Baseline Demographics, Comorbidities, Treatment Patterns and Burden of Atopic Dermatitis in Adults and Adolescents from the GLOBOSTAD Long-Term Observational Study

Introduction - Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. Methods - The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. Results - Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. Conclusion - Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Hydrogen Uptake and Embrittlement of Carbon Steels in Various Environments

To avoid failures due to hydrogen embrittlement, it is important to know the amount of hydrogen absorbed by certain steel grades under service conditions. When a critical hydrogen content is reached, the material properties begin to deteriorate. The hydrogen uptake and embrittlement of three different carbon steels (API 5CT L80 Type 1, P110 and 42CrMo4) was investigated in autoclave tests with hydrogen gas (H2) at elevated pressure and in ambient pressure tests with hydrogen sulfide (H2S). H2 gas with a pressure of up to 100 bar resulted in an overall low but still detectable hydrogen absorption, which did not cause any substantial hydrogen embrittlement in specimens under a constant load of 90% of the specified minimum yield strength (SMYS). The amount of hydrogen absorbed under conditions with H2S was approximately one order of magnitude larger than under conditions with H2 gas. The high hydrogen content led to failures of the 42CrMo4 and P110 specimens

Bogus refugees? The determinants of asylum migration to Western Europe

This article analyses the determinants of asylum migration to Western Europe. Potential asylum seekers balance the costs of staying versus the costs of migrating. Estimation results confirm that economic hardship and economic discrimination against ethnic minorities lead to higher flows of asylum seekers. However, political oppression, human rights abuse, violent conflict and state failure are also important determinants. Migration networks and geographical proximity are important facilitators of asylum flows as predicted by theory. Colonial experience, religious similarity and casual contact with the developed world (aid, trade and tourism) are not. Natural disasters and famines are also not statistically significant determinants. These events are typically short-term and unexpected, whereas asylum migration to Western Europe requires preparatory planning. If Western European countries want to tackle the root causes of asylum migration, then they need to undertake policy measures that promote economic development, democracy, respect for human rights and peaceful conflict resolution in countries of origin

Accidental hypothermia–an update

Background: This paper provides an up-to-date review of the management and outcome of accidental hypothermia patients with and without cardiac arrest. Methods: The authors reviewed the relevant literature in their specialist field. Summaries were merged, discussed and approved to produce this narrative review. Results: The hospital use of minimally-invasive rewarming for non-arrested, otherwise healthy, patients with primary hypothermia and stable vital signs has the potential to substantially decrease morbidity and mortality for these patients. Extracorporeal life support (ECLS) has revolutionised the management of hypothermic cardiac arrest, with survival rates approaching 100 % in some cases. Hypothermic patients with risk factors for imminent cardiac arrest (temperature <28 °C, ventricular arrhythmia, systolic blood pressure <90 mmHg), and those who have already arrested, should be transferred directly to an ECLS-centre. Cardiac arrest patients should receive continuous cardiopulmonary resuscitation (CPR) during transfer. If prolonged transport is required or terrain is difficult, mechanical CPR can be helpful. Delayed or intermittent CPR may be appropriate in hypothermic arrest when continuous CPR is impossible. Modern post-resuscitation care should be implemented following hypothermic arrest. Structured protocols should be in place to optimise pre-hospital triage, transport and treatment as well as in-hospital management, including detailed criteria and protocols for the use of ECLS and post-resuscitation care. Conclusions: Based on new evidence, additional clinical experience and clearer management guidelines and documentation, the treatment of accidental hypothermia has been refined. ECLS has substantially improved survival and is the treatment of choice in the patient with unstable circulation or cardiac arrest.Medicine, Faculty ofNon UBCEmergency Medicine, Department ofReviewedFacult

Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication

AbstractEmerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis

Asylum recognition rates in Western Europe : their determinants, variation, and lack of convergence

Substantial variation in recognition rates for asylum claims from the same countries of origin and therefore prima facie equal merit subjects refugees to unfair and discriminatory treatment. This article demonstrates the extent of variation and lack of convergence over the period 1980 to 1999 across Western European destination countries. Refugee interest groups also suspect that political and economic conditions in destination countries as well as the number of past asylum claims unduly impact upon recognition rates. This article estimates the determinants of asylum recognition rates. Origin-specific recognition rates vary, as they should, with the extent of political oppression, human rights violations, inter-state armed conflict and events of genocide and politicide in countries of origin. Recognition rates for the full protection status only are lower in times of high unemployment in destination countries. Such rates are also lower if many asylum seekers from a country of origin have already applied for asylum in the past