LarvaTagger: Manual and automatic tagging of drosophila larval behaviour.

MOTIVATION: As more behavioural assays are carried out in large-scale experiments on Drosophila larvae, the definitions of the archetypal actions of a larva are regularly refined. In addition, video recording and tracking technologies constantly evolve. Consequently, automatic tagging tools for Drosophila larval behaviour must be retrained to learn new representations from new data. However, existing tools cannot transfer knowledge from large amounts of previously accumulated data.We introduce LarvaTagger, a piece of software that combines a pre-trained deep neural network, providing a continuous latent representation of larva actions for stereotypical behaviour identification, with a graphical user interface to manually tag the behaviour and train new automatic taggers with the updated ground truth. RESULTS: We reproduced results from an automatic tagger with high accuracy, and we demonstrated that pre-training on large databases accelerates the training of a new tagger, achieving similar prediction accuracy using less data. AVAILABILITY: All the code is free and open source. Docker images are also available. See gitlab.pasteur.fr/nyx/LarvaTagger.jl. SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.

Urticaria and the risk of cancer: a Danish population-based cohort study.

BACKGROUND: Urticaria has been tentatively linked to cancer, but epidemiological evidence supporting this link is sparse and conflicting. We therefore conducted a population-based cohort study using healthcare databases of the Danish population (January 1980-December 2022). We followed 87,507 people for a median of 10.1 years after first hospital contact for urticaria. OBJECTIVES: To examine associations of a hospital diagnosis of urticaria with incident cancer. METHODS: We computed absolute risk of cancer and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) standardized to Danish national cancer rates. In a cross-sectional analysis, we examined whether the extent of cancer spread differed between people with vs. without a previous urticaria diagnosis. RESULTS: The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11) based on 7,788 observed vs. 7,161 expected cases. The risk for any cancer was 0.7% (95% CI, 0.6-0.7) for the first year of follow-up. Cancer was diagnosed in 588 people with urticaria during the first year of follow-up (SIR 1.49, 95% CI, 1.38-1.62) and in 7,200 people thereafter (SIR 1.06, 95% CI, 1.04-1.09). During the first year of follow-up, we found strong associations with hematological cancers (e.g., non-Hodgkin lymphoma SIR 2.91, 95% CI, 1.92-4.23). Cancer stage was similar in people with vs. without previous urticaria diagnosis. CONCLUSIONS: At the time of urticaria diagnosis, or in the first year afterwards, we found a large increase in the risk for cancer. In subsequent years, a persistent 6% increase in risk remained. Diagnostic efforts may partly explain the elevated short-term risk, but occult cancer may promote urticaria, or cancer and urticaria share common risk factors.

Simulation-based inference for non-parametric statistical comparison of biomolecule dynamics.

Numerous models have been developed to account for the complex properties of the random walks of biomolecules. However, when analysing experimental data, conditions are rarely met to ensure model identification. The dynamics may simultaneously be influenced by spatial and temporal heterogeneities of the environment, out-of-equilibrium fluxes and conformal changes of the tracked molecules. Recorded trajectories are often too short to reliably discern such multi-scale dynamics, which precludes unambiguous assessment of the type of random walk and its parameters. Furthermore, the motion of biomolecules may not be well described by a single, canonical random walk model. Here, we develop a two-step statistical testing scheme for comparing biomolecule dynamics observed in different experimental conditions without having to identify or make strong prior assumptions about the model generating the recorded random walks. We first train a graph neural network to perform simulation-based inference and thus learn a rich summary statistics vector describing individual trajectories. We then compare trajectories obtained in different biological conditions using a non-parametric maximum mean discrepancy (MMD) statistical test on their so-obtained summary statistics. This procedure allows us to characterise sets of random walks regardless of their generating models, without resorting to model-specific physical quantities or estimators. We first validate the relevance of our approach on numerically simulated trajectories. This demonstrates both the statistical power of the MMD test and the descriptive power of the learnt summary statistics compared to estimates of physical quantities. We then illustrate the ability of our framework to detect changes in α-synuclein dynamics at synapses in cultured cortical neurons, in response to membrane depolarisation, and show that detected differences are largely driven by increased protein mobility in the depolarised state, in agreement with previous findings. The method provides a means of interpreting the differences it detects in terms of single trajectory characteristics. Finally, we emphasise the interest of performing various comparisons to probe the heterogeneity of experimentally acquired datasets at different levels of granularity (e.g., biological replicates, fields of view, and organelles).

Treat-to-target in dermatology: A scoping review and International Eczema Council survey on the approach in atopic dermatitis.

Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.

TRamWAy: mapping physical properties of individual biomolecule random motion in large-scale single-particle tracking experiments.

MOTIVATION: Single-molecule localization microscopy allows studying the dynamics of biomolecules in cells and resolving the biophysical properties of the molecules and their environment underlying cellular function. With the continuously growing amount of data produced by individual experiments, the computational cost of quantifying these properties is increasingly becoming the bottleneck of single-molecule analysis. Mining these data requires an integrated and efficient analysis toolbox. RESULTS: We introduce TRamWAy, a modular Python library that features: (i) a conservative tracking procedure for localization data, (ii) a range of sampling techniques for meshing the spatio-temporal support of the data, (iii) computationally efficient solvers for inverse models, with the option of plugging in user-defined functions and (iv) a collection of analysis tools and a simple web-based interface. AVAILABILITY AND IMPLEMENTATION: TRamWAy is a Python library and can be installed with pip and conda. The source code is available at https://github.com/DecBayComp/TRamWAy.

Smartphone photographs of chronic urticaria taken by patients are of good quality and useful in the clinic.

BACKGROUND: Chronic urticaria (CU) is characterized by transient wheals and angioedema, which are often not present when patients see their treating physician. AIM: To evaluate the diagnostic value of smartphone photographs captured by patients prior to their first visit at an urticaria outpatient clinic. METHODS: A survey regarding the quality and utility of smartphone photographs of urticarial skin lesions in patients with CU attending the outpatient clinic for the first time was conducted. Up to three random patient-selected photographs of skin lesions were evaluated by a physician. RESULTS: Of 148 patients, 118 (79.7%) had taken photographs of their skin lesions prior to the consultation, and 75% took photographs with the intention of presenting it to their physician. The photographs were of wheals in 90% of the cases, and angioedema in 8%. In total, 72% of the smartphone photographs had the skin lesion in focus, 64% had good resolution, 48% had good lighting. Only 9% of the smartphone photographs were blurred, 10% had bad lighting, 4% had bad resolution, and 8% did not have the lesion in focus. Moreover, 86% of the smartphone photographs were found to be useful for clinical evaluation. At least one photograph of good/very good quality was presented by 86% of the patients, and 97% had at least one photograph that was useful for clinical evaluation. CONCLUSION: Patients with CU often take smartphone photographs of their skin lesions on their own initiative prior to their first consultation to present the photographs to their physician. These smartphone photographs are very often of good quality and suitable for clinical evaluation.

A nationwide 104 weeks real-world study of dupilumab in adults with atopic dermatitis: Ineffectiveness in head-and-neck dermatitis.

BACKGROUND: Evaluation of effectiveness and safety of new systemic treatments for atopic dermatitis (AD) after approval is important. There are few published data exceeding 52-week therapy with dupilumab. OBJECTIVES: To examine the safety, effectiveness and drug survival of dupilumab in a Danish nationwide cohort with moderate-to-severe AD up to 104 weeks exposure. METHODS: We included 347 adult patients with AD who were treated with dupilumab and registered in the SCRATCH registry during 2017-2022. RESULTS: At all visits, we observed improvement in AD severity measured by Eczema Area and Severity Index (EASI) [median (IQR)]. EASI score at baseline was 18.0 (10.6-25.2), at week 4: 6.5 (3.5-11.6), at week 16: 3.7 (1.2-6.2), at week 52: 2.0 (0.8-3.6), at week 104: 1.7 (0.8-3.8). While drug survival was high (week 52: 90%; week 104: 86%), AD in the head-and-neck area remained present in most patients at high levels; proportion with head-and-neck AD at baseline was 76% and 68% at week 104. 35% of patients reported any AE. Conjunctivitis was the most frequent (25% of all patients) and median time to first registration of conjunctivitis was 201 days. CONCLUSIONS: While 2-year drug survival was 86%, dupilumab was unable to effectively treat AD in the head-and-neck area, and conjunctivitis was found in 25% of patients.

Validity and reliability of the Rosacea Area and Severity Index: A novel scoring system for clinical assessment of rosacea severity.

