUND: Valrubicin is a semisynthetic anthracycline developed as an anti-cancer drug able to ameliorate psoriasis and non-melanoma skin cancer (NMSC) by topical application in animal models. Valrubicin decreases cell proliferation, and induces apoptosis; however its mode of action is still unknown. Valrubicin localizes in the cytoplasm and its valerate moiety resembles diacylglycerol, an activator of protein kinase C (PKC) α, which belongs to the PKC family of cytoplasmic serine/threonine protein kinases. PKCα is observed in the suprabasal layers of normal skin and is associated to keratinocyte growth arrest and differentiation processes. In hyper-proliferative skin diseases the presence of PKCα is altered. OBJECTIVE: The aim of the present study was to investigate valrubicin's mode of action in keratinocytes by studying its possible effect on PKCα activation. METHODS: PKCα's characteristic to translocate from the cytoplasm to the cellular membrane when activated was assessed by measuring the amount of PKCα in the soluble and membrane-bound protein fractions isolated from valrubicin stimulated keratinocytes and by visualizing PKCα in stimulated cells over time. Downstream signaling was investigated by measuring the amount of phosphorylated Myristoylated Alanine-rich C-kinase substrate (MARCKS) and extracellular signal-regulated kinases (ERK) 1/2 of valrubicin-stimulated keratinocytes. To investigate whether there was a direct interaction between valrubicin and PKCα, an activity assay employing purified PKCα protein was used. RESULTS: Valrubicin activates PKCα in vitro as shown by PKCα's translocation and phosphorylation of downstream signaling molecules. CONCLUSION: Valrubicin stimulates PKCα activity and downstream signaling which may contribute to its beneficial effect in psoriasis and NMSC.

Pharmacological undertreatment of coronary risk factors in patients with psoriasis: observational study of the Danish nationwide registries.

BACKGROUND: Patients with psoriasis have increased prevalence of coronary risk factors and limited recent results have suggested that these risk factors are undertreated in patients with psoriasis. This may contribute to the increased risk of cardiovascular diseases observed in patients with psoriasis. OBJECTIVE: To examine the pharmacological treatment of coronary risk factors in patients with severe psoriasis treated with biologic agents in a real-world setting. METHODS AND FINDINGS: Medical history of patients with severe psoriasis treated with biologic agents in the time period 2007-09 was retrieved from a Danish nationwide registry (DERMBIO). Individual-level linkage of nationwide administrative registries of hospitalizations, concomitant medications, and socioeconomic status was performed to gain insights into the use of pharmacological treatment. A total of 693 patients (mean age 46.1 ± 12.7 years, 65.7% male) with severe psoriasis treated with biologic agents were identified. Hypertension, hypercholesterolemia, and diabetes mellitus were identified in 16.6%, 9.2%, and 6.7% of cases, respectively. Patients with severe psoriasis were significantly less likely to receive cardiovascular pharmacotherapy compared to age, sex, and coronary risk factor matched controls. In psoriatic patients with hypertension 27.7% received no antihypertensive pharmacotherapy. Patients with dyslipidemia received cholesterol-lowering medications in 55.8% of cases and patients with diabetes mellitus received angiotensin converting enzyme inhibitors/angiotensin II receptor blockers and cholesterol-lowering medications in 42.1% and 23.7% of cases, respectively. Similar results were found for the subset of patients with >1 coronary risk factor and for high risk patients with established atherosclerotic disease. CONCLUSION: This nationwide study of patients with severe psoriasis demonstrated substantial undertreatment of coronary risk factors. Increased focus on identifying cardiovascular risk factors and initiation of preventive cardiovascular pharmacotherapy in patients with psoriasis is warranted.

Statistical evaluation and experimental design of a psoriasis xenograft transplantation model treated with cyclosporin A.

Psoriasis xenograft transplantation models where human skin is transplanted onto immune-deficient mice are generally accepted in psoriasis research. Over the last decade, they have been widely employed to screen for new therapeutics with a potential anti-psoriatic effect. However, experimental designs differ in several parameters. Especially, the number of donors and grafts per experimental design varies greatly; numbers that are directly related to the probability of detecting statistically significant drug effects. In this study, we performed a statistical evaluation of the effect of cyclosporine A, a recognized anti-psoriatic drug, to generate a statistical model employable to simulate different scenarios of experimental designs and to calculate the associated statistical study power, defined as the probability of detecting a statistically significant anti-psoriatic drug treatment effect. Results showed that to achieve a study power of 0.8, at least 20 grafts per treatment group and a minimum of five donors should be included in the chosen experimental setting. To our knowledge, this is the first time that study power calculations have been performed to evaluate treatment effects in a psoriasis xenograft transplantation model. This study was based on a defined experimental protocol, thus other parameters such as drug potency, treatment protocol, mouse strain and graft size should, also, be taken into account when designing an experiment. We propose that the results obtained in this study may lend a more quantitative support to the validity of results obtained when exploring new potential anti-psoriatic drug effects.

Valrubicin in a topical formulation treats psoriasis in a xenograft transplantation model.

Valrubicin is a cytostatic drug currently approved by the American Federal Drug Administration as a trademarked Valstar sterile solution for the treatment of bladder cancer. Valrubicin has shown an excellent therapeutic potential with minimal toxicity. This study investigated the effect in vivo of treating psoriasis with a daily topical application of valrubicin cream in a psoriasis xenograft transplantation model. Psoriasis is characterized by an accelerated keratinocyte proliferation, resulting in increased epidermal thickness. We thus studied the cytostatic potential of valrubicin on epidermal keratinocytes. In vivo, valrubicin treatment resulted in a normalization of epidermal morphology and a reduction in epidermal thickness after 12 days. In addition, the dermal vessel pattern was reduced and the stratum granulosum was regained. Staining for a regenerative proliferation marker showed a decrease in keratinocyte proliferation, and scattered epidermal cells showed apoptosis. In vitro, valrubicin was shown to localize solely to the cell cytoplasm in cultured keratinocytes and to reduce keratinocyte proliferation as well as increase apoptosis by activation of caspases 3, 7, and 9. Our results indicated that valrubicin successfully treats psoriasis in a xenograft transplantation model, suggesting that topical valrubicin may become an upcoming treatment for psoriasis.

Application of stereology to dermatological research.

Stereology is a set of mathematical and statistical tools to estimate three-dimensional (3-D) characteristics of objects from regular two-dimensional (2-D) sections. In medicine and biology, it can be used to estimate features such as cell volume, cell membrane surface area, total length of blood vessels per volume tissue and total number of cells. The unbiased quantification of these 3-D features allows for a better understanding of morphology in vivo compared with 2-D methods. This review provides an introduction to the field of stereology with specific emphasis on the application of stereology to dermatological research by supplying a short insight into the theoretical basis behind the technique and presenting previous dermatological studies in which stereology was an integral part. Both the theory supporting stereology and a practical approach in a dermatological setting are reviewed with the aim to provide the reader with the capability to better assess papers employing stereological estimators and to design stereological studies independently.

[Interleukin-20--a new target in psoriasis treatment]. / Interleukin 20--et nyt mål for psoriasisbehandling.

Interleukin-20 (IL-20) is suggested as a new target in psoriasis treatment. It was first described in 2001, and the potential role of this cytokine in psoriasis was suggested because mice which were over-expressing IL-20 developed a psoriasis-like phenotype of the skin. Subsequently, IL-20 expression levels were found to be increased in psoriasis skin, and it was observed that these levels normalized upon psoriasis treatment. In the psoriasis xenograft transplantation model, administration of IL-20 to non-lesional psoriasis skin transplanted onto immune-deficient mice demonstrated that IL-20 was involved in the psoriasis induction. More interestingly, improvement of psoriasis was induced by blocking IL-20 signaling.

Pan-selectin antagonism improves psoriasis manifestation in mice and man.

The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant (P=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases.