Trends of atropinic (anticholinergic) exposure in the elderly: a 10‐year analysis in the French EGB database

Atropinic drugs are known to potentially induce physical and/or mental impairments in the elderly. The aim of this study was to investigate trends of atropinic exposure in patients ≥65 years in France between 2006 and 2015. A repeated cross‐sectional study was performed quarterly from January 1, 2006 to December 31, 2015, in the ‘Echantillon Généraliste des Bénéficiaires (EGB)’, a representative sample of the French population. Exposed patients were identified using the Anticholinergic Durán's list. Outcomes were rate of patients exposed to at least one atropinic drug (atropinic prevalence rate) and atropinic burden per patient (sum of atropinic burden scores). Interrupted time series were used to analyze the impact of market withdrawal of some drugs with atropinic properties during the period of the study. The number of patients ≥65 years registered in the EGB ranged from 75 611 in 2006 to 95 389 in 2015. Atropinic prevalence rate decreased significantly from 45.6% in 2006 to 33.2% in 2015 (?12.4%, slope significance P < 0.05). Subjects aged ≥85 years were the most exposed. Total atropinic burden decreased significantly between 2006 and 2015 (2.2 ± 1.7 in 2006; 2.0 ± 1.5 in 2015; slope significance P < 0.05), especially in patients ≥85 years. Market withdrawals for safety reasons of some atropinic drugs were significantly associated with a decrease in the atropinic prevalence rate (P < 0.05) and atropinic burden per patient (P < 0.05). In conclusion, atropinic drug exposure in the elderly significantly decreased in France between 2006 and 2015. This decrease can be partly explained by regulatory measures against some atropinic drugs.     

S1 guideline on occupational skin products: protective creams,skin cleansers,skin care products (ICD 10: L23, L24) – short version

Job‐related hand dermatitis heads up the list of reported occupational diseases. So‐called skin products – understood to mean protective creams, skin cleansers and skin care products – are used for the primary and secondary prevention of job‐ related hand dermatitis. In the interests of evidence‐based medicine, the only preventive measures and/or occupational skin products that should be used are those whose potential uses and efficacy are underpinned by scientific research. To this end, the Arbeitsgemeinschaft für Berufs‐ und Umweltdermatologie e.V. (Working Group for Occupational and Environmental Dermatology, ABD) of the DDG (German Dermatological Society) and the Deutsche Gesellschaft für Arbeits‐ und Umweltmedizin (German Society for Occupational and Environmental Medicine, DGAUM) have summed up the latest scientific findings and recommendations in the updated guideline. The benefit of the combined application of protective creams and skin care products in the primary and secondary prevention of work‐related contact dermatitis has been widely confirmed by recent clinical‐epidemiological studies. The guideline clearly explains the necessity of demonstrating the efficacy of protective creams and cleansing products by means of in vivo methods in the sense of repetitive applications. Transferable standardised testing systems designed to examine the irritation potential and thus the compatibility of occupational skin cleansers and the reduction of irritation by protective skin creams have now been developed and validated by multicentre studies for skin protection creams and cleansers. The status of the current assessment of the safety of occupational skin products is also summarised.     

Target antigen expression on a professional antigen-presenting cell induces superior proliferative antitumor T-cell responses via chimeric T-cell receptors

Human T cells expressing tumor antigen-specific chimeric receptors fail to sustain their growth and activation in vivo, which greatly reduces their therapeutic value. The defective proliferative response to tumor cells in vitro can partly be overcome by concomitant CD28 costimulatory signaling. We investigated whether T-cell activation via chimeric receptors (chRec) can be further improved by ligand expression on antigen-presenting cells of B-cell origin. We generated Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) expressing a CD19-specific chRec. These CTLs are provided with native receptor stimulation by autologous EBV-transformed B-lymphoblastoid cell lines (LCLs) but exclusively with chRec (CD19-specific) stimulation by allogeneic, human leukocyte antigen (HLA)-mismatched CD19+ LCLs. CD19zeta-transduced EBV-specific CTLs specifically lysed both allogeneic EBV targets and CD19+ tumor cells through the chRec in a major histocompatibility complex-independent manner, while maintaining their ability to recognize autologous EBV targets through the native T-cell receptor. The transduced CTLs failed to proliferate in response to CD19+ tumor targets even in the presence of CD28 costimulatory signaling. By contrast, CD19 expressed on HLA-mismatched LCL-induced T-cell activation and long-term proliferation that essentially duplicated the result from native receptor stimulation with autologous LCLs, suggesting that a deficit of costimulatory molecules on target cells in addition to CD28 is indeed responsible for inadequate chRec-mediated T-cell function. Hence, effective tumor immunotherapy may be favored if engagement of the chRec on modified T cells is complemented by interaction with multiple costimulator molecules. The use of T cells with native specificity for EBV may be one means of attaining this objective.     

Self-labelling and stigma as predictors of attitudes towards help-seeking among people at risk of psychosis: 1-year follow-up

Mental health service use is helpful but rare among young people at risk of psychosis. The label and stigma associated with mental illness may affect attitudes towards help-seeking. We examined 67 individuals at risk of psychosis over the course of 1 year. An increase of self-labelling as “mentally ill” predicted more positive attitudes towards psychiatric medication, while increased perceived stigma and the cognitive appraisal of stigma as a stressor predicted poorer attitudes towards psychotherapy after 1 year. Early intervention could improve non-stigmatizing awareness of at-risk mental state and reduce the public stigma associated with at-risk status to facilitate help-seeking.     

Detection of Haemophilus influenzae type b by real-time PCR

A real-time PCR assay targeting the capsulation locus of Haemophilus influenzae type b (Hib) was developed. The linear detection range was from 1 to 10(6) microorganisms per reaction mixture. No H. influenzae other than Hib or any other control bacteria typically found in the upper respiratory tract was detected.     

Fibrin-polyurethane composites for articular cartilage tissue engineering: a preliminary analysis

In this study we investigated the use of a fibrin hydrogel to improve the potential of a polyurethane (PU) scaffold-based system for articular cartilage tissue engineering. PU-only ("no-fibrin") and PU-fibrin ("fibrin") composites were cultured for up to 28 days and analyzed for DNA content, glycosaminoglycan (GAG) content, type II collagen content, GAG release, and gene expression of aggrecan, collagen I, and collagen II. The use of fibrin allowed for higher viable cell-seeding efficiency (10% higher DNA content on day 2 in fibrin versus no-fibrin composites) and more even cell distribution on seeding, a more than 3-fold increase in the percentage of newly synthesized GAG retained in the constructs, and 2- to 6-fold higher levels of type II collagen and aggrecan gene expression through day 14. Addition of aprotinin to the medium inhibited fibrin degradation, most noticeably in the center of the constructs, but had little effect on biochemical composition or gene expression. Short-term mechanical compression (0-10% sinusoidal strain at 0.1 Hz for 1 h, applied twice daily for 3 days) doubled the rate of GAG release from the constructs, but had little effect on gene expression, regardless of the presence of fibrin. Although further work is needed to optimize this system, the addition of fibrin hydrogel to encapsulate cells in the stiff, macroporous PU scaffold is a step forward in our approach to articular cartilage tissue engineering.     

Evaluation of a novel rapid one-step immunochromatographic assay for detection of monoclonal Helicobacter pylori antigen in stool samples from children

A new rapid one-step immunochromatographic test using monoclonal antibodies for detection of Helicobacter pylori antigen in stool in children was evaluated on coded stool samples from 159 children (mean age, 9.7 +/- 5.0 years; 118 from Munich, 41 from Vienna): 86 children were H. pylori infected defined by positive culture and/or > or =2 other positive tests ([13C]urea breath test, histology, rapid urease test), and 73 children showed concordant negative results. Seventy-nine patients (12.1 +/- 3.8 years; 42 from Munich; 37 from Vienna) were tested 6 to 8 weeks after anti-Helicobacter pylori therapy with urea breath test and stool test. In Munich, all 160 tests (118 pre- and 42 posttreatment) were independently read by two observers. Equivocal results were excluded for calculation of sensitivity and specificity but were considered as false to assess accuracy. The two observers in Munich agreed in 63 out of 65 positive and 89 out of 95 negative results, while eight times (5.0%) they judged the test as equivocal. Pretreatment and posttreatment results for sensitivity were 88.1% (79.2 to 94.1) and 88.9% (51.8 to 99.7), specificity 88.1% (77.8 to 94.1) and 93.9% (85.2 to 98.3), and accuracy 83.5% and 81.5%, respectively. We conclude that the new monoclonal immunochromatographic quick test shows a good interobserver agreement, but equivocal results occur in 5%. Performance is comparable before and after therapy. The test may become a good alternative in children in settings where a [13C]urea breath test or a reliable enzyme immunoassay stool test are not available.     

Influence of catheter intervention on platelet function and activation in a pig model for endovascular embolization of arteriovenous malformations

Catheter interventions are associated with the risk of thromboembolism; however, the extent of platelet activation is not known. Samples from an arteriovenous malformation model (n?=?21 pigs) were examined. The pigs received a continuous infusion of 66?IU?kg^?1?h^?1 (n?=?11) or 100?IU?kg^?1?h^?1 (n?=?10) heparin applied 20?min after an initial bolus of 100?IU/kg. Platelet aggregation according to Born and ADVIA 120? platelet activation indices were used to study platelet function and activation. Samples were taken previous to vascular puncture, following vascular puncture, 20?min after application of heparin bolus, following placement of microcatheters and after endovascular embolization. Reactivity of platelets was increased after puncture of the vessels (ADP: P?<?0. 0001, collagen: P?=?0.0053). Further on activity of platelets was constrained by heparinization (ADP: P?<?0.0001, collagen P?<?0.0001). It can be concluded that the puncture of vessels yields the highest risk of thromboembolic complications.