BACKGROUND: Rosacea is a common chronic inflammatory facial skin disorder. Standardized evaluation of the severity and extent of rosacea is important for baseline assessment and treatment effect. The currently used Investigator's Global Assessment (IGA) is unspecific and fails to consider subtypes/phenotypes of rosacea and area involvement. The Rosacea Area and Severity Index (RASI) was developed to give a more nuanced evaluation of rosacea features in four facial skin areas adjusted to the relative importance of each area of the face to obtain an overall severity score. OBJECTIVES: To validate RASI against the IGA and to assess the inter- and intraobserver reliability for RASI. METHODS: Sixteen dermatologists evaluated photographs of 60 adult patients with rosacea (3 photographs per patient, one from the front and one from each side). IGA and RASI scores were performed for interobserver reliability assessment. To determine intraobserver reliability, 14 dermatologists evaluated 10 other patients twice with at least 1 week interval. RESULTS: The IGA and RASI correlated well (Spearman correlation coefficient (SCC) = 0.75, 95% confidence interval (CI) = 0.72-0.78). Interobserver reliability was moderate for RASI and poor to moderate for IGA. Reliability was strongest for rhinophyma, followed by papules/pustules and erythema, and rather weak for telangiectasia. For area scores, interobserver reliability was strongest for cheeks, followed by nose, chin and forehead. We found a moderate-to-strong intraobserver agreement both for IGA and RASI. CONCLUSIONS: We have designed a new practical tool to examine clinical severity of rosacea. RASI proved simple and reliable in scoring clinical severity of rosacea with an agreement comparable to the currently used IGA although RASI will provide a more nuanced view of the current rosacea extent and severity. We suggest that RASI is used in the daily clinical setting as well as in clinical studies assessing the efficacy of rosacea therapies.

Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce.

BACKGROUND: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. OBJECTIVES: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. METHODS: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). RESULTS AND CONCLUSIONS: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses.

The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry.

BACKGROUND: Limited data are available on the effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis (AD). OBJECTIVE: To investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments, using a global registry platform. METHODS: Clinicians were encouraged to report cases of COVID-19 in their patients with AD in the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD) registry. Data entered from 1 April 2020 to 31 October 2021 were analysed using multivariable logistic regression. The primary outcome was hospitalization from COVID-19, according to AD treatment groups. RESULTS: 442 AD patients (mean age 35.9 years, 51.8% male) from 27 countries with strongly suspected or confirmed COVID-19 were included in analyses. 428 (96.8%) patients were treated with a single systemic therapy (n = 297 [67.2%]) or topical therapy only (n = 131 [29.6%]). Most patients treated with systemic therapies received dupilumab (n = 216). Fourteen patients (3.2%) received a combination of systemic therapies. Twenty-six patients (5.9%) were hospitalized. No deaths were reported. Patients treated with topical treatments had significantly higher odds of hospitalization, compared with those treated with dupilumab monotherapy (odds ratio (OR) 4.65 [95%CI 1.71-14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4-20.84]). Combination systemic therapy which did not include systemic corticosteroids was associated with increased odds of hospitalization, compared with single agent non-steroidal immunosuppressive systemic treatment (OR 8.09 [95%CI 0.4-59.96], aOR 37.57 [95%CI 1.05-871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16-207.49], aOR 45.75 [95%CI 4.54-616.22]). CONCLUSIONS: Overall, the risk of COVID-19 complications appears low in patients with AD, even when treated with systemic immunomodulatory agents. Dupilumab monotherapy was associated with lower hospitalization than other therapies. Combination systemic treatment, particularly combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.

Biomarkers for Monitoring Treatment Response of Omalizumab in Patients with Chronic Urticaria.

Chronic urticaria (CU) is a debilitating skin disease affecting around 1% of the population. CU can be subdivided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Different pathophysiological mechanisms have been proposed to play a role in the development of CU, and these are also being investigated as potential biomarkers in the diagnosis and management of the disease. As of now the only assessment tools available for treatment response are patient reported outcomes (PROs). Although these tools are both validated and widely used, they leave a desire for more objective measurements. A biomarker is a broad subcategory of observations that can be used as an accurate, reproducible, and objective indicator of clinically relevant outcomes. This could be normal biological or pathogenic processes, or a response to an intervention or exposure, e.g., treatment response. Herein we provide an overview of biomarkers for CU, with a focus on prognostic biomarkers for treatment response to omalizumab, thereby potentially aiding physicians in personalizing treatments.

