Evaluation of existing and desired antimicrobial stewardship activities and strategies in Swiss hospitals.

Antimicrobial stewardship (AMS) is an important component in the fight against antimicrobial resistance. Currently, few hospitals have an ongoing institutional AMS programme. Swissnoso - the national centre for infection prevention - has launched a national Swiss AMS initiative supported by the office of public health. To guide AMS priorities and resources, current AMS activities in Switzerland were assessed. We distributed an internet-based questionnaire directed mainly to board-certified infectious diseases specialists and, if not available, senior internal medicine staff. Responses were received from 63/134 hospitals surveyed. More than 90% were in favour of national treatment guidelines currently in development under the umbrella of the Swiss society for infectious diseases. Many AMS activities - such as antimicrobial formulary restrictions and approval systems, review of antimicrobial prescriptions with point of care intervention, and direct feedback or therapeutic drug monitoring - are currently lacking in the majority of Swiss hospitals surveyed. Development of a modular formal AMS standard for Swiss hospitals may aid in advancing current AMS strategies and in introducing AMS programmes in Switzerland. In combination with the surveillance of antimicrobial use and resistance by ANRESIS, the national antimicrobial resistance surveillance system, this approach may reduce the use of antimicrobial agents and consequently the risk of emergence of multi-resistant pathogens

The perspective of people with axial spondyloarthritis regarding physiotherapy : room for the implementation of a more active approach

Objectives. Physiotherapy is recommended in the management of people with axial spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. The aim of this study was to describe the use and preferences regarding individual and group physiotherapy among people with axSpA. Methods. A cross-sectional survey was conducted among people with axSpA living in The Netherlands (NL) and Switzerland (CH). Results. Seven hundred and thirteen people with axSpA participated (56.7% male, median age 55 years, median Assessment of Spondyloarthritis International Society Health Index score 4.2). Response rates were 45% (n¼206) in NL and 29% in CH (n¼507). Of these participants, 83.3% were using or had been using physiotherapy. Individual therapy only was used or had been used by 36.7%, a combination of individual plus land- and water-based group therapy by 29.1% and group therapy by only 5.3%. Fewer than half of the participants attending individual therapy reported active therapy (such as aerobic, muscle strength and flexibility exercises). Although the majority (75.9%) were not aware of the increased cardiovascular risk, participants showed an interest in cardiovascular training, either individually or in a supervised setting. If supervised, a majority, in CH (75.0%) more than in NL (55.7%), preferred supervision by a specialized physiotherapist. Conclusion. The majority of people with axSpA use or have used physiotherapy, more often in an individual setting than in a group setting. The content of individual therapy should be more active; in both therapy settings, aerobic exercises should be promoted. In particular, enabling people with axSpA to perform exercises independently would meet their needs and might enhance their daily physical activity

Serum antibodies in first-degree relatives of patients with IBD: A marker of disease susceptibility? A follow-up pilot-study after 7 years

Introduction: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. Patients and Methods: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. Results: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p = 1). Discussion: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Serum antibodies in first-degree relatives of patients with IBD: A marker of disease susceptibility? A follow-up pilot-study after 7 years

Introduction: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. Patients and Methods: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. Results: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p = 1). Discussion: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn

Evidence for strong, widespread chlorine radical chemistry associated with pollution outflow from continental Asia

The chlorine radical is a potent atmospheric oxidant, capable of perturbing tropospheric oxidative cycles normally controlled by the hydroxyl radical. Significantly faster reaction rates allow chlorine radicals to expedite oxidation of hydrocarbons, including methane, and in polluted environments, to enhance ozone production. Here we present evidence, from the CARIBIC airborne dataset, for extensive chlorine radical chemistry associated with Asian pollution outflow, from airborne observations made over the Malaysian Peninsula in winter. This region is known for persistent convection that regularly delivers surface air to higher altitudes and serves as a major transport pathway into the stratosphere. Oxidant ratios inferred from hydrocarbon relationships show that chlorine radicals were regionally more important than hydroxyl radicals for alkane oxidation and were also important for methane and alkene oxidation (>10%). Our observations reveal pollution-related chlorine chemistry that is both widespread and recurrent, and has implications for tropospheric oxidizing capacity, stratospheric composition and ozone chemistry

A Case of Hypocomplementemic Urticarial Vasculitis Syndrome With Severe Renal and Gastrointestinal Involvement

We present a severe case of hypocomplementemic urticarial vasculitis syndrome (HUVS) and its diagnostic and therapeutic challenges. A 56-year-old male presenting with fever and impaired kidney function was diagnosed with HUVS. Before the initiated treatment was effective, he developed severe colon ischemia, and a subtotal colectomy was required. We discuss other affected organs, such as kidneys, lungs, the heart, and the skin. Pathophysiology is briefly reviewed and the difficulty of overlapping autoimmune diseases is discussed. Treatment continues to be challenging, as there is no consensus about the optimal immunosuppressive therapy

No association of complement mannose-binding lectin deficiency with cardiovascular disease in patients with Systemic Lupus Erythematosus.

Cardiovascular (CV) morbidity is the major cause of death in patients with Systemic Lupus Erythematosus (SLE). Previous studies on mannose-binding lectin (MBL) gene polymorphisms in SLE patients suggest that low levels of complement MBL are associated with cardiovascular disease (CVD). However, as large studies on MBL deficiency based on resulting MBL plasma concentrations are lacking, the aim of our study was to analyze the association of MBL concentrations with CVD in SLE patients. Plasma MBL levels SLE patients included in the Swiss SLE Cohort Study were quantified by ELISA. Five different CV organ manifestations were documented. Of 373 included patients (85.5% female) 62 patients had at least one CV manifestation. Patients with MBL deficiency (levels below 500 ng/ml or 1000 ng/ml) had no significantly increased frequency of CVD (19.4% vs. 15.2%, P = 0.3 or 17.7% vs. 15.7%, P = 0.7). After adjustment for traditional CV risk factors, MBL levels and positive antiphospholipid serology (APL+) a significant association of CVD with age, hypertension, disease duration and APL+ was demonstrated. In our study of a large cohort of patients with SLE, we could not confirm previous studies suggesting MBL deficiency to be associated with an increased risk for CVD

Eucapnic Voluntary Hyperpnea: Gold Standard for Diagnosing Exercise-Induced Bronchoconstriction in Athletes?

In athletes, a secure diagnos is of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the ‘gold standard’. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a ‘gold standard’ test for EIB