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Background: The lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) population historically has faced stigma and discrimination, including in health care. Although discrimination in health care generally has improved, barriers to culturally congruent care remain. Education for nurses and other health care workers is key to addressing these barriers; however, little is known about the status of LGBTQ health education in nursing schools., Method: A survey on LGBTQ health education provided to undergraduate nursing students was sent to all Commission on Collegiate Nursing Education-accredited schools., Results: Nearly two-thirds of responding schools indicated their graduates were not adequately prepared to care for this population, and 38% of schools agreed their faculty had the knowledge needed to adequately teach this content. Barriers included time constraints and lack of faculty knowledge., Conclusion: In addition to a need for expanded LGBTQ health education for students, there is a need for faculty education about LGBTQ content. [ J Nurs Educ . 2021;60(10):552-558.] .

Objectives: To create a deep learning algorithm capable of video classification, using a long short-term memory (LSTM) network, to analyze collapsibility of the inferior vena cava (IVC) to predict fluid responsiveness in critically ill patients., Methods: We used a data set of IVC ultrasound (US) videos to train the LSTM network. The data set was created from IVC US videos of spontaneously breathing critically ill patients undergoing intravenous fluid resuscitation as part of 2 prior prospective studies. We randomly selected 90% of the IVC videos to train the LSTM network and 10% of the videos to test the LSTM network's ability to predict fluid responsiveness. Fluid responsiveness was defined as a greater than 10% increase in the cardiac index after a 500-mL fluid bolus, as measured by bioreactance., Results: We analyzed 211 videos from 175 critically ill patients: 191 to train the LSTM network and 20 to test it. Using standard data augmentation techniques, we increased our sample size from 191 to 3820 videos. Of the 175 patients, 91 (52%) were fluid responders. The LSTM network was able to predict fluid responsiveness moderately well, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval [CI], 0.43-1.00), a positive likelihood ratio of infinity, and a negative likelihood ratio of 0.3 (95% CI, 0.12-0.77). In comparison, point-of-care US experts using video review offline and manual diameter measurement via software caliper tools achieved an area under the receiver operating characteristic curve of 0.94 (95% CI, 0.83-0.99)., Conclusions: We demonstrated that an LSTM network can be trained by using videos of IVC US to classify IVC collapse to predict fluid responsiveness. Our LSTM network performed moderately well given the small training cohort but worse than point-of-care US experts. Further training and testing of the LSTM network with a larger data sets is warranted., (© 2020 American Institute of Ultrasound in Medicine.)

Background: Antibiotic stewardship in the pretravel care of older adults is important to effectively treat infections while minimizing harm from side effects and unnecessary antibiotic use. The objective of this study was to compare the characteristics, risk behaviors, infectious diseases, and antibiotic use between older (≥60 years) and younger (18-59 years) travelers., Methods: TravMil is a prospective, observational cohort of United States (US) Department of Defense beneficiaries traveling outside the continental US for ≤6.5 months. For this analysis, we included adults enrolled pretravel between January 2010 and August 2018 and excluded active duty personnel on deployment. Pre and post-travel surveys captured trip characteristics, exposures, illnesses, and antibiotic use., Results: A total of 1742 travelers were analyzed: 747 (42.9%) were aged ≥60 years and 995 (57.1%) were aged 18-59 years. Older travelers were less likely to engage in high-risk dietary behaviors and experience travelers' diarrhea than younger travelers (18.2% vs 22.9%; P  < .05). Influenza-like illness (12.5%) and febrile illness (3.4%) occurred less frequently in the older cohort. Antibiotic use for self-treatment was common in both age groups (25.7% vs 26.7%) and often inappropriate, for example, for treatment of occasional loose stool or mild travelers' diarrhea (67.0% [67/100] in older adults vs 57.6% [83/144] in younger adults; P  < .05), and influenza-like illness (63.4% [64/101] vs 58.6% [68/116], respectively; P  < .05)., Conclusions: Older travelers were less likely to engage in high-risk behaviors and experience travelers' diarrhea, and both age groups experienced mild, self-limited infections. Inappropriate use of antibiotics was common, suggesting that antimicrobial stewardship should be emphasized at pretravel counseling with international travelers., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

An interaction between pharmacological agents can trigger unexpected adverse events. Capturing richer and more comprehensive information about drug-drug interactions (DDIs) is one of the key tasks in public health and drug development. Recently, several knowledge graph (KG) embedding approaches have received increasing attention in the DDI domain due to their capability of projecting drugs and interactions into a low-dimensional feature space for predicting links and classifying triplets. However, existing methods only apply a uniformly random mode to construct negative samples. As a consequence, these samples are often too simplistic to train an effective model. In this paper, we propose a new KG embedding framework by introducing adversarial autoencoders (AAEs) based on Wasserstein distances and Gumbel-Softmax relaxation for DDI tasks. In our framework, the autoencoder is employed to generate high-quality negative samples and the hidden vector of the autoencoder is regarded as a plausible drug candidate. Afterwards, the discriminator learns the embeddings of drugs and interactions based on both positive and negative triplets. Meanwhile, in order to solve vanishing gradient problems on the discrete representation-an inherent flaw in traditional generative models-we utilize the Gumbel-Softmax relaxation and the Wasserstein distance to train the embedding model steadily. We empirically evaluate our method on two tasks: link prediction and DDI classification. The experimental results show that our framework can attain significant improvements and noticeably outperform competitive baselines. Supplementary information: Supplementary data and code are available at https://github.com/dyf0631/AAE&#95;FOR&#95;KG., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Electronic Health Records (EHRs) have become the primary form of medical data-keeping across the United States. Federal law restricts the sharing of any EHR data that contains protected health information (PHI). De-identification, the process of identifying and removing all PHI, is crucial for making EHR data publicly available for scientific research. This project explores several deep learning-based named entity recognition (NER) methods to determine which method(s) perform better on the de-identification task. We trained and tested our models on the i2b2 training dataset, and qualitatively assessed their performance using EHR data collected from a local hospital. We found that 1) Bi-LSTM-CRF represents the best-performing encoder/decoder combination, 2) character-embeddings tend to improve precision at the price of recall, and 3) transformers alone under-perform as context encoders. Future work focused on structuring medical text may improve the extraction of semantic and syntactic information for the purposes of EHR deidentification., (©2021 AMIA - All rights reserved.)

Objectives: The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these 5 objectives: (1) describe sport related concussion (SRC) epidemiology; (2) classify prevention strategies; (3) define objective, diagnostic tests; (4) identify treatment; and (5) integrate science and clinical care into prioritized action plans and policy., Methods: Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session., Results: To (1) establish a national and international hockey database for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care; and (6) mandate baseline testing to improve concussion diagnosis for all age groups., Conclusions: Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Anginal symptoms can connote increased cardiac risk and a need for change in cardiovascular management. In this study, a pre-trained transformer architecture was used to automatically detect and characterize anginal symptoms from within the history of present illness sections of 459 primary care physician notes. Consecutive patients referred for cardiac testing were included. Notes were annotated for positive and negative mentions of chest pain and shortness of breath characterization. The results demonstrate high sensitivity and specificity for the detection of chest pain or discomfort, substernal chest pain, shortness of breath, and dyspnea on exertion. Model performance extracting factors related to provocation and palliation of chest pain were limited by small sample size. Overall, this study shows that pre-trained transformer architectures have promise in automating the extraction of anginal symptoms from clinical texts., (©2020 AMIA - All rights reserved.)

Germany is the highest populated country in Europe with a population of 82.3 million in 2019. As in many other developed countries, it has an aging population. Approximately 10% of the gross domestic product is spent on healthcare. The healthcare system is characterized by its accessibility. Patients are generally free to choose their primary care physicians, both family doctors and specialists, pharmacy, dentist, or emergency service. Up to a certain income, health insurance is mandatory with the statutory health insurance (SHI) system, covering 88% of the population. Major challenges are the lack of cooperation and integration between the different sectors and healthcare providers. This is expected to change with the introduction of a telematic infrastructure that is currently being implemented. It will not only connect all providers in primary and secondary care in a secure network but will also enable access to patients' electronic record/medical data and at the same time switch from paper to electronic prescriptions. Approximately 52,000 of the 67,000 pharmacists are working in approximately 19,000 community pharmacies. These pharmacies are owner-operated by a pharmacist. Pharmacists may own up to three subsidiaries nearby to their main pharmacy. Community pharmacy practice mainly consists of dispensing drugs, counselling patients on drug therapy and safety, and giving advice on lifestyle and healthy living. Many cognitive pharmaceutical services have been developed and evaluated in the past 20 years. Discussions within the profession and with stakeholders on the national level on the roles and responsibilities of pharmacists have resulted in nationally agreed guidelines, curricula, and services. However, cognitive services remunerated by the SHI funds on the national level remain to be negotiated and sustainably implemented. A law passed in November 2020 by parliament will regulate the remuneration of pharmaceutical services by the SHI funds with an annual budget of EUR 150 million. The type of services and their remuneration remain to be negotiated in 2021. The profession has to continue on all levels to advocate for a change in pharmacy practice by introducing pharmacy services into routine care., Competing Interests: CONFLICT OF INTEREST None., (Copyright: © Pharmacy Practice and the Authors.)

Background Large vessel occlusion (LVO) stroke is one of the most time-sensitive diagnoses in medicine and requires emergent endovascular therapy to reduce morbidity and mortality. Leveraging recent advances in deep learning may facilitate rapid detection and reduce time to treatment. Purpose To develop a convolutional neural network to detect LVOs at multiphase CT angiography. Materials and Methods This multicenter retrospective study evaluated 540 adults with CT angiography examinations for suspected acute ischemic stroke from February 2017 to June 2018. Examinations positive for LVO ( n = 270) were confirmed by catheter angiography and LVO-negative examinations ( n = 270) were confirmed through review of clinical and radiology reports. Preprocessing of the CT angiography examinations included vasculature segmentation and the creation of maximum intensity projection images to emphasize the contrast agent-enhanced vasculature. Seven experiments were performed by using combinations of the three phases (arterial, phase 1; peak venous, phase 2; and late venous, phase 3) of the CT angiography. Model performance was evaluated on the held-out test set. Metrics included area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results The test set included 62 patients (mean age, 69.5 years; 48% women). Single-phase CT angiography achieved an AUC of 0.74 (95% confidence interval [CI]: 0.63, 0.85) with sensitivity of 77% (24 of 31; 95% CI: 59%, 89%) and specificity of 71% (22 of 31; 95% CI: 53%, 84%). Phases 1, 2, and 3 together achieved an AUC of 0.89 (95% CI: 0.81, 0.96), sensitivity of 100% (31 of 31; 95% CI: 99%, 100%), and specificity of 77% (24 of 31; 95% CI: 59%, 89%), a statistically significant improvement relative to single-phase CT angiography ( P = .01). Likewise, phases 1 and 3 and phases 2 and 3 also demonstrated improved fit relative to single phase ( P = .03). Conclusion This deep learning model was able to detect the presence of large vessel occlusion and its diagnostic performance was enhanced by using delayed phases at multiphase CT angiography examinations. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ospel and Goyal in this issue.

Acute kidney injury (AKI) is a major complication after cardiothoracic surgery. Early prediction of AKI could prompt preventive measures, but is challenging in the clinical routine. One important reason is that the amount of postoperative data is too massive and too high-dimensional to be effectively processed by the human operator. We therefore sought to develop a deep-learning-based algorithm that is able to predict postoperative AKI prior to the onset of symptoms and complications. Based on 96 routinely collected parameters we built a recurrent neural network (RNN) for real-time prediction of AKI after cardiothoracic surgery. From the data of 15,564 admissions we constructed a balanced training set (2224 admissions) for the development of the RNN. The model was then evaluated on an independent test set (350 admissions) and yielded an area under curve (AUC) (95% confidence interval) of 0.893 (0.862-0.924). We compared the performance of our model against that of experienced clinicians. The RNN significantly outperformed clinicians (AUC = 0.901 vs. 0.745, p  < 0.001) and was overall well calibrated. This was not the case for the physicians, who systematically underestimated the risk ( p  < 0.001). In conclusion, the RNN was superior to physicians in the prediction of AKI after cardiothoracic surgery. It could potentially be integrated into hospitals' electronic health records for real-time patient monitoring and may help to detect early AKI and hence modify the treatment in perioperative care., Competing Interests: Competing interestsA.M. declares the receipt of consulting and lecturing fees from Medtronic GmbH and Edwards Lifesciences Services GmbH, and consulting fees from Pfizer. C.E. declares ownership of shares in codiag AG. F.S. declares the receipt of honoraria, consultancy fees or travel support from Medtronic GmbH, Biotronik SE & Co., Abbott GmbH & Co. KG, Sanofi S.A., Cardiorentis AG, Novartis Pharma GmbH. J.K. declares the receipt of lecturing fees from, Boston Scientific, LSI Solutions, Edwards, Medtronic, Abbott, Ascyrus Medical GmbH. V.F. declares (institutional) financial activities with Medtronic, Biotronik, Abbott, Boston, Edwards, Berlin Heart, Novartis, Jotec, Zurich Heart in relation to Educational Grants, honoraria, consultancy, research & study funds, fees for travel support. All other authors declare no competing interests., (© The Author(s) 2020.)

Diagnostic errors can pose a serious threat to patient safety, leading to serious harm and even death. Efforts are being made to develop interventions that allow physicians to reassess for errors and improve diagnostic accuracy. Our study presents an exploration of misdiagnosis patterns mined from PubMed abstracts. Article titles containing certain phrases indicating misdiagnosis were selected and frequencies of these misdiagnoses calculated. We present the resulting patterns in the form of a directed graph with frequency-weighted misdiagnosis edges connecting diagnosis vertices. We find that the most commonly misdiagnosed diseases were often misdiagnosed as many different diseases, with each misdiagnosis having a relatively low frequency, rather than as a single disease with greater probability. Additionally, while a misdiagnosis relationship may generally exist, the relationship was often found to be one-sided., (©2020 AMIA - All rights reserved.)

The American College of Surgeons requires that trauma centers collect and enter data into the National Trauma Data Registry in compliance with the National Trauma Data Standard. ProMedica supports employment of 4 trauma data analysts who are responsible for entering information in a timely manner, validating the data, and analyzing data to evaluate established benchmarks and support the performance improvement and patient safety process. Historically, these analysts were located on-site at ProMedica Toledo Hospital. In 2017, a proposal was developed including modifications to data collection to streamline processes, move toward paperless documentation, and allow for the analysts to telecommute. To measure the effect of these changes, the timeliness of data entry, rate of data validation, productivity, and staff satisfaction were measured. After the transition to electronic data management and home-based workstations, registry data were being entered within 30 days and 100% of cases were being validated, without sacrificing effective and efficient communication between in-hospital and home-based staff. The institution also benefitted from reduced expense for physical space, employee turnover, and decreased employee absenteeism. The analysts appreciated benefits related to time, travel, environment, and job satisfaction.It is feasible to transition trauma data analysts to a work-from-home situation. An all-electronic system of data management and communication makes such an arrangement possible and sustainable. This quality improvement project solved a workspace issue and was beneficial to the trauma program overall, with the timeliness and validation of data entry vastly improved.

Current biodegradation screening tests are not specifically designed for persistence assessment of chemicals, often show high inter- and intra-test variability, and often give false negative biodegradation results. Based on previous studies and recommendations, an international ring test involving 13 laboratories validated a new test method for marine biodegradation with a focus on improving the reliability of screening to determine the environmental degradation potential of chemicals. The new method incorporated increased bacterial cell concentrations to better represent the microbial diversity; a chemical is likely to be exposed in the sampled environments and ran beyond 60 days, which is the half-life threshold for chemical persistence in the marine environment. The new test provided a more reliable and less variable characterization of the biodegradation behavior of five reference chemicals (sodium benzoate, triethanolamine, 4-nitrophenol, anionic polyacrylamide, and pentachlorophenol), with respect to REACH and OSPAR persistence thresholds, than the current OECD 306 test. The proposed new method provides a cost-effective screening test for non-persistence that could streamline chemical regulation and reduce the cost and animal welfare implications of further higher tier testing.

Background and Purpose: Manual annotation and categorization of non-standardized text ("free-text") of drug orders entered into electronic health records is a labor-intensive task. However, standardization is required for drug order analyses and has implications for clinical decision support. Machine learning could help to speed up manual labelling efforts. The objective of this study was to analyze the performance of deep machine learning methods to annotate non-standardized text of drug order entries with their therapeutically active ingredients., Materials and Methods: The data consisted of drug orders entered 8/2009-4/2014 into the electronic health records of inpatients at a large tertiary care academic medical center. We manually annotated the most frequent order entry patterns with the active ingredient they contain (e.g. "Prograf"⟵"Tacrolimus"). We heuristically included additional orders by means of character sequence comparisons to augment the training dataset. Finally, we trained and employed character-level recurrent deep neural networks to classify non-standardized text of drug order entries according to their active ingredients., Results: A total of 26,611 distinct order patterns were considered in our study, of which the top 7.6% (2028) had been annotated with one of 558 distinct ingredients, leaving 24,583 unlabeled observations. Character-level recurrent deep neural networks achieved a Mean Reciprocal Rank (MRR) of 98% and outperformed the best representative baseline, a trigram-based Support Vector Machine, by 2 percentage points., Conclusion: Character-level recurrent deep neural networks can be used to map the active ingredient to non-standardized text of drug order entries, outperforming other representative techniques. While machine learning might help to facilitate categorization tasks, still a considerable amount of manual labelling and reviewing work is required to train such systems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Failure of the most recent tuberculosis (TB) vaccine trial to boost bacillus Calmette-Guérin-mediated anti-TB immunity despite the induction of Th1-specific central memory cell and effector memory cell responses highlights the importance of identifying optimal T cell targets for protective vaccines. In this study, we describe a novel, Mycobacterium tuberculosis -specific IFN-γ + CD4 + T cell population expressing surface markers characteristic of naive-like memory T cells (T NLM ), which were induced in both human (CD45RA + CCR7 + CD27 + CD95 - ) and murine (CD62L + CD44 - Sca-1 + CD122 - ) systems in response to mycobacteria. In bacillus Calmette-Guérin-vaccinated subjects and those with latent TB infection, T NLM were marked by the production of IFN-γ but not TNF-α and identified by the absence of CD95 expression and increased surface expression CCR7, CD27, the activation markers T-bet, CD69, and the survival marker CD74. Increased tetramer-positive T NLM frequencies were noted in the lung and spleen of ESAT-6 1-20 -specific TCR transgenic mice at 2 wk postinfection with M. tuberculosis and progressively decreased at later time points, a pattern not seen with TNF-α + CD4 + T cells expressing naive cell surface markers. Importantly, adoptive transfer of highly purified T NLM alone, from vaccinated ESAT-6 1-20 -specific TCR transgenic mice, conferred equivalent protection against M. tuberculosis infection in the lungs of Rag -/- mice when compared with total memory populations (central and effector memory cells). Thus, T NLM may represent a memory T cell population that, if optimally targeted, may significantly improve future TB vaccine responses., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Complementary and integrative health (CIH) services are being used more widely across the nation, including in both military and veteran hospital settings. Literature suggests that a variety of CIH services show promise in treating a wide range of physical and mental health disorders. Notably, the Department of Veterans Affairs is implementing CIH services within the context of a health care transformation, changing from disease based health care to a personalized, proactive, patient-centered approach where the veteran, not the disease, is at the center of care. This study examines self-reported physical and mental health outcomes associated with participation in the Integrative Health and Wellness Program, a comprehensive CIH program at the Washington DC VA Medical Center and one of the first wellbeing programs of its kind within the VA system. Using a prospective cohort design, veterans enrolled in the Integrative Health and Wellness Program filled out self-report measures of physical and mental health throughout program participation, including at enrollment, 12 weeks, and 6 months. Analyses revealed that veterans reported significant improvements in their most salient symptoms of concern (primarily pain or mental health symptoms), physical quality of life, wellbeing, and ability to participate in valued activities at follow-up assessments. These results illustrate the potential of CIH services, provided within a comprehensive clinic focused on wellbeing not disease, to improve self-reported health, wellbeing, and quality of life in a veteran population. Additionally, data support recent VA initiatives to increase the range of CIH services available and the continued growth of wellbeing programs within VA settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Motivation: Technological advancements in high-throughput DNA sequencing have led to an exponential growth of sequencing data being produced and stored as a byproduct of biomedical research. Despite its public availability, a majority of this data remains hard to query for the research community due to a lack of efficient data representation and indexing solutions. One of the available techniques to represent read data is a condensed form as an assembly graph. Such a representation contains all sequence information but does not store contextual information and metadata., Results: We present two new approaches for a compressed representation of a graph coloring: a lossless compression scheme based on a novel application of wavelet tries as well as a highly accurate lossy compression based on a set of Bloom filters. Both strategies retain a coloring even when adding to the underlying graph topology. We present construction and merge procedures for both methods and evaluate their performance on a wide range of different datasets. By dropping the requirement of a fully lossless compression and using the topological information of the underlying graph, we can reduce memory requirements by up to three orders of magnitude. Representing individual colors as independently stored modules, our approaches can be efficiently parallelized and provide strategies for dynamic use. These properties allow for an easy upscaling to the problem sizes common to the biomedical domain., Availability and Implementation: We provide prototype implementations in C++, summaries of our experiments as well as links to all datasets publicly at https://github.com/ratschlab/graph&#95;annotation., Supplementary Information: Supplementary data are available at Bioinformatics online.

