effects drug on result laboratory test
207446910
Information comparison of the effects of drugs on laboratory tests in drug labels and Young's book
Abstract Background: The effects of drugs on laboratory tests may lead to misinterpretation of laboratory data, unnecessary tests, higher costs and missed diagnoses. This study compared the information on drug laboratory effects (DLE) described in 200 drug labels with that in Young's book. Methods: Information on DLE was searched in the drug labels of 200 frequently prescribed drugs using the keywords 'interfer* 'influence' and 'laborator* This information was compared with the information in Young's book. Each item of information scored 1 point if it was specific and exactly the same. Primary outcome was the percentage of DLE with completely the same information. Results: In 23 (11.5% of the 200 drug labels 83 DLE were described. Most DLE were described in drug labels of contraceptives (71% and antibacterials (15% The most frequently affected laboratory tests were adrenal gland (17% urine tests (15% liver tests (10% and renal function tests (10% Comparison of six DLE with Young's book was not possible because the information was not described in the book. Twelve (14.5% DLE of the information in the drug label was identical to that in Young's book. Detailed information about nature of the effect, strength of the effect and body fluid was not described in the drug labels. Conclusions: In a limited number of DLE in the drug labels the information was the same as in Young's book. Overall, the information on DLE provided in drug labels is unclear, inconsistent and incomplete and does not support healthcare professionals in making evidence based monitoring decisions.
Clinical chemistry and laboratory medicine
Arjen F J Geerts Fred H P De Koning Toine C G Egberts Peter Agm de Smet Wouter W van Solinge
31232411
Drug Induced Behavioral Changes: Using Laboratory Observations to Predict Field Observations
Behavioral assays constitute important research tools when assessing how fish respond to environmental change. However, it is unclear how behavioral modifications recorded in laboratory assays are expressed in natural ecosystems, a limitation that makes it difficult to evaluate the predictive power of laboratory based measurements. In this study, we hypothesized that exposure to a benzodiazepine (i.e. oxazepam) increases boldness and activity in laboratory assays as well as in field assays that is, laboratory results can be used to predict field results. Moreover, we expected the modified behavior to affect other important ecological measures such as habitat selection and home range. To test our hypothesis, we exposed European perch (Perca fluviatilis) to oxazepam and measured subsequent changes in behavioral trials both in laboratory assays and in a lake ecosystem populated with a predatory fish species, pike (Esox lucius) In the lake, the positions of both perch and pike were tracked every three minutes for a month using acoustic telemetry. In the laboratory assay, the oxazepam exposed perch were bolder and more active than the non exposed perch. In the lake assay, the oxazepam exposed perch were also more bold and active, had a larger home range, and used pelagic habitats more than the non exposed perch. We conclude that ecotoxicological behavioral assays are useful for predicting the effects of exposure in natural systems. However, although individual responses to exposure were similar in both the laboratory and field trials, effects were more obvious in the field study, mainly due to reduced variability in the behavior measures from the lake. Hence, short term behavioral assays may fail to detect all the effects expressed in natural environments. Nevertheless, our study clearly demonstrates that behavior modifications observed in laboratory settings can be used to predict how fish perform in aquatic ecosystems.
Front. Environ. Sci.
Jonatan Klaminder Gustav Hellstrom Johan Fahlman Micael Jonsson Jerker Fick Annelie Lagesson E Bergman Tomas Brodin
1247997
Probing the Behavioral and Neurophysiological Effects of Acute Smoking Abstinence on Drug and Nondrug Reinforcement During a Cognitive Task
Introduction Smoking abstinence is theorized to increase smoking reinforcement and decrease nondrug reinforcement. A separate literature demonstrates the detrimental effects of abstinence on cognition. The present study integrates these two areas by examining the separate and combined effects of reinforcement and smoking abstinence on behavior and a neurophysiological index of response monitoring (ie, error related negativity [ERN] during a cognitive task. Methods After a screening visit, adult smokers attended two laboratory visits, once while smoking and once while abstinent. Participants completed a flanker task under cigarette money and no reinforcement conditions. The initial 15 participants had an easier reaction time (RT) requirement; to ensure sufficient error rates for ERN computation, a harder RT deadline was employed for the remaining 21 participants. Results Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with the harder RT deadline. Cigarette and money reinforcement each increased speeded accuracy and ERN amplitude compared to no reinforcement. The effect of cigarette reinforcement tended to be greater during abstinence for speeded accuracy but not the ERN. The effect of money reinforcement was unaffected by abstinence. Conclusions The impact of smoking abstinence on reinforcement may depend on task demands. However, the effects of cigarette and money reinforcement generalize well from operant paradigms to cognitive tasks, fostering integration between the two literatures. Results provided modest evidence of abstinence induced increases in smoking reinforcement; the absence of abstinence induced reductions in nondrug reinforcement is consistent with recent work in suggesting that such effects are limited to a subset of sensory reinforcers. Implications This study draws attention to the need for greater integration of reinforcement and cognition to better understand the mechanisms that contribute to smoking relapse. Results emphasize thoughtful consideration of the nature of the nondrug reinforcer(s) included in the study of smoking abstinence in addition to the levels of cognitive demand impacted by acute smoking abstinence.
Nicotine tobacco research official journal of the Society for Research on Nicotine and Tobacco
Nicolas J Schlienz Larry W Hawk
199379886
Laboratory mice born to wild mice have natural microbiota and model human immune responses
Born to be a wildling Inbred laboratory mouse strains are used extensively in basic and translational immunology research. However, the commensal and pathogenic repertoire of resident microbes encountered in the wild is not replicated in a lab setting. This can substantially distort how the immune system develops and functions, leading to false assumptions of how our own "wild" immune system works. Rosshart et al. circumvented this dilemma by implanting lab strain embryos into wild mice (see the Perspective by Nobs and Elinav) The resultant "wildlings" had a systemic immune phenotype and a bacterial, viral, and fungal microbiome much closer to those of their wild counterparts. In two preclinical experiments, where lab mice had previously failed to predict the human response to drug treatments, wildlings accurately phenocopied patient outcomes. Science, this issue p. eaaw4361; see also p. 444 The wildling model fuses lab mouse strains with naturally occurring microorganisms for increased translational research value. INTRODUCTION Laboratory mice are a mainstay of biomedical research and have been instrumental for many important discoveries in the field of immunology. However, there are also major limitations, including conflicting results rooted in divergent microbiota among research facilities and the limited ability to predict the complex immune responses of humans. Recent studies have shown that conventional laboratory mice are too far removed from natural environmental conditions to faithfully mirror the physiology of free living mammals such as humans. Mammals and their immune systems evolved to survive and thrive in a microbial world and behave differently in a sanitized environment. RATIONALE To generate a mouse model that more closely resembles the natural mammalian metaorganism with coevolved microbes and pathogens, we transferred C57BL/6 embryos into wild mice. This resulted in a colony of C57BL/6 mice, which we call "wildlings." RESULTS Wildlings resembled wild mice and differed substantially from conventional laboratory mice with regard to their bacterial microbiome at important epithelial barrier sites (gut, skin, and vagina) their gut mycobiome and virome, and their level of pathogen exposure. The natural microbiota of wildlings were stable over multiple generations and resilient against antibiotic, dietary, and microbial challenges. Next, we delineated the immune landscape of wildlings, wild mice, and laboratory mice at immunologically important barrier sites (gut, skin, and vagina) a central nonlymphoid organ (liver) and a central lymphoid organ (spleen) by mass cytometry. Additionally, we characterized the blood immune cell profile by RNA sequencing. The differential contribution of microbial and host genomes in shaping the immune phenotype varied among tissues. Wildlings closely mirrored the wild mouse immune phenotype in the spleen and blood. Finally, we tested the translational research value of wildlings in a retrospective bench to bedside approach. This required well documented, rodent based studies that had failed upon transitioning to clinical trials in humans. We chose the CD28 superagonist (CD28SA) trial as representative for treatments targeting adaptive immune responses. Although CD28SA expanded anti inflammatory regulatory T cells (Tregs) in laboratory mice and showed therapeutic effects in multiple models of autoimmune and inflammatory diseases, the first phase 1 clinical trial resulted in life threatening activation of inflammatory T cells and cytokine storms. Similarly, the CD28SA treatment of wildlings, but not laboratory mice, resulted in an inflammatory cytokine response and lack of Treg expansion. As a representative for trials targeting innate immune responses, we chose anti tumor necrosis factor alpha (TNF a) treatment (anti TNF a or TNF receptor:Fc fusion protein) during septic shock, which was successful in animal models, but failed in humans. Anti TNF a treatment during lethal endotoxemia rescued laboratory mice, but not wildlings. Thus, wildlings better phenocopied human immune responses than did conventional laboratory mice in the two models studied. CONCLUSION The wildling model combines resilient natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6. Given the wide ranging effects of microbiota on host physiology, natural microbiota based models may benefit different research fields (e.g. metabolism and neurodegenerative diseases) and may also be applicable to other animals. Such models may enhance the validity and reproducibility of biomedical studies among research institutes, facilitate the discovery of disease mechanisms and treatments that cannot be studied in regular laboratory mice, and increase the translatability of immunological results to humans. Harnessing natural microbiota and pathogens to address shortcomings of current mouse models. To restore the natural microbiome while preserving the research benefits of tractable genetics, we transferred C57BL/6 embryos into wild mice and created a colony of C57BL/6 mice, which we call "wildlings." Their microbiome was stable over time and resilient to environmental challenges. Wildlings also exhibited an increased translational research value in immunological studies. Laboratory mouse studies are paramount for understanding basic biological phenomena but also have limitations. These include conflicting results caused by divergent microbiota and limited translational research value. To address both shortcomings, we transferred C57BL/6 embryos into wild mice, creating "wildlings." These mice have a natural microbiota and pathogens at all body sites and the tractable genetics of C57BL/6 mice. The bacterial microbiome, mycobiome, and virome of wildlings affect the immune landscape of multiple organs. Their gut microbiota outcompete laboratory microbiota and demonstrate resilience to environmental challenges. Wildlings, but not conventional laboratory mice, phenocopied human immune responses in two preclinical studies. A combined natural microbiota and pathogen based model may enhance the reproducibility of biomedical studies and increase the bench to bedside safety and success of immunological studies.
Science
Stephan P Rosshart Jasmin Herz Brian G Vassallo Ashli Hunter Morgan K Wall Jonathan H Badger John A McCulloch Dimitrios G Anastasakis Aishe A Sarshad Irina Leonardi Nicholas Collins Joshua A Blatter Seong-Ji Han Samira Tamoutounour Svetlana Potapova Mark B Foster St Claire Wuxing Yuan Matthew S Dreier Benedikt Hild Markus Hafner David Wang Iliyan D Iliev Yasmine Belkaid Giorgio Trinchieri Barbara Rehermann
80272900
Effects of IONIS HTTRx in Patients with Early Huntington's Disease, Results of the First HTT Lowering Drug Trial (CT.002)
Objective: To characterize safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of IONIS HTT Rx an antisense oligonucleotide (ASO) designed to target huntingtin HTT mRNA, in patients with early manifest Huntington's disease (HD) Background: HD is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the HTT gene resulting in polyglutamine expansion in the mutant huntingtin protein (mHTT) with a toxic gain of function disease mechanism. No disease modifying treatments are currently available. In transgenic rodent models of HD, suppressing HTT production delays disease progression and reverses disease phenotype (Kordasiewicz et al. 2012; Stanek et al. 2013) A comprehensive drug discovery effort, including extensive preclinical testing, was undertaken to design a well tolerated ASO with high specificity to human HTT mRNA that potently suppresses HTT production. Design/Methods: In this first in human, multi center, double blind clinical trial (NCT02519036) 46 patients were randomized (3:1) to receive four doses of IONIS HTT Rx or placebo by monthly bolus intrathecal (IT) injection followed by a 4 month untreated period. Five ascending dose cohorts were enrolled with independent Data Safety Monitoring Board review of safety, PK and target engagement prior to dose escalation. Results: IONIS HTT Rx was well tolerated at all doses tested. Adverse events were mostly mild and unrelated to study drug. There were no adverse trends in laboratory parameters. No patients prematurely discontinued from treatment. ASO was measurable in CSF and plasma, and concentrations were generally aligned with predictions from a linked PK/PD preclinical model. Significant, dose dependent reductions in CSF mutant HTT (mHTT) were observed. Conclusions: ASO technology has the potential to provide disease modifying benefits to patients with neurodegenerative diseases. In this Phase 1/2a trial in early stage HD patients, IONIS HTT Rx delivered via IT injection was well tolerated with no study drug related adverse safety signals during the treatment or follow up periods. Significant dose dependent reductions in CSF mHTT were observed, suggesting that IONIS HTT Rx is a promising therapeutic for the treatment of HD. Study Supported by: Ionis Pharmaceuticals Disclosure: Dr. Tabrizi has nothing to disclose. Dr. Leavitt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Ionis, uniQure, Teva, Lifemax. Dr. Leavitt has received personal compensation in an editorial capacity for Editor in chief of the Journal of Huntington's Disease. Dr. Leavitt has received research support from Teva, uniQure, Lifemax. Dr. Kordasiewcz has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals. Dr. Swayze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals. Dr. Norris has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals. Dr. Baumann has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals. Dr. Lane has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals. Dr. Bennett has nothing to disclose.
Sarah J Tabrizi Blair R Leavitt Holly B Kordasiewicz Christian Czech Eric E Swayze Daniel A Norris Tiffany L Baumann Irene Gerlach Scott A Schobel Anne V Smith Roger M Lane C Frank Bennett
4959268
Emerging Gram negative resistance to last line antimicrobial agents fosfomycin, colistin and ceftazidime avibactam epidemiology, laboratory detection and treatment implications
ABSTRACT Introduction: Multidrug resistant (MDR) and extensively drug resistant (XDR) Gram negative bacteria have emerged as a major threat to human health globally. This has resulted in the 're discovery' of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas covered: Here we describe recent developments in resistance to three of the most important last line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime avibactam. Expert commentary: A key challenge for microbiologists and clinicians using these agents for treating patients with MDR and XDR Gram negative infections is the need to ensure appropriate reference methods are being used to test susceptibility to these agents, especially colistin and fosfomycin. These methods are not available in all laboratories meaning accurate results are either delayed, or potentially inaccurate as non reference methods are employed. Combination therapy for MDR and XDR Gram negatives is likely to become more common, and future studies should focus on the clinical effects of monotherapy vs combination therapy, as well as validation of synergy testing methods. Effective national and international surveillance systems to detect and respond to resistance to these last line agents are also critical.
Expert review of anti infective therapy
Norelle L Sherry Benjamin P Howden
79783200
Urine Drug Testing in Pain Medicine
Abstract The widespresad use of opioids to treat chronic nonmalignant pain has resulted in a parallel increase in misuse, abuse, addiction, overdose, and diversion. Because self reporting is unreliable and clinician ability to predict aberrant drug related behavior is poor, urine drug testing should be incorporated as a part of a consensual adherence monitoring program to confirm compliance with prescribed medications and to confirm the absence of nonprescribed medications and illicit drugs. Comprehensive urine drug testing is a two step process. The first step is an enzyme mediated immunoassay screen, which is strictly a qualitative test used to screen for the presence or absence of drug classes. The second step is a confirmatory urine drug test, which requires laboratory based testing using gas chromatography mass spectrometry or liquid chromatography mass spectrometry. A confirmatory urine drug test is a quantitative test that identifies, where applicable, the specific drug within a class as well as drug metabolite and drug concentration. Caution should be exercised when interpreting test results because of limitations related to thresholds of detection, variables that affect drug concentration, and variables related to the specimen itself. Keeping these limitations in mind, patient care can be improved by coupling urine drug testing with performing a comprehensive history and physical exam, accessing the prescription drug monitoring program, behavior monitoring, and documenting relief, functional improvement, and side effects from chronic opioid therapy.
Gagan Mahajan
20761708
Effects of clinical and laboratory variables and of pretreatment with cardiovascular drugs in acute ischaemic stroke: a retrospective chart review from the GIFA study.
BACKGROUND Few studies have examined the role of cardiovascular drugs on acute ischaemic stroke prognosis. AIMS To evaluate the relationship between a favourable outcome in patients with acute ischaemic stroke and specific demographic, clinical and laboratory variables and cardiovascular drug pretreatment. METHODS The 1096 patients enrolled in the GIFA study (who had a main discharge diagnosis of ischaemic stroke) represent the final patient sample used in this analysis. Drugs considered in the analysis included angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, statins, calcium channel blockers, anti platelet drugs, vitamin K antagonists and heparins. The outcomes analyzed included in hospital mortality, cognitive function evaluated by the Hodkinson Abbreviated Mental Test (HAMT) and functional status evaluated by activities of daily living (ADL) The definition of a good outcome was no in hospital mortality, a HAMT score of 6 and no ADL impairment. RESULTS Patients with no in hospital mortality, a HAMT score of >6 and no ADL impairment were more likely to be younger at baseline and have a lower blood glucose level and a systolic blood pressure (SBP) between 120 and 180 mmHg, a higher plasma total cholesterol level, a lower white blood cell count, and a lower Charlson Index (CI) score, a higher rate of pretreatment with ACE inhibitors, calcium channel blockers and a lower rate of pretreatment with heparin. CONCLUSIONS Predictors of good outcome, in terms of in hospital mortality and cognitive and functional performance at discharge, included higher SBP at admission between 120 and 180 mmHg, a SBP plasma total cholesterol levels, a lower CI score, and pretreatment with ACE inhibitors, calcium channel blockers and anti platelets.
International journal of cardiology
Antonino Tuttolomondo Riccardo di Sciacca Domenico Di Raimondo Claudio Pedone Sergio La Placa Antonio Pinto Giuseppe Licata
40114767
Induction of depressive like effects by subchronic exposure to cocaine or heroin in laboratory rats
The effect of psychoactive drugs on depression has usually been studied in cases of prolonged drug addiction and/or withdrawal, without much emphasis on the effects of subchronic or recreational drug use. To address this issue, we exposed laboratory rats to subchronic regimens of heroin or cocaine and tested long term effects on (i) depressive like behaviors, (ii) brain derived neurotrophic factor (BDNF) levels in reward related brain regions, and (iii) depressive like behavior following an additional chronic mild stress procedure. The long term effect of subchronic cocaine exposure was a general reduction in locomotor activity whereas heroin exposure induced a more specific increase in immobility during the forced swim test. Both cocaine and heroin exposure induced alterations in BDNF levels that are similar to those observed in several animal models of depression. Finally, both cocaine and heroin exposure significantly enhanced the anhedonic effect of chronic mild stress. These results suggest that subchronic drug exposure induces depressive like behavior which is accompanied by modifications in BDNF expression and increases the vulnerability to develop depressive like behavior following chronic stress. Implications for recreational and small scale drug users are discussed.
Journal of neurochemistry
Noga Zilkha Eugene Feigin Noam Barnea-ygael Abraham Zangen
10261960
Distinguishing Hazards and Harms, Adverse Drug Effects and Adverse Drug Reactions
The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel) and the encounter results in an adverse effect (a physiological or pathological change) which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization) and adverse reactions by their clinical manifestations (symptoms and/or signs) This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."
Drug Safety
Jeffrey K Aronson