Development of a context model to prioritize drug safety alerts in CPOE systems.

BACKGROUND: Computerized physician order entry systems (CPOE) can reduce the number of medication errors and adverse drug events (ADEs) in healthcare institutions. Unfortunately, they tend to produce a large number of partly irrelevant alerts, in turn leading to alert overload and causing alert fatigue. The objective of this work is to identify factors that can be used to prioritize and present alerts depending on the 'context' of a clinical situation. METHODS: We used a combination of literature searches and expert interviews to identify and validate the possible context factors. The internal validation of the context factors was performed by calculating the inter-rater agreement of two researcher's classification of 33 relevant articles. RESULTS: We developed a context model containing 20 factors. We grouped these context factors into three categories: characteristics of the patient or case (e.g. clinical status of the patient); characteristics of the organizational unit or user (e.g. professional experience of the user); and alert characteristics (e.g. severity of the effect). The internal validation resulted in nearly perfect agreement (Cohen's Kappa value of 0.97). CONCLUSION: To our knowledge, this is the first structured attempt to develop a comprehensive context model for prioritizing drug safety alerts in CPOE systems. The outcome of this work can be used to develop future tailored drug safety alerting in CPOE systems.

Holistic Control of Herbal Teas and Tinctures Based on Sage (Salvia officinalis L.) for Compounds with Beneficial and Adverse Effects using NMR Spectroscopy.

A methodology that utilizes (1)H-NMR spectroscopy has been developed to simultaneously analyze toxic terpenes (thujone and camphor), major polyphenolic compounds, the total antioxidant capacity (ORAC) and the Folin-Ciocalteu (FC) index in foods and medicines containing sage. The quantitative determination of rosmarinic acid (limit of detection (LOD) = 10 mg/L) and total thujone (LOD = 0.35 mg/L) was possible using direct integration of the signals. For other parameters (derivatives of rosmarinic acid, carnosol and flavone glycosides, ORAC and FC index), chemometric regression models obtained separately for alcohol-based tinctures (R(2) = 0.94-0.98) and aqueous tea infusions (R(2) = 0.79-0.99) were suitable for screening analysis. The relative standard deviations for authentic samples were below 10%. The developed methodology was applied for the analysis of a wide variety of sage products (n = 108). The total thujone content in aqueous tea infusions was found to be in the range of not detectable (nd) to 37.5 mg/L (average 9.2 mg/L), while tinctures contained higher levels (range nd-409 mg/L, average 107 mg/L). The camphor content varied from 2.1 to 43.7 mg/L in aqueous infusions and from not detectable to 748 mg/L in tinctures (averages were 14.1 and 206 mg/L, respectively). Phenolic compounds were also detected in the majority of the investigated products. (1)H-NMR spectroscopy was proven to have the ability to holistically control all important adverse and beneficial compounds in sage products in a single experiment, considerably saving time, resources and costs as NMR replaces four separate methodologies that were previously needed to analyze the same parameters.

Determination of the biologically active flavour substances thujone and camphor in foods and medicines containing sage (Salvia officinalis L.).

BACKGROUND: The sage plant Salvia officinalis L. is used as ingredient in foods and beverages as well as in herbal medicinal products. A major use is in the form of aqueous infusions as sage tea, which is legal to be sold as either food or medicine. Sage may contain two health relevant substances, thujone and camphor. The aim of this study was to develop and validate an analytical methodology to determine these active principles of sage and give a first overview of their concentrations in a wide variety of sage foods and medicines. RESULTS: A GC/MS procedure was applied for the analysis of α- and ß-thujone and camphor with cyclodecanone as internal standard. The precision was between 0.8 and 12.6%, linearity was obtained from 0.1 - 80 mg/L. The recoveries of spiked samples were between 93.7 and 104.0% (average 99.1%). The time of infusion had a considerable influence on the content of analytes found in the teas. During the brewing time, thujone and camphor show an increase up to about 5 min, after which saturation is reached. No effect was found for preparation with or without a lid on the pot used for brewing the infusion. Compared to extracts with ethanol (60% vol), which provide a maximum yield, an average of 30% thujone are recovered in the aqueous tea preparations. The average thujone and camphor contents were 4.4 mg/L and 16.7 mg/L in food tea infusions and 11.3 mg/L and 25.4 mg/L in medicinal tea infusions. CONCLUSIONS: The developed methodology allows the efficient determination of thujone and camphor in a wide variety of sage food and medicine matrices and can be applied to conduct surveys for exposure assessment. The current results suggest that on average between 3 and 6 cups of sage tea could be daily consumed without reaching toxicological thresholds.

Antioxidant Capacity and Polyphenolic Composition as Quality Indicators for Aqueous Infusions of Salvia officinalis L. (sage tea).

