Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 109
Filter
1.
Med Sci Educ ; 34(1): 193-200, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38510385

ABSTRACT

Considering laboratory results are used to make medical decisions, a fundamental understanding of laboratory medicine is paramount to enhance patient care, optimize health care cost containment, and prevent legal repercussions. With increasing laboratory testing complexity, this education is needed now more than ever. This article is a call to action to have medical schools adequately incorporate practical laboratory medicine content into their undergraduate medical education (UME) curricula. The authors discuss the definition of laboratory medicine, what it encompasses, who uses it and why it matters, and propose that a core laboratory medicine curriculum is a necessary part of UME.

2.
J Thromb Haemost ; 14(11): 2148-2157, 2016 11.
Article in English | MEDLINE | ID: mdl-27543785

ABSTRACT

Essentials Anti-activated factor X (Anti-Xa) monitoring is more precise than activated partial thromboplastin (aPTT). 20 804 hospitalized cardiovascular patients monitored with Anti-Xa or aPTT were analyzed. Adjusted transfusion rates were significantly lower for patients monitored with Anti-Xa. Adoption of Anti-Xa protocols could reduce transfusions among cardiovascular patients in the US. SUMMARY: Background Anticoagulant activated factor X protein (Anti-Xa) has been shown to be a more precise monitoring tool than activated partial thromboplastin time (aPTT) for patients receiving unfractionated heparin (UFH) anticoagulation therapy. Objectives To compare red blood cell (RBC) transfusions between patients receiving UFH who are monitored with Anti-Xa and those monitored with aPTT. Patients/Methods A retrospective cohort study was conducted on patients diagnosed with acute coronary syndrome (ACS) (N = 14 822), diagnosed with ischemic stroke (STK) (N = 1568) or with a principal diagnosis of venous thromboembolism (VTE) (N = 4414) in the MedAssets data from January 2009 to December 2013. Anti-Xa and aPTT groups were identified from hospital billing details, with both brand and generic name as search criteria. Propensity score techniques were used to match Anti-Xa cases to aPTT controls. RBC transfusions were identified from hospital billing data. Multivariable logistic regression was used to identify significant drivers of transfusions. Results Anti-Xa patients had fewer RBC transfusions than aPTT patients in the ACS population (difference 17.5%; 95% confidence interval [CI] 16.4-18.7%), the STK population (difference 8.2%; 95% CI 4.4-11.9%), and the VTE population (difference 4.7%; 95% CI 3.3-6.1%). After controlling for patient age and gender, diagnostic risks (e.g. anemia, renal insufficiency, and trauma), and invasive procedures (e.g. cardiac catheterization, hemodialysis, and coronary artery bypass graft), Anti-Xa patients were less likely to have a transfusion while hospitalized for ACS (odds ratio [OR] 0.16, 95% CI 0.14-0.18), STK (OR 0.41, 95% CI 0.29-0.57), and VTE (OR 0.35, 95% CI 0.26-0.48). Conclusion Anti-Xa monitoring was associated with a significant reduction in RBC transfusions as compared with aPTT monitoring alone.


Subject(s)
Anticoagulants/therapeutic use , Erythrocytes/cytology , Factor Xa/therapeutic use , Heparin/therapeutic use , Thromboplastin/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Blood Transfusion , Cardiovascular Diseases/blood , Cardiovascular Diseases/immunology , Comorbidity , Drug Monitoring/methods , Erythrocyte Transfusion , Factor Xa Inhibitors/therapeutic use , Female , Hospitalization , Humans , Infusions, Intravenous , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Partial Thromboplastin Time , Propensity Score , Prospective Studies , Retrospective Studies , Young Adult
3.
Pharmacogenomics J ; 16(4): 393-8, 2016 08.
Article in English | MEDLINE | ID: mdl-26261062

ABSTRACT

Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring prescriptions, but clinicians do not agree on how to appropriately assign clinical responsibility for actionable results from a multiplexed panel.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.57.


Subject(s)
Attitude of Health Personnel , Drug-Related Side Effects and Adverse Reactions/genetics , Health Knowledge, Attitudes, Practice , Pharmacogenetics , Pharmacogenomic Variants/genetics , Physicians/psychology , Adult , Aged , Female , Genotype , Humans , Male , Middle Aged , Perception , Pharmacogenomic Testing , Phenotype , Precision Medicine , Predictive Value of Tests , Risk Assessment , Risk Factors , Surveys and Questionnaires , Young Adult
4.
Clin Pharmacol Ther ; 100(1): 67-74, 2016 07.
Article in English | MEDLINE | ID: mdl-26693963

ABSTRACT

Physician responses to genomic information are vital to the success of precision medicine initiatives. We prospectively studied a pharmacogenomics implementation program for the propensity of clinicians to select antiplatelet therapy based on CYP2C19 loss-of-function variants in stented patients. Among 2,676 patients, 514 (19.2%) were found to have a CYP2C19 variant affecting clopidogrel metabolism. For the majority (93.6%) of the cohort, cardiologists received active and direct notification of CYP2C19 status. Over 12 months, 57.6% of poor metabolizers and 33.2% of intermediate metabolizers received alternatives to clopidogrel. CYP2C19 variant status was the most influential factor impacting the prescribing decision (hazard ratio [HR] in poor metabolizers 8.1, 95% confidence interval [CI] [5.4, 12.2] and HR 5.0, 95% CI [4.0, 6.3] in intermediate metabolizers), followed by patient age and type of stent implanted. We conclude that cardiologists tailored antiplatelet therapy for a minority of patients with a CYP2C19 variant and considered both genomic and nongenomic risks in their clinical decision-making.


Subject(s)
Cytochrome P-450 CYP2C19/genetics , Pharmacogenetics , Platelet Aggregation Inhibitors/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Ticlopidine/analogs & derivatives , Age Factors , Aged , Clinical Decision-Making , Clopidogrel , Female , Genetic Variation , Genotype , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/metabolism , Precision Medicine/methods , Prospective Studies , Stents , Ticlopidine/metabolism , Ticlopidine/therapeutic use
5.
Clin Pharmacol Ther ; 92(1): 87-95, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22588608

ABSTRACT

The promise of "personalized medicine" guided by an understanding of each individual's genome has been fostered by increasingly powerful and economical methods to acquire clinically relevant information. We describe the operational implementation of prospective genotyping linked to an advanced clinical decision-support system to guide individualized health care in a large academic health center. This approach to personalized medicine entails engagement between patient and health-care provider, identification of relevant genetic variations for implementation, assay reliability, point-of-care decision support, and necessary institutional investments. In one year, approximately 3,000 patients, most of whom were scheduled for cardiac catheterization, were genotyped on a multiplexed platform that included genotyping for CYP2C19 variants that modulate response to the widely used antiplatelet drug clopidogrel. These data are deposited into the electronic medical record (EMR), and point-of-care decision support is deployed when clopidogrel is prescribed for those with variant genotypes. The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine.


Subject(s)
Aryl Hydrocarbon Hydroxylases/genetics , Cardiac Catheterization/drug effects , Pharmacogenetics , Precision Medicine , Ticlopidine/analogs & derivatives , Cardiac Catheterization/methods , Clopidogrel , Computer-Aided Design , Cytochrome P-450 CYP2C19 , Decision Support Systems, Clinical , Genetic Variation , Genotyping Techniques/methods , Humans , Patient Selection , Pharmacogenetics/methods , Pharmacogenetics/trends , Platelet Aggregation Inhibitors/therapeutic use , Precision Medicine/methods , Precision Medicine/trends , Ticlopidine/therapeutic use
7.
Lipids ; 38(3): 269-73, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12784867

ABSTRACT

The role of fatty acid ethyl esters (FAEE), the nonoxidative ethanol metabolites, as mediators of alcohol-induced organ damage is increasingly being recognized. FAEE are detectable in the blood and in liver and adipose tissue after ethanol ingestion, and on that basis, FAEE can be used as markers of ethanol intake. In this study, 10 samples of human brain were collected at autopsy at the Massachusetts Medical Examiner's Office and analyzed for FAEE. FAEE were isolated and quantified as mass per gram of wet weight. The blood ethanol level was also obtained in each case along with the other drugs detected in routine postmortem toxicology screening tests. Ethyl arachidonate was the predominant FAEE species in the brain, representing up to 77.4% of total FAEE in the brain. The percent age of ethyl arachidonate of the total FAEE in the brain was significantly higher than what has been found in all other organs and tissues previously analyzed. Linoleate, the precursor of arachidonate, was a poor substrate for FAEE synthesis, as the percentage of ethyl linoleate of the total FAEE content was extremely low. Thus, this reflects preferred incorporation of arachidonate into newly synthesized FAEE in the brain. Since arachidonate is derived from linoleate, which is depleted in FAEE while arachidonate is enriched, the synthesis of FAEE may be linked to the desaturation and elongation of linoleate to arachidonate.


Subject(s)
Alcoholic Intoxication/metabolism , Arachidonic Acids/analysis , Brain/metabolism , Adipose Tissue/chemistry , Adipose Tissue/pathology , Arachidonic Acids/metabolism , Autopsy , Brain/pathology , Ethanol/blood , Humans , Linoleic Acids/analysis , Linoleic Acids/metabolism , Liver/chemistry , Liver/pathology
9.
Surgery ; 129(6): 736-44, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11391373

ABSTRACT

BACKGROUND: Alcohol abuse is a major cause of pancreatic damage. Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, injure pancreatic acinar cells. Linkage between oxidative and nonoxidative metabolism of ethanol in the pancreas may contribute to increased FAEE levels. METHODS: To study the association between oxidative and nonoxidative ethanol metabolism, FAEE concentration and FAEE synthase activity in rat pancreatic and liver homogenates incubated with ethanol were evaluated with and without inhibitors of oxidative ethanol metabolism. For toxicity studies, trypsinogen activation peptide synthesis as a measure of pancreatic cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreatic acinar cells incubated with ethanol or FAEE. RESULTS: Inhibition of oxidative ethanol metabolism results in a 2- to 3-fold increase in nonoxidative ethanol metabolism to FAEE in pancreas and in liver. Both ethanol and FAEE induce increased intracellular trypsinogen activation by more than 50% in the presence of physiologic concentrations of cerulein in vitro. CONCLUSIONS: These findings demonstrate that the inhibition of oxidative ethanol metabolism results in an increase in flux through the nonoxidative pathway and support the proposition that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which are important products of pancreatic ethanol metabolism.


Subject(s)
Ethanol/metabolism , Pancreas/metabolism , Acyltransferases/metabolism , Animals , Cholecystokinin/pharmacology , Ethanol/toxicity , Male , Oxidation-Reduction , Pancreas/drug effects , Rats , Rats, Sprague-Dawley
11.
Alcohol Clin Exp Res ; 25(3): 338-43, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11290843

ABSTRACT

BACKGROUND: Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol produced by the esterification of fatty acids and ethanol. FAEEs have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro. They are detectable in the blood and in many organs after ethanol ingestion, and on this basis they are useful markers of ethanol intake in living patients as well as subjects at autopsy. FAEEs found in human plasma after ethanol ingestion bind to lipoproteins and albumin. METHODS: In this study, we used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because FAEEs have been shown to decrease HepG2 cellular proliferation and protein synthesis, their removal from cells potentially could reestablish normal cell activity. HepG2 cells were incubated with 100 mM ethanol and 6 nM 3H oleic acid to generate 3H-FAEEs within the cells. Dose response and time course studies were performed by using low density lipoproteins, high density lipoproteins, and albumin as FAEE acceptors. RESULTS: The results indicate that FAEEs are extracted efficiently by each of these FAEE carriers and that FAEE synthesis also is stimulated by the addition of FAEE carriers to the extracellular medium. CONCLUSION: These observations indicate that lipoproteins and albumin can extract ethyl esters from HepG2 cells and thereby may limit alcohol-induced liver damage.


Subject(s)
Central Nervous System Depressants/pharmacology , Cholesterol, HDL/pharmacology , Cholesterol, LDL/pharmacology , Ethanol/pharmacology , Oleic Acids/biosynthesis , Serum Albumin/pharmacology , Fatty Acids/biosynthesis , Humans , Oleic Acid/pharmacology , Tumor Cells, Cultured/drug effects
13.
Clin Chem ; 47(4): 722-5, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11274023

ABSTRACT

BACKGROUND: Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol. FAEEs are found in liver, pancreas, and adipose tissues up to 24 h after consumption of ethanol, and on that basis, they are potentially useful markers for ethanol intake. In this study with rats, we investigated the efficacy of using FAEEs in liver and in adipose tissue as postmortem markers for premortem ethanol ingestion. METHODS: An animal study was conducted in which test rats received injections of ethanol and control rats received injections of normal saline. The rats were killed 2 h after the injections. The bodies of the animals were stored at 4 degrees C up to 12 h, and samples of liver and adipose tissues were collected at different time intervals and processed for FAEE quantification. In another set of experiments, the rats received injections and were killed as described above, but bodies of animals from both groups were stored at 4, 25, or 37 degrees C for up to 72 h, and liver samples were collected and processed for FAEE quantification. RESULTS: FAEEs were detected up to 12 h after death in liver and adipose tissue samples from the bodies of ethanol-treated animals stored at 4 degrees C; negligible amounts were detected in the bodies of animals that received normal saline. Adipose tissues contained higher amounts of FAEEs than liver, as well as more species: eight FAEE species in adipose tissue and five in liver tissue. Higher concentrations of FAEEs were detected in livers of treated animals stored at 25 degrees C for up to 48 h than in livers of controls stored under the same conditions. CONCLUSIONS: For at least 12 h after death, FAEEs in liver and adipose tissues are useful postmortem markers of premortem ethanol ingestion.


Subject(s)
Adipose Tissue/chemistry , Ethanol/metabolism , Fatty Acids/metabolism , Liver/chemistry , Animals , Biomarkers/analysis , Esters , Ethanol/chemistry , Ethanol/toxicity , Fatty Acids/chemistry , Postmortem Changes , Rats , Rats, Sprague-Dawley , Time Factors
14.
Proc Natl Acad Sci U S A ; 98(7): 4050-4, 2001 Mar 27.
Article in English | MEDLINE | ID: mdl-11259654

ABSTRACT

Omega--3 polyunsaturated fatty acids (PUFAs) are essential components required for normal cellular function and have been shown to exert many preventive and therapeutic actions. The amount of n--3 PUFAs is insufficient in most Western people, whereas the level of n--6 PUFAs is relatively too high, with an n--6/n--3 ratio of >18. These two classes of PUFAs are metabolically and functionally distinct and often have important opposing physiological functions; their balance is important for homeostasis and normal development. Elevating tissue concentrations of n--3 PUFAs in mammals relies on chronic dietary intake of fat rich in n--3 PUFAs, because mammalian cells lack enzymatic activities necessary either to synthesize the precursor of n--3 PUFAs or to convert n--6 to n--3 PUFAs. Here we report that adenovirus-mediated introduction of the Caenorhabditis elegans fat-1 gene encoding an n--3 fatty acid desaturase into mammalian cells can quickly and effectively elevate the cellular n--3 PUFA contents and dramatically balance the ratio of n--6/n--3 PUFAs. Heterologous expression of the fat-1 gene in rat cardiac myocytes rendered cells capable of converting various n--6 PUFAs to the corresponding n--3 PUFAs, and changed the n--6/n--3 ratio from about 15:1 to 1:1. In addition, an eicosanoid derived from n--6 PUFA (i.e., arachidonic acid) was reduced significantly in the transgenic cells. This study demonstrates an effective approach to modifying fatty acid composition of mammalian cells and also provides a basis for potential applications of this gene transfer in experimental and clinical settings.


Subject(s)
Caenorhabditis elegans/genetics , Fatty Acid Desaturases/genetics , Fatty Acids/chemistry , Myocardium/metabolism , Adenoviridae/genetics , Animals , Caenorhabditis elegans/enzymology , Cells, Cultured , Eicosanoids/biosynthesis , Fatty Acid Desaturases/metabolism , Fatty Acids/metabolism , Gene Transfer Techniques , Genetic Vectors , Humans , Rats
16.
Am J Clin Pathol ; 116 Suppl: S123-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11993697

ABSTRACT

As the clinical laboratory test menu has significantly expanded in volume and complexity, there is a rapidly growing need by clinicians for narrative interpretations of complex studies that resemble those provided in anatomic pathology and radiology. In this report, the impact of advice on laboratory test selection and interpretation is presented with regard to providing adequate quality of care, reducing medical error, and reducing the cost for health care. In addition, past and current attempts to address the physician's need for advice on laboratory test selection and interpretation are also described. These include curbside consultations, intelligent laboratory information systems, and medical information from the Internet. Each is presented with examples from the literature and with its advantages and disadvantages for practicing clinicians confronting large, expensive test menus and the results of esoteric assays.


Subject(s)
Clinical Laboratory Techniques , Interprofessional Relations , Clinical Laboratory Information Systems , Humans , Internet , Medical Errors/prevention & control , Quality of Health Care , Referral and Consultation
17.
Am J Clin Pathol ; 116 Suppl: S129-32, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11993698

ABSTRACT

The use of reflexive test selection and patient-specific narrative interpretations in laboratory medicine is associated with a host of compliance issues and government regulations. Reflexive testing is associated with many advantages for patients and their physicians, but if not adequately organized it has the potential for inefficient test ordering and abuse by physicians and laboratories. Patient-specific narrative interpretations in laboratory medicine, much more than fixed comments generated by a computer with a specific test result, also provide clinical and financial benefit when done effectively. Regulations exist to ensure that the physician-provided information has clinical value. This report describes the compliance and billing regulations regarding reflex testing and narrative interpretations. The codes used for narrative interpretations in laboratory medicine are also presented, as well as the use of those codes to obtain payment for the interpretation provided.


Subject(s)
Clinical Laboratory Techniques , Algorithms , Clinical Laboratory Techniques/economics , Health Care Costs , Humans , Laboratories , Medical Records , Physicians , Reimbursement Mechanisms
18.
Am J Clin Pathol ; 116 Suppl: S133-40, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11993699

ABSTRACT

The logistical details for organizing effective interpretive rounds in a laboratory medicine subspecialty must be carefully established so that expert opinions are provided in a timely fashion in a patient-specific report, rather than as a collection of fixed comments associated with a particular laboratory result generated by a computer This report describes the test batteries for interpretations, the billing for interpretations, clinical examples of interpretations, and interpretations for which billing is not typically performed in several clinical or laboratory areas in our institution. These include coagulation disorders, hemoglobin and anemia evaluations, autoimmune disorders, serum protein analysis, toxicology, molecular diagnostics, and transfusion medicine. The information in this report should provide sufficient detail to allow development of interpretive services with successful billing for the areas in laboratory medicine described.


Subject(s)
Clinical Laboratory Techniques , Anemia/diagnosis , Autoimmune Diseases/diagnosis , Blood Coagulation Disorders/diagnosis , Blood Protein Electrophoresis/economics , Blood Transfusion/economics , Clinical Laboratory Techniques/economics , Expert Testimony , Humans , Medical Records , Molecular Biology , Reimbursement Mechanisms , Toxicology/economics
19.
Alcohol Clin Exp Res ; 24(10): 1488-91, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11045855

ABSTRACT

BACKGROUND: Fatty acid ethyl esters (FAEE) are nