Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

BACKGROUND: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. OBJECTIVES: To determine the potential of retinoids to repair photoaged black skin. METHODS: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. RESULTS: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. CONCLUSIONS: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

Perioperative myocardial injury is associated with increased postoperative non-cardiac complications in patients undergoing vascular surgery: a post hoc analysis of a randomised clinical pilot trial.

BACKGROUND: Elevated cardiac biomarkers, such as high-sensitivity cardiac Troponin T and N-terminal pro-B-type natriuretic peptide improve the prediction of major adverse cardiac events. However, very few trials have investigated the association between perioperative cardiac injury and non-cardiac complications. The primary aim of this study was to determine the association between peri-operative myocardial injury and non-cardiac complications in patients undergoing vascular surgery. Additionally, the association between elevated pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide and non-cardiac complications was explored. METHODS: This study is a post hoc analysis of a multicentre randomised controlled trial. Patients were recruited from three centres in Sweden between 2016 and 2019. Cardiac troponin level was measured pre-operatively and at 4, 24, and 48 h after the start of surgery in patients undergoing vascular surgery. N-terminal pro-B-type natriuretic peptide was measured pre-operatively. The primary outcome was a composite of major postoperative non-cardiac complications assessed at 30 days. RESULTS: A total of 184 patients undergoing peripheral or aortic vascular surgery were included in this study. The primary endpoint occurred in 67 (36%) patients. Perioperative myocardial injury was significantly associated with non-cardiac complications, with an adjusted odds ratio (OR) of 2.71 (95% confidence interval 1.33-5.55, P = 0.01). Sensitivity and specificity were 0.40 and 0.81, respectively. No association was found between pre-operative hs-cTnT or NT-proBNP and non-cardiac complications. CONCLUSION: In this pilot study, we found that new peri-operative myocardial injury is associated with an increased risk of non-cardiac complications within 30 days after index surgery in patients undergoing vascular surgery. Pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide did not appear to predict non-cardiac complications. Larger studies are needed to confirm our findings. TRIAL REGISTRATION: EudraCT database: 2016-001584-36.

Health disparities among older adults following tropical cyclone exposure in Florida.

Tropical cyclones (TCs) pose a significant threat to human health, and research is needed to identify high-risk subpopulations. We investigated whether hospitalization risks from TCs in Florida (FL), United States, varied across individuals and communities. We modeled the associations between all storms in FL from 1999 to 2016 and over 3.5 million Medicare hospitalizations for respiratory (RD) and cardiovascular disease (CVD). We estimated the relative risk (RR), comparing hospitalizations during TC-periods (2 days before to 7 days after) to matched non-TC-periods. We then separately modeled the associations in relation to individual and community characteristics. TCs were associated with elevated risk of RD hospitalizations (RR: 4.37, 95% CI: 3.08, 6.19), but not CVD (RR: 1.04, 95% CI: 0.87, 1.24). There was limited evidence of modification by individual characteristics (age, sex, or Medicaid eligibility); however, risks were elevated in communities with higher poverty or lower homeownership (for CVD hospitalizations) and in denser or more urban communities (for RD hospitalizations). More research is needed to understand the potential mechanisms and causal pathways that might account for the observed differences in the association between tropical cyclones and hospitalizations across communities.

Exploring within-ecodistrict lake organic matter variability and identifying possible environmental contaminant biomarkers using sedimentomics.

Sedimentomics methods offer insight into the physiological parameters that influence freshwater sediment organic matter (sedOM). To date, most sedimentomics studies characterized variations across large spatial and environmental gradients; here we examine whether sedimentomics methods capture subtle sedOM variations within a relatively homogeneous study area in southwestern Nova Scotia, Canada. Additionally, we explore the lake sedimentome for candidate biomarkers related to ongoing carnivorous animal farming in the region. Sediment cores were recovered from seven lakes across a trophic (oligo- to eu- trophic) and anthropogenic land use gradient (carnivorous animal farming in catchment, downstream of farming, no farming nearby). Subsamples that dated prior to 1910 (pre-carnivorous animal farming) and later than 2010 (during carnivorous animal farming) were analyzed using UHPLC-HRMS in both negative (ESI-) and positive (ESI+) electrospray ionization modes. Cluster analysis (k-means) showed replicate samples from a given lake clustered distinctly from one another in both ESI modes, indicating sedOM captured subtle variations between lake systems. PCA combined with multiple linear regression indicated carnivorous animal farming and OM source explained most of the observed variation in lake sedOM. Principal component analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) of ESI- and ESI+ data sets identified 103 unique candidate biomarkers. Ten strong candidate biomarkers were identified using graphical methods; more research is required for biomarker verification and molecular characterization. Our results indicate sedimentomics could be used in environmentally homogeneous areas, offering insight into the controls of sedOM cycling. Additionally, we identified prospective biomarkers related to carnivorous animal farming that could be used to understand relative contributions of farming to ongoing eutrophication issues in southwestern Nova Scotia.

Validation of medical service insurance claims as a surrogate for ascertaining vitiligo cases.

The epidemiology of vitiligo, especially its disease burden on the healthcare system, can be assessed indirectly by analyzing health insurance claims data. Validating this approach is integral to ensuring accurate case identification and cohort characterization. The primary aim of this study was to develop and validate an indirect measure of vitiligo ascertainment using health insurance claims data. These data were used secondarily to identify demographic characteristics, body site involvement, vitiligo subtypes, disease associations, and treatments. This study assessed the validity of identifying vitiligo from billing claims within a Canadian provincial universal health insurance program, versus vitiligo cases accrued from direct medical chart reviews. Claims-based algorithms combining ICD-9-CM diagnostic code 709 with treatment-specific data were derived and tested to identify vitiligo patients. This was compared against cases arising from the manual review of medical records of 606 patient with a diagnostic code for "dyschromia" (ICD-9-CM diagnostic code 709) from January 1 to December 31, 2016. Based on the chart reviews, 204 (33.7%) patients were confirmed to have vitiligo. 42 separate claims-based algorithms combining ICD-9-CM diagnostic code 709 with treatment data specific to vitiligo were modeled and individually tested to evaluate their accuracy for vitiligo ascertainment. One algorithm achieved a sensitivity, specificity, PPV and NPV of 86.8% (95% CI 82.1-91.4), 92.5% (95% CI 90.0-95.1), 85.5% (95% CI 80.7-90.3), and 93.2% (95% CI 90.8-95.7), respectively. There was a 2.2 female-to-male ratio. The most common medical treatments were tacrolimus (74.5%) and topical corticosteroids (54.3%). Hypertension (24.2%) and hypothyroidism (19.6%) were the predominant co-morbidities associated with vitiligo. Health insurance claims data can be used to indirectly ascertain vitiligo for epidemiologic purposes with relatively high diagnostic performance between 85.5 and 93.2%.

Axonal TAU Sorting Requires the C-terminus of TAU but is Independent of ANKG and TRIM46 Enrichment at the AIS.

Somatodendritic missorting of the axonal protein TAU is a hallmark of Alzheimer's disease and related tauopathies. Rodent primary neurons and iPSC-derived neurons are used for studying mechanisms of neuronal polarity, including TAU trafficking. However, these models are expensive, time-consuming, and/or require the killing of animals. In this study, we tested four differentiation procedures to generate mature neuron cultures from human SH-SY5Y neuroblastoma cells and assessed the TAU sorting capacity. We show that SH-SY5Y-derived neurons, differentiated with sequential RA/BDNF treatment, are suitable for investigating axonal TAU sorting. These human neurons show pronounced neuronal polarity, axodendritic outgrowth, expression of the neuronal maturation markers TAU and MAP2, and, importantly, efficient axonal sorting of endogenous and transfected human wild-type TAU, similar to mouse primary neurons. We demonstrate that the N-terminal half of TAU is not sufficient for axonal targeting, as a C-terminus-lacking construct (N-term-TAUHA) is not axonally enriched in both neuronal cell models. Importantly, SH-SY5Y-derived neurons do not show the formation of a classical axon initial segment (AIS), indicated by the lack of ankyrin G (ANKG) and tripartite motif-containing protein 46 (TRIM46) at the proximal axon, which suggests that successful axonal TAU sorting is independent of classical AIS formation. Taken together, our results provide evidence that (i) SH-SY5Y-derived neurons are a valuable human neuronal cell model for studying TAU sorting readily accessible at low cost and without animal need, and that (ii) efficient axonal TAU targeting is independent of ANKG or TRIM46 enrichment at the proximal axon in these neurons.

Why do healthcare professionals fail to escalate as per the early warning system (EWS) protocol? A qualitative evidence synthesis of the barriers and facilitators of escalation.

