Effect of atorvastatin and pravastatin on platelet inhibition by aspirin and clopidogrel treatment in patients with coronary stent thrombosis

We sought to determine a potential interaction between statins and antiplatelet therapy with aspirin and clopidogrel. Previous laboratory studies have shown a possible drug-drug interaction of statins metabolized by cytochrome P450 3A4 and clopidogrel (prodrug metabolized by cytochrome P450 3A4), resulting in an impaired inhibitory effect of clopidogrel on platelet aggregation. However, conclusive prospective data assessing this potentially relevant interaction are lacking. In 73 patients, 23 with previous coronary stent thrombosis (ST) (ST group) and 50 without coronary ST (control group), platelet aggregation was measured 3 times in monthly intervals using light transmission aggregometry (adenosine diphosphate [ADP] and arachidonic acid induction). Measurements were carried out with aspirin monotherapy (100 mg/day), dual antiplatelet therapy with aspirin plus clopidogrel (75 mg/day), and additional treatment of 20 mg/day of atorvastatin or 40 mg/day of pravastatin. ADP (5 and 20 micromol)-induced platelet aggregation was significantly decreased with clopidogrel (p <0.001) but remained stable under additional treatment with atorvastatin or pravastatin in the 2 groups. Patients with previous ST showed a higher ADP-induced aggregation level than control subjects. This difference was not influenced by clopidogrel or statin treatment. In conclusion, patients with previous ST show a higher aggregation level than control subjects independent of statin treatment. Atorvastatin and pravastatin do not interfere with the antiaggregatory effect of aspirin and clopidogrel. In conclusion, drug-drug interaction between dual antiplatelet therapy and atorvastatin or pravastatin seems not to be associated with ST.

Palliative in-patient cancer treatment in an anthroposophic hospital: II. Quality of life during and after stationary treatment, and subjective treatment benefits

BACKGROUND: There is an increasing demand for comprehensive forms of palliative cancer care, meeting physical as well as emotional, cognitive, spiritual and social needs. Therapy programs of anthroposophic hospitals are aimed at improving health and quality of life (QoL) at these levels. However, data on the influence of these programs on QoL of patients with advanced cancer are scarce. PATIENTS AND METHODS: 144 in-patients with advanced epithelial cancers were treated at the anthroposophic Lukas Klinik, Arlesheim, Switzerland. QoL was assessed upon admission, discharge and after 4 months, using 20 functional scales from the questionnaires EORTC QLQ-C30, HADS and SELT-M. Statistical testing was performed with the Wilcoxon signed rank test. At month 4, subjectively perceived benefits from anthroposophic medicine (AM) and conventional cancer therapy (CCT) were assessed by telephone. OBJECTIVE: The aim was to provide an account of global, physical, emotional, cognitive-spiritual and social QoL developments in advanced cancer patients, during and after in-patient AM treatment, and to investigate subjective benefits from AM and CCT. RESULTS: QoL improvements were observed in all 20 dimensions (12 significant). Compared to related studies, improvements were fairly high. At month 4, QoL scores had decreased but were still above baseline in all 20 dimensions. Both AM and CCT were perceived as beneficial. CONCLUSION: Our data provide evidence that in-patient therapy at an anthroposophic hospital can lead to significant QoL improvements, especially in emotional, but also global, physical, cognitive-spiritual and social aspects. Benefits of AM were experienced on the physical, emotional, cognitive- spiritual and social level. Benefits of CCT were tumor-focused.

The association of the composite IL-1 genotype with periodontitis progression and/or treatment outcomes: a systematic review

BACKGROUND: Genetically transmitted traits such as cytokine gene polymorphisms may accentuate the host inflammatory response to the bacterial challenge and influence susceptibility to periodontitis. OBJECTIVE: To systematically review the evidence of an association between the interleukin-1 (IL-1) composite genotype, i.e. presence of the allele 2 in the gene clusters IL-1A-889 and in IL-1B +3953, and periodontitis progression and/or treatment outcomes. Material and Methods: Based on the focused question, a search was conducted for longitudinal clinical trials comparing progression of periodontitis and/or treatment outcomes in IL-1 genotype-positive (carrying allele 2) and IL-1 genotype-negative (not carrying allele 2) subjects. A search in the National Library of Medicine computerized bibliographic database MEDLINE and a manual search were performed. Selection of publications, extraction of data and validity assessment were made independently by two reviewers. RESULTS: The search provided 122 titles of which 11 longitudinal publications were included. The heterogeneity of the data prevented the performance of a meta-analysis. While findings from some publications rejected a possible role of IL-1 composite genotype on progression of periodontitis after various therapies, other reported a prognostic value for disease progression of the positive IL-1 genotype status. When assessed on a multivariate risk assessment model, several publications concluded that the assessment of the IL-1 composite genotype in conjunction with other covariates (e.g. smoking and presence of specific bacteria) may provide additional information on disease progression. The small sample size of the available publications, however, requires caution in the interpretation of the results. CONCLUSION: Based on these findings, (i) there is insufficient evidence to establish if a positive IL-1 genotype status contributes to progression of periodontitis and/or treatment outcomes. Therefore, (ii) results obtained with commercially available tests should be interpreted with caution.

Fibula free flap reconstruction of the mandible in cancer patients: Evaluation of a combined surgical and prosthodontic treatment concept

The final goal of mandibular reconstruction following ablative surgery for oral cancer is often considered to be dental implant-supported oral rehabilitation, for which bone grafts should ideally be placed in a suitable position taking subsequent prosthetic restoration into account. The aim of this study was to evaluate the efficacy of a standardized treatment strategy for mandibular reconstruction according to the size of the bony defect and planned subsequent dental prosthetic rehabilitation. Data of 56 patients, who had undergone such a systematic mandibular fibula free flap reconstruction, were retrospectively analyzed. Early complications were observed in 41.5% of the patients but only in those who had been irradiated. Late complications were found in 38.2%. Dental implant survival rate was 92%, and dental prosthetic treatment has been completed in all classes of bony defects with an overall success rate of 42.9%. The main reasons for failure of the complete dental reconstruction were patients' poor cooperation (30.4%) and tumour recurrence (14.3%) followed by surgery-related factors (10.8%) such as implant failure and an unfavourable intermaxillary relationship between the maxilla and the mandible. A comparison of our results with the literature findings revealed no marked differences in the complication rates and implant survival rates. However, a systematic concept for the reconstructive treatment like the method presented here, plays an important role in the successful completion of dental reconstruction. The success rate could still be improved by some technical progress in implant and bone graft positioning.

Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol

BACKGROUND: There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study. METHODS: This study aims to examine if1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP.This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study.Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data. CONCLUSION: This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.

CCN2/CTGF is required for matrix organization and to protect growth plate chondrocytes from cellular stress

CCN2 (connective tissue growth factor (CTGF/CCN2)) is a matricellular protein that utilizes integrins to regulate cell proliferation, migration and survival. The loss of CCN2 leads to perinatal lethality resulting from a severe chondrodysplasia. Upon closer inspection of Ccn2 mutant mice, we observed defects in extracellular matrix (ECM) organization and hypothesized that the severe chondrodysplasia caused by loss of CCN2 might be associated with defective chondrocyte survival. Ccn2 mutant growth plate chondrocytes exhibited enlarged endoplasmic reticula (ER), suggesting cellular stress. Immunofluorescence analysis confirmed elevated stress in Ccn2 mutants, with reduced stress observed in Ccn2 overexpressing transgenic mice. In vitro studies revealed that Ccn2 is a stress responsive gene in chondrocytes. The elevated stress observed in Ccn2-/- chondrocytes is direct and mediated in part through integrin α5. The expression of the survival marker NFκB and components of the autophagy pathway were decreased in Ccn2 mutant growth plates, suggesting that CCN2 may be involved in mediating chondrocyte survival. These data demonstrate that absence of a matricellular protein can result in increased cellular stress and highlight a novel protective role for CCN2 in chondrocyte survival. The severe chondrodysplasia caused by the loss of CCN2 may be due to increased chondrocyte stress and defective activation of autophagy pathways, leading to decreased cellular survival. These effects may be mediated through nuclear factor κB (NFκB) as part of a CCN2/integrin/NFκB signaling cascade.

Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials.

BACKGROUND: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled using a random-effects model. Fourteen trials including 1,221 patients were included. In placebo-controlled trials, topical PR appeared to have therapeutic activity against the old world and new world CL, with increased local reactions, when used with methylbenzethonium chloride (MBCL) compared to when used alone (risk ratio [RR] for clinical cure, 2.58 versus 1.01: RR for local reactions, 1.60 versus 1.07). In SbV-controlled trials, the efficacy of topical PR was not significantly different from that of intralesional SbV in the old world CL (RR, 0.70; 95% confidence interval, 0.26-1.89), whereas topical PR was inferior to parenteral SbV in treating the new world CL (0.67; 0.54-0.82). No significant difference in efficacy was found between parenteral PR and parenteral SbV in the new world CL (0.88; 0.56-1.38). Systemic side effects were fewer with topical or parenteral PR than parenteral SbV. CONCLUSIONS/SIGNIFICANCE: Topical PR with MBCL could be a therapeutic alternative to SbV in selected cases of the old world CL. Development of new formulations with better efficacy and tolerability remains to be an area of future research.

Predictors of satisfaction with treatment decision, decision-making preferences, and main treatment goals in patients with advanced cancer

Purpose This study investigated satisfaction with treatment decision (SWTD), decision-making preferences (DMP), and main treatment goals, as well as evaluated factors that predict SWTD, in patients receiving palliative cancer treatment at a Swiss oncology network. Patients and methods Patients receiving a new line of palliative treatment completed a questionnaire 4–6 weeks after the treatment decision. Patient questionnaires were used to collect data on sociodemographics, SWTD (primary outcome measure), main treatment goal, DMP, health locus of control (HLoC), and several quality of life (QoL) domains. Predictors of SWTD (6 = worst; 30 = best) were evaluated by uni- and multivariate regression models. Results Of 480 participating patients in eight hospitals and two private practices, 445 completed all questions regarding the primary outcome measure. Forty-five percent of patients preferred shared, while 44 % preferred doctor-directed, decision-making. Median duration of consultation was 30 (range: 10–200) minutes. Overall, 73 % of patients reported high SWTD (≥24 points). In the univariate analyses, global and physical QoL, performance status, treatment goal, HLoC, prognosis, and duration of consultation were significant predictors of SWTD. In the multivariate analysis, the only significant predictor of SWTD was duration of consultation (p = 0.01). Most patients indicated hope for improvement (46 %), followed by hope for longer life (26 %) and better quality of life (23 %), as their main treatment goal. Conclusion Our results indicate that high SWTD can be achieved in most patients with a 30-min consultation. Determining the patient’s main treatment goal and DMP adds important information that should be considered before discussing a new line of palliative treatment.

[Risk factors for the oral use of antibiotics and animal treatment incidence of weaners in Switzerland].

In the present study, risk factors for the use of oral antibiotics in weaned piglets were collected on 112 pig farms by a personal questionaire. The most common indication for an antibiotic group therapy was diarrhoea, and the most frequently used antibiotic was Colistin. On average, 27.33 daily doses in the control farms and 387.21 daily doses in the problem farms per 1000 weaners were administered on a given day. The significant risk factors in the multivariate model were poor hygiene in the water supply of suckling piglets, less than two doses ofprestarter feed daily, lack of an all-in-and-all-out production system in weaners, no herd book performance data analysis, and less than two of the legally prescribed veterinary visits per year. Furthermore, the treatment incidence of weaners for oral antibiotics was calculated on the basis of the drug inventory. This study provides evidence that the use of oral antibiotics in weaners can be reduced by interventions in hygiene and management.

The Global Plankton Database: an inventory and data from the Former Soviet Union expeditions

At present time, there is a lack of knowledge on the interannual climate-related variability of zooplankton communities of the tropical Atlantic, central Mediterranean Sea, Caspian Sea, and Aral Sea, due to the absence of appropriate databases. In the mid latitudes, the North Atlantic Oscillation (NAO) is the dominant mode of atmospheric fluctuations over eastern North America, the northern Atlantic Ocean and Europe. Therefore, one of the issues that need to be addressed through data synthesis is the evaluation of interannual patterns in species abundance and species diversity over these regions in regard to the NAO. The database has been used to investigate the ecological role of the NAO in interannual variations of mesozooplankton abundance and biomass along the zonal array of the NAO influence. Basic approach to the proposed research involved: (1) development of co-operation between experts and data holders in Ukraine, Russia, Kazakhstan, Azerbaijan, UK, and USA to rescue and compile the oceanographic data sets and release them on CD-ROM, (2) organization and compilation of a database based on FSU cruises to the above regions, (3) analysis of the basin-scale interannual variability of the zooplankton species abundance, biomass, and species diversity.