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Background: The large amount of clinical signals in intensive care units can easily overwhelm health-care personnel and can lead to treatment delays, suboptimal care, or clinical errors. The aim of this study was to apply deep machine learning methods to predict severe complications during critical care in real time after cardiothoracic surgery., Methods: We used deep learning methods (recurrent neural networks) to predict several severe complications (mortality, renal failure with a need for renal replacement therapy, and postoperative bleeding leading to operative revision) in post cardiosurgical care in real time. Adult patients who underwent major open heart surgery from Jan 1, 2000, to Dec 31, 2016, in a German tertiary care centre for cardiovascular diseases formed the main derivation dataset. We measured the accuracy and timeliness of the deep learning model's forecasts and compared predictive quality to that of established standard-of-care clinical reference tools (clinical rule for postoperative bleeding, Simplified Acute Physiology Score II for mortality, and the Kidney Disease: Improving Global Outcomes staging criteria for acute renal failure) using positive predictive value (PPV), negative predictive value, sensitivity, specificity, area under the curve (AUC), and the F 1 measure (which computes a harmonic mean of sensitivity and PPV). Results were externally retrospectively validated with 5898 cases from the published MIMIC-III dataset., Findings: Of 47 559 intensive care admissions (corresponding to 42 007 patients), we included 11 492 (corresponding to 9269 patients). The deep learning models yielded accurate predictions with the following PPV and sensitivity scores: PPV 0·90 and sensitivity 0·85 for mortality, 0·87 and 0·94 for renal failure, and 0·84 and 0·74 for bleeding. The predictions significantly outperformed the standard clinical reference tools, improving the absolute complication prediction AUC by 0·29 (95% CI 0·23-0·35) for bleeding, by 0·24 (0·19-0·29) for mortality, and by 0·24 (0·13-0·35) for renal failure (p<0·0001 for all three analyses). The deep learning methods showed accurate predictions immediately after patient admission to the intensive care unit. We also observed an increase in performance in our validation cohort when the machine learning approach was tested against clinical reference tools, with absolute improvements in AUC of 0·09 (95% CI 0·03-0·15; p=0·0026) for bleeding, of 0·18 (0·07-0·29; p=0·0013) for mortality, and of 0·25 (0·18-0·32; p<0·0001) for renal failure., Interpretation: The observed improvements in prediction for all three investigated clinical outcomes have the potential to improve critical care. These findings are noteworthy in that they use routinely collected clinical data exclusively, without the need for any manual processing. The deep machine learning method showed AUC scores that significantly surpass those of clinical reference tools, especially soon after admission. Taken together, these properties are encouraging for prospective deployment in critical care settings to direct the staff's attention towards patients who are most at risk., Funding: No specific funding., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Since 1 October 2016, all legally insured persons are entitled to a nationwide medication plan (BMP) under certain conditions (according to § 31a SGB V, E-Health Law). The catalogue of measures of the 3rd Action Plan 2013-2015 for the improvement of drug therapy safety (AMTS) provided for the testing of a medication plan in practice, including its acceptance and practicability in three model projects. These three projects - MetropolMediplan 2016, Erfurt, and PRIMA - are presented and recommendations are derived on the basis of the collected findings. Overall, the BMP was welcomed by the participating patients in all projects and led to an increase in satisfaction and an improvement in competence with regard to medication. Both doctors and pharmacists rated the interdisciplinary cooperation via the medium BMP very positively. The high effort and lack of technical infrastructure without electronic availability of the last current version of a BMP of the individual patient was perceived as negative. An original data comparison of the BMP data with the drugs actually taken in the MetropolMediplan 2016 project showed that only 36% of the patients were in agreement with the BMP and the drugs presently taken. The paper version of the BMP has therefore not yet been able to solve the problem of the timeliness and completeness of the medication. In addition to various proposals for the further development of BMP, all parties involved require the BMP to be available electronically across all sectors. The BMP should therefore be an important instrument for improving AMTS in the future.

Introduction: Crohn's disease (CD) is a chronic condition associated with the risk of malabsorption. The incidence of obesity worldwide is increasing, and the effect of obesity on patients with CD is unknown. We aim to identify traits related to obesity in a cohort of patients with CD., Methods: We conducted a retrospective study of 209 adult patients with CD. Age, Montreal disease classification, sex, race, duration of disease, erythrocyte sedimentation rate, C-reactive protein levels, physician global assessment, endoscopic appearance, histologic activity, medication use, and body mass index (BMI) were collected about each patient., Results: The mean age was 43.4 ± 14.9 years; 68.9% were white, and 51.7% were male. The mean duration of disease was 11.0 ± 10.6 years. The mean BMI was 26.8 ± 5.7: underweight 7.7%; normal weight 29.3%; overweight 38.0%; and obese 25%. Patients with higher BMI were more likely to have extraintestinal manifestations (EIM) (P = 0.005) and more likely to have nonarthralgia extraintestinal manifestations (P = 0.047). There was a linear association between proximal CD and decreasing BMI (underweight 31.3%, normal weight 14.8%, overweight 15.0%, obese 7.7%; P = 0.046). There was no difference in BMI between patients with and without perianal disease (P = 0.216)., Conclusions: Most patients were overweight or obese, which correlates with national population trends. Our data suggest disease location plays a role in weight modulation in patients with CD. Increased extraintestinal manifestations in patients with high BMI suggests that the chronic inflammation associated with obesity may play a role in extraintestinal inflammation.

Tickborne diseases are increasing in the United States, and the geographic range of tick vectors is expanding. Tickborne diseases are challenging to diagnose, as they present with vague symptoms such as fever, constitutional symptoms, and nonspecific laboratory abnormalities. A high degree of clinical suspicion is required to make a diagnosis, as patients often do not recall a tick bite. The availability of laboratory testing for tickborne diseases is limited, especially in the acute setting. Therefore, if a tickborne disease is suspected, empiric therapy should often be initiated before laboratory confirmation of the disease is available. This article summarizes the most common non-Lyme tickborne diseases in the United States., (Copyright © 2017 Cleveland Clinic.)

Purpose: A standardized medication plan for patients has been developed and recently enacted into German law depicting all medicines taken. It can only increase medication safety if patients use and understand it. We evaluated patients' comprehensibility of the medication plan and analyzed potential variables influencing patients' understanding., Methods: The medication plan template v2.0 was first tested in N = 40 patients, and the "Evaluation Tool to test the handling of the Medication Plan" (ET-MP) was developed, rating patients' understanding from 0 to 100 %. The cut-off, distinguishing if patients understand the medication plan, was set at 90 %. The ET-MP was then applied to an amended medication plan questioning N = 40 general internal medicine (GIM) and N = 50 patients with chronic heart failure (CHF)., Results: The mean (± standard deviation (SD)) age of the study cohort was 69 ± 13 years, 47 % female. Patients took 8 ± 3 drugs chronically. The CHF patients had a lower level of education compared to the GIM group (p = 0.004). The overall ET-MP score was 82 ± 21 % (GIM 86 ± 19 %, CHF 78 ± 23 %; p = 0.16). Forty-three percent achieved a score >90 %. A moderate correlation was found between the ET-MP score and the level of education (r = 0.45) and age (r = -0.46), respectively (both p < 0.001). Cognitively impaired CHF patients (p = 0.03) and patients with advanced CHF (p = 0.006) achieved a lower ET-MP score. In the CHF cohort, signs of depression or a lower level of self-care behaviour were not associated with a lower ET-MP score., Conclusion: The ET-MP is suitable to explore patients' understanding of a medication plan. Less than 50 % of the patients reached a score above 90 %. Higher age and lower level of education but not the diagnosis of CHF seem to correlate with impaired understanding of the standardized medication plan. In addition to a medication plan, a significant number of patients are in need of further and continuous care to improve medication safety.

Purpose: The Action Plan for Medication Safety by the German Federal Ministry of Health introduced a standardized medication plan (MP), a printable document for the patient. The practical handling needs to be tested before the nationwide implementation in Germany. Therefore, the aims of our study were 1) to develop an instrument to evaluate the usage of the standardized MP, 2) to assess if patients can locate, and 3) understand important information. Moreover, we explored patients' opinion and suggestions regarding the standardized MP template., Patients and Methods: We conducted a cross-sectional study to evaluate the practical handling of the standardized MP. We interviewed 40 adult patients in seven community pharmacies in Germany, who took at least five medicines regularly and gave their written informed consent. The interview consisted of questions regarding finding and understanding information provided on a mock-up MP, patients' opinion and the execution of the information on the MP by filling pill boxes. We eventually developed a new evaluation method to quantify the practical handling of the MP by rating the pill boxes filled by the patients., Results: Overall, the participants rated the MP positively. Thirty-nine (98%) participants found important information on a mock-up standardized MP. Patients were questioned to identify if they understood information on medical intake as it relates to meals. In particular, they were questioned about medicine intake "1 hour before a meal", which 98% (n=39) interpreted correctly, and "during a meal", which 100% (n=40) interpreted correctly. The less precise advice of "before a meal" was interpreted correctly by 73% (n=29), and only 15% (n=6) correctly interpreted the term "after the meal". The evaluation of the filled pill boxes resulted in the "Evaluation Tool to test the handling of the Medication Plan" (ET-MP) - a weighted scoring system., Conclusion: The standardized MP is clearly arranged, and patients are able to find important information. The findings of this study resulted in minor but important revisions of the standardized MP template. The developed evaluation tool ET-MP may serve as an objective instrument to assess patients' ability to transfer written information on the MP into practical handling of medicines.

Background/aim: To determine if Boys Bantam and Peewee and Girls U14 sustain fewer concussions, head hits, 'other injuries' and penalties in hockey tournaments governed by intensified fair play (IFP) than non-intensified fair play (NIFP)., Methods: A prospective comparison of IFP, a behaviour modification programme that promotes sportsmanship, versus control (non-intensified, NIFP) effects on numbers of diagnosed concussions, head hits without diagnosed concussion (HHWDC), 'other injuries', number of penalties and fair play points (FPPs). 1514 players, ages 11-14 years, in 6 IFP (N=950) and 5 NIFP (N=564) tournaments were studied., Results: Two diagnosed concussions, four HHWDC, and six 'other injuries' occurred in IFP tournaments compared to one concussion, eight HHWDC and five 'other injuries' in NIFP. There were significantly fewer HHWDC in IFP than NIFP (p=0.018). However, diagnosed concussions, 'other injuries', penalties and FPPs did not differ significantly between conditions. In IFP, a minority of teams forfeited the majority of FPPs. Most diagnosed concussions, HHWDC, and other injuries occurred to Bantam B players and usually in penalised teams that forfeited their FPPs., Conclusions: In response to significant differences in HHWDC between IFP and NIFP tournaments, the following considerations are encouraged: mandatory implementation of fair play in regular season and tournaments, empowering tournament directors to not accept heavily penalised teams, and introducing 'no body checking' in Bantam.

Context: A movement exists within the Veterans Health Administration (VHA) toward incorporating complementary and alternative medicine (CAM) as an integrative complement to care for veterans. The Integrative Health and Wellness (IHW) Program is a comprehensive CAM clinic offering services such as integrative restoration (iRest) yoga nidra, individual acupuncture, group auricular acupuncture, chair yoga, qigong, and integrative health education., Objectives: The current study intended to detail the development of the CAM program, its use, and the characteristics of the program's participants., Design: Using a prospective cohort design, this pilot study tracked service use and aspects of physical and mental health for veterans enrolled in the program., Participants: During the first year, the IHW Program received 740 consults from hospital clinics; 325 veterans enrolled in the program; and 226 veterans consented to participate in the pilot study., Outcome Measures: Outcome measures included data from self-report questionnaires and electronic medical records., Results: Veterans enrolled in the program reported clinically significant depression, stress, insomnia, and pain-related interference in daily activities and deficits in health-related quality of life. Regarding use of the program services, individual acupuncture showed the greatest participation by veterans, followed by group auricular acupuncture and iRest yoga nidra. Of the 226 veterans who enrolled in the program and consented to participate in this study, 165 (73.01%) participated in >1 services in the first year of programming. Broadly speaking, enrollment in services appeared to be associated with gender and service branch but not with age or symptom severity., Conclusions: Results have assisted with a strategic planning process for the IHW Program and have implications for expansion of CAM services within the VHA.

Background: Gulf War veterans represent a unique subset of the veteran population. It has been challenging to identify interventions that result in improvements in physical and mental health for this population. Recently, there has been recognition of a potential role for complementary and alternative medicine (CAM) interventions., Objectives: This paper examines the characteristics of Gulf War and non-Gulf War veterans referred to a CAM clinic, and explores the utilization of services by this population., Method and Subjects: Participants included 226 veterans enrolled in a CAM clinic at a Veterans Affairs medical center, 42 of whom were Gulf War veterans. Self-report measures of physical/mental health were administered, and service utilization was obtained from participants' medical records for a 6-month period., Results: Gulf War veterans enrolled in the program reported more severe physical and mental health symptoms than non-Gulf War veterans. However, examining only veterans who participated in services in the 6 months following enrollment, the 2 groups reported similar symptom severity. Both groups were similar in their attendance of individual acupuncture and iRest yoga nidra, although Gulf War veterans attended fewer sessions of group acupuncture., Conclusions: Although Gulf War veterans who enroll in a CAM program may have more severe symptoms than non-Gulf War veterans, those who actually participate in services are similar to non-Gulf War veterans on these measures. These groups also differ in their pattern of service utilization. Future research should explore the reasons for these differences, and to identify ways to promote treatment engagement with this population.

