Management and efficacy of intensified insulin therapy starting in outpatients

Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6%±2.4% to 8.0%±1.3% (means±SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients

Diagnostik und Therapie asymptomatischer Nebennierentumoren

Bei 23 Frauen und neun Männern im mittleren Alter von 54 (25-73) Jahren wurde bei der Klärung anderer Beschwerden zufällig ein asymptomatischer Nebennierentumor entdeckt. In allen Fällen ließen sich die Tumoren computertomographisch darstellen. Achtmal waren sie beidseits lokalisiert, in je 12 Fällen rechts- oder linksseitig. Der durchschnittliche Tumordurchmesser betrug 3 (1-9) cm. Vier Tumoren (12,5 %) wiesen eine endokrine Aktivität auf (ein Phäochromozytom, drei cortisolproduzierende Tumoren). Acht Patienten wurden adrenalektomiert, dabei ergaben sich sechs Nebennierenadenome, ein benignes Phäochromozytom und ein Ganglioneurom. Eine Feinnadelbiopsie wurde bei zwei Patienten vorgenommen, der zytologische Befund war benigne. Computertomographische Verlaufskontrollen bei elf (34,4 %) der nicht-operierten Patienten 6-48 Monate (im Mittel 14 Monate) später zeigten bei keinem der Patienten eine Größenzunahme des Tumors. Daher erscheint es bei zufällig diagnostizierten Nebennierentumoren gerechtfertigt, zunächst einmal den Verlauf zu beobachten, da gutartige Prozesse offensichtlich weitaus häufiger sind als maligne. Bei einem Tumordurchmesser von mehr als 6 cm ist jedoch wegen des Malignitätsrisikos eine Adrenalektomie durchzuführen

Inefficacy of different strategies to improve guideline awareness – 5-year follow-up of the hypertension evaluation project (HEP)

<p>Abstract</p> <p>Background</p> <p>In spite of numerous guidelines for evidence based diagnostic and therapy adequate knowledge of current recommendations is disappointingly low. In the Hypertension Evaluation Project (HEP I) we showed that awareness of national hypertension guidelines under German practitioners was less than 25% in the year 2000. This indicates the need for efficient strategies to relevantly improve guideline awareness.</p> <p>Methods</p> <p>To asses different tools for amending guideline knowledge we used three strategies (guideline in print, interactive guideline, expert seminars) to train 8325 randomised physicians, who had participated in the HEP I trial. Guideline knowledge of the trained physicians was again tested with the HEP questionnaire and compared to a control group of HEP I physicians.</p> <p>Results</p> <p>The return rate of questionnaires was 57.9% without a significant distinction between the groups. Overall guideline awareness was still low but remarkably improved compared to the results of HEP I (37.1% vs. 23.7%, p < 0.0001). There was no difference between the trained physicians and the control group (35.8% and 35.9% vs. 39.7%, p = n.s.).</p> <p>Conclusion</p> <p>We investigated the influence of different strategies to improve guideline awareness among German physicians. None of our interventions (guideline in print, interactive guideline, expert seminars) brought a notable benefit compared to control group. However, overall knowledge of guideline contents increased from 23.7% to 37.1% over five years. Therefore, other probably multimodal interventions are necessary to significantly improve guideline awareness beyond spontaneous advancement.</p> <p>Trial Registration</p> <p>ISRCTN53383289</p

Development and implementation of clinical guidelines : an artificial intelligence perspective

Clinical practice guidelines in paper format are still the preferred form of delivery of medical knowledge and recommendations to healthcare professionals. Their current support and development process have well identified limitations to which the healthcare community has been continuously searching solutions. Artificial intelligence may create the conditions and provide the tools to address many, if not all, of these limitations.. This paper presents a comprehensive and up to date review of computer-interpretable guideline approaches, namely Arden Syntax, GLIF, PROforma, Asbru, GLARE and SAGE. It also provides an assessment of how well these approaches respond to the challenges posed by paper-based guidelines and addresses topics of Artificial intelligence that could provide a solution to the shortcomings of clinical guidelines. Among the topics addressed by this paper are expert systems, case-based reasoning, medical ontologies and reasoning under uncertainty, with a special focus on methodologies for assessing quality of information when managing incomplete information. Finally, an analysis is made of the fundamental requirements of a guideline model and the importance that standard terminologies and models for clinical data have in the semantic and syntactic interoperability between a guideline execution engine and the software tools used in clinical settings. It is also proposed a line of research that includes the development of an ontology for clinical practice guidelines and a decision model for a guideline-based expert system that manages non-compliance with clinical guidelines and uncertainty.This work is funded by national funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within project PEst-OE/EEI/UI0752/2011"

Extracellular vesicles are independent metabolic units with asparaginase activity.

Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1). Critically, we show that Asrgl1 activity is selective for asparagine and is devoid of glutaminase activity. We found that mouse and human NSC EVs traffic Asrgl1. Our results demonstrate, for the first time, that NSC EVs function as independent metabolic units that are able to modify the concentrations of critical nutrients, with the potential to affect the physiology of their microenvironment.This work has received support from the Italian Multiple Sclerosis Association (AISM, grant 2010/R/31 and grant 2014/PMS/4 to SP), the Italian Ministry of Health (GR08-7 to SP), the European Research Council (ERC) under the ERC-2010-StG Grant agreement n° 260511-SEM_SEM, the Medical Research Council, the Engineering and Physical Sciences Research Council, and the Biotechnology and Biological Sciences Research Council UK Regenerative Medicine Platform Hub “Acellular Approaches for Therapeutic Delivery” (MR/K026682/1 to SP), The Evelyn Trust (RG 69865 to SP), The Bascule Charitable Trust (RG 75149 to SP) and core support grant from the Wellcome Trust and Medical Research Council to the Wellcome Trust – MRC Cambridge Stem Cell Institute. N.I. was supported by a FEBS long-term fellowship. C.F., A.S.H., and E.G. were funded by the Medical Research Council, Core Fund SKAG006