BACKGROUND: Early warning systems (EWSs) are used to assist clinical judgment in the detection of acute deterioration to avoid or reduce adverse events including unanticipated cardiopulmonary arrest, admission to the intensive care unit and death. Sometimes healthcare professionals (HCPs) do not trigger the alarm and escalate for help according to the EWS protocol and it is unclear why this is the case. The aim of this qualitative evidence synthesis was to answer the question 'why do HCPs fail to escalate care according to EWS protocols?' The findings will inform the update of the National Clinical Effectiveness Committee (NCEC) National Clinical Guideline No. 1 Irish National Early Warning System (INEWS). METHODS: A systematic search of the published and grey literature was conducted (until February 2018). Data extraction and quality appraisal were conducted by two reviewers independently using standardised data extraction forms and quality appraisal tools. A thematic synthesis was conducted by two reviewers of the qualitative studies included and categorised into the barriers and facilitators of escalation. GRADE CERQual was used to assess the certainty of the evidence. RESULTS: Eighteen studies incorporating a variety of HCPs across seven countries were included. The barriers and facilitators to the escalation of care according to EWS protocols were developed into five overarching themes: Governance, Rapid Response Team (RRT) Response, Professional Boundaries, Clinical Experience, and EWS parameters. Barriers to escalation included: Lack of Standardisation, Resources, Lack of accountability, RRT behaviours, Fear, Hierarchy, Increased Conflict, Over confidence, Lack of confidence, and Patient variability. Facilitators included: Accountability, Standardisation, Resources, RRT behaviours, Expertise, Additional support, License to escalate, Bridge across boundaries, Clinical confidence, empowerment, Clinical judgment, and a tool for detecting deterioration. These are all individual yet inter-related barriers and facilitators to escalation. CONCLUSIONS: The findings of this qualitative evidence synthesis provide insight into the real world experience of HCPs when using EWSs. This in turn has the potential to inform policy-makers and HCPs as well as hospital management about emergency response system-related issues in practice and the changes needed to address barriers and facilitators and improve patient safety and quality of care.

A validated photonumeric scale for infraorbital dark circles and its application in evaluating the efficacy of a cosmetic treatment product in a split-face randomized clinical trial.

OBJECTIVE: As a result of their complex aetiology and periodicity, dark circles are difficult to characterize and measure, with current assessment techniques relying on specialist equipment, image analysis or proprietary grading scales. There is therefore a need to develop and validate a photonumeric scale for assessing infraorbital dark circles, which can provide an objective and consumer relevant tool for evaluating this condition and the efficacy of treatment products and procedures. METHODS: A panel of expert clinical evaluators reviewed approximately three thousand facial photographs collected over a 5-year period and selected images representing a dynamic range of dark circles. A 10-point photonumeric scale was created, with corresponding descriptors and images for each grade of the scale. To rigorously validate the scale, linearity, sensitivity and precision were assessed by colorimetry and in-clinic evaluation. Reproducibility was assessed photographically with both experienced and inexperienced clinical evaluators, whereas intragrader repeatability was assessed live in-clinic. The scale was then employed in a split-face randomized clinical trial on 58 subjects to evaluate the efficacy of a cosmetic treatment product over 8 weeks. RESULTS: Colour analysis of the images showed the scale was linear, with statistically significant correlations observed when colour data (CIElab; Individual Typology Angle) were plotted against the corresponding grades (r > 0.9, P < 0.001). Colour difference (Delta E) was calculated between the infraorbital zone and the surrounding skin, and when data were plotted against the grades, a statistically significant correlation was observed (r = 0.99, P < 0.01). The magnitude of the Delta E suggested that changes in grade are visibly perceptible to the human eye, and therefore, the scale is sensitive and clinically relevant. Intergrader reproducibility showed strong correlation (0.96) and >90% agreement between experienced evaluators, whereas intragrader repeatability assessment showed >90% perfect agreement between grades. Use of this scale in a clinical trial demonstrated the efficacy of a cosmetic product, with a mean statistically significant (P < 0.001) decrease in grade of 0.74 compared to baseline, and 0.59 versus the untreated control, after 8 weeks of treatment. CONCLUSION: Our photonumeric scale for infraorbital dark circles is sensitive and robust and provides an objective and easy-to-use tool to evaluate dark circles and their treatment.