Sage (Salvia officinalis L.) is used as an herbal medicinal product, with the most typical form of application as infusion with boiling water (sage tea). The well-established traditional uses include symptomatic treatment of mild dyspeptic complaints, the treatment of inflammations in the mouth and the throat, and relief of excessive sweating and relief of minor skin inflammations. In this study, sage teas prepared from commercially available products were chemically analyzed for polyphenolic content using liquid chromatography, for antioxidant potential using the oxygen radical absorbance capacity method, and for the Folin-Ciocalteu (FC) index. The sage teas showed a high variation for all parameters studied (up to 20-fold differences for rosmarinic acid). Univariate and multivariate analyses showed that the antioxidant potential, which varied between 0.4 and 1.8 mmol trolox equivalents/100 mL, was highly dependent on rosmarinic acid and its derivatives. The FC index also showed a high correlation to these polyphenols, and could therefore be used as a screening parameter for sage tea quality. The considerable differences in polyphenolic composition and antioxidant capacity between the brands lead to a demand for quality standardization, especially if these sage teas are to be used for therapeutic purposes. Further research also appears to be necessary to characterize the dose-benefit relationship, as sage may also contain a constituent (thujone) with potentially adverse effects.

Rapid UHPLC determination of polyphenols in aqueous infusions of Salvia officinalis L. (sage tea).

Sage tea, the aqueous infusion of dried sage leaves (Salvia officinalis L.), is used as a form of food as well as a form of traditional herbal medicine. Several in vivo and in vitro studies point to sage polyphenols as active principles that may inhibit lipid peroxidation and improve antioxidant defences. This study describes an UHPLC methodology with MS/MS and UV detection, which allows the separation, identification and quantification of the major phenolic constituents in sage tea within 34 min, and was used to characterize 16 commercial brands of sage tea.The quantitatively dominating compounds were either rosmarinic acid (12.2­296 mg/l) or luteolin-7-o-glucuronide (37.9­166 mg/l) [corrected].In general, considerable differences in polyphenolic composition between the brands were detected, leading to the demand for quality standardization and control, especially if these sage teas are to be used for therapeutic purposes.

Influence of department volume on cancer survival for gynaecological cancers--a population-based study in Tyrol, Austria.

OBJECTIVE: The objective of this study was to assess the effect of department volume on survival of patients with gynaecological cancer. METHODS: We conducted an observational population-based study in Tyrol, Austria. The analysis includes all patient data on incident gynaecological cancer collected by the Cancer Registry of Tyrol. Data were collected since 1988 on a population-based perspective; publication of incidence data since 1988 in Cancer Incidence in Five Continents gives evidence for good completeness and validity of the database. Patient survival status is assessed in a passive way by probabilistic record linkage between incidence data and official mortality data. We applied a multivariate Cox regression with variables age, sex, stage, year of diagnosis, histological verification of diagnosis, transfer to other hospital and department volume. Department volume was categorised in < or = 11/12-23/24-35/ > or = 36 patients per year reflecting one/two/three/more than three patients per month; categories were computed separately for every site we analysed. Departments with up to 11 patients per year were called small departments. RESULTS: For 4,191 breast cancer patients, we found a negative effect for small departments; hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.22, 1.58. For ovarian cancer patients, we also found a negative effect for small departments (HR 1.27, 95% CI 1.05, 1.54). For cervical cancer patients, we found a positive effect for small departments (HR 0.67, 95% CI 0.51, 0.88). No effect was shown for corpus cancer (HR 0.80, 95% CI 0.63, 1.01). CONCLUSION: The results indicate that, in our country, rules on minimum department case-load can further improve survival for breast and ovarian cancer patients.

Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing.

The objective of this study was to analyze in detail the time trend in prostate cancer mortality in the population of Tyrol, Austria. In Tyrol, prostate-specific antigen tests were introduced in 1988-1989 and, since 1993, have been offered to all men aged 45-74 years free of charge. More than three quarters of all men in this age group had at least one such test in the last decade. The authors applied the age-period-cohort model by Poisson regression to mortality data covering more than three decades, from 1970 to 2003. For Tyrol, the full model with age and period and cohort terms fit fairly well. Period terms showed a significant reduction in prostate cancer mortality in the last 5 years, with a risk ratio of 0.81 (95% confidence interval: 0.68, 0.98) for Tyrol; for Austria without Tyrol, no effect was seen, with a risk ratio of 1.00 (95% confidence interval: 0.95, 1.05). Each was compared with the mortality rate in the period 1989-1993. Although the results of randomized screening trials are not expected until 2008-2010, these findings support the evidence that prostate-specific antigen testing offered to a population free of charge can reduce prostate cancer mortality.