Patients receiving novel oral anticoagulants (NOACs) frequently undergo interventional procedures. Short half-lives and rapid onset of action allow for short periods of NOAC interruption without ...heparin bridging. However, outcome data for this approach are lacking. We evaluated the peri-interventional NOAC management in unselected patients from daily care.
Effectiveness and safety data were collected from an ongoing, prospective, non-interventional registry of >2100 NOAC patients. Outcome events were adjudicated using standard event definitions. Of 2179 registered patients, 595 (27.3%) underwent 863 procedures (15.6% minimal, 74.3% minor, and 10.1% major procedures). Until Day 30 ± 5 post-procedure, major cardiovascular events occurred in 1.0% of patients 95% confidence interval (95% CI) 0.5-2.0 and major bleeding complications in 1.2% (95% CI 0.6-2.1). Cardiovascular and major bleeding complications were highest after major procedures (4.6 and 8.0%, respectively). Heparin bridging did not reduce cardiovascular events, but led to significantly higher rates of major bleeding complications (2.7%; 95% CI 1.1-5.5) compared with no bridging (0.5%; 0.1-1.4; P = 0.010). Multivariate analysis demonstrated diabetes odds ratio (OR) 13.2 and major procedures (OR 7.3) as independent risk factors for cardiovascular events. Major procedures (OR 16.8) were an independent risk factor for major bleeding complications. However, if major and non-major procedures were separately assessed, heparin bridging was not an independent risk factor for major bleeding.
Continuation or short-term interruption of NOAC is safe strategies for most invasive procedures. Patients at cardiovascular risk undergoing major procedures may benefit from heparin bridging, but bleeding risks need to be considered.
Bleeding complications are common side effects of vitamin-K antagonist (VKA) therapy. Data on the in-hospital management and outcomes of these bleeding events are scarce and information is mostly ...derived from trial cohorts.
The objective was to collect data on the management and clinical outcome of hospitalizations owing to VKA-related bleeding in real-world practice.
We performed a multicenter observational cohort study involving 21 secondary and tertiary care hospitals in the administrative district Dresden, Saxony, Germany throughout the year 2005. All consenting patients presenting with VKA-related bleeding complications were included. No exclusion criteria applied. Data were collected at admission, at discharge and at 90 days to evaluate resource consumption, length of hospital stay and risk factors for in-hospital- and 3-month mortality.
Two hundred and ninety patients were included (median age 74 years; 50.7% male). The main indications for VKA therapy were atrial fibrillation (63.4%), prior thromboembolism (18.6%) and mechanical heart valves (11.4%), and most common bleeding localizations were large hematoma (23.1%), upper gastrointestinal (GI) tract (17.9%) and intracranial bleeding (14.1%). On hospital admission, the median International Normalized Ratio (INR) was 3.0 (range 0.9-12.5, interquartile range IQR 2.1-3.9). In-hospital mortality was 7.6% with impaired renal function as the most relevant risk factor. At 90 days mortality was 14.1% and 15.3% of survivors were help-dependent.
VKA-related bleeding leading to hospitalization is associated with long hospitalization, relevant resource utilization, high mortality or persistent sequlae. Patient-related factors such as impaired renal function, chronic cardiac or pulmonary disease and dementia are predictive of in-hospital and 3-month mortality.
Abstract The aim of this animal study was to investigate and compare the osseointegration of zirconia and titanium dental implants. 14 one-piece zirconia implants and 7 titanium implants were ...inserted into the mandibles of 7 minipigs. The zirconia implants were alternately placed submerged and non-submerged. To enable submerged healing, the supraosseous part was removed, using a diamond saw. The titanium implants were all placed submerged. After a healing period of 4 weeks, a histological analysis of the soft and hard tissue and a histomorphometric analysis of the bone–implant contact (BIC) and relative peri-implant bone-volume density (rBVD; relation to bone-volume density of the host bone) was performed. Two zirconia implants were found to be loose. All other implants were available for evaluation. For submerged zirconia and titanium implants, the implant surface showed an intimate connection to the neighbouring bone, with both types achieving a BIC of 53%. For the non-submerged zirconia implants, some crestal epithelial downgrowth could be detected, with a resultant BIC of 48%. Highest rBVD values were found for submerged zirconia (80%), followed by titanium (74%) and non-submerged zirconia (63%). The results suggest that unloaded zirconia and titanium implants osseointegrate comparably, within the healing period studied.
Yttria-stabilized zirconia ceramics is a high-performance material with excellent
biocompatibility and mechanical properties, which suggest its suitability for
posterior fixed partial dentures. The ...hypothesis under examination is that the
strength and reliability of Y-TZP zirconia ceramics are affected by the inner surface
grinding of crowns, and vary with the grinding parameter. Flexural strength, surface
roughness, and fracture toughness were determined on samples machined by face and
peripheral grinding with varied feed velocities and cutting depths. Results have been
compared with those on lapped samples. Analysis of variance and Weibull parameter
were used for statistical analysis. It was found that inner surface grinding
significantly reduces the strength and reliability of Y-TZP zirconia compared with
the lapped control sample. Co-analysis of flexural strength, Weibull parameter, and
fracture toughness showed counteracting effects of surface compressive stress and
grinding-introduced surface flaws. In conclusion, grinding of Y-TZP needs to be
optimized to achieve the CAD/CAM manufacture of all-ceramic restorations with
improved strength and reliability.
St John's wort (SJW) is known to induce cytochrome P450 (CYP) 3A4 and P‐glycoprotein through pregnane X‐receptor activation. Our study evaluated the effects of long‐term SJW administration on oral ...and intravenous pharmacokinetics of the nonmetabolized in vivo probe of P‐glycoprotein, talinolol, in relation to intestinal P‐glycoprotein expression. In a controlled, randomized study (N=9), the pharmacokinetics of oral (50 mg) and intravenous talinolol (30 mg) was determined before and after 12 days SJW (900 mg daily, Jarsin 300®). Duodenal biopsies were taken and MDR1 genotypes assessed. SJW reduced the oral talinolol bioavailability by 25% (P=0.049) compared with water control. A 93% increase in oral clearance (P=0.177) and a 31% reduction in area under the serum concentration time curve (AUC; P=0.030) were observed. Renal and nonrenal clearance (CLNR), elimination half‐life, peak serum drug concentration (Cmax), and time to reach Cmax were not significantly altered. After intravenous talinolol, SJW affected only CLNR (35% increase compared with water, P=0.006). SJW increased MDR1 messenger ribonucleic acid (mRNA) as well as P‐glycoprotein levels in the duodenal mucosa. Subjects with the combined MDR1 genotype comprising 1236C>T, 2677G>T/A, and 3435C>T polymorphisms had lower intestinal MDR1 mRNA levels and displayed an attenuated inductive response to SJW as assessed by talinolol disposition. Long‐term SJW decreased talinolol AUC with a corresponding increase in intestinal MDR1 expression, suggesting that SJW has a major inductive effect on intestinal P‐glycoprotein. Interestingly, the magnitude of induction appeared to be affected by MDR1 genotype.
Clinical Pharmacology & Therapeutics (2007) 81, 669–678. doi:10.1038/sj.clpt.6100191; published online 28 March 2007
Both Candida albicans and lactobacilli are common colonizers of carious lesions in children and adolescents. The purpose of this study is to compare the velocity of acid production between C. ...albicans and several Lactobacillus species at different pH levels and concentrations of glucose. Washed, pure resting-cell suspensions were obtained by culturing a total of 28 oral isolates comprising the species C. albicans, Lactobacillus rhamnosus, Lactobacillus paracasei paracasei, Lactobacillus paracasei tolerans and Lactobacillus delbrueckii lactis. Acid production from glucose was determined at a constant pH of 7.0, 5.5, 5.0 and 4.0 by repeated titrations with NaOH in an automated pH-stat system. Acid formation rates of yeast and lactobacilli proved to be similar at both neutral and low pH, while in a moderately acidic environment C. albicans produced less acid than the lactobacilli. Ion chromatographic analysis of the cell-free medium after titration revealed pyruvate to be the predominant organic acid anion secreted by C. albicans. The proportion of organic acids to overall acid production by the yeast was below 10% at neutral conditions, in contrast to 42–66% at pH 4.0. Compared to lactobacilli, yeast required a concentration of glucose that was about 50 times higher to allow acid production at half the maximum speed. Considering the clinical data in the literature about the frequency and proportions of microorganisms present in early childhood caries lesions, the contribution of oral lactobacilli as well as C. albicans to overall microbial acid formation appears to be important.
Summary
Background
The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge.
Aim
To investigate the efficacy of rifabutin‐based ...triple therapy and high‐dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome.
Methods
Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism.
Results
Intention‐to‐treat and per‐protocol eradication rates were: ERA 74% (62.4–83.6) and 78% (66.7–87.3); high‐dose OA 70% (57.5–79.7) and 75% (62.5–84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non‐significant trend to lower eradication rates in homozygous extensive metabolizers.
Conclusions
Triple therapy with esomeprazole, rifabutin and amoxicillin and high‐dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.
Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has never been directly compared with fondaparinux (F), ...which also shows superior efficacy over enoxaparin. The clinical impact of switching from fondaparinux to rivaroxaban thromboprophylaxis is unclear.
To evaluate the efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected patients undergoing MOS.
This is a monocentric, retrospective cohort study in 5061 consecutive patients undergoing MOS at our centre, comparing rates of symptomatic VTE, bleeding and surgical complications, length of hospital stay and risk factors for VTE.
Rates of symptomatic VTE were 5.6% (F) and 2.1% (R; P < 0.001), with rates for distal DVT being 3.9 vs. 1.1% (P < 0.001). Rates of major VTE were numerically higher with fondaparinux (1.8 vs. 1.1%), but not statistically significant. Rates of severe bleeding (bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban compared with fondaparinux (2.9 vs. 4.9%; P = 0.010). The mean length of hospital stay was significantly shorter in the rivaroxaban group (8.3 days, 95% CI 8.1-8.5 vs. 9.3 days, 9.1-9.5; P < 0.001).
Based on an indirect comparison of two consecutive cohorts, our data suggest that thromboprophylaxis with rivaroxaban is associated with less VTE and bleeding events than fondaparinux in unselected patients undergoing MOS. Prospective comparisons are warranted to confirm our findings.
To establish reliable methods to aid the timing of brain damage after traumatic brain injury (TBI), brain tissue from 56 autopsy cases with TBI and known survival times, ranging from a few minutes to ...126 days, were tested for apoptotic changes to the neuronal and glial cells. Apoptosis was established using the TdT-mediated dUTP nick end labelling (TUNEL) method of in-situ labelling and immunohistochemical reaction of caspase 3. In addition, cellular reaction and astroglial cell differentiation were investigated using histological and immunohistochemical markers. From a survival time of 120 min up to 12 days, TUNEL-positive apoptotic neuronal cells were frequently detected in the contusion zone. The earliest positive caspase 3 reaction in cortical neurons was evident after a posttraumatic interval of 80 min. Detection of apoptotic glial cells using the TUNEL technique showed that as in the case of neuronal cells, the earliest positive TUNEL reaction was obtained after 110 min. In cases of survival times of 120 min up to 4 days, apoptotic glial cells could frequently be detected. However, the first caspase 3-positive glial cells appeared 5 h after injury. Cerebral apoptosis was significantly associated with TBI cases as compared to control cases (P<0.001). The reference histological findings of neutrophilic granulocytes, CD3-positive T-lymphocytes, CD68-positive activated microglial cells/macrophages and TUNEL-positive neuronal cells increases the degree of certainty in determining the probable age of traumatic brain injury to 87.5%.
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