Immune response to influenza vaccination in children treated with methotrexate or/and tumor necrosis factor-alpha inhibitors

In children treated with immunosuppressive medication such as methotrexate and tumor necrosis factor-alpha (TNF-α) inhibitors, additional immunizations are recommended because of increased susceptibility to infections. However, it is unclear if adequate antibody response to vaccinations can be established in children receiving methotrexate and/or TNF-α inhibitors. In a prospective open label study, we assessed seroprotection and seroconversion following influenza vaccination during 2 seasons (6 strains) in 36 children with autoimmune disease treated either with methotrexate (n=18), TNF-α inhibitors (n=10) or both (n=8) and a control group of 16 immunocompetent children. Influenza antibody titers were determined by hemagglutinin inhibition assay, before and 4-8 weeks after vaccination. Post-vaccination seroprotection (defined as a titer ≥1:40) did not significantly differ between immunosuppressed and immunocompetent subjects. Seroconversion, defined as the change from a nonprotective (< 1:40) to a protective titer (≥1:40) with at least a 4-fold titer increase, was less likely to occur in immunosuppressed patients, although no significant difference from the control group was established. Safety evaluation of vaccination showed no serious adverse events. Children receiving methotrexate and/or TNF-α inhibitors can be safely and effectively immunized against influenza, with a seroprotection after vaccination comparable to immunocompetent children.

Natalizumab: targeting alpha4-integrins in multiple sclerosis

In 1992, it was shown that monoclonal antibodies blocking alpha(4)-integrins prevent the development of experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (MS). As alpha(4)beta(1)-integrin was demonstrated to mediate the attachment of immune-competent cells to inflamed brain endothelium in experimental autoimmune encephalomyelitis, the therapeutic effect was attributed to the inhibition of immune cell extravasation and inflammation in the central nervous system. This novel therapeutic approach was rapidly and successfully translated into the clinic. The humanized anti-alpha(4)-integrin antibody natalizumab demonstrated an unequivocal therapeutic effect in preventing relapses and slowing down the pace of neurological deterioration in patients with relapsing-remitting MS in phase II and phase III clinical trials. The occurrence of 3 cases of progressive multifocal leukoencephalopathy in patients treated with natalizumab led to the voluntary withdrawal of the drug from the market. After a thorough safety evaluation of all patients receiving this drug in past and ongoing studies for MS and Crohn's disease, natalizumab again obtained approval in the US and the European Community. A treatment targeting leukocyte trafficking in MS has now re-entered the clinic. Further thorough evaluation is necessary for a better understanding of the risk-benefit balance of this new treatment option for relapsing MS. In this review, we discuss the basic mechanism of action, key clinical results of clinical trials and the emerging indication of natalizumab in MS.

SPIRIT Women, evaluation of the safety and efficacy of the XIENCE V everolimus-eluting stent system in female patients: referral time for coronary intervention and 2-year clinical outcomes

SPIRIT Women is the first interventional trial dedicated exclusively to women, focusing on symptoms at presentation, referral time to coronary intervention and the safety and performance of the XIENCE V stent.

Epicardial ventricular tachycardia ablation a multicenter safety study

The aim of this study was to perform a systematic evaluation of safety and midterm complications after epicardial ventricular tachycardia (VT) ablation.

Transjugular intravascular ultrasound for the evaluation of hepatic vasculature and parenchyma in patients with chronic liver disease

Background The evaluation of the hepatic parenchyma in patients with chronic liver disease is important to assess the extension, localization and relationship with adjacent anatomical structures of possible lesions. This is usually performed with conventional abdominal ultrasound, CT-scan or magnetic resonance imaging. In this context, the feasibility and the safety of intravascular ultrasound in the liver have not been assessed yet. Methods We tested the safety and performance of an intracardiac echography (ICE) catheter applied by a transjugular approach into the hepatic veins in patients with chronic liver disease undergoing hepatic hemodynamic measurements. Results Five patients were enrolled in this pilot study. The insertion of the ICE catheter was possible into the right and middle, but not into the left hepatic vein. The position of the ICE was followed using fluoroscopy and external conventional ultrasound. Accurate imaging of focal hepatic parenchymal lesions, Doppler ultrasound of surrounding blood vessels and assessment of liver surface and ascites were achieved without complications. Conclusions This study demonstrated that a diagnostic approach using an ICE device inserted in the hepatic veins is feasible, safe and well tolerated. However, it remains for the moment only an experimental investigative tool. Whether ICE adds further information regarding parenchymal lesions and associated vascular alterations as compared to other techniques, needs additional investigation.

Experimental Evaluation of Immediate Recanalization Effect and Recanalization Efficacy of a New Thrombus Retriever for Acute Stroke Treatment In Vivo

BACKGROUND AND PURPOSE: Currently, several new stent retriever devices for acute stroke treatment are under development and early clinical evaluation. Preclinical testing under standardized conditions is an important first step to evaluate the technical performance and potential of these devices. The aim of this study was to evaluate the immediate recanalization effect, recanalization efficacy, thrombus-device interaction, and safety of a new stent retriever intended for thrombectomy in patients with acute stroke. MATERIAL AND METHODS: The pREset thrombectomy device (4 × 20 mm) was evaluated in 16 vessel occlusions in an established swine model. Radiopaque thrombi (10-mm length) were used for visualization of thrombus-device interaction during application and retrieval. Flow-restoration effect immediately after deployment and after 5-minute embedding time before retrieval, recanalization rate after retrieval, thromboembolic events, and complications were assessed. High-resolution FPCT was performed to illustrate thrombus-device interaction during the embedding time. RESULTS: Immediate flow restoration was achieved in 75% of occlusions. An increase or stable percentage of recanalizations during embedding time before retrieval was seen in 56.3%; a decrease, in 12.5%; reocclusion of a previously recanalized vessel, in 18.8%; and no recanalization effect at all, in 12.5%. Complete recanalization (TICI 3) after retrieval was achieved in 93.8%; partial recanalization (TICI 2b), in 6.2%. No distal thromboembolic events were observed. High-resolution FPCT illustrated entrapment of the thrombus between the stent struts and compression against the contralateral vessel wall, leading to partial flow restoration. During retrieval, the thrombus was retained in a straight position within the stent struts. CONCLUSIONS: In this experimental study, the pREset thrombus retriever showed a high recanalization rate in vivo. High-resolution FPCT allows detailed illustration of the thrombus-device interaction during embedding time and is advocated as an add-on tool to the animal model used in this study.

Safety and outcome of patients with an acute ST-elevation myocardial infarction transferred for primary coronary intervention: the Neuchâtel experience

BACKGROUND: Transferring patients with ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI) from a community hospital to a PCI centre has been evaluated in randomised trials and shown to be safe and effective. A prolonged transfer time may restrict the benefit of this strategy. AIM: We sought to assess 1) safety of transfer from Neuchâtel to Berne, 2) time intervals of patients transferred either directly from on-site or after evaluation in the local emergency room, and 3) clinical long-term outcome. METHODS AND RESULTS: 42 patients with STEMI eligible for reperfusion therapy were prospectively included between January 2003 and June 2004. Twenty patients (48%, group 1) were directly transferred to the PCI centre from on-site. Twenty-two were transferred after initial treatment in the local emergency room: 11 patients (26%, group 2) presented spontaneously at the hospital and 11 patients (26%, group 3) were admitted by the rescue team. No major complication occurred during transport. Median transport time was 33 minutes. Median time from first healthcare contact to balloon consisted of 131 minutes in group 1, 158 minutes in group 2 and 174 minutes in group 3. The overall rate of Major Adverse Cardiac Events (MACE) at 6 months amounted to 9.5%. CONCLUSIONS: Transfer for primary PCI of our patients with acute STEMI was safe. Direct transfer from on-site to the PCI centre reduced the time of ischaemia. The overall MACE rate was low.

Effectiveness, safety and cost-effectiveness of homeopathy in general practice - summarized health technology assessment

Introduction: The Health Technology Assessment report on effectiveness, cost-effectiveness and appropriateness of homeopathy was compiled on behalf of the Swiss Federal Office for Public Health (BAG) within the framework of the 'Program of Evaluation of Complementary Medicine (PEK)'. Materials and Methods: Databases accessible by Internet were systematically searched, complemented by manual search and contacts with experts, and evaluated according to internal and external validity criteria. Results: Many high-quality investigations of pre-clinical basic research proved homeopathic high-potencies inducing regulative and specific changes in cells or living organisms. 20 of 22 systematic reviews detected at least a trend in favor of homeopathy. In our estimation 5 studies yielded results indicating clear evidence for homeopathic therapy. The evaluation of 29 studies in the domain 'Upper Respiratory Tract Infections/Allergic Reactions' showed a positive overall result in favor of homeopathy. 6 out of 7 controlled studies were at least equivalent to conventional medical interventions. 8 out of 16 placebocontrolled studies were significant in favor of homeopathy. Swiss regulations grant a high degree of safety due to product and training requirements for homeopathic physicians. Applied properly, classical homeopathy has few side-effects and the use of high-potencies is free of toxic effects. A general health-economic statement about homeopathy cannot be made from the available data. Conclusion: Taking internal and external validity criteria into account, effectiveness of homeopathy can be supported by clinical evidence and professional and adequate application be regarded as safe. Reliable statements of cost-effectiveness are not available at the moment. External and model validity will have to be taken more strongly into consideration in future studies.

Staged surgical therapy of basal cell carcinoma of the head and neck region: an evaluation of 500 procedures

QUESTIONS UNDER STUDY / PRINCIPLES: The surgical therapy of basal cell carcinoma (BCC) is especially demanding in the facial area. This retrospective study was undertaken to evaluate the outcome of staged surgical therapy (SST) of BCC of the head and neck region performed on an interdisciplinary basis at our institution. METHODS: Patients treated for BCC in the head and neck area between 1/1/1997 and 31/12/2001 were included in the study. The lesions were histologically evaluated. Diameter of lesion, number of stages, defect coverage, operation time, and recurrence and infection rates were analysed using descriptive and inferential statistical procedures. RESULTS: 281 patients were included in the study. SST was performed in two stages in 43.7%, in three stages in 12.9% and in four or more stages in 2.7%, depending on the type of tumour and the patient's pretreatment status. The total operating time per lesion averaged one hour. Defect coverage was achieved by direct closure (37.7%), by full thickness skin graft (39.5%), by split skin graft (1.1%), by local flaps (20.3%) or by composite grafts (1.1%). Median follow-up time was 58.5 months. Low rates of recurrence (3.6%) and infection (2%) were observed with this technique. CONCLUSIONS: The staged surgical therapy of basal cell carcinoma evaluated here offers a series of advantages in respect of patient comfort and safety and economy, while allowing precise histological safety with low infection rates and reliable long-term results.

The Cardica C-Port System: clinical and angiographic evaluation of a new device for automated, compliant distal anastomoses in coronary artery bypass grafting surgery--a multicenter prospective clinical trial

OBJECTIVES: The C-Port System (Cardica, Inc, Redwood City, Calif) integrates in one tool all functions necessary to enable rapid automated distal coronary anastomoses. The goal of this prospective, nonrandomized, and multicenter study is to determine the safety and efficacy of this novel anastomotic system. METHODS: Five centers enrolled 133 patients awaiting elective coronary artery bypass grafting surgery. Outcome variables were intraoperative device performance, incidence of device-related adverse events, predischarge and 6-month angiographic graft patency, and 12-month clinical outcome. Independent core laboratories performed qualitative and quantitative angiographic and computed tomographic assessments. RESULTS: The C-Port was used to perform a vein-to-coronary anastomosis in 130 patients. Intraoperative conversion to a hand-sewn anastomosis was necessary in 11 patients because of inadequate target site preparation, inappropriate target vessel selection, or both. Inadequate blood flow related to poor runoff required conversion in 3 additional patients. Three patients died before discharge of causes unrelated to the device. At discharge, 113 patients had a C-Port implant in place, and 104 C-Port anastomoses were studied by means of angiography, resulting in 100 FitzGibbon A, 3 FitzGibbon B, and 1 FitzGibbon 0 classifications. At 6 months, one additional patient died of a device-unrelated cause, and 98 patients were evaluated by means of angiography (n = 89). Overall patency (FitzGibbon A) was 92.1%. Three C-Port anastomoses were rated FitzGibbon B, and 4 were rated FitzGibbon 0. At 12 months, 107 (98.2%) of 109 alive patients were followed up, without any reports of device-related major adverse cardiac events. CONCLUSIONS: The C-Port System allows for a rapid, reliable, and compliant distal anastomosis and yields favorable 6-month angiographic and 12-month clinical results when compared with published studies.

Effects of an educational patient safety campaign on patients' safety behaviours and adverse events

Rationale, aims and objectives  The study aims to investigate the effects of a patient safety advisory on patients' risk perceptions, perceived behavioural control, performance of safety behaviours and experience of adverse incidents. Method  Quasi-experimental intervention study with non-equivalent group comparison was used. Patients admitted to the surgical department of a Swiss large non-university hospital were included. Patients in the intervention group received a safety advisory at their first clinical encounter. Outcomes were assessed using a questionnaire at discharge. Odds ratios for control versus intervention group were calculated. Regression analysis was used to model the effects of the intervention and safety behaviours on the experience of safety incidents. Results  Two hundred eighteen patients in the control and 202 in the intervention group completed the survey (75 and 77% response rates, respectively). Patients in the intervention group were less likely to feel poorly informed about medical errors (OR = 0.55, P = 0.043). There were 73.1% in the intervention and 84.3% in the control group who underestimated the risk for infection (OR = 0.51, CI 0.31-0.84, P = 0.009). Perceived behavioural control was lower in the control group (meanCon  = 3.2, meanInt  = 3.5, P = 0.010). Performance of safety-related behaviours was unaffected by the intervention. Patients in the intervention group were less likely to experience any safety-related incident or unsafe situation (OR for intervention group = 0.57, CI 0.38-0.87, P = 0.009). There were no differences in concerns for errors during hospitalization. There were 96% of patients (intervention) who would recommend other patients to read the advisory. Conclusions  The results suggest that the safety advisory decreases experiences of adverse events and unsafe situations. It renders awareness and perceived behavioural control without increasing concerns for safety and can thus serve as a useful instrument for communication about safety between health care workers and patients.

Comparison of Newer-Generation Drug-Eluting With Bare-Metal Stents in Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pooled Analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) Trials

OBJECTIVES This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. METHODS Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. RESULTS Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. CONCLUSIONS Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Predictors of health care professionals' attitudes towards involvement in safety-relevant behaviours

BACKGROUND Patients can make valuable contributions towards promoting the safety of their health care. Health care professionals (HCPs) could play an important role in encouraging patient involvement in safety-relevant behaviours. However, to date factors that determine HCPs' attitudes towards patient participation in this area remain largely unexplored. OBJECTIVE To investigate predictors of HCPs' attitudes towards patient involvement in safety-relevant behaviours. DESIGN A 22-item cross-sectional fractional factorial survey that assessed HCPs' attitudes towards patient involvement in relation to two error scenarios relating to hand hygiene and medication safety. SETTING Four hospitals in London PARTICIPANTS   Two hundred sixteen HCPs (116 doctors; 100 nurses) aged between 21 and 60 years (mean: 32): 129 female. OUTCOME MEASURES Approval of patient's behaviour, HCP response to the patient, anticipated effects on the patient-HCP relationship, support for being asked as a HCP, affective rating response to the vignettes. RESULTS HCPs elicited more favourable attitudes towards patients intervening about a medication error than about hand sanitation. Across vignettes and error scenarios, the strongest predictors of attitudes were how the patient intervened and how the HCP responded to the patient's behaviour. With regard to HCP characteristics, doctors viewed patients intervening less favourably than nurses. CONCLUSIONS HCPs perceive patients intervening about a potential error less favourably if the patient's behaviour is confrontational in nature or if the HCP responds to the patient intervening in a discouraging manner. In particular, if a HCP responds negatively to the patient (irrespective of whether an error actually occurred), this is perceived as having negative effects on the HCP-patient relationship.

Comparative evaluation of the My5-FU™ immunoassay and LC-MS/MS in monitoring the 5-fluorouracil plasma levels in cancer patients

BACKGROUND: Chemotherapies of solid tumors commonly include 5-fluorouracil (5-FU). With standard doses of 5-FU, substantial inter-patient variability has been observed in exposure levels and treatment response. Recently, improved outcomes in colorectal cancer patients due to pharmacokinetically guided 5-FU dosing were reported. We aimed at establishing a rapid and sensitive method for monitoring 5-FU plasma levels in cancer patients in our routine clinical practice. METHODS: Performance of the Saladax My5-FU™ immunoassay was evaluated on the Roche Cobas® Integra 800 analyzer. Subsequently, 5-FU concentrations of 247 clinical plasma samples obtained with this assay were compared to the results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and other commonly used clinical analyzers (Olympus AU400, Roche Cobas c6000, and Thermo Fisher CDx90). RESULTS: The My-FU assay was successfully validated on the Cobas Integra 800 analyzer in terms of linearity, precision, accuracy, recovery, interference, sample carryover, and dilution integrity. Method comparison between the Cobas Integra 800 and LC-MS/MS revealed a proportional bias of 7% towards higher values measured with the My5-FU assay. However, when the Cobas Integra 800 was compared to three other clinical analyzers in addition to LC-MS/MS including 50 samples representing the typical clinical range of 5-FU plasma concentrations, only a small proportional bias (≤1.6%) and a constant bias below the limit of detection was observed. CONCLUSIONS: The My5-FU assay demonstrated robust and highly comparable performance on different analyzers. Therefore, the assay is suitable for monitoring 5-FU plasma levels in routine clinical practice and may contribute to improved efficacy and safety of commonly used 5-FU-based chemotherapies.