OBJECTIF: En raison de leur étiologie et de leur périodicité complexes, les cernes sont difficiles à caractériser et à mesurer, les techniques d'évaluation actuelles reposant sur des équipements spécialisés, l'analyse d'images ou des échelles de notation exclusives. Il est donc nécessaire de développer et de valider une échelle photonumérique pour évaluer les cernes infraorbitaires, laquelle peut fournir un outil objectif et pertinent pour le consommateur et tester l'efficacité des produits et des procédures de traitement. MÉTHODES: Un panel d'évaluateurs cliniques experts a examiné environ trois mille photographies du visage recueillies sur une période de 5 ans, ainsi que des images sélectionnées représentant une plage dynamique de cernes. Une échelle photonumérique à 10 points a été créée, avec des descripteurs et des images correspondants à chaque grade de l'échelle. Afin de valider rigoureusement l'échelle, la linéarité, la sensibilité et la précision ont été évaluées par colorimétrie et en clinique. La reproductibilité a été évaluée sur le plan photographique par des évaluateurs cliniques expérimentés et inexpérimentés, tandis que la répétabilité intragrade a été évaluée en direct en clinique. L'échelle a ensuite été utilisée dans un essai clinique randomisé à deux parties sur 58 sujets, afin d'évaluer l'efficacité d'un produit de traitement cosmétique sur 8 semaines. RÉSULTATS: L'analyse des couleurs des images a montré que l'échelle était linéaire, avec des corrélations statistiquement significatives observées lorsque les données de couleurs (CIElab ; angle de typologie individuel) ont été tracées par rapport aux grades correspondants (r > 0,9, P < 0,001). La différence de couleur (Delta E) a été calculée entre la zone infraorbitaire et la peau environnante, et lorsque les données ont été tracées par rapport aux grades, une corrélation statistiquement significative a été observée (r = 0,99, P < 0,01). L'ampleur du delta E a suggéré que les changements de grade sont visiblement perceptibles à l'œil humain, l'échelle étant par conséquent sensible et cliniquement pertinente. La reproductibilité intergrade a montré une forte corrélation (0,96) et une concordance > 90 % entre les évaluateurs expérimentés, tandis que l'évaluation de la répétabilité intragrade a montré une concordance parfaite > 90 % entre les grades. L'utilisation de cette échelle lors d'un essai clinique a démontré l'efficacité d'un produit cosmétique, avec une diminution moyenne statistiquement significative (P < 0,001) du grade de 0,74 par rapport à la référence, et de 0,59 par rapport au témoin non traité, après 8 semaines de traitement. CONCLUSION: Notre échelle photonumérique pour les cernes infraorbitaires est sensible et robuste, fournissant un outil objectif et facile à utiliser afin d'évaluer les cernes et leur traitement.

Cell shape regulates subcellular organelle location to control early Ca2+ signal dynamics in vascular smooth muscle cells.

The shape of the cell is connected to its function; however, we do not fully understand underlying mechanisms by which global shape regulates a cell's functional capabilities. Using theory, experiments and simulation, we investigated how physiologically relevant cell shape changes affect subcellular organization, and consequently intracellular signaling, to control information flow needed for phenotypic function. Vascular smooth muscle cells going from a proliferative and motile circular shape to a contractile fusiform shape show changes in the location of the sarcoplasmic reticulum, inter-organelle distances, and differential distribution of receptors in the plasma membrane. These factors together lead to the modulation of signals transduced by the M3 muscarinic receptor/Gq/PLCß pathway at the plasma membrane, amplifying Ca2+ dynamics in the cytoplasm, and the nucleus resulting in phenotypic changes, as determined by increased activity of myosin light chain kinase in the cytoplasm and enhanced nuclear localization of the transcription factor NFAT. Taken together, our observations show a systems level phenomenon whereby global cell shape affects subcellular organization to modulate signaling that enables phenotypic changes.

Seasonality of suicide: a multi-country multi-community observational study.

AIMS: We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations. METHODS: Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986-2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression. RESULTS: We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33-1.62) to 1.05 (95% CI: 1.01-1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05). CONCLUSIONS: Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.

On the use of Europium (Eu) for designing new metal-based anticancer drugs.

Europium oxide (Eu2O3) was used to evaluate the affinity of this rare earth element for interacting with double-stranded (ds) DNA molecules. To perform the study, we used single molecule force spectroscopy with optical tweezers and gel electrophoresis assays. Force spectroscopy experiments show that Eu2O3 presents a strong interaction with dsDNA, and the binding is independent on the ionic strength used in the surrounding environment. Among the main characteristics of the interaction, Eu2O3 tends to bind in a cooperative way, forming bound clusters of ∼ 3 molecules, and presents a high equilibrium association binding constant on the order of 105 M-1. In addition, gel electrophoresis confirm the weak electrostatic character of the interaction and explicit show that Eu2O3 does not interfere on drug intercalation into the double-helix. Such results demonstrate the potential of europium for interacting with nucleic acids and strongly suggest that this rare earth element may be considered for the design of new metal-based anticancer drugs in the future.

The missing sink - quantification, categorisation and sourcing of beached macro-debris in the Scottish Orkney Islands.

Around the coastline of the UK, macro-debris has been observed in average densities of over 700 items per metre. Systematic beach-cleans were conducted at 35 sites around the Scottish Orkney Islands, in order to quantify and categorise the level of marine debris found there. Litter was collected from 100 m transects and categorised by its material, broad source (terrestrial or marine) and potential sector source. Variation between sites, and the relative contribution of pre-determined environmental variables in influencing said variation, were analysed using the "capscale" function for a canonical analysis of principle coordinates (CAP). 513 items/m were observed, (77% plastic), with "String/cord (<1cm diameter)" being the most abundant and widely distributed litter type. 47% of macro-debris was attributed to the fishing sector and < 10% to leisure, living and tourism-associated activities. Conversely, the unique regional hydrodynamics must be examined further, before the source of any given item can be categorically assigned.

Mars Extant Life: What's Next? Conference Report.

On November 5-8, 2019, the "Mars Extant Life: What's Next?" conference was convened in Carlsbad, New Mexico. The conference gathered a community of actively publishing experts in disciplines related to habitability and astrobiology. Primary conclusions are as follows: A significant subset of conference attendees concluded that there is a realistic possibility that Mars hosts indigenous microbial life. A powerful theme that permeated the conference is that the key to the search for martian extant life lies in identifying and exploring refugia ("oases"), where conditions are either permanently or episodically significantly more hospitable than average. Based on our existing knowledge of Mars, conference participants highlighted four potential martian refugium (not listed in priority order): Caves, Deep Subsurface, Ices, and Salts. The conference group did not attempt to reach a consensus prioritization of these candidate environments, but instead felt that a defensible prioritization would require a future competitive process. Within the context of these candidate environments, we identified a variety of geological search strategies that could narrow the search space. Additionally, we summarized a number of measurement techniques that could be used to detect evidence of extant life (if present). Again, it was not within the scope of the conference to prioritize these measurement techniques-that is best left for the competitive process. We specifically note that the number and sensitivity of detection methods that could be implemented if samples were returned to Earth greatly exceed the methodologies that could be used at Mars. Finally, important lessons to guide extant life search processes can be derived both from experiments carried out in terrestrial laboratories and analog field sites and from theoretical modeling.

A Rare Case of Infertility: SRY Positive 46, XX Testicular Disorder of Sexual Differentiation.

Aim To highlight the complexity of infertility causes by describing the rare case of a man with a testicular disorder of sexual differentiation. Diagnosis A 33 years old Caucasian male presented with a 3-year-old history of primary infertility. His investigations revealed a low testosterone and a raised LH and FSH levels. A sample sent for sperm analysis revealed azoospermia. Chromosomal analysis and karyotyping revealed a 46 XX SRY positive karyotype. Treatment The patient was initiated on testosterone replacement and on calcium/vitamin D supplements. Conclusion Fertility evaluation requires complex assessments and a broad knowledge of possible causes.

Non-use of cancer information services among people experiencing cancer in Ireland.

PURPOSE: The purpose of this study was to explore the reasons for non-use of a national cancer society's cancer information services among people experiencing cancer. METHOD: This study used a qualitative design. Semi-structured interviews were conducted with a total of 17 participants who had not previously utilised the Cancer Society's information services. Data were analysed using Thematic Analysis. RESULTS: The key themes to emerge from the date were 'living in the here and now' and 'awareness of the Cancer Society'. For most participants, not utilising cancer information services was a means of coping with the initial diagnosis and the impact of treatment. Those who progressed to being ready to seek information identified the multi-disciplinary team as the primary source of trusted information, with particular mention of cancer nurse specialists. For participants with children, their role as a parent was central in how they managed their diagnosis. The majority of participants lacked awareness of the range of services provided by the Cancer Society. CONCLUSIONS: Reasons for non-use of cancer information services were identified as: readiness to seek information and a lack of knowledge of the Cancer Societies' services. Cancer information services need to continue make a concerted effort to enhance visibility and awareness of its services to optimise patient engagement.

Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

PURPOSE: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. METHODS: At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. RESULTS: Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. CONCLUSION: Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.