Clinical pharmacists play an important role in improving drug safety on hospital wards. However, little is known about the impact of pharmacy interns. The objective of our study was, therefore, to investigate the impact of hospital ward-based pharmacy interns on drug safety. This study was conducted as part of the project "P-STAT 2: Pharmacy interns on the ward" on 14 surgical wards in seven hospitals in Germany and a total of 27 pharmacy interns participated. All patients admitted to the participating wards from 1st June 2008 until 31st October 2008 and from 1st December 2008 till 30th April 2009 were included. The pharmacy interns were involved in medication reconciliation, and identifying, resolving, and preventing drug-related problems (DRPs) using the classification system APS-Doc. A total of 6,551 patients were included. Patients received on average (+/- SD) 4.4 +/- 3.9 drugs. The pharmacy interns detected a total of 4,085 DRPs and on average 0.6 +/- 1.2 DRPs per patient. Most frequently detected DRPs were potential drug-drug interactions (n = 591, 14%), missing drug strength, when different strengths were available (n = 373, 9%), and incomplete medication record (n = 296, 7%). The pharmacy interns conducted an intervention for 98% (n = 4,011) of all DRPs. According to their documentation, 74% of the DRPs (n = 3,038) were solved. Drugs which were most often related with DRPs were simvastatin, diclofenac, and ibuprofen. This is the very first study exploring the potential impact of pharmacy interns on drug safety on surgical wards in Europe. Pharmacy interns can play an important role to improve drug safety on hospital wards.

Renal infarction (RI) is rare, and usually occurs in patients with associated comorbidities. The majority of reported cases have presented with laboratory abnormalities, most notably leukocytosis and elevated lactate dehydrogenase (LDH). A 50-year-old active duty white male nonsmoker without medical history presented with flank pain. Urinalysis, complete blood count, LDH, and serum creatinine were normal. Contrast-enhanced computed tomography of the abdomen and pelvis showed a right-sided RI. The patient was admitted to the hospital and anticoagulated. Laboratory values remained normal, and a comprehensive workup failed to reveal an etiology for his RI. RI is rare, and affected patients often present with symptoms similar to more common conditions such as lumbago or nephrolithiasis. Elevated LDH may be a clue to the diagnosis, but unlike 92% of the reviewed cases, our patient presented with a normal value. This case suggests that clinicians should consider RI in patients with persistent symptoms for whom more common causes of flank pain have been excluded; including in nonsmoking patients without apparent risk factors for infarction who present with a normal LDH and no leukocytosis., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Background: Drug-related problems (DRPs) can have an important impact on the effectiveness and safety of pharmacotherapy. In Germany, the frequency of DRPs in prescribed medicines in ambulatory care is not yet known. Objective To quantify DRPs in prescribed medicines identified by community pharmacists (CPs) at the time the medicine is dispensed., Setting: German CPs in four different regions., Method: We invited CPs to document one hundred consecutive patients presenting prescriptions using a standardized documentation form. For each patient, person- and medication-related as well as identified DRP-related data were documented. Data were transcribed electronically, coded if necessary, checked for validity, and analyzed., Main Outcome Measure: Nature and frequency of DRPs., Results: In total, 143 CPs documented 14,231 patients with 24,422 prescribed drugs and identified DRPs in 2,556 patients (18.0%). Analyses resulted in 0.23 DRPs per patient and 0.13 DRPs per prescribed medicine. Four DRPs were responsible for almost 70% of all DRPs: Potential drug-drug interaction (22.9%), dose not known to patient (21.7%), patient insecure due to generic substitution (13.5%), and insufficient patient knowledge of correct drug use (10.9%). If a patient's drug file was kept in the pharmacy, specific types of DRPs were detected more frequently e.g., drug-drug interactions (p < 0.001). Interventions primarily comprised counselling, monitoring, and changing drug or instructions for use. The prescribing physician was contacted in 28% of DRPs resulting in a change of these prescriptions in 50% of the cases. Overall and according to the pharmacists, more than 90% of the DRPs detected were partially (10.4%) or completely (85.4%) solved., Conclusion: We quantified DRPs in prescribed medicines in daily ambulatory care practice in Germany. When filling a prescription, in nearly 20% of the patients relevant DRPs were revealed. According to the pharmacists, the majority could be partially or completely solved during the encounter at the pharmacy. Keeping a patient's drug file including patient specific data may facilitate the detection of DRPs and shall, therefore, be offered to patients more often.

Mixed self-assembled monolayers (SAMs) of alkanethiolates carrying azobenzene chromophores with either a trifluoromethyl or a cyano substituent have been studied. High-resolution x-ray photoelectron spectroscopy proves that the ratio of adsorbed molecules can be arbitrarily adjusted via the molar fractions in solution. As a function of these molar fractions core level shifts are observed which are attributed to local work-function changes. By simulating the electric dipole field distribution, the continuous core level shifts are ascribed to a homogeneous mixture of molecules with different end groups adsorbed on adjacent lattice sites. Near-edge x-ray absorption fine structure measurements reveal formation of well-ordered SAMs. Despite the difference in dipole moment of the end groups, the molecular tilt and twist angles are identical for both single-component SAMs and a 1:1 mixed SAM.

Standard protocols are given for assessing metabolic stability in rainbow trout using the liver S9 fraction. These protocols describe the isolation of S9 fractions from trout livers, evaluation of metabolic stability using a substrate depletion approach, and expression of the result as in vivo intrinsic clearance. Additional guidance is provided on the care and handling of test animals, design and interpretation of preliminary studies, and development of analytical methods. Although initially developed to predict metabolism impacts on chemical accumulation by fish, these procedures can be used to support a broad range of scientific and risk assessment activities including evaluation of emerging chemical contaminants and improved interpretation of toxicity testing results. These protocols have been designed for rainbow trout and can be adapted to other species as long as species-specific considerations are modified accordingly (e.g., fish maintenance and incubation mixture temperature). Rainbow trout is a cold-water species. Protocols for other species (e.g., carp, a warm-water species) can be developed based on these procedures as long as the specific considerations are taken into account., (© 2012 by John Wiley & Sons, Inc.)

Despite the existence of antithrombotic guidelines, there is low compliance with these guidelines in clinical practice. Until now pharmacy interns (PIs) have not been involved in this process. The objectives were to involve PIs to evaluate compliance with antithrombotic guidelines for VTE prophylaxis in surgery patients, and in cases of noncompliance to carry out pharmaceutical interventions. The study was conducted in 7 hospitals in Germany involving 27 PIs within the project "Pharmacy interns on the ward" (P-STAT 2). Pharmacy interns determined the thromboembolic risk, documented antithrombotic medication, and checked the compliance with current antithrombotic guidelines. A total of 6491 patients were enrolled; 5695 patients received antithrombotic prophylaxis. Antithrombotic guideline was followed in 77.5% patients. Many patients are not receiving appropriate VTE prophylaxis or heparin bridging regimen despite the fact that evidence-based antithrombotic guidelines are available. Pharmacy interns may play an important role in antithrombotic management.

Background and Aim: Surgical site infections (SSIs) are associated with a high morbidity, mortality and healthcare costs. The prevention of SSIs is based on a combination of preoperative preparation, surgical techniques, perioperative antibiotic prophylaxis (PAP) and postoperative wound care. Despite an abundance of evidence demonstrating the effectiveness of antimicrobials to prevent SSIs, the use of antimicrobial prophylaxis in this clinical setting is associated with inappropriate timing and selection and excessive duration of administration. To date, pharmacy interns (PIs) have not been involved in this process. The aim of this study was to evaluate feasibility of involving PIs in monitoring adherence to the guidelines for antibiotic prophylaxis in surgery patients., Methods: The study was conducted in seven hospitals in Germany within the framework of the project "Pharmacy interns on the ward" (P-STAT2). Twenty-seven PIs participated, either from either May to October 2008 or from November 2008 to April 2009. Each patient admitted to the participating wards was consecutively monitored. PIs documented the antibiotic prophylaxis and checked the adherence with the hospital ward's PAP guidelines taking both the choice of antibiotic drug and the duration of PAP into account. The costs of antibiotics, personnel and material were calculated in cases of non-adherence with guidelines., Results: This is the first time that PIs were involved in monitoring antibiotic prophylaxis guidelines. A total of 6,167 patients were enrolled (mean age 58.3 ± 19.6 years; 47.1% male); of these, 5,064 patients underwent surgery and were ultimately available for evaluation. Guidelines for antibiotic prophylaxis were followed in 70.7% of the cases., Conclusions: The study revealed that many patients do not receive the appropriate antibiotic prophylaxis despite the fact that guidelines are in place. Based on these results, we conclude that PIs may play an important role in antibiotic prophylaxis management.

Purpose: To quantify drug-related problems (DRPs) in self-medication (over-the-counter [OTC] drug use) identified by community pharmacists (CPs) in Germany at the time the drug is dispensed., Methods: One hundred CPs were asked to document 100 consecutive customers presenting symptoms or requesting OTC drugs using a standardized documentation form. The number of 10,000 encounters seemed reasonable to evaluate the set objective. For each encounter, data such as age, sex, and first or repeated request and the availability of a patient file in the pharmacy including drug history were documented. Furthermore, identified DRPs, problem descriptions, and solutions were documented. Data were transcribed electronically, coded, checked for validity, and analyzed., Results: In total, 109 CPs documented 12,567 encounters identifying DRPs in 17.6% of all cases. Four indications comprised more than 70% of all DRPs: pain, respiratory, gastrointestinal, and skin disorders. Four DRPs were responsible for almost 75% of all DRPs identified: self-medication inappropriate (29.7%), requested product inappropriate (20.5%), intended duration of drug use too high including abuse (17.1%), and wrong dosage (6.8%). If a drug history was available, significantly more cases with wrong dosage (p < 0.05) and drug-drug interactions (p < 0.001) were detected. All patients with identified DRPs were counseled accordingly. Furthermore, the most frequent interventions were referral to a physician (39.5%) and switching to a more appropriate drug (28.1%)., Conclusions: In nearly one of five encounters, a direct pharmacist-patient interaction about self-medication revealed relevant DRPs. Having access to patient files including data on prescription and OTC drugs may increase patient safety., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To evaluate the internal reliability, factor structure and construct validity of the Pharmacy Safety Climate Questionnaire (PSCQ) when applied to a pan-European sample of community pharmacies., Design: A cross-sectional survey design was used., Setting: Community pharmacies in Denmark, Germany, the Netherlands, Portugal and Great Britain., Participants: A total of 4105 members of the community pharmacy workforce, all drawn from one of the five participating countries., Main Outcome Measures: Each participant completed a copy of the Pharmacy Safety Climate Questionnaire in his or her respective language and rated the perceived safety of the pharmacy in which he or she worked., Results: Exploratory and confirmatory factor analyses of the data identified four factors that accounted for item responses, with 24 of the original 34 items loading onto them. They were labelled organizational learning, blame culture, working conditions and safety focus. These factors were found to have an acceptable level of reliability (with Cronbach's alpha values ranging from 0.70 to 0.92) and to predict the rating of pharmacy safety., Conclusions: This study provided information on the PSCQ's psychometric properties when used in community pharmacies in different European countries. A modified version of the original PSCQ (known as PSCQ-4) is presented, and further work is proposed to demonstrate its application to safety improvements in pharmacies.

Fano resonances are well-known manifestations of the interference between a direct and an indirect ionization process. Here we report on a more complicated interference pattern observed in two-photon photoemission at the Si(100) surface. This two-dimensional Fano profile involves two discrete surface resonances which couple as initial and intermediate states to the silicon valence and conduction band, respectively. Tuning the photon energy across the surface resonance reveals asymmetric line profiles with pronounced destructive interference in the two-photon photoelectron intensities of both initial and intermediate states. The interference pattern is explained by an analytic extension of Fano's model to describe the coupling of two discrete states with two continua. This coupling strongly modifies the photoabsorption and is of general importance for light conversion in nanostructures and light-harvesting devices., (© 2011 American Physical Society)

Introduction: Although for conventional dosing of carboplatin, several strategies are available to individualize the dose based on renal function measurements, such approaches are still rare for high-dose regimens with autologous stem cell support. The purpose of this study was to investigate the influence of patient- and regimen-specific factors on the pharmacokinetics of carboplatin and to compare the performance of different dose individualization strategies (Calvert, Newell, Chatelut, flat dosing, dosing according to body surface area)., Patients and Methods: A combined data set with 69 patients from five studies, including 13 pediatric patients, was subject to a population pharmacokinetic analysis using NONMEM., Results: The covariate analysis revealed that carboplatin clearance after high-dose chemotherapy was highly related to creatinine clearance, body height, and infusion duration. After inclusion of these covariates, the population parameter variability of clearance decreased from 53% in the base model to 21% in the final model. We also developed an alternative model that related body weight, instead of height, to clearance by means of allometric scaling. An evaluation of the predictive performance of existing a priori dose individualization strategies revealed that flat dosing is appropriate for adult patients with normal renal function receiving a 1-hour infusion. For a long-term infusion schedule, a dose increase may be necessary. The existing dosing strategies performed poorly for the children in our data set. For this subpopulation, our allometric scaling model may be most appropriate., Conclusion: The two population pharmacokinetic models presented can be applied to estimate individual carboplatin clearance in high-dose chemotherapy based on body weight or height, infusion duration, and creatinine clearance. After prospective evaluation, our models may be suitable for dose adjustments.

Food ingestion is the major route of exposure to many hydrophobic organic contaminants (HOCs) such as benzo[a]pyrene (BaP). It has been proposed that food-bound HOCs may become bioavailable after their mobilization by gastrointestinal fluids. The purpose of this research was to measure the uptake efficiency of [(14)C]-BaP bound to skim milk powder using an in vitro model of gastrointestinal digestion followed by sorption to human enterocytes (Caco-2 cells). Neutralization of intestinal fluids released [(14)C]-BaP into the soluble fraction. Ageing of benzo[a]pyrene onto skim milk for 6 months significantly decreased the mobilized fraction but did not affect the amount of benzo[a]pyrene taken up into Caco-2 cells. Hence, significant differences in aqueous phase concentrations may not always be reflected in significant differences in uptake. We obtained evidence that the digestion/uptake of skim milk lipids is accompanied by the diffusive uptake of BaP (the fat flush hypothesis) as trans-cellular transfer of BaP was favoured in the apical to basolateral direction. These data support the theory that non-polar substances including HOCs are preferentially transferred from the lumen into the bloodstream and provide indirect evidence that the uptake is related to the fugacity gradient created by the unidirectional uptake of dietary lipids.

A major route of exposure to hydrophobic organic contaminants (HOCs), such as benzo[a]pyrene (BaP), is ingestion. Matrix-bound HOCs may become bioavailable after mobilization by the gastrointestinal fluids followed by sorption to the intestinal epithelium. The purpose of this research was to measure the bioavailability of [14C]-BaP bound to pristine soils or field-contaminated sediment using an in vitro model of gastrointestinal digestion followed by sorption to human enterocytes (Caco-2 cells) or to a surrogate membrane, ethylene vinyl acetate (EVA) thin film. Although Caco-2 cells had a twofold higher lipid-normalized fugacity capacity than EVA, [14C]-BaP uptake by Caco-2 lipids and EVA thin film demonstrated a linear relationship within the range of BaP concentrations tested. These results suggest that EVA thin film is a good membrane surrogate for passive uptake of BaP. The in vitro system provided enough sensitivity to detect matrix effects on bioavailability; after 5 h, significantly lower concentrations of [14C]-BaP were sorbed into Caco-2 cells from soil containing a higher percentage of organic matter compared to soil with a lower percentage of organic matter. The [14C]-BaP desorption rate from Caco-2 lipids consistently was twofold higher than from EVA thin film for all matrices tested. The more rapid kinetics observed with Caco-2 cells probably were due to the greater surface area available for absorption/desorption in the cells. After 5 h, the uptake of BaP into Caco-2 lipid was similar in live and metabolically inert Caco-2 cells, suggesting that the primary route of BaP uptake is by passive diffusion. Moreover, the driving force for uptake is the fugacity gradient that exists between the gastrointestinal fluid and the membrane.

Objective: To discuss the provision of pharmaceutical care in community pharmacies in Germany including community pharmacy, organization and delivery of health services, pharmacy education, community pharmacy services, research in community pharmacy, and future plans for community pharmacy services., Findings: In Germany, cognitive pharmaceutical services have been developed for more than 12 years. Several studies and programs have shown that pharmaceutical care and other pharmaceutical services are feasible in community pharmacy practice and that patients benefit from these services. In 2003, a nationwide contract was established between representatives of the community pharmacy owners and the largest German health insurance fund. In this so-called family pharmacy contract, remuneration of pharmacists for provision of pharmaceutical care services was successfully negotiated for the first time. In 2004, a trilateral integrated care contract was signed that additionally included general practitioners, combining the family pharmacy with the family physician. Within a few months, the vast majority (>17 000) of community pharmacies have registered to participate in this program., Conclusions: German community pharmacies are moving from the image of mainly supplying drugs toward the provision of cognitive pharmaceutical services.

Objectives: To investigate a new method for evaluating counselling performance of staff in community pharmacies and to assess the quality of patient counselling., Method: Trained pseudo customers, instructed to play their role according to two different self-medication scenarios, visited voluntarily participating community pharmacies in Berlin. After documenting the counselling process, immediately after each visit, outside the pharmacy on an assessment form, the pseudo customer re-entered the pharmacy and gave detailed performance feedback to the counsellor and the pharmacist in charge in order to provide support for improving counselling skills and practice behaviour, when appropriate. This was followed with a written summary of the general performance of all participating pharmacies and additional individual feedback and suggestions for improvement. Educational needs were identified for subsequent performance-based educational strategies such as group-workshops, team-training and on-site team-coaching., Results: Forty-nine community pharmacies in Berlin volunteered to participate in this pilot study. Ninety-eight per cent of the participating pharmacies offered advice. However, in 36% of the cases, advice was only given on request. The different types of scenarios--presentation of a symptom or request for a specific product--made a great difference to the spontaneity of questions and advice. At least one question to check on accuracy of self-diagnosis was asked in 95% of the cases of symptom presentation but in only 47% of the cases of specific product request. Information on appropriate self-medication was provided on at least one item in 74% of pseudo customer visits, but most of the time the information was not sufficient. Communication skills (nonverbal elements, comprehensibility etc.) were very good or good in 54% of the visits. Potential for improvement was mainly in relation to the use of open-ended questions to gain more information and on counselling about appropriate self-medication. Direct feedback was given in 96% of the pharmacies (one person refused to accept feedback and one feedback had to be postponed because of time shortage). All of the participants regarded counselling as an important subject in pharmacy practice., Conclusion: The pseudo customer method was successfully used in this study of German community pharmacies. It was shown that pseudo customer visits and performance feedback following the counselling process, were feasible in daily practice and well accepted by the participants. A training program, focussing on areas in most need of improvement, has been developed. The promising results have led to the Federal Chamber of Pharmacists in Germany adopting this method as part of a continuous quality improvement program in community pharmacies.

The aim of this study was to compare efficacy and safety of perioperative antibiotic prophylaxis in patients undergoing abdominal or vaginal hysterectomy or gynaecological laparotomy to improve the prevention of surgical wound infections. One hundred and ninety-nine patients were prospectively randomized into two groups: the first group (n = 100) received perioperative prophylaxis using 1 g cefotiam (Spizef) and 0.5 g metronidazole (Clont) intravenously 30 min before surgery, whereas the second group (n = 99) was treated with 2 g cefoxitin (Mefoxitin) intravenously, also 30 min before surgery. The efficacy of the perioperative antibiotic prophylaxis was assessed clinically and on the basis of laboratory parameters. No wound infections were observed in 97 patients (97%) of the cefotiam-treated group and in 94 patients (94%) of the cefoxitin-treated group. No systemic postoperative infections were observed in 81% of the patients treated with cefotiam combined with metronidazole and in 85% of the patients treated with cefoxitin. The good tolerability of the drugs administered was proven in 98% of the patients treated with cefotiam and metronidazole and in 97% of the patients treated with cefoxitin. In both groups 3 patients developed nausea and/or vomiting, respectively, due to the antibiotic prophylaxis. A low infection rate after gynaecological surgery was observed. Cefotiam as a low dosage combined with metronidazole was as effective as cefoxitin. Cephalosporins of the second generation in combination with metronidazole can, therefore, be considered effective and safe drugs in the prevention of postsurgical infections., (Copyright 2001 S. Karger AG, Basel)

The rare case of a decidualized endometriosis of the appendix vermiformis is reported in a woman who developed HELLP syndrome during the 32nd week of a twin pregnancy. Cesarean section and simultaneous appendectomy were performed. An inspection of the appendix should always be carried out if an endometriosis-associated anamnesis is known. No pathophysiological correlations between the HELLP syndrome and the endometriosis of the appendix vermiformis could be found.