Pyoderma Gangrenosum and Interleukin Inhibitors: A Semi-Systematic Review.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerating skin disease associated with multiple comorbidities and increased mortality. In recent decades, newer biologics such as interleukin inhibitors have been used to treat PG; however, the literature is scarce, consisting predominantly of case reports and caseseries. The aim of our review was to evaluate the effectiveness and safety of interleukin inhibitors for the treatment of PG in adults. SUMMARY: A literature search was conducted using search terms related to PG and interleukin inhibitors in databases such as PubMed, Embase, Scopus, Web of Science, and Cochrane Library. The study eligibility criteria included patients diagnosed with PG, over the age of 18, and treated with an interleukin inhibitor. Our study included 60 papers describing 81 patients fulfilling the eligibility criteria. The treatment with interleukin inhibitors resulted in 70% (95% CI 59-80%) response and 57% (95% CI 45-68%) complete response rates, and few (4%) mild adverse events, hence supporting the off-label use for the treatment of recalcitrant PG in adults. The response and complete response rates were 59% (17/29) and 38% (11/29) for anakinra, 64% (7/11) and 55% (6/11) for canakinumab, and 79% (27/34) and 71% (24/34) for ustekinumab, respectively. Limitations include publication bias that might have overestimated the efficacy as successful cases responding to treatment are more likely to be reported than nonresponding cases. Additionally, the heterogeneity of the treatment groups does not allow conclusions of superiority or inferiority of the different interleukin inhibitors to be drawn. Further studies are needed to investigate the efficacy of the different interleukin inhibitors and to investigate the importance of underlying disease for treatment response.

Non-Atopic Chronic Nodular Prurigo (Prurigo Nodularis Hyde): A Systematic Review of Best-Evidenced Treatment Options.

BACKGROUND: Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood, and the condition is difficult to treat with no targeted therapies. The aim of this systematic review was to review the evidence of therapies for non-atopic CNPG and conduct a meta-analysis of the results. SUMMARY: We conducted a systematic review of the literature concerning effect of treatment for non-atopic CNPG. Due to few randomized controlled trials (RCTs) and case series, the literature was unfortunately too sparse to conduct a meta-analysis of the results. Instead, we thoroughly report important data from the three existing RCTs and 6 case studies with more than 15 patients. Evaluated therapies include nemolizumab, aprepitant, topical therapy with hydrocortisone and pimecrolimus, thalidomide, UVA phototherapy, pregabalin, and naltrexone. Included RCTs and case studies all had a heterogeneous methodology making direct comparison almost impossible. KEY MESSAGES: There is sparse evidence for the currently used therapies for non-atopic CNPG. Several RCTs on new therapies are running or in the pipeline, hopefully providing new, effective, and targeted treatment possibilities for CNPG patients both with and without an atopic predisposition.

Treatment Patterns and Clinical Outcomes of Chronic Urticaria: Two-year Follow-up Results from the Scandinavian AWARE Study.

The AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) study investigated outcomes in patients with chronic urticaria refractory to H1-antihistamine. The objective of the current study was to analyse the effects of treatment on patients' symptoms and quality of life for a period of up to 2 years. Over the 2 years, there was clear improvement in the high rates of disease burden from baseline, as evidenced by lower scores for disease severity scales, better quality of life, and a decreasing rate of medical resource utilization. However, this is the result of treatment adherence to the guidelines in highly specialized Scandinavian urticaria centres, and has its basis in the relatively low treatment intensity and control at enrolment. There is a need for greater adherence to the treatment guidelines and better management of antihistamine-refractory chronic urticaria.

Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH): A Danish Real-world Evidence Atopic Dermatitis Treatment Registry.

Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to describe the baseline characteristics of adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic Atopic dermatitis Treatment CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29-54 years), and median age at onset of AD was 1 year (IQR 0-6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9-25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0-25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0-19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0-9.0) and 6.0 (IQR 4.0-8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies.

Unmet medical needs in the treatment of atopic dermatitis in infants: An Expert consensus on safety and efficacy of pimecrolimus.

Atopic dermatitis (AD) is a common skin disease during infancy, which imposes a considerable burden on patients, their families, and the society, requiring effective treatment options that result in rapid and sustained symptom relief. Additionally, early treatment may prevent the development of atopic comorbidities by restoring the skin barrier. Currently, topical standard-of-care for AD in infants includes emollients and topical corticosteroids (TCS) to treat and reduce the risk of flares. However, only few have been approved for infants and long-term maintenance therapy with TCS is not indicated due to potential local and systemic side effects, including skin atrophy. Accordingly, the recently updated European guidelines for treatment of AD recommend topical calcineurin inhibitors (TCIs) for long-term use, treatment of sensitive skin areas, and for use in the pediatric population. Evidence on the use of TCIs for infants has almost been exclusively collected for pimecrolimus, with >4000 infants evaluated in clinical trials, consistently confirming that pimecrolimus is a safe and effective treatment for infants with AD. Nevertheless, its use is still restricted in most countries to children above the age of 2 years due to initial and mostly theoretical safety concerns. Based on a careful review of the available evidence of clinical trials, post-marketing surveillance, and epidemiological studies, an Expert Panel of European dermatologists and pediatric allergologists concluded that these safety concerns are no longer valid. Therefore, pimecrolimus offers a safe and effective alternative to TCS in infants aged 3 months and above, and labeling restrictions in this age group are no longer justified.

Healthcare utilization in Danish children with atopic dermatitis and parental topical corticosteroid phobia.

BACKGROUND: Atopic dermatitis (AD) is a prevalent relapsing inflammatory skin disease. There is currently little knowledge about healthcare utilization and medication use along with parental corticosteroid phobia in relation to severity of pediatric AD. OBJECTIVES: To study the association between parental-reported healthcare utilization, medication use, and topical corticosteroid phobia and pediatric AD severity. METHODS: The study population included all children in Denmark with a diagnostic code of AD (ICD-10 code, group L20) given at a hospital department of dermatology between 2014 and 2018. A questionnaire containing 158 response items was sent to the legal parents. We surveyed disease severity, AD treatment, corticosteroid phobia, and healthcare use along with other variables. Disease severity was assessed using the Patient-Oriented Eczema Measure tool, and corticosteroid phobia was assessed using the Topical Corticosteroid Phobia (TOPICOP) score. RESULTS: In total, 1343 (39%) parents completed the questionnaire and 95.3% were completed by the biological mother. Children's mean age was 8.9 ± 4.5 years, and 52.8% were boys. Severe AD was associated with a higher number of healthcare visits to GPs, private dermatologists, and hospital departments. Mean global TOPICOP score was 38.27 ± 19.9%. There was a significant inverse linear trend between global TOPICOP score and parental educational level (Ptrend  < .0005). CONCLUSIONS: The significant association between high global TOPICOP score and low parental educational level, resulting in delayed treatment of AD flares, indicates that improved family education ultimately may reduce healthcare expenses and burden of disease.

Societal Costs of Moderate-to-severe Atopic Dermatitis Occurring in Adulthood: A Danish Register-based Study.

To estimate the cost of illness in adult patients with moderate-to-severe atopic dermatitis (AD) a cohort study was conducted identifying Danish citizens (≥ 18 years) diagnosed with AD between 1997 and 2018 in the Danish National Patient Register. Moderate-to-severe AD was defined as ≥3 hospital contacts regarding AD the first year after diagnosis. Each patient with AD was matched to 3 reference individuals through the Central Person Registry. Societal costs included the direct costs for primary-sector visits, inpatient hospitalizations, outpatient contacts, prescription medicine and indirect costs of lost productivity 3 years before and 5 years after the index date (the study period). A total of 5,245 patients with moderate-to-severe AD were identified. The mean attributable healthcare costs for patients with moderate-to-severe AD were EUR 10,835 (p < 0.0001) during the study period. Moderate-to-severe AD among adults inferred substantial economic burden compared with a group of matched reference individuals.

SARS-CoV-2 Transmission from Presymptomatic Meeting Attendee, Germany.

During a meeting in Munich, Germany, a presymptomatic attendee with severe acute respiratory syndrome coronavirus 2 infected at least 11 of 13 other participants. Although 5 participants had no or mild symptoms, 6 had typical coronavirus disease, without dyspnea. Our findings suggest hand shaking and face-to-face contact as possible modes of transmission.

Correction: Temporal Gillespie algorithm: Fast simulation of contagion processes on time-varying networks.

[This corrects the article DOI: 10.1371/journal.pcbi.1004579.].