The prevalence of 'triple whammy' prescriptions in surgical inpatients and associated pharmacist recommendations.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are beneficial in surgical settings, they may however lead to adverse drug reactions including decreased renal function, a risk, which is exacerbated by combination with other nephrotoxics, and particularly when NSAIDs are given as part of a so-called 'Triple Whammy' (TW) with diuretics and renin-angiotensin system blockers. The objective of this study was to identify the prevalence of TW-prescriptions in a surgical inpatient setting and to document the changes in renal function after pharmacist recommendations. A prospective, observational single centre pilot study was performed using a series of eleven weekly Point-Prevalence Analyses (PPA). Adult surgical inpatients were screened for a TW-prescription by a clinical pharmacist, who made one of two recommendations on identification of a TW: for patients with eGFR > 60 ml/min/1.73m² close monitoring of renal function; for patients with eGFR ≤ 60 ml/min/1.73m² discontinuation of NSAID. A TW was identified in 18 of 317 patients (prevalence 5.7%; mean age 75 years). NSAID discontinuation was recommended for 7/18 patients (39%) and implemented for six (33%). In cases where the NSAID was de-prescribed, an improvement in renal function until the time of discharge was observed, whilst in patients with eGFR > 60 ml/min/1.73m² for whom monitoring was recommended eGFR remained stable. TW-prescriptions were found to be a potential problem in the studied group of older surgical inpatients. Clinical pharmacists are well placed to identify patients who are prescribed a TW, and to advise on the management of these patients.

[Personalized drug therapy based on genetics. Possibilities and examples from clinical practice]. / Personalisierte Arzneitherapie auf genetischer Grundlage. Möglichkeiten und Beispiele aus der Praxis.

BACKGROUND: Pharmacogenetics are an important component in the individualization of treatment; however, pharmacogenetic diagnostics have so far not been used to any great extent in clinical practice. A consistent consideration of individual patient factors, such as pharmacogenetics may help to improve drug therapy and increase individual safety and efficacy aspects. OBJECTIVE: A brief summary of structures and effects of genetic variations on drug efficacy is presented. Some frequently prescribed pharmaceuticals are specified. Furthermore, the feasibility of pharmacogenetic diagnostics and dose recommendations in the clinical practice are described. CURRENT DATA: The European Medicines Agency (EMA) as the European approval authority has already extended the drug labels of more than 70 pharmaceuticals by information on pharmacogenetic biomarkers and the U.S. Food and Drug Administration (FDA) more than 150. This is a crucial step towards targeted medicine. Guidelines on dose and therapy adjustments are provided by the Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. CONCLUSION: It is fundamental to consider individual patient factors for successful drug therapy. Dose and therapy recommendations based on pharmacogenetic diagnostics are highly important for individualization as well as improvement of safety and efficiency of drug therapy.

Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas.

Comparative genomic hybridization serves as a screening test for regions of copy number changes in tumor genomes. We have applied the technique to map DNA gains and losses in 33 cases of formalin-fixed, paraffin-embedded primary breast tumors (13 fibroadenomas and 10 diploid and 10 aneuploid carcinomas). No genomic imbalances were found in fibroadenomas. Recurrent findings in adenocarcinomas include copy number increases for chromosomes 1q (14 of 20 samples), 8q (10 of 20), 17q (5 of 20), 6p (3 of 20), 13q (3 of 20), and 16p (3 of 20), and copy number decreases for chromosomes 22 (7 of 20), 17p (6 of 20), and 20 (3 of 20). Regional high level copy number increases were observed on chromosome bands 1q32, 8p11, 8q24, 10p, 11q13, 12p, 12q15, 17q11-12, and 17q22-24. The majority of the samples were studied for gene amplification of c-myc, c-erbB2, cycD1, and int-2 by means of Southern blot analysis. The comparison with DNA ploidy measurements revealed a different distribution and a significantly higher number of chromosomal aberrations in aneuploid tumors than in diploid tumors and in fibroadenomas.

Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung.

Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25 squamous cell carcinomas of the lung for chromosomal imbalances. DNA copy number decreases common to both entities were observed on chromosomes 1p, 3p, 4q, 5q, 6q, 8p, 9p, 13q, 18q, and 21q. Similarly, DNA gains were observed for chromosomes 5p, 8q, 11q13, 16p, 17q, and 19q. Adenocarcinomas showed more frequently DNA overrepresentations of chromosome 1q and DNA losses on chromosomes 3q, 9q, 10p, and 19, whereas squamous cell carcinomas were characterized by increased overrepresentations of chromosome 3q and 12p as well as deletions of 2q. For the first time, we used a histogram representation and statistical analysis to evaluate the differences between both tumor groups. In particular, the overrepresentation of the chromosomal band 1q23 and the deletion at 9q22 were significantly associated with adenoid differentiation, whereas the DNA loss of chromosomal band 2q36-37 and the overrepresentations at 3q21-22 and 3q24-qter were statistically significant markers for the squamous cell type. The study strengthens the notion that different tumor subgroups of the respiratory tract are characterized by distinct patterns of chromosomal alterations.

Listing's plane and the 3D-VOR in microgravity--the role of the otolith afferences.

The study addresses the question as to what extent the otolith-mediated gravity vector maintains the stability of the coordinate frames of the vestibulo-ocular reflex and the oculomotor system, described by Listing's Plane. Under normal 1 G conditions it has been demonstrated in the monkey that Listing's Plane (LP) and the 3D vestibulo-ocular response (3D-VOR) are close to collinear [10]. In the present study the coordinate frames of the oculomotor system and the three-dimensional vestibulo-ocular reflex (3D-VOR) system were measured under one-g gravity conditions and during a period of prolonged microgravity, on-board the International Space Station (ISS). To this end, the coordinate frame of the oculomotor system is described in Listing's coordinates and that of the 3D-VOR system by the minimal gain vector. The findings demonstrate that under Earthbound, one-g conditions the two coordinate frames diverge by approximately 20° in the human. In the absence of the gravity vector the radical loss in the otolith-mediated contribution to the dynamic VOR leads to a reduction of the torsional VOR component and in turn to a forward tilt of the oculomotor coordinate frame, described by the minimal gain vector. In contrast, the torsional component of LP during horizontal and vertical saccades was found to increase, resulting in a backward tilt of LP. Together with the backward tilt of LP a small but consistent change in LP vergence was observed. The thickness of LP did not appear to change in the absence of gravity. The changes in coordinate frame orientation persisted over the six-month periods spent in zero gravity. The postflight measurements demonstrate that re-adaptation to preflight values proceeds over several days to weeks. The findings demonstrate that the gravity vector represents a common reference for vestibular and oculomotor responses. They also support the idea that the gravity vector provides a central reference for the entire sensorimotor complex.

The ABCs of effective communication.

Communication is affected by the aim of the communicators, their bias, and the climate in which they are communicating. It is also affected by their attitudes, their behaviors, and their self-concepts. Finally, before communicating, they should assess the communication situation, create a blueprint for the communication, and choose a communication style. In other words, they should practice the ABCs of communication.

Sharp interpersonal skills: your key to business success.

In today's more participative work environments, it is more important than ever to have strong interpersonal skills. Several recent studies cite interpersonal skills as a critical element in the selection of leader's in today's organizations. No longer are we relying upon power and control, but rather on empowerment and commitment. This article deals with building interpersonal working relationships, the type that helps to create synergy and teamwork within a workgroup or organization.

Oxygen uptake in whole-body vibration exercise: influence of vibration frequency, amplitude, and external load.

Vibration exercise (VbX) is a new type of physical training to increase muscle power. The present study was designed to assess the influence of whole-body VbX on metabolic power. Specific oxygen uptake (sVO(2)) was assessed, testing the hypotheses that sVO(2) increases with the frequency of vibration (tested in 10 males) and with the amplitude (tested in 8 males), and that the VbX-related increase in sVO(2) is enhanced by increased muscle force (tested in 8 males). With a vibration amplitude of 5 mm, a linear increase in sVO(2) was found from frequencies 18 to 34 Hz (p < 0.01). Each vibration cycle evoked an oxygen consumption of approximately 2.5 micro l x kg(-1). At a vibration frequency of 26 Hz, sVO(2) increased more than proportionally with amplitudes from 2.5 to 7.5 mm. With an additional load of 40 % of the lean body mass attached to the waist, sVO(2) likewise increased significantly. A further increase was observed when the load was applied to the shoulders. The present findings indicate that metabolic power in whole-body VbX can be parametrically controlled by frequency and amplitude, and by application of additional loads. These results further substantiate the view that VbX enhances muscular metabolic power, and thus muscle activity.

Monitoring noise susceptibility: sensitivity of otoacoustic emissions and subjective audiometry.

The capacity of different audiological methods to detect a high noise susceptibility was examined in 20 normally hearing and 26 especially noise-susceptible subjects. The latter were selected from 422 soldiers in field studies: they had shown a temporary threshold shift (TTS) in pure tone audiometry (PTA) after regular training with firearms. In laboratory experiments, the TTS-positive soldiers were re-examined using greatly reduced sound intensities, which caused no TTS in a control subject group. Before and after acoustic stimulation, different subjective (PTA, high frequency audiometry (HFA), upper limit of hearing (ULH)) and objective (transiently evoked otoacoustic emissions (TEOAE), distortion products (DPOAE)) audiological tests were performed. After exposure to low impact noise in the laboratory, in both PTA and HFA, a TTS was observed in 11.5% (N = 3) of the noise-susceptible group (compared to 0% in the control group). In the TTS-positive group, deterioration of the ULH occurred in 28% (N = 7) (compared to 15% (N = 3) in the control group). An ULH improvement occurred in only one subject (3.8%) (compared to 25% (N = 5) in the control group). Significant alterations of click-evoked OAE-amplitudes were found in 26.9% (N = 7) of the selected groups, whereas stable emissions were observed in all but one subject (5%) of the control group. However, DPOAE alterations were seen in 19.2% (N = 5) of the TTS-positive soldiers but also in 25% (N = 5) of the control group. These results suggest that TEOAE provides a more sensitive and more objective method of detecting a subtle noise-induced disturbance of cochlear function than do PTA or DPOAE.