ObjectivesThe prognostic value of lactate in the setting of an emergency department (ED) has not been studied extensively. The goal of this study was to assess 28-day mortality in ED patients in whom ...lactate was elevated (≥4.0 mmol/L), <4.0 mmol/L or not determined and to study the impact of the underlying cause of hyperlactatemia, that is, type A (tissue hypoxia) or type B (non-hypoxia), on mortality.DesignRetrospective study.SettingA secondary and tertiary referral centre in the Netherlands.Materials and methodsAll internal medicine patients with hyperlactatemia (≥4.0 mmol/L) at the ED between January 2011 and October 2014 were included in this study. Samples of patients with lactate levels <4.0 mmol/L and of patients in whom no lactate was measured were included as a reference.ResultsIn 1144 of 19 822 patients (5.8%), lactate was measured. Hyperlactatemia (n=197) was associated with a higher 28-day mortality than in those with lactate <4.0 mmol/L (40.6% vs 18.5%; p<0.001) and in those without lactate measurements (9.5%). Type A hyperlactatemia, present in 84% of those with hyperlactatemia, was associated with higher mortality than type B hyperlactatemia (45.8% vs 12.5%, p=0.001).ConclusionsThis study demonstrates that the prognostic value of lactate depends largely on the underlying cause and the population in whom lactate has been measured. Prospective studies are required to address the true added value of lactate at the ED.
Measurements of plasma-free normetanephrine and metanephrine provide a sensitive test for diagnosis of pheochromocytoma but may fail to detect tumors that produce predominantly dopamine. Such tumors ...are extremely rare, usually found as extraadrenal paragangliomas. This report describes measurements of plasma concentrations of free methoxytyramine, the O-methylated metabolite of dopamine, in 120 patients with catecholamine-producing tumors, including nine with extraadrenal paragangliomas secreting predominantly dopamine. In seven of these nine patients, tumors were found incidentally or secondary to the space-occupying complications of the lesions. Plasma concentrations of free methoxytyramine and dopamine were increased in all nine patients, including two with normal plasma and urinary normetanephrine and metanephrine and normal urinary outputs of dopamine. Relative increases above normal for plasma methoxytyramine (104-fold) and dopamine (56-fold) were much greater (P < 0.001) than those for urinary dopamine (3-fold). Insensitivity of the latter for identification of dopamine-secreting tumors was due to dependence of the urinary amine on renal extraction and decarboxylation of circulating 3,4-dihydroxyphenylalanine. Measurements of plasma-free methoxytyramine, in addition to normetanephrine and metanephrine, are unlikely to improve diagnosis of pheochromocytomas in hypertensive patients with symptoms of catecholamine excess but may be useful in selected patients for identification of tumors that produce predominantly dopamine.
To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.
An Update Committee ...reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched.
The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews.
For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.
Mammalian sperm cells are activated prior to fertilization by high bicarbonate levels, which facilitate lipoprotein-mediated cholesterol efflux. The role of bicarbonate and cholesterol acceptors on ...the cholesterol organization in the sperm plasma membrane was tested. Bicarbonate induced an albumin-independent change in lipid architecture that was detectable by an increase in merocyanine staining (due to protein kinase A-mediated phospholipid scrambling). The response was limited to a subpopulation of viable sperm cells that were sorted from the non-responding subpopulation by flow cytometry. The responding cells had reduced cholesterol levels (30% reduction) compared with non-responding cells. The subpopulation differences were caused by variable efficiencies in epididymal maturation as judged by cell morphology. Membrane cholesterol organization was observed with filipin, which labeled the entire sperm surface of non-stimulated and non-responding cells, but labeled only the apical surface area of bicarbonate-responding cells. Addition of albumin caused cholesterol efflux, but only in bicarbonate-responding cells that exhibited virtually no filipin labeling in the sperm head area. Albumin had no effect on other lipid components, and no affinity for cholesterol in the absence of bicarbonate. Therefore, bicarbonate induces first a lateral redistribution in the low cholesterol containing spermatozoa, which in turn facilitates cholesterol extraction by albumin. A model is proposed in which phospholipid scrambling induces the formation of an apical membrane raft in the sperm head surface that enables albumin mediated efflux of cholesterol.
Abstract Background: Clinically relevant drug-drug interactions (DDIs) must be recognized in a timely manner and managed appropriately to prevent adverse drug reactions or therapeutic failure. ...Because the evidence for most DDIs is based on case reports or poorly documented clinical information, there is a need for better assessment of their clinical relevance. Objective: This study evaluates the interdisciplinary agreement between rheumatologists and clinical (hospital) pharmacists in assessing the clinical relevance of DDIs with disease-modifying antirheumatic drugs (DMARDs) and non-DMARD medications. Methods: Potential DDIs were identified from the medical literature using MEDLINE and EMBASE for the years 1968–2009. The following search terms were used for the key word, title, and abstract sections of the publications: interaction(s), DMARD, disease-modifying antirheumatic drug(s), antirheumatic, rheumatology, rheumatoid arthritis , and the names of the individual DMARDs of interest ( abatacept, adalimumab, anakinra, auranofin, aurothioglucose, aurothiomalate, d-penicillamine, etanercept, gold, hydroxy-chloroquine, interleukin-1 receptor antagonist, IL1-RA, infliximab, leflunomide, methotrexate, rituximab, and sulfasalazine/sulphasalazine ). Reference lists of the retrieved publications were searched for further information on potential DDIs. All pharmacodynamic or pharmacokinetic DDIs between a DMARD and a non-DMARD identified were included in the study, with the exception of evidence regarding DMARD doses higher than used in the treatment of rheumatoid arthritis and interactions with phytothera-peutic or homeopathic preparations. Using a standard information set for each DDI (eg, from product labeling, textbooks, and the medical literature), a group of rheumatologists and a group of clinical pharmacists independently assessed whether the individual drug-DMARD combinations interacted and whether they required immediate intervention. Both groups consisted of 3 members (2 men and 1 woman), aged 40 to 60 years, who had >5 years of clinical experience and were currently involved in clinical practice in large, nonacademic teaching hospitals in the Netherlands. Results: Forty potential DDIs with DMARDs were retrieved and assessed by the 2 groups. For 30 (75%) of these, rheumatologists and clinical pharmacists agreed about the requirement for immediate intervention. Specifically, 17 drug combinations (43%) were judged to interact and to require immediate intervention, and 13 combinations (33%) were judged either not to interact or to interact but not to require immediate intervention. For 10 combinations (25%), rheu-matologists and clinical pharmacists were not in agreement. Overall, agreement between the groups was good (κ = 0.80) for judging whether the drug combinations were interactions, and agreement was fair (κ = 0.39) for judging whether immediate intervention was required. Prospective analysis of the data showed that rheumatologists tended to recommend immediate intervention more often when the adverse reaction to the DDI involved an increased risk of tox-icity of the DMARD. In contrast, clinical pharmacists more often advocated immediate intervention when the adverse reaction involved decreased effectiveness of the DMARD. Conclusion: For a subset of DMARD-drug combinations, rheumatologists and clinical pharmacists differed in their assessments of clinical relevance.
Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously ...difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th–18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies.
OBJECTIVE The study aimed to identify both the frequency and the determinants of drug administration errors in the intensive care unit.
DESIGN Administration errors were detected by using the ...disguised-observation technique (observation of medication administrations by nurses, without revealing the aim of this observation to the nurses).
SETTING Two Dutch hospitals.
PATIENTS The drug administrations to patients in the intensive care units of two Dutch hospitals were observed during five consecutive days.
INTERVENTIONS None.
MEASUREMENTS AND MAIN RESULTS A total of 233 medications for 24 patients were observed to be administered (whether ordered or not) or were observed to be omitted. When wrong time errors were included, 104 administrations with at least one error were observed (frequency, 44.6%), and when they were excluded, 77 administrations with at least one error were observed (frequency, 33.0%). When we included wrong time errors, day of the week (Monday, odds ratio OR 2.69, confidence interval CI 1.42–5.10), time of day (6–10 pm, OR 0.28, CI 0.10–0.78), and drug class (gastrointestinal, OR 2.94, CI 1.48–5.85; blood, OR 0.12, CI 0.03–0.54; and cardiovascular, OR 0.38, CI, 0.16–0.90) were associated with the occurrence of errors. When we excluded wrong time errors, day of the week (Monday, OR 3.14, CI 1.66–5.94), drug class (gastrointestinal, OR 3.47, CI 1.76–6.82; blood, OR 0.21, CI 0.05–0.91; and respiratory, OR 0.22, CI 0.08–0.60), and route of administration (oral by gastric tube, OR 5.60, CI 1.70–18.49) were associated with the occurrence of errors. In the hospital without full-time specialized intensive care physicians (which also lacks pharmacy-provided protocols for the preparation of parenteral drugs), more administration errors occurred, both when we included (OR 5.45, CI 3.04–9.78) and excluded wrong time errors (OR 4.22, CI 2.36–7.54).
CONCLUSIONS Efforts to reduce drug administration errors in the intensive care unit should be aimed at the risk factors we identified in this study. Especially, focusing on system differences between the two intensive care units (e.g., presence or absence of full-time specialized intensive care physicians, presence or absence of protocols for the preparation of all parenteral drugs) may help reduce suboptimal drug administration.
Social network analysis is an approach to study the interactions and exchange of resources among people. It can help understanding the underlying structural and behavioral complexities that influence ...the process of capacity building towards evidence-informed decision making. A social network analysis was conducted to understand if and how the staff of a public health department in Ontario turn to peers to get help incorporating research evidence into practice.
The staff were invited to respond to an online questionnaire inquiring about information seeking behavior, identification of colleague expertise, and friendship status. Three networks were developed based on the 170 participants. Overall shape, key indices, the most central people and brokers, and their characteristics were identified.
The network analysis showed a low density and localized information-seeking network. Inter-personal connections were mainly clustered by organizational divisions; and people tended to limit information-seeking connections to a handful of peers in their division. However, recognition of expertise and friendship networks showed more cross-divisional connections. Members of the office of the Medical Officer of Health were located at the heart of the department, bridging across divisions. A small group of professional consultants and middle managers were the most-central staff in the network, also connecting their divisions to the center of the information-seeking network. In each division, there were some locally central staff, mainly practitioners, who connected their neighboring peers; but they were not necessarily connected to other experts or managers.
The methods of social network analysis were useful in providing a systems approach to understand how knowledge might flow in an organization. The findings of this study can be used to identify early adopters of knowledge translation interventions, forming Communities of Practice, and potential internal knowledge brokers.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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This review summarizes the current knowledge on anatomy and physiology of the human gastrointestinal tract in comparison with that of common laboratory animals (dog, pig, rat and ...mouse) with emphasis on in vivo methods for testing and prediction of oral dosage form performance. A wide range of factors and methods are considered in addition, such as imaging methods, perfusion models, models for predicting segmental/regional absorption, in vitro in vivo correlations as well as models to investigate the effects of excipients and the role of food on drug absorption. One goal of the authors was to clearly identify the gaps in today’s knowledge in order to stimulate further work on refining the existing in vivo models and demonstrate their usefulness in drug formulation and product performance testing.
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