Frequent users of the emergency department in a universal health coverage system : a randomized controlled trial of a case-management intervention

BACKGROUND: Frequent emergency department users represent a small number of patients but account for a large number of emergency department visits. They should be a focus because they are often vulnerable patients with many risk factors affecting their quality of life (QoL). Case management interventions have resulted in a significant decrease in emergency department visits, but association with QoL has not been assessed. One aim of our study was to examine to what extent an interdisciplinary case management intervention, compared to standard emergency care, improved frequent emergency department users' QoL. METHODS: Data are part of a randomized, controlled trial designed to improve frequent emergency department users' QoL and use of health-care resources at the Lausanne University Hospital, Switzerland. In total, 250 frequent emergency department users (≥5 attendances during the previous 12 months; ≥ 18 years of age) were interviewed between May 2012 and July 2013. Following an assessment focused on social characteristics; social, mental, and somatic determinants of health; risk behaviors; health care use; and QoL, participants were randomly assigned to the control or the intervention group (n=125 in each group). The final sample included 194 participants (20 deaths, 36 dropouts, n=96 in the intervention group, n=99 in the control group). Participants in the intervention group received a case management intervention by an interdisciplinary, mobile team in addition to standard emergency care. The case management intervention involved four nurses and a physician who provided counseling and assistance concerning social determinants of health, substance-use disorders, and access to the health-care system. The participants' QoL was evaluated by a study nurse using the WHOQOL-BREF five times during the study (at baseline, and at 2, 5.5, 9, and 12 months). Four of the six WHOQOL dimensions of QoL were retained here: physical health, psychological health, social relationship, and environment, with scores ranging from 0 (low QoL) to 100 (high QoL). A linear, mixed-effects model with participants as a random effect was run to analyze the change in QoL over time. The effects of time, participants' group, and the interaction between time and group were tested. These effects were controlled for sociodemographic characteristics and health-related variables (i.e., age, gender, education, citizenship, marital status, type of financial resources, proficiency in French, somatic and mental health problems, and behaviors at risk).

Was bringt die Masern-Passivimpfung nach Exposition? [What is the value of measles passive vaccination after exposure?].

In der Schweiz, wie in vielen anderen Ländern, ist die Durchimpfungsrate zu tief, um die Verbreitung von Masern zu stoppen. Es kommt immer wieder zu Masern-Ausbrüchen. Die Gabe von Immunglobulinen (Passivimpfung) ist für nicht-immune Personen gedacht, die Kontakt zu Masernvirus-Ausscheidern hatten. Sie wird in der Schweiz für Hochrisiko-Personen wie z.B. schwangere Frauen, immunsupprimierte Personen und Säuglinge <6 Monate ohne nachgewiesene Immunität empfohlen. Schätzungen über die Wirksamkeit der Passivimpfung variieren; es wurde keine minimalwirksame Dosierung festgelegt. Ziel dieses Reviews war, die Wirksamkeit und Sicherheit einer intramuskulären oder intravenösen Gabe von Immunglobulinen zur Masern-Prophylaxe nach Exposition jedoch vor Symptombeginn bei für Masern empfänglichen Personen zu untersuchen.

Vaccination against Staphylococcus aureus experimental endocarditis using recombinant Lactococcus lactis expressing ClfA or FnbpA.

Staphylococcus aureus is a major cause of serious infections in humans and animals and a vaccine is becoming a necessity. Lactococcus lactis is a non-pathogenic bacterium that can be used as a vector for the delivery of antigens. We investigated the ability of non-living L. lactis heterologously expressing S. aureus clumping factor A (ClfA) and fibronectin-binding protein A (FnbpA), alone or together, to elicit an immune response in rats and protect them from S. aureus experimental infective endocarditis (IE). L. lactis ClfA was used for immunization against S. aureus Newman (expressing ClfA but not FnbpA), while L. lactis ClfA, L. lactis FnbpA, as well as L. lactis ClfA/FnbpA, were used against S. aureus P8 (expressing ClfA and FnbpA). Vaccination of rats with L. lactis ClfA elicited antibodies that inhibited binding of S. aureus Newman to fibrinogen, triggered the production of IL-17A and conferred protection to 13/19 (68%) of the animals from IE (P<0.05). Immunization with L. lactis ClfA, L. lactis FnbpA or L. lactis ClfA/FnbpA also produced antibodies against the target proteins, but these did not prevent binding of S. aureus P8 to fibrinogen or fibronectin and did not protect animals against S. aureus P8 IE. Moreover, immunization with constructs containing FnbpA did not increase IL-17A production. These results indicate that L. lactis is a valuable antigen delivery system able to elicit efficient humoral and cellular responses. However, the most appropriate antigens affording protection against S. aureus IE are yet to be elucidated.

Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer.

There is growing interest in the association of radiotherapy and immunotherapy for the treatment of solid tumors. Here, we report an extremely effective combination of local irradiation (IR) and Shiga Toxin B (STxB)-based human papillomavirus (HPV) vaccination for the treatment of HPV-associated head and neck squamous cell carcinoma (HNSCC). The efficacy of the irradiation and vaccine association was tested using a model of HNSCC obtained by grafting TC-1/luciferase cells at a submucosal site of the inner lip of immunocompetent mice. Irradiation and the STxB-E7 vaccine acted synergistically with both single and fractionated irradiation schemes, resulting in complete tumor clearance in the majority of the treated mice. A dose threshold of 7.5 Gy was required to elicit the dramatic antitumor response. The combined treatment induced high levels of tumor-infiltrating, antigen-specific CD8(+) T cells, which were required to trigger the antitumor activity. Treatment with STxB-E7 and irradiation induced CD8(+) T-cell memory, which was sufficient to exert complete antitumor responses in both local recurrences and distant metastases. We also report for the first time that a combination therapy based on local irradiation and vaccination induces an increased pericyte coverage (as shown by αSMA and NG2 staining) and ICAM-1 expression on vessels. This was associated with enhanced intratumor vascular permeability that correlated with the antitumor response, suggesting that the combination therapy could also act through an increased accessibility for immune cells. The combination strategy proposed here offers a promising approach that could potentially be transferred into early-phase clinical trials.

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p < 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections.

When Langmuir is too simple: H2 dissociation on Pd(111) at high coverage

Recent experiments of H2 adsorption on Pd(111) [T. Mitsui et al., Nature (London) 422, 705 (2003)] have questioned the classical Langmuir picture of second order adsorption kinetics at high surface coverage requiring pairs of empty sites for the dissociative chemisorption. Experiments find that at least three empty sites are needed. Through density functional theory, we find that H2 dissociation is favored on ensembles of sites that involve a Pd atom with no direct interaction with adsorbed hydrogen. Such active sites are formed by aggregation of at least 3 H-free sites revealing the complex structure of the "active sites."

Les infections pneumococciques: état des lieux et perspectives en matière de vaccination de l'adulte [Pneumococcal infections: Appraisal and perspectives in terms of adult vaccination].

Pneumococcal diseases are the first cause of bacterial infections in adult and in the aged adult. While its considerable morbi-mortality is potentially preventable through vaccination, the interest of anti-pneumococcal vaccination in these populations is still debated. Effectiveness appraisal of current anti-pneumococcal vaccines and the perspectives in terms of preventive strategies against Streptococcus pneumoniae infections in the adult population are presented.

Long-term persistence of immunity induced by OVA-coupled gas-filled microbubble vaccination partially protects mice against infection by OVA-expressing Listeria.

Vaccination aims at generating memory immune responses able to protect individuals against pathogenic challenges over long periods of time. Subunit vaccine formulations based on safe, but poorly immunogenic, antigenic entities must be combined with adjuvant molecules to make them efficient against infections. We have previously shown that gas-filled microbubbles (MB) are potent antigen-delivery systems. This study compares the ability of various ovalbumin-associated MB (OVA-MB) formulations to induce antigen-specific memory immune responses and evaluates long-term protection toward bacterial infections. When initially testing dendritic cells reactivity to MB constituents, palmitic acid exhibited the highest degree of activation. Subcutaneous immunization of naïve wild-type mice with the OVA-MB formulation comprising the highest palmitic acid content and devoid of PEG2000 was found to trigger the more pronounced Th1-type response, as reflected by robust IFN-γ and IL-2 production. Both T cell and antibody responses persisted for at least 6 months after immunization. At that time, systemic infection with OVA-expressing Listeria monocytgenes was performed. Partial protection of vaccinated mice was demonstrated by reduction of the bacterial load in both the spleen and liver. We conclude that antigen-bound MB exhibit promising properties as a vaccine candidate ensuring prolonged maintenance of protective immunity.

Vaccination anti-grippe et anti-pneumococcique: un nouvel outil de prévention cardiovasculaire ?

Malgré l'existence de vaccins efficaces, l'incidence des infections respiratoires, causées par la grippe et le pneumococcque, reste élevée dans la population adulte occasionnant une importante morbi/mortalité. Ensemble elles représentent la 4ème cause de mortalité, affectant principalement les adultes de 60 ans ou plus. Après une rapide présentation de l'efficacité de ces deux vaccins, nous détaillerons leurs impacts sur la santé cardiovasculaire et la prévention des événements thrombotiques.