A vaccine formulation combining rhoptry proteins NcROP40 and NcROP2 improves pup survival in a pregnant mouse model of neosporosis.

Currently there are no effective vaccines for the control of bovine neosporosis. During the last years several subunit vaccines based on immunodominant antigens and other proteins involved in adhesion, invasion and intracellular proliferation of Neospora caninum have been evaluated as targets for vaccine development in experimental mouse infection models. Among them, the rhoptry antigen NcROP2 and the immunodominant NcGRA7 protein have been assessed with varying results. Recent studies have shown that another rhoptry component, NcROP40, and NcNTPase, a putative dense granule antigen, exhibit higher expression levels in tachyzoites of virulent N. caninum isolates, suggesting that these could be potential vaccine candidates to limit the effects of infection. In the present work, the safety and efficacy of these recombinant antigens formulated in Quil-A adjuvant as monovalent vaccines or pair-wise combinations (rNcROP40+rNcROP2 and rNcGRA7+rNcNTPase) were evaluated in a pregnant mouse model of neosporosis. All the vaccine formulations elicited a specific immune response against their respective native proteins after immunization. Mice vaccinated with rNcROP40 and rNcROP2 alone or in combination produced the highest levels of IFN-γ and exhibited low parasite burdens and low IgG antibody levels after the challenge. In addition, most of the vaccine formulations were able to increase the median survival time in the offspring. However, pup survival only ensued in the groups vaccinated with rNcROP40+rNcROP2 (16.2%) and rNcROP2 (6.3%). Interestingly, vertical transmission was not observed in those survivor pups immunized with rNcROP40+rNcROP2, as shown by PCR analyses. These results show a partial protection against N. caninum infection after vaccination with rNcROP40+rNcROP2, suggesting a synergistic effect of the two recombinant rhoptry antigens.

Resident work hour restrictions do not improve patient safety in surgery: a critical appraisal based on 7 years of experience in Switzerland

In 2005 the Swiss government implemented new work-hour limitations for all residency programs in Switzerland, including a 50-hour weekly limit. The reduction in the working hours of doctors in training implicate an increase in their rest time and suggest an amelioration of doctors' clinical performance and consequently in patients' outcomes and safety - which was not detectable in a preliminary study at a large referral center in Switzerland. It remains elusive why work-hour restrictions did not improve patient safety. We are well advised to thoroughly examine and eliminate the known adverse effects of reduced work-hours to improve our patients' safety.

[Immunosuppressive drugs - how they work, their side effects and interactions]

The central issue in organ transplantation remains suppression of allograft rejection. Immunosuppression can be achieved by depleting lymphocytes, diverting lymphocyte traffic, or blocking lymphocyte response pathways. Immunosuppressive drugs include small-molecule drugs, depleting and nondepleting protein drugs (polyclonal and monoclonal antibodies), fusion proteins, intravenous immune globulin, and glucocorticoids. Small-molecule immunosuppressive agents include calcineurin-inhibitors (cyclosporine, tacrolimus), Target-of-Rapamycin Inhibitors (Sirolimus, Everolimus), inhibitors of nucleotide synthesis and azathioprine. The review covers the mode of action of these drugs with a special focus on belatacept, a new promising fusion protein. Different immuo-suppressive strategies mean also different safety profiles. Common side effects include the consequences of diminished immuno- response, i.e. infections and cancer (mainly involving the skin). Toxic side effects of immunosuppressive drugs range in a wide spectrum that involves almost every organ. The major interest of this toxic effects is the cardiovascular tolerance (with large differences from drug to drug), that are discussed seperately. The calcineurin- and mTOR-inhibitors are both metabolized by the CYP450 3A4 enzyme, which is also involved in the metabolism of many other drugs. The review discusses the most important interactions that in- or decreases the through level of these drugs.

'New perspectives on well-known issues': patients' experiences and perceptions of safety in Swiss hospitals

Patients' reports of safety-related events and perceptions of safety can be a valuable source for hospitals. Patients of eight acute care hospitals in Switzerland were surveyed for safety-related events and concerns for safety. In workshops with hospitals areas for improvement were analyzed and priorities for change identified. To evaluate the benefit of the approach, semi-structured interviews were conducted with hospital risk managers. 3,983 patients returned the survey (55% response rate). 21.4% reported at least one definite safety event, and the mean number of 'definite' incidents per patient was 0.31 (95% CI=0.29 to 0.34). 3.2% were very concerned and 14.7% were somewhat concerned about medical errors and safety. Having experienced a safety-related event, younger age, length of stay, poor health and a poor education increased the probability of reporting concerns. With some exceptions, results confirmed the hospitals' a priori expectations regarding the strengths and weaknesses of their institutions. Risk managers emphasized the usability of results for their work and the special value of referring to the patient's perspective at their home institutions. A considerable fraction of patients subjectively experiences safety-related events and is concerned about safety. Patient-generated data introduced a new quality into the discussion of safety issues within hospitals, and some expected that patients' experiences and concerns could affect patient volumes. Though the study is limited by the short time horizon and the lack of follow-up, the results suggest that the described approach is feasible and can serve as a supplemental tool for risk identification and management.

782 consecutive construction work accidents: who is at risk? A 10-year analysis from a Swiss university hospital trauma unit

BACKGROUND: Mortality and morbidity are particularly high in the building industry. The annual rate of non-fatal occupational accidents in Switzerland is 1,133 per 100,000 inhabitants. METHODS: Retrospective analysis of the electronic database of a university emergency centre. Between 2001 and 2011, 782 occupational accidents to construction workers were recorded and analysed using specific demographic and medical keywords. RESULTS: Most patients were aged 30-39 (30.4%). 66.4% of the injured workers were foreigners. This is almost twice as high as the overall proportion of foreigners in Switzerland or in the Swiss labour market. 16% of the Swiss construction workers and 8% of the foreign construction workers suffered a severe injury with ISS >15. There was a trend for workers aged 60 and above to suffer an accident with a high ISS (p = 0.089). CONCLUSIONS: As in other European countries, most patients were in their thirties. Older construction workers suffered fewer injuries, although these tended to be more severe. The injuries were evenly distributed through the working days of the week. A special effort should be made that current health and safety measures are understood and applied by foreign and older construction workers.

Morbidity in surgery: impact of the 50-hour work-week limitation in Switzerland

Work-hour regulations for residency programmes in Switzerland, including a 50-hour weekly limit, were set in on 1 January 2005. Patient safety was one of the major arguments for the implementation. As the effect of the restriction of residency work hours on patient care in Switzerland has not yet been evaluated on objective data, the aim of the present study was to assess its impact by comparing the patients' morbidity and mortality before (2001-2004) and after (2005-2008) the implementation.

Treating intermittent claudication with Tibetan medicine Padma 28: does it work?

Herbal drugs are being increasingly used in medical practice, often without appropriate scrutiny of their safety and efficacy. The medicinal product Padma 28 is a fixed combination with Tibetan origin, used in Europe since the 1960s for the symptomatic treatment of circulatory disorders, including those of peripheral arterial occlusive disease (PAOD). We have conducted an analysis of all available data on this herbal drug from published literature as well as from original data we obtained from contacting the authors of published papers, reports and the manufacturer. A total of 19 trials have reported on 2084 patients to date, 444 of whom were in six controlled clinical studies on PAOD. A meta-analysis of five trials showed Padma 28 to increase walking distance by >100m in 18.2% of the patients with verum, versus 2.1% with placebo (P<0.001; odds ratio: 10 [95% CI 3.03, 33.33]; RR: 0.12; number needed to treat=6.2). The safety profile appears to be favourable. Available evidence shows that Padma 28 provides significant relief from PAOD-related symptoms (i.e. walking distance), probably of the same order of magnitude as other employed medications. However, larger confirmatory RCTs are desirable.

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

Safety of Active Implantable Devices during MRI Examinations: A Finite Element Analysis of an Implantable Pump

The goal of this study was to propose a general numerical analysis methodology to evaluate the magnetic resonance imaging (MRI)-safety of active implants. Numerical models based on the finite element (FE) technique were used to estimate if the normal operation of an active device was altered during MRI imaging. An active implanted pump was chosen to illustrate the method. A set of controlled experiments were proposed and performed to validate the numerical model. The calculated induced voltages in the important electronic components of the device showed dependence with the MRI field strength. For the MRI radiofrequency fields, significant induced voltages of up to 20 V were calculated for a 0.3T field-strength MRI. For the 1.5 and 3.0T MRIs, the calculated voltages were insignificant. On the other hand, induced voltages up to 11 V were calculated in the critical electronic components for the 3.0T MRI due to the gradient fields. Values obtained in this work reflect to the worst case situation which is virtually impossible to achieve in normal scanning situations. Since the calculated voltages may be removed by appropriate protection circuits, no critical problems affecting the normal operation of the pump were identified. This study showed that the proposed methodology helps the identification of the possible incompatibilities between active implants and MR imaging, and can be used to aid the design of critical electronic systems to ensure MRI-safety