Benchmarking atlas-level data integration in single-cell genomics.

Single-cell atlases often include samples that span locations, laboratories and conditions, leading to complex, nested batch effects in data. Thus, joint analysis of atlas datasets requires reliable data integration. To guide integration method choice, we benchmarked 68 method and preprocessing combinations on 85 batches of gene expression, chromatin accessibility and simulation data from 23 publications, altogether representing >1.2 million cells distributed in 13 atlas-level integration tasks. We evaluated methods according to scalability, usability and their ability to remove batch effects while retaining biological variation using 14 evaluation metrics. We show that highly variable gene selection improves the performance of data integration methods, whereas scaling pushes methods to prioritize batch removal over conservation of biological variation. Overall, scANVI, Scanorama, scVI and scGen perform well, particularly on complex integration tasks, while single-cell ATAC-sequencing integration performance is strongly affected by choice of feature space. Our freely available Python module and benchmarking pipeline can identify optimal data integration methods for new data, benchmark new methods and improve method development.

Altered resting-state functional connectivity of default mode network in brachioradial pruritus.

BACKGROUND: Patients with chronic pruritus (CP) have a low quality of life, thus it is important to gain a better understanding of the underlying processes. Previous functional magnetic resonance imaging studies at rest (rsfMRI) have shown that mainly areas associated with the default mode network (DMN), sensorimotor (SMN), frontoparietal (FPN) and salience networks (SN) are involved in the processing of itch in patients with chronic pruritus (CP), as well as the cortico-striatal circuit, which is involved in the motoric preparation of scratching. rsfMRI studies on functional connectivity (FC) patterns of resting-state networks (RSNs) in patients with inflammatory atopic dermatitis (AD) or with neuropathic brachioradial pruritus (BRP) compared with healthy controls (HC) are lacking. OBJECTIVES: The main goals of this study were to investigate whether functional connectivity within networks and areas associated with itch detection and processing are altered in patients with AD and BRP compared with matched healthy controls by rsfMRI, respectively. METHODS: Patients with AD (n = 28) and with BRP (n = 28) were compared with corresponding matched healthy controls by rsfMRI. Group-specific RSNs were identified by independent component analysis (ICA) and between-group differences in the RSNs were analysed by dual regression technique. Seed-based functional connectivity was analysed in several itch-related brain regions belonging to the DMN, SN and FPN, respectively. RESULTS: ICA and seed-based analyses revealed decreased functional connectivity in BRP compared with HC specially within the DMN including the precuneus and cingulate cortex. For AD patients in comparison with HC, as well as when BRP and AD patients were compared directly, no significant FC differences at rest were seen. CONCLUSIONS: Our findings point towards decreased FC particularly in the DMN at rest in patients with BRP. These results seem to indicate that central connectivity patterns at rest differentially encode itch in BRP and AD.

Serum concentrations of dihydrotestosterone are associated with symptoms of hypogonadism in biochemically eugonadal men.

PURPOSE: Symptoms of hypogonadism are often reported by subjects with normal serum testosterone (T) levels. We aimed to assess the association between clinical symptoms in andrological outpatients and sex steroids levels. METHODS: This is a retrospective cross-sectional cohort study in an Academic clinic and research unit. International Index of Erectile Function (IIEF, EF domain) and Aging Males Symptoms scale (AMS) questionnaires were completed by 635 and 574 men, respectively (mean age: 47.3 ± 13.9 and 47.4 ± 13.8 years, p = 0.829), free of interfering medications with complaints possibly related to hypogonadism. RESULTS: Serum total/free T as well as dihydro-T (DHT) was associated with IIEF-EF and AMS scores in the overall population using univariate analyses. Multivariate approaches revealed DHT concentrations in subjects with normal T levels (n = 416, Total T > 12 nmol/L) to be significant predictors of AMS scores. A 0.1 nmol/l serum DHT increase within the eugonadal range was associated with a 4.67% decrease in odds of having worse symptoms (p = 0.011). In men with biochemical hypogonadism (Total T < 12 nmol/L), total and free T rather than DHT were associated with AMS results. This association was not found for IIEF-EF scores. Indirect effects of age and BMI were seen for relations with hormone concentrations but not questionnaire scores. CONCLUSION: DHT can be associated with symptoms of hypogonadism in biochemically eugonadal men. Serum DHT measurement might be helpful once the diagnosis of hypogonadism has been ruled out but should not be routinely included in the primary diagnostic process.

The burden in chronic prurigo: patients with chronic prurigo suffer more than patients with chronic pruritus on non-lesional skin: A comparative, retrospective, explorative statistical analysis of 4,484 patients in a real-world cohort.

BACKGROUND: Chronic prurigo (CPG) is known as a high burdensome disease characterized by severe pruritus and multiple pruriginous lesions. Interestingly, the disease-specific burden is not well established and there are no data which compare the impact of CPG with chronic pruritus (CP) on non-lesional skin (CP-NL). OBJECTIVES: To address this issue, we analysed datasets from 4484 patients with either CPG or CP-NL. METHODS: Demographic medical data and additional information collected by validated patient reported outcome tools were analysed. The visual analogue scale and numerical rating scale (NRS) were used for assessing the pruritus intensity, the ItchyQoL for patients' quality of life, the Hospital Anxiety and Depression Scale and the Patient Needs Questionnaire' as a part of Patient Benefit Index for Pruritus for measuring the importance of 27 patient needs in terms of treatment goals. The Neuroderm questionnaire was used to assess the history of pruritus characteristics and the impact on sleep. RESULTS: Patients with CPG suffered longer and with a higher intensity from pruritus [NRS worst the last 24 h, CPG 6.0 (4.0;8.0) vs. CP-NL 3.0 (5.0;7.0), P < 0.001]. In them, pruritus occurred more often and the whole day and night which led to more loss in sleeping hours [CPG 3.0 h (2.0;4.0) vs. CP-NL 2.0 h (1.0;4.0), P < 0.001]. Patients with CPG showed higher scores for depression [HADS-D, CPG 6.0 (3.0;10.0) vs. CP-NL 5.0 (2.0;8.0), P < 0.001], more impaired quality of life [ItchyQol; CPG: 72.6 (61.6;83.6) vs. CP-NL 59.4 (48.4;70.4), P < 0.001] and higher weighted needs in the predefined treatment goals. DISCUSSION: Not only the presence of severe pruritus and pruriginous lesions but also sleep disorders and other mental symptoms may contribute to a higher burden in patients with CPG when compared with patients with CP-NL.

Pruritus Intensity Scales across Europe: a prospective validation study.

BACKGROUND: Chronic pruritus (CP) is a subjective symptom, and it is necessary to assess its intensity with validated patient-reported outcome tools in order to allow determination of the treatment course. OBJECTIVES: So far, the itch intensity scales were validated in small cohorts and in single languages. Here, we report the validation of the numerical rating scale, the verbal rating scale and the visual analogue scale for the worst and average pruritus intensity in the last 24h in several languages across Europe and across different pruritic dermatoses. METHODS: After professional translation, the intensity scales were digitized for use as a tablet computer application. Validation was performed in clinics for Dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: A total of 547 patients with contact dermatitis, chronic nodular prurigo, psoriasis vulgaris, lichen planus or cutaneous T-cell lymphoma were included. The intensity scales showed a high level of reproducibility and inter-correlations with each other. The correlation with the Dermatology Life Quality Index was weak to strong in nearly all countries and dermatoses with the exception of France and patients with chronic nodular prurigo, for which no statistically significant correlations were found. CONCLUSIONS: The numerical rating scale, the verbal rating scale und the visual analogue scales are valid instruments with good reproducibility and internal consistency in German (Germany, Austria, Switzerland), French, Italian, Polish, Russian, Spanish and Turkish for different pruritic dermatoses. VAS worst was the best reproducible and consistent measuring instrument in all countries.

Chronic nodular prurigo: clinical profile and burden. A European cross-sectional study.

BACKGROUND: Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this condition, especially regarding its clinical characteristics and impact on quality of life is still lacking. OBJECTIVES: Aim of this pan-European multicentre cross-sectional study was to establish the clinical profile of CNPG, including its associated burden. METHODS: Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres' own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co-morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed. RESULTS: A total of 509 patients (210 male, median age: 64 years [52; 72]) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to severe worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the disease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%). CONCLUSIONS: This multicentre cross-sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe.

[Medical apps-possibilities for pruritus]. / Medizinische Apps ­ Möglichkeiten bei Pruritus.

BACKGROUND: Apps have become part of our daily lives. Apps for pruritus could also play a role in the management of symptoms. AIM: The aim of this article is to review existing apps for pruritus. In addition, we will discuss whether these apps have been validated and how and which offers might still be lacking. MATERIALS AND METHODS: The two largest app stores as well as PubMed and Google were searched for apps regarding pruritus. Relevant medical apps were documented and categorized with respect to their functions. PubMed was searched to identify validation studies. RESULTS: In total 21 apps for pruritus were identified. Of those 12 explicitly focused on pruritus, while 8 included pruritus as a symptom of an underlying disease (especially eczema and urticaria). The following app categories were derived: medical history of chronic pruritus, assessment of pruritus in clinical trials, assessment of nocturnal pruritus, information about pruritus, and diseases with pruritus as a symptom. Three of the apps with explicit focus on pruritus have been scientifically validated. DISCUSSION: There are different apps for pruritus available. Most apps which explicitly focus on pruritus are aimed at physicians and scientists, while apps for diseases with pruritus as a symptom are more patient-centered. Due to technological advances, apps and wearables could improve management of pruritus in the future.

Cross-European validation of the ItchyQoL in pruritic dermatoses.

BACKGROUND: Chronic pruritus (CP) is a frequently occurring symptom in inflammatory dermatoses, causing a high burden and limitations to health-related quality of life (HRQoL). OBJECTIVE: The ItchyQoL was developed to assess the impairment to HRQoL in patients with CP. However, it has only been validated in English and German. Here, we report the validation in several languages across Europe. METHODS: After professional translation, the versions of ItchyQoL were digitized for use as a tablet application. Validation was performed in clinics for dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey. RESULTS: Five hundred and thirty-five patients with either contact dermatitis, chronic prurigo - nodular type, psoriasis vulgaris, lichen planus or mycosis fungoides/Sézary syndrome and with CP ≥ 3 on the numerical rating scale were included. ItchyQoL showed a high level of consistency (Cronbach's-α, all: 0.95) and test-retest reliability (intraclass correlation: 0.91). It strongly correlated with the Dermatology Life Quality Index (r = 0.72, P < 0.001) and moderately correlated with itch intensity scales in the study population (visual analogue scale r = 0.46; numerical rating scale r = 0.51; verbal rating scale r = 0.51, for all: P < 0.001). CONCLUSION: ItchyQoL is now also validated in French, Italian, Polish, Russian, Spanish and Turkish and can be used in clinical trials in countries speaking these languages.

Male-male aggression is unlikely to stabilize a poison frog polymorphism.

Phenotypic polymorphism is common in animals, and the maintenance of multiple phenotypes in a population requires forces that act against homogenizing drift and selection. Male-male competition can contribute to the stability of a polymorphism when males compete primarily with males of the same phenotype. In and around a contact zone between red and blue lineages of the poison frog Oophaga pumilio, we used simulated territorial intrusions to test the nonexclusive predictions that males would direct more aggression towards males of (i) their own phenotype and/or (ii) the phenotype that is most common in their population. Males in the monomorphic red and blue populations that flank the contact zone were more aggressive towards simulated intruders that matched the local coloration. However, males in the two polymorphic populations biased aggression towards neither their own colour nor the colour most common in their population. In sympatry, the rarer colour morph gains no advantage via reduced male-male aggression from territorial males in these O. pumilio populations, and so male aggression seems unlikely to stabilize colour polymorphism on its own. More broadly, these results suggest that the potential for divergent male aggression biases to maintain phenotypic diversity depends on the mechanism(s) that generate the biases and the degree to which these mechanisms persist in sympatry.

European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo.

BACKGROUND: The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch-related prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat. OBJECTIVE: To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross-sectional EPP were discussed and agreed upon. METHODS: Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members. RESULTS: Twenty-four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle. CONCLUSION: This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross-sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP.

Tadpole begging reveals high quality.

Parents can benefit from allocating limited resources nonrandomly among offspring, and offspring solicitation (i.e. begging) is often hypothesized to evolve because it contains information valuable to choosy parents. We tested the predictions of three 'honest begging' hypotheses - Signal of Need, Signal of Quality and Signal of Hunger - in the tadpoles of a terrestrial frog (Oophaga pumilio). In this frog, mothers provision tadpoles with trophic eggs, and when mothers visit, tadpoles perform a putative begging signal by stiffening their bodies and vibrating rapidly. We assessed the information content of intense tadpole begging with an experimental manipulation of tadpole condition (need/quality) and food deprivation (hunger). This experiment revealed patterns consistent with the Signal of Quality hypothesis and directly counter to predictions of Signal of Need and Signal of Hunger. Begging effort and performance were higher in more developed and higher condition tadpoles and declined with food deprivation. Free-living mothers were unlikely to feed tadpoles of a nonbegging species experimentally cross-fostered with their own, and allocated larger meals to more developed tadpoles and those that vibrated at higher speed. Mother O. pumilio favour their high-quality young, and because their concurrent offspring are reared in separate nurseries, must do so by making active allocation decisions. Our results suggest that these maternal choices are based at least in part on offspring signals, indicating that offspring solicitation can evolve to signal high quality.

Chronic pruritus: evaluation of patient needs and treatment goals with a special regard to differences according to pruritus classification and sex.

BACKGROUND: Chronic pruritus (CP) is present in approximately one-third of all dermatological patients. Diagnostics and treatment are challenging and impair patients' quality of life. OBJECTIVES: To analyse therapeutic needs in terms of the importance of treatment goals in a large sample of patients with CP. METHODS: Routine data of 2747 patients with CP were analysed with descriptive methods and significance tests (univariate and multivariate variance analyses). The importance of 27 need items was measured using the Patient Needs Questionnaire of the Patient Benefit Index. RESULTS: The most important needs were to find a clear diagnosis and treatment, to no longer experience itching and to have confidence in the therapy, which were quite or very important to > 90% of the patients. The least important goals concerned a normal working or sex life. Nine needs related mostly to disease and psychological symptoms, and some social needs differed in importance between sexes (P ≤ 0·05). Patients with pruritus on inflamed skin or with chronic scratch lesions judged more than half of all needs as more important than did patients with pruritus on noninflamed skin (P ≤ 0·05). In the multivariate model, age, pruritus intensity and quality of life had a significant effect on the importance of therapeutic needs besides sex and pruritus classification. CONCLUSIONS: Patients with CP present high levels of various therapeutic needs with differences by sex and clinical phenotype. The most important needs can be addressed through medical activities such as appropriate itch medication and a trustful doctor-patient relationship.

The pay-offs of maternal care increase as offspring develop, favouring extended provisioning in an egg-feeding frog.

Offspring quantity and quality are components of parental fitness that cannot be maximized simultaneously. When the benefits of investing in offspring quality decline, parents are expected to shift investment towards offspring quantity (other reproductive opportunities). Even when mothers retain complete control of resource allocation, offspring control whether to allocate investment to growth or development towards independence, and this shared control may generate parent-offspring conflict over the duration of care. We examined these predictions by, in a captive colony, experimentally removing tadpoles of the strawberry poison frog (Oophaga pumilio) from the mothers that provision them with trophic eggs throughout development. Tadpoles removed from their mothers were no less likely to survive to nutritional independence (i.e. through metamorphosis) than were those that remained with their mothers, but these offspring were smaller at metamorphosis and were less likely to survive to reach adult size, even though they were fed ad libitum. Tadpoles that remained with their mothers developed more slowly than those not receiving care, a pattern that might suggest that offspring extracted more care than was in mothers' best interests. However, the fitness returns of providing care increased with offspring development, suggesting that mothers would be best off continuing care until tadpoles initiated metamorphosis. Although the benefits of parental investment in offspring quality are often thought to asymptote at high levels, driving parent-offspring conflict over weaning, this assumption may not hold over natural ranges of investment, with selection on both parents and offspring favouring extended durations of parental care.

European EADV network on assessment of severity and burden of Pruritus (PruNet): first meeting on outcome tools.

BACKGROUND: Chronic pruritus is a frequently occurring symptom of various dermatoses that causes a high burden and impaired quality of life. An effective anti pruritic therapy is important for the patient, but its effectiveness is difficult to evaluate. Diverse methods and interpretations of pruritic metrics are utilized in clinical trials and the daily clinical practice in different countries, resulting in difficulties comparing collected data. METHODS: We founded a European Network on Assessment of Severity and Burden of Pruritus (PruNet) that is supported by the EADV. PruNet consists of 28 experts from 15 EU countries (21 dermatologists, 5 medical informaticists, 2 psychologists) and aims to unify the assessment of itch in routine dermatological care. Following a preliminary survey, a consensus conference was held in order to agree upon the prioritization of patient-reported outcome tools. RESULTS: Through utilizing the Delphi method, it was agreed that tools for measuring itch intensity (ex. the visual analogue scale) and quality of life (ex. ItchyQoL) are of primary importance and should urgently be foremost validated. CONCLUSION: The validation and harmonization of standards are needed for the improvement of quality care for patients suffering from pruritic dermatoses. This summer, the first validation studies in several EADV member countries already began.

[Chronic pruritus : Care in daily practice]. / Chronischer Pruritus : Versorgung in der Praxis.

Chronic pruritus is a highly prevalent, multifactorial symptom requiring extensive diagnostics, treatment and consideration of accompanying symptoms (reduced quality of life, sleep disorders, psychic factors). Patient care is thus complex and requires consideration of individual treatment goals. Patients indicate their wish for a symptom-free life an explanation of the causes and a trustful physician-patient relationship. The targeted use of questionnaires is thus advisable in order to structurally survey the history, pruritus intensity, quality of life and treatment progression. Nevertheless, there are many administrative and economical hurdles in the health care system to overcome in order to provide patients with chronic pruritus the best possible care, also per the recommended guidelines. The development of specialized centers and training courses for medical practitioners is thus urgently needed.

Electronic health records: new opportunities for clinical research.

Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.

[Assessment of pruritus - current standards and implications for clinical practice : consensus paper of the Action Group Pruritus Parameter of the International Working Group on Pruritus Research (AGP)]. / Erfassung von Pruritus - aktuelle Standards und Implikationen für die Praxis : Konsensuspaper der Initiative Pruritusparameter der Arbeitsgemeinschaft Pruritusforschung (AGP).

With a prevalence of 20%, chronic pruritus is a symptom of many diseases with major impact on healthcare costs. The lack of specific therapeutic measures makes the development of new drugs and their testing in clinical trials urgent. It is not possible to measure pruritus in an objective way. For these reasons, it is necessary to have a series of standardized measures to characterize pruritus in a reliable way. Intensity scales such as the visual analog scale (VAS) are most frequently used to document the course of the symptoms. However, for assessing pruritus intensity, VAS is not an optimal instrument, although it cannot be dispensed with. The VAS should be combined with other scales in clinical studies in order to internally test the consistency of data. Other instruments for assessing intensity and course of pruritus are in the process of development. Presently scratch activity and scratch-associated lesions can be documented in a descriptive fashion. There are some studies that have employed devices to document scratch activity; however, methodological studies are not yet available. The patient-benefit index is an indispensable tool in clinical trials. A questionnaire for gathering data on the history and some pruritus-specific parameters has been developed and published. Questionnaires on patient quality of life, anxiety and depression are helpful in obtaining data on other cost-relevant parameters. A questionnaire on the quality of life, for instance, can provide important help in the assessment of the burden of the disease. The results of these questionnaires can be correlated with data on pruritus intensity scales. The relevant questionnaires have been partially digitalized so that they are available immediately as part of patient care. Additional methodological developments and studies are required in order to define a robust set of instruments for measuring pruritus in daily practice and in clinical studies.

[Providing vulnerable populations in subSaharan Africa access to obstetrical care: strategy for improving prenatal services]. / Donner aux populations vulnérables de l'Afrique subsaharienne un accès aux soins obstétricaux: stratégie avancée de consultations prénatales.

The outlook for reaching key Millennium Development goals in Africa in 2015 is mostly positive. However, two critical indicators, i.e., maternal and neonatal mortality, show lagging progress. The purpose of this report is to underline the importance of prenatal care in efforts to reduce maternal mortality. It describes the minimum prenatal care package recommended by WHO and propses strategies for increasing access to prenatal examination. Health education, improvement of care quality and outreach services are promising avenues to increasing the use of prenatal services.

Serum concentration of baseline mast cell tryptase: evidence for a decline during long-term immunotherapy for Hymenoptera venom allergy.

BACKGROUND: Baseline serum mast cell tryptase concentration (BTC) is thought to reflect the constitutive mast cell load or activity of an individual patient. Little is known about the individual stability of BTC during long-term venom immunotherapy (VIT). OBJECTIVE: To investigate the intra-individual stability of BTC over time in patients with Hymenoptera venom allergy. METHODS: Three hundred and two patients were studied. BTC was measured before and at least twice during VIT. At least 4 weeks lay between BTC measurements and the most recent field sting, in-hospital sting, or preceding venom injection. Multifactorial mixed linear models were used to analyse BTC changes over time. RESULTS: Median observation time was 4.2 years (range 2-12 years). Before VIT, the median BTC was 6.8 microg/L (range 1.14-177 microg/L). The median coefficient of variation (CV) over time was 15.3% (range 1.9-63.8%). The median CV was significantly smaller in patients presenting with an elevated BTC (>11.4 microg/L) than in patients with a normal BTC (11.4%, range 2.6-39.5%; vs. 17.6%, range 1.9- 63.8%; P<0.001). During VIT and after adjusting for age and gender, we found a slight but significant decrease of BTC over time (2.5% per year, 95% confidence interval 2.0-3.0%, P<0.001). CONCLUSION: Individual variation of BTC during VIT does not rise when BTC is increased before therapy. VIT is associated with a small, but continuous decrease of BTC over time possibly indicating a dampened mast cell function or a decline in mast cell burden.

Electronic Collection of Multilingual Patient-Reported Outcomes across Europe.

BACKGROUND: Patient-reported outcomes (PROs) are information provided directly by patients that helps in improving patient diagnosis and treatment. Validated translations of PROs can be used to treat international patients. Electronic systems and especially mobile devices provide a great opportunity for their collection; however, these systems are normally study-oriented and therefore single language, not scalable, and not interoperable. OBJECTIVES: This article reports the development of a multicenter, multilingual, and interoperable electronic PRO (ePRO) system and evaluates its user satisfaction in an international clinical study. METHODS: The ePRO named "MoPat2" was developed using Java 8 and jQuery Mobile 1.4.5. The system was evaluated in the context of the European dermatology project "European Network on Assessment of Severity and Burden of Pruritus"(PruNet), which aimed to unify the assessment of itch in routine dermatological care in Europe. Twenty-six clinicians and 468 patients from 8 European clinical centers were asked to complete a user satisfaction questionnaire regarding the use of MoPat2 with a tablet personal computer. The results were then analyzed and correlated with the age, gender, and language of the respondents. RESULTS: MoPat2 was enhanced with multilingual capabilities and is now able to conduct surveys in several languages, as well as store and display the results in the local language. The interviewed clinicians rated the system with an average score of 2.0 ("good") in a 1 to 5 Likert scale. Note that 93.9% of the patients (439 of 468) reported having got on well using the system and 88.9% (416 of 456) would be willing to further use it. The age of the patients not willing to further use MoPat2 was, in average, considerably higher than the age of patients willing to use the system. CONCLUSIONS: This study represents the first use of an ePRO system for the collection of multilingual PROs in an international, multicenter setting. MoPat2 has been evaluated by both clinicians and patients in the context of a European dermatological study, resulting in a high user satisfaction. The system will be further developed to include new features such as patient follow-ups outside of the clinical setting.