High temperature ceramics for automobile gas turbines. Part 2: Development of ceramic components

The development of ceramic components for automobile gas turbine engines is described with attention given to the steady and unsteady thermal conditions the ceramics will experience, and their anti-corrosion and strain-resistant properties. The ceramics considered for use in the automobile turbines include hot-pressed Si3N4, reaction-sintered, isostatically pressed Si3N4, hot-pressed SiC, reaction-bonded SiC, and glass ceramics. Attention is given to the stress analysis of ceramic structures and the state of the art of ceramic structural technology is reviewed, emphasizing the use of ceramics for combustion chambers and ceramic shrouded turbomachinery (a fully ceramic impeller)

Antiepileptic Drugs and Suicide: A Systematic Review of Adverse Effects

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Since the FDA (Food and Drug Administration) report on antiepileptic drugs (AEDs) and suicide risk was released (2008), several studies have been published on this controversial relationship. This systematic review (SR) gives an updated approach to this health issue. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; We searched 6 databases. We ultimately included 11 publications: 4 cohort studies, 1 case-crossover study, 2 community case-control studies, and 4 SRs. Overall, 1 SR described studies already included; 3 studies reported a 2- to 4-fold overall increase in risk; 1 study reported an increased risk of suicide among epilepsy patients on AEDs with high risk of depression; 1study showed a protective effect among epilepsy patients; 2 studies were conducted with patients with bipolar disorder (1 showed a protective effect, whereas the other showed a 3-fold increase in risk of suicide), and the other 3 studies reported results for single AEDs. Several biases affected the published results. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; There is no clear evidence of an association between the use of AEDs and an increased risk of suicide because of the heterogeneity in the studies at the clinical and methodological level. A future study should cover all indications for use, retrieve information from a healthcare database, and include a defined set of covariates to avoid bias.</jats:p

Dose-Specific Adverse Drug Reaction Identification in Electronic Patient Records: Temporal Data Mining in an Inpatient Psychiatric Population

BACKGROUND: Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. OBJECTIVES: The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. METHODS: We used a psychiatric hospital’s EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. RESULTS: When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five patients exhibited a significant difference (p < 0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). CONCLUSIONS: The developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40264-014-0145-z) contains supplementary material, which is available to authorised users

Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015)

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH)

Self-medication with over-the-counter and prescribed drugs causing adverse-drug-reaction-related hospital admissions: Results of a prospective, long-term multi-centre study.

Background: Self-medication, including both the use of over-the-counter (OTC) drugs and the use of formerly prescribed drugs taken without a current physician&#39;s recommendation, is a public health concern; however, little data exist regarding the actual risk. Objective: We aimed to analyse self-medication-related adverse drug reactions (ADRs) leading to hospitalisation. Methods: In a multi-centre, observational study covering a hospital catchment area of approximately 500,000 inhabitants, we analysed self-medication-related ADRs leading to hospital admissions in internal medicine departments. Data of patients with ADRs were comprehensively documented, and ADR causality was assessed using B&eacute;gaud&#39;s algorithm. The included ADRs occurred between January 2000 and December 2008 and were assessed to be at least &#39;possibly&#39; drug related. Results: Of 6,887 patients with ADRs, self-medication was involved in 266 (3.9 %) patients. In 143 (53.8 %) of these patients, ADRs were due to OTC drugs. Formerly prescribed drugs and potential OTC drugs accounted for the remaining ADRs. Most self-medication-related ADRs occurred in women aged 70-79&nbsp;years and in men aged 60-69&nbsp;years. Self-medication-related ADRs were predominantly gastrointestinal complaints caused by non-steroidal anti-inflammatory drugs (most frequently OTC acetylsalicylic acid [ASA, aspirin]). In 102 (38.3&nbsp;%) of the patients with self-medication-related ADRs, a relevant drug-drug interaction (DDI), occurring between a self-medication and a prescribed medication, was present (most frequently ASA taken as an OTC drug and prescribed diclofenac). Conclusion: In the general population, self-medication plays a limited role in ADRs leading to hospitalisation. However, prevention strategies focused on elderly patients and patients receiving interacting prescribed drugs would improve patient safety

Inhaled beta-2-agonists/muscarinic antagonists and acute myocardial infarction in COPD patients.

OBJECTIVE: Empirical results indicate an increased risk for cardiovascular (CV) adverse drug events (ADE) in chronic obstructive pulmonary disease (COPD) patients treated with beta-2-agonists (B2A) and muscarinic antagonists (MA). A systematic review (including a meta-analysis for drug classes with sufficient sample size) was conducted assessing the association between B2A or MA and acute myocardial infarctions (MI) in COPD patients. METHODS: Comprehensive literature search in electronic databases (MEDLINE, Cochrane database) was performed (January 1, 1946-April 1, 2013). Results were presented by narrative synthesis including a comprehensive quality assessment. In the meta-analysis, a random effects model was used for estimating relative risk estimates for acute MI. RESULTS: Eight studies (two systematic reviews, two randomized controlled trials, and four observational studies) were comprised. Most studies comparing tiotropium vs. placebo showed a decreased MI risk for tiotropium, whereas for studies with active control arms no clear tendency was revealed. For short-acting B2A, an increased MI risk was shown after first treatment initiation. For all studies, a good quality was found despite some shortcomings in ADE-specific criteria. A meta-analysis could be conducted for tiotropium vs. placebo only, showing a relative risk reduction of MI (0.74 [0.61-0.90]) with no evidence of statistical heterogeneity among the included trials (I(2)&nbsp;=&nbsp;0%; p&nbsp;=&nbsp;0.8090). CONCLUSIONS: An MI-protective effect of tiotropium compared to placebo was found, which might be attributable to an effective COPD treatment leading to a decrease in COPD-related cardiovascular events. Further studies with effective control arms and minimal CV risk are required determining precisely tiotropium&#39;s cardiovascular risk

Aufladesysteme fuer Pkw-Antriebe

TIB: RN 6495 (8206) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman