Einfluss der Peergruppen auf die erste Berufswahl - Situationsanalyse und Möglichkeiten für einen Nutzen in der Berufsorientierung

Gegenstand dieser Arbeit ist eine Analyse des Einflusses, den Jugendliche im Berufswahlprozess durch ihre Peers erfahren. Antworten darauf wurden in der Theorie gefunden und durch qualitativen Interviews erhoben und verifiziert. Ebenso gibt diese Arbeit den Jugendlichen eine Plattform, ihre Ideen und Tipps an eine nächste Generation von Berufswählenden weiterzugeben. Diese werden gesammelt und interpretiert. Die Gleichaltrigengruppe ist für Jugendliche eine zentrale Lebenswelt. Soziale Kompetenzen, Sach- und Fachkompetenzen werden in dieser geübt und erworben, Lebensstil, Werte, Normen und Ausdrucksweisen entwickelt und überprüft. Um die altersspezifischen Entwicklungsaufgaben lösen zu können, brauchen sie die Gleichaltrigengruppe. Die Bedeutung der Gleichaltrigengruppe in der Berufswahl wird von Jugendlichen unterschiedlich bewertet. Untereinander erzählen sie sich von ihren Berufswünschen und bewerten diese. Ihnen ist wichtig voneinander eine Bewertung ihres Berufswunsches zu erhalten. Diese hilft ihnen dabei, ihre Entscheidung zu überdenken, bestätigt sie in ihrem Vorhaben oder bringt sie dazu, einen Beruf fallen zu lassen. In der Unterstützung durch Peers liegt ein grosses Potenzial. Jugendliche können einander helfen, die Berufswahlbereitschaft zu fördern, wenn sie eine wertschätzende Gesprächskultur untereinander entwickelt haben. Neben dieser sind alle Interventionen, die Jugendliche anregen, das Thema Berufswahl zu diskutieren förderlich für eine Steigerung der Berufswahlbereitschaft

Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial).

OBJECTIVE Proteome analyses in patients with newly diagnosed, untreated giant cell arteritis (GCA) have not been reported previously, nor are changes of protein expression upon treatment with glucocorticoids (GC) and/or tocilizumab (TCZ) known. The GUSTO trial allows to address these questions, provides the opportunity to learn about the differential effects of GC and TCZ on proteomics and may help to identify serum proteins to monitor disease activity. METHODS Serum samples obtained from 16 patients with new-onset GCA at different time points (day 0, 3, 10, and week 4, 24, 52) during the GUSTO trial (NCT03745586) were examined for 1436 differentially expressed proteins (DEPs) based on proximity extension assay technology. The patients received 500 mg methylprednisolone intravenously for 3 consecutive days followed by TCZ monotherapy. RESULTS When comparing day 0 (before the first GC infusion) with week 52 (lasting remission), 434 DEPs (213↑, 221↓) were identified. In response to treatment, the majority of changes occurred within 10 days. GC inversely regulated 25 proteins compared to remission. No difference was observed between weeks 24 and 52 during established remission and ongoing TCZ treatment. Expression of CCL7, MMP12, and CXCL9 was not regulated by IL6. CONCLUSION Disease-regulated serum proteins improved within 10 days and were normalized within 24 weeks, showing a kinetic corresponding to the gradual achievement of clinical remission. The proteins inversely regulated by GC and TCZ shed light on the differential effects of the two drugs. CCL7, CXCL9, and MMP12 are biomarkers that reflect disease activity despite normalized C-reactive protein levels

Seasonality of the antibiotic resistance gene blaCTX-M in temperate Lake Maggiore

The beta lactamase gene blaCTX-M, responsible of the resistance to cephalosporins, has been detected in microbes from hospitals to open waters. We studied the seasonality and stability of blaCTX-M in Lake Maggiore over 3 years and the role of potential inputs of allochthonous bacteria and/or antibiotic pollution in promoting its occurrence. blaCTX-M was mainly present from January to July in the pelagic microbial community and the gene occurrence was significantly related to low water temperature. To evaluate its temporal stability in the bacterial community over a short period, we measured blaCTX-M daily over the course of 6 days. The gene was below the limit of quantification except for one sampling when its abundance peaked, suggesting a point contamination. The bacterial community of the lake in which blaCTX-M was detected suggests that at least two distinct bacterial populations contained the gene. The occurrence of known blaCTX-M containing genera and the occurrence of the gene, however, did not overlap. Furthermore, the experimental addition of cefotaxime to lake water incubations did not promote abundance of the gene. These data imply that blaCTX-M was present in the environmental microbial community. Increases of gene abundances were likely caused by environmental parameters other than antibiotic contamination

Lake water as reservoir of antibiotic resistance genes constitutively present within the natural microbial community

The fate of antibiotic resistance genes (ARGs) in environmental microbial community is largely unknown although ARGs can constitute a threat for human health. In order to understand the dynamics and the relations of ARGs with biotic and abiotic factors in aquatic environment, we sampled water for 1.5 year in four stations of Lake Maggiore; for one of them (Ghiffa), we also sampled water from the whole water column. Moreover, for Ghiffa station, limnological parameters and prokaryotic cell abundance were determined. Each water sample was filtered and processed for the presence of twelve ARGs by PCR and, for the positive ARGs, qPCR protocols were developed. In order to investigate the relations between ARGs profiles and microbial community composition, we also sampled water every day for one week in Pallanza station. The DNA recovered during both the 18 months\u27 (long term) and the week (short term) monitoring were analyzed for the presence and abundance of ARGs and for the microbial community composition by 16SrDNA Illumina sequencing. Four ARGs were detectable in all stations during the whole sampling campaign, for instance tet(A) and sulII genes resulted quantifiable in more than half of the samples, and their abundance was positively correlated to oxygen and negatively to chlorophyll a, while str(B) and blaCTXM were present but rarely quantifiable. The composition of the microbial community was stable during the week while a seasonality was observed during 1.5 year of analysis. Moreover a potential relation between the presence of blaCTXM and the abundance of Flavobacteria was observed. All together, these results suggest the Lake as reservoir of ARGs fixed within the natural microbial community, thus it can constitute a hazardous hotspot for the transmission of antibiotic resistance to human pathogens

Influence of Antihypertensive Treatment on RAAS Peptides in Newly Diagnosed Hypertensive Patients.

(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1-7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1-7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II (p < 0.0005 for 8 a.m., 12 a.m.) and Ang (1-7) (p = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p < 0.0005), amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001). Ang (1-7) was increased by perindopril and olmesartan (p = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide

Management of giant-cell arteritis in Switzerland: an online national survey.

AIMS OF THE STUDY To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools. METHODS We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics. RESULTS Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice. CONCLUSIONS This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas

Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on childre

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Importance: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants: The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions: HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures: The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results: A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance: Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration: isrctn.org Identifier: ISRCTN5437125