Aims To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the ...frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs.
Methods Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation.
Results The charts and ALS of 98 patients were analysed. In 18 cases a drug‐related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious.
Conclusions Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor’s awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them.
Risperidone, a widely used atypical and potent neuroleptic drug, is assumed to induce fewer hepatic side-effects than phenothiazine anti-psychotics. Recently, we observed a case of ...risperidone-induced cholestatic hepatotoxicity. A 37-year-old male developed a rapid increase in liver enzymes and cholestatic parameters after starting treatment with risperidone for paranoid psychosis. Work-up for other potential aetiologies was negative. The results of a percutaneous liver biopsy were consistent with drug-induced liver injury and cholestasis. Over the course of one month after the discontinuance of all anti-psychotic agents, the liver function test results returned to near-normal values. This observation supports the need to monitor cholestatic parameters in addition to liver function enzymes during initiation and the first weeks of risperidone intake.
Background:
It has been claimed that the risk of adverse drug reactions increases with age. However, only limited data exist for disease‐group specific risks and none for patients with liver and ...gastrointestinal diseases.
Aims:
To determine the incidence and characteristics of adverse drug reactions and the physicians’ awareness of adverse drug reactions.
Methods:
During a 7‐month period, a prospective survey of 532 male patients (158 aged 65 years or older; 30%) was conducted on a hepatogastroenterological ward of a tertiary‐care university hospital, using intensive bedside and computer‐assisted drug surveillance methods.
Results:
No difference was found in the overall rate of adverse drug reactions between older and younger patients (25.9% vs. 24.2%) during 6213 treatment days. However, a significantly higher risk for developing adverse drug reactions could be shown for the elderly with biliary tract diseases (P < 0.01). Independently of age, patients suffering from gastric ulcers, acute episodes of pancreatitis, cholangitis or inflammatory bowel diseases were at high risk of adverse drug reactions. Adverse drug reaction‐associated mortality was encountered in four elderly and none of the younger patients. Secondary pharmacological effects and drug toxicity were the main types of adverse drug reactions for both age groups. Although 75.3% of the adverse drug reactions were predictable, only 37.5% of all adverse drug reactions were recognized by the staff physicians.
Conclusion:
In hepatogastroenterological patients, advancing age was not associated with an overall increased risk of adverse drug reactions except for patients with biliary tract diseases. In the elderly, adverse drug reactions were more severe and carried higher mortality. Guidelines and educational programs should be developed to increase the awareness of adverse drug reactions and their prevention, especially in high risk patients and, thus, to improve patient outcomes.
A small percentage of dopant atoms can completely change the physical properties of the host material. For example, chemical doping controls the electronic transport behavior of semiconductors and ...gives rise to a wide range of emergent electric and magnetic phenomena in oxides. Imaging of individual dopant atoms in lightly doped systems, however, remains a major challenge, hindering characterization of the site-specific effects and local dopant concentrations that determine the atomic-scale physics. Here, we apply atom-probe tomography (APT) to resolve individual Ti atoms in the narrow band gap semiconductor ErMnO3 with a nominal proportion of 0.04 atomic percent. Our 3D imaging measures the Ti concentration at the unit cell level, providing quantitative information about the dopant distribution within the ErMnO3 crystal lattice. High-resolution APT maps reveal the 3D lattice position of individual Ti atoms, showing that they are located within the Mn layers with no signs of clustering or other chemical inhomogeneities. The 3D atomic-scale visualization of individual dopant atoms provides new opportunities for the study of local structure-property relations in complex oxides, representing an important step toward controlling dopant-driven quantum phenomena in next-generation oxide electronics.
Strain engineering with different substrate facets is promising for tuning functional properties of thin film perovskite oxides. By choice of facet, different surface symmetries and chemical bond ...directions for epitaxial interfaces can be tailored. Here, preparation of well-defined pseudo-cubic (111)-oriented orthorhombic substrates of DyScO3 , GdScO3 , and NdGaO3 is reported. The choice of orthorhombic facet, (011)o or (101)o , both corresponding to pseudo-cubic (111)pc , gives vicinal surfaces with single or double (111pc layer terrace step heights, respectively, impacting subsequent thin film growth. Orthorhombic LaFeO3 epitaxy on the (101)o facet reveals a distinction between alternating (111)pc layers, both during and after growth. The observed differences are explained based on the oxygen octahedral tilt pattern relative to the two orthorhombic (111)pc surfaces. This robust structural detail in the orthorhombic perovskite oxides enables utilisation of different (111)pc facets for property engineering, through polyhedral connectivity control and cation coordination at epitaxial interfaces.
Rationale. Nicotine and agonists at alpha sub(4) beta sub(2) and alpha sub(7) nicotinic acetylcholine receptors (nAChRs) improve learning and memory. The alpha sub(7)-nAChR subtype is of special ...interest, since it appears to play no role in the abuse liability of nicotine.Objectives and methods. To further investigate the role of the alpha sub(7)-nAChR in learning and memory, the effects of the specific alpha sub(7)-nAChR agonist AR-R17779 on cognition were measured in the rat social recognition test (SRT) and the effect of the alpha sub(7)-nAChR antagonist methyllycaconitine (MLA) was studied. The SRT and a scopolamine-induced deficit version were validated with the acetylcholinesterase inhibitor metrifonate. Social memory was measured by the ability of an adult rat to recognize a juvenile rat after a delay. The difference in social interaction time (SIT) was measured between two encounters. The difference in SIT is expressed as percent reduction in social interaction time (%RSIT).Results. Metrifonate (10 and 30 mg/kg PO) increased %RSIT in a behaviorally specific manner, employing a 24-h interval and reversed the scopolamine-induced deficit at a retention time of 15 min. Likewise, AR-R17779 increased %RSIT in unimpaired animals (1, 3, 10 and 30 mg/kg SC) employing a 24-h retention interval, and reversed the scopolamine-induced deficit (0.3 and 1 mg/kg SC) after a 15-min retention interval. The effects of AR-R17779 (1 mg/kg SC) in unimpaired animals were reversed by MLA (10 mu g ICV), which induced a decrease of %RSI at a 15-min retention interval when given alone.Conclusions. AR-R17779 increased social recognition memory by activation of alpha sub(7)-nAChRs, suggesting that alpha sub(7)-nAChR agonists possess cognitive-enhancing properties.
Urinary tract infections (UTI) belong to the most frequent bacterial infections in outpatients. Increasing antibiotic resistance rates and a new appreciation of the epidemiological side effects of ...antibiotics ("collateral damage") have warranted an update of the guidelines on uncomplicated UTI as an S3 clinical guideline.
The guideline was developed by the Deutsche Gesellschaft für Urologie (DGU) in collaboration with the Deutsche Gesellschaft für Allgemein- und Familienmedizin (DEGAM), Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Hygiene und Mikrobiologie (DGHM), Deutsche Gesellschaft für Infektiologie (DGI), Deutsche Gesellschaft für Nephrologie (DGfN), Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG) and a patient representative. The systematic review of the literature on the topics of the guideline was performed for the time period of 1 January 1998 to 30 April 2008 in the databases of the Cochrane Library and MEDLINE. International guidelines of the years 1999-2007 were included.
Uncomplicated UTI comprise uncomplicated cystitis and uncomplicated pyelonephritis. The leading uropathogen is Escherichia coli. The choice of the antibiotic substance follows the five primary aspects: (1) individual patient risk and antibiotic pretreatment; (2) bacterial spectrum and antibiotic susceptibility; (3) effectivity of the antimicrobial substance demonstrated in clinical studies; (4) epidemiological effects ("collateral damage"); and (5) adverse effects. If antibiotics such as trimethoprim/sulfamethoxazole or fluoroquinolones have previously been given, the risk for pathogens to become resistant against these substances is increased. Because of increasing resistance rates of E. coli against trimethoprim/sulfamethoxazole also in uncomplicated UTI, trimethoprim alone or in combination with sulfamethoxazole is no longer regarded as the first-line agent in the empiric treatment of uncomplicated cystitis, unless the regional resistance rate is below 20%. The antibiotic resistance rates of fluoroquinolones in uncomplicated UTI are still below 10% in Germany, but there is a significant emergence of resistance compared to earlier years. Moreover, fluoroquinolones and group 3 cephalosporins exhibit negative epidemiological effects resulting in selection of multi-resistant pathogens. Because these antibiotic classes are needed in therapy of life-threatening infections, such effects should be taken seriously. For substances like fosfomycin, nitrofurantoin or mecillinam"collateral damage" has not been documented or only to a lesser degree. Therefore, for empiric therapy of frequent uncomplicated cystitis fosfomycin-trometamol, nitrofurantoin or pivmecillinam (not listed in Germany) are recommended as first-line antibiotics. For oral first-line treatment of uncomplicated pyelonephritis, fluoroquinolones are still recommended in sufficiently high dosage due to the resistance rates of E. coli still being below 10% and the superior effectivity compared to other antibiotics. Asymptomatic bacteriuria (ASB) should only be treated in exceptional cases such as pregnant women or prior to expected mucocutaneous traumatising interventions of the urinary tract.
The S3 guideline on uncomplicated urinary tract infections is a comprehensive set of evidence- and consensus-based recommendations dealing with epidemiology, diagnosis, therapy and management of uncomplicated bacterial UTI of adult outpatients. A broad implementation in all disciplines taking care of patients with UTI is necessary in order to ensure a prudent antibiotic policy in these frequent infections and thus improve patient care.
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