The Management of Patients on Oral Anticoagulation Undergoing Coronary Stent Implantation: A Survey among Interventional Cardiologists from Eight European Countries.

Purpose:  To evaluate the current management, and adherence to recommendations, of patients on oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S). Methods:  By means of a contact person who had been previously identified in 8 European countries, a questionnaire was electronically forwarded between April and July 2010 to the national institutions where PCI-S is performed. Results:  A total of  202 questionnaires (median response rate: 50%, range 33-78%) was received. The prevalence of OAC patients among those undergoing PCI-S is mostly reported 5-10% (97%). The peri-procedural pharmacological management mostly encompasses: preprocedural OAC interruption and bridging with low-molecular-weight heparin (59%), intraprocedural administration of an unfractionated heparin bolus (81%), and use of glycoprotein IIb/IIIa inhibitors on an individual basis (79%). The radial approach is reported as the preferred option (58%), as well as the implantation of bare metal stents (76%). Triple therapy (warfarin, aspirin, clopidogrel) is the most frequently prescribed (80%), generally for 1 month after bare metal stent (77%) and for at least 12 months after drug-eluting stent (60%). Throughout triple therapy, the International Normalized Ratio is mostly targeted to the lower end of the therapeutic range (77%), and gastric protection is routinely prescribed (69%), mostly by giving proton-pump inhibitors (70%). Conclusions:  Among the 202 interventional cardiologists from the 8 European countries interviewed, the management of patients on OAC undergoing PCI-S appears variable and only partially adherent to currently available recommendations. (J Interven Cardiol 2012;25:163-169).

Oral cancer treatments and adherence: medication event monitoring system assessment for capecitabine

Background: Oncological treatments are traditionally administered via intravenous injection by qualified personnel. Oral formulas which are developing rapidly are preferred by patients and facilitate administration however they may increase non-adherence. In this study 4 common oral chemotherapeutics are given to 50 patients, who are still in the process of inclusion, divided into 4 groups. The aim is to evaluate adherence and offer these patients interdisciplinary support with the joint help of doctors and pharmacists. We present here the results for capecitabine. Materials and Methods: The final goal is to evaluate adhesion in 50 patients split into 4 groups according to oral treatments (letrozole/exemestane, imatinib/sunitinib, capecitabine and temozolomide) using persistence and quality of execution as parameters. These parameters are evaluated using a medication event monitoring system (MEMS®) in addition to routine oncological visits and semi-structured interviews. Patients were monitored for the entire duration of treatment up to a maximum of 1 year. Patient satisfaction was assessed at the end of the monitoring period using a standardized questionary. Results: Capecitabine group included 2 women and 8 men with a median age of 55 years (range: 36−77 years) monitored for an average duration of 100 days (range: 5-210 days). Persistence was 98% and quality of execution 95%. 5 patients underwent cyclic treatment (2 out of 3 weeks) and 5 patients continuous treatment. Toxicities higher than grade 1 were grade 2−3 hand-foot syndrome in 1 patient and grade 3 acute coronary syndrome in 1 patient both without impact on adherence. Patients were satisfied with the interviews undergone during the study (57% useful, 28% very useful, 15% useless) and successfully integrated the MEMS® in their daily lives (57% very easily, 43% easily) according to the results obtained by questionary at the end of the monitoring period. Conclusion: Persistence and quality of execution observed in our Capecitabine group of patients were excellent and better than expected compared to previously published studies. The interdisciplinary approach allowed us to better identify and help patients with toxicities to maintain adherence. Overall patients were satisfied with the global interdisciplinary follow-up. With longer follow up better evaluation of our method and its impact will be possible. Interpretation of the results of patients in the other groups of this ongoing trial will provide us information for a more detailed analysis.

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

Objective. Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx.Study Design. Case series with chart review.Setting. University tertiary care center for head and neck oncology.Subjects and Methods. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses.Results. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002).Conclusion. Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Clinicobiological progression and prognosis of oral squamous cell carcinoma in relation to the tumor invasive front: impact on prognosis

CONCLUSION: There are several factors that influence the final outcome when treating oral squamous cell carcinoma (OSCC). Invasive front phenomena and more importantly their clinicopathological translation can have a direct impact on survival, and subsequently on the decision for an adjuvant treatment. OBJECTIVES: In recent years, the concept of tumor-host interaction has been the subject of substantial efforts in cancer research. Tumoral behavior may be better understood when studying the changes occurring at the tumor-host interface. This study evaluated the influence of several clinicopathological features on the outcome of OSCCs. METHODS: The clinical records and pathology specimens of 54 patients with OSCC treated by primary resection were reviewed retrospectively. The pathologic features reviewed were: invasive front grading (IFG), stromal reaction, lymphovascular invasion (LVI), perineural invasion (PNI), margin status, and depth of invasion. RESULTS: High IFGs had a significant relationship with pT status and pN status. High IFGs were strongly correlated with nodal metastases (odds ratio (OR) = 4.77; confidence interaval (CI) = 1.37-16.64). Concerning survival, IFG had a strong impact on disease-free survival in patients treated unimodally, as did the depth of invasion in the same group. Lymphovascular involvement was found to have a negative impact on overall survival in patients treated multimodally.

Cost-effectiveness of full-course oral levofloxacin in severe community-acquired pneumonia.

Oral levofloxacin is as efficient as sequential antibiotic treatment in community-acquired pneumonia (CAP). The current authors assessed whether oral levofloxacin treatment of patients with severe CAP, followed-up for 30 days, would save money. Over a 12-month period, 129 hospitalised patients with severe non-intensive care unit CAP were randomly assigned to receive either oral levofloxacin or sequential antibiotic treatment. Direct and indirect costs were compared over a 30-day period from several perspectives. CAP resolved in 71 out of 77 oral levofloxacin (92%) and in 34 out of 37 sequential antibiotic treatment patients (92%). Patients' characteristics, treatment duration, hospital length of stay and mortality were similar in both groups. Drug acquisition costs were 1.7-times smaller in oral levofloxacin patients, who were less often transferred to rehabilitation centres, but they used more physicians' visits during follow-up and their total costs were lower. As only a minority of patients was still active, inability to work and, hence, indirect costs were similar in both groups. In this study, oral levofloxacin for severe non-intensive care unit community-acquired pneumonia was equally effective as sequential antibiotic treatment, but did not lead to major costs savings except for drug acquisition costs. External factors linked with patients' characteristics and/or medical practice are likely to play a role and should be addressed.

The oral cancer epidemic in central and eastern Europe.

To monitor recent trends in oral and pharyngeal cancer mortality in 38 European countries, we analyzed data provided by the World Health Organization over the period 1975-2004. Joinpoint analysis was used to identify significant changes in trends. In the European Union (EU), male mortality rates rose by 2.1% per year between 1975 and 1984, by 1.0% between 1984 and 1993, and declined by 1.3% between 1993 and 2004, to reach an overall age-standardized rate of 6.1/100,000 in 2000-2004. Mortality rates were much lower in women, and the rate in the EU rose by 0.9% per year up to 2000, and levelled off to 1.1/100,000 in 2000-2004. In France and Italy - which had the highest rates in the past - male rates have steadily declined during the last two decades (annual percent change, APC=-4.8% in 1998-2004 in France, and -2.6% in 1986-2003 in Italy). Persisting rises were, however, observed in several central and eastern European countries, with exceedingly high rates in Hungary (21.1/100,000; APC=6.9% in 1975-1993 and 1.4% in 1993-2004) and Slovakia (16.9/100,000; APC=0.14% in 1992-2004). In middle aged (35 to 64) men, oral and pharyngeal cancer mortality rates in Hungary (55.2/100,000) and Slovakia (40.8/100,000) were comparable to lung cancer rates in several major European countries. The highest rates for women were in Hungary (3.3/100,000; APC=4.7% in 1975-2004) and Denmark (1.6/100,000; APC=1.3% in 1975-2001). Oral and pharyngeal cancer mortality essentially reflects the different patterns in tobacco smoking and alcohol drinking, including drinking patterns and type of alcohol in central Europe. (c) 2009 UICC.

Peut-on évaluer te risque hémorragique tors d'anticoagutation orale [Oral anticoagulation and the risk of major bleeding]

Oral anticoagulants are frequently used in clinical practice. The most important complication of oral anticoagulation is major bleeding. The incidence of major bleeding is about 2-3%/year in randomized controlled trials but may be considerably higher under real life conditions. Major bleeding risk in patients receiving oral anticoagulants depends on factors related to anticoagulation itself (intensity and quality), patient-related factors (demographic characteristics and comorbid diseases), and concomitant treatments with antiplatelet or non-steroidal anti-inflammatory drugs. The role of clinical prediction rules for major bleeding is discussed.

Two cases of "cannabis acute psychosis" following the administration of oral cannabis.

BACKGROUND: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users. CASE PRESENTATIONS: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented. CONCLUSION: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

Urinary analysis of four testosterone metabolites and pregnanediol by gas chromatography-combustion-isotope ratio mass spectrometry after oral administrations of testosterone.

The most frequently used method to demonstrate testosterone abuse is the determination of the testosterone and epitestosterone concentration ratio (T/E ratio) in urine. Nevertheless, it is known that factors other than testosterone administration may increase the T/E ratio. In the last years, the determination of the carbon isotope ratio has proven to be the most promising method to help discriminate between naturally elevated T/E ratios and those reflecting T use. In this paper, an excretion study following oral administration of 40 mg testosterone undecanoate initially and 13 h later is presented. Four testosterone metabolites (androsterone, etiocholanolone, 5 alpha-androstanediol, and 5 beta-androstanediol) together with an endogenous reference (5 beta-pregnanediol) were extracted from the urines and the delta(13)C/(12)C ratio of each compound was analyzed by gas chromatography-combustion-isotope ratio mass spectrometry. The results show similar maximum delta(13)C-value variations (parts per thousand difference of delta(13)C/(12)C ratio from the isotope ratio standard) for the T metabolites and concomitant changes of the T/E ratios after administration of the first and the second dose of T. Whereas the T/E ratios as well as the androsterone, etiocholanolone and 5 alpha-androstanediol delta(13)C-values returned to the baseline 15 h after the second T administration, a decrease of the 5 beta-androstanediol delta-values could be detected for over 40 h. This suggests that measurements of 5 beta-androstanediol delta-values allow the detection of a testosterone ingestion over a longer post-administration period than other T metabolites delta(13)C-values or than the usual T/E ratio approach.

Santé buccale: déterminants sociaux d'un terrain majeur des inégalités [Oral health: social determinants of a health inequality]

The oral health of disadvantaged social groups is worse at all the ages than that of the favored groups. If tooth decay prevalence decreases, this disease is still unequally distributed: 20% of the children, those with the weakest socio-economic statute (SES), concentrate 60% of the decays. Edentulism strikes significantly more people with weak SES. The inequalities of oral health reflect those of general health. Evidence of the inequalities in oral health is exposed even in the developed countries. Different models of intervention are presented: risk groups identification and targeting by specific programs; oral health community approach which includes socio-economic and public health measures aiming all the population; insurance approach to be combined with the preceding ones.

Allergen-specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice.

BACKGROUND: Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders. OBJECTIVE: To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen-specific responses. METHODS: BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra-gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability. RESULTS: OVA-specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra-gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T-helper type 2 cytokines (IL-5, IL-13), but also IL-10, IFN-gamma and IL-17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently. CONCLUSION: This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN-gamma, the importance of antigen-specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL-17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge.

Single-dose oral amoxicillin or linezolid for prophylaxis of experimental endocarditis due to vancomycin-susceptible and vancomycin-resistant Enterococcus faecalis.

Endocarditis prophylaxis following genitourinary or gastrointestinal procedures targets Enterococcus faecalis. Prophylaxis recommendations advocate oral amoxicillin (2 g in the United States and 3 g in the United Kingdom) in moderate-risk patients and intravenous amoxicillin (2 g) or vancomycin (1 g) plus gentamicin in high-risk patients. While ampicillin-resistant (or amoxicillin-resistant) E. faecalis is still rare, there is a concern that these regimens might fail against vancomycin-resistant and/or aminoglycoside-resistant isolates. The present study tested oral linezolid as an alternative. Rats with catheter-induced aortic vegetations were given prophylaxis simulating human pharmacokinetics of oral amoxicillin (2- to 3-g single dose), oral linezolid (600 mg, single or multiple oral doses every 12 h), or intravenous vancomycin (1-g single dose). Rats were then inoculated with the minimum inoculum infecting 90% of the animals (90% infective dose [ID(90)]) or with 10 times the ID(90) of the vancomycin-susceptible E. faecalis strain JH2-2 or the vancomycin-resistant (VanA phenotype) E. faecalis strain UCN41. Amoxicillin was also tested with two additional vancomycin-susceptible E. faecalis strains, 309 and 1209. Animals were sacrificed 3 days later. All the tested bacteria were susceptible to amoxicillin and gentamicin. Single-dose amoxicillin provided 100% protection against all four isolates at both the ID(90) and 10 times the ID(90). In contrast, linezolid required up to four consecutive doses to provide full protection against the vancomycin-resistant isolate. Vancomycin protected only against the vancomycin-susceptible strain. The high efficacy of single-dose oral amoxicillin suggests that this regimen could be used for prophylaxis in both moderate-risk and high-risk patients without additional aminoglycosides. Linezolid appears to be less reliable, at least against the vancomycin-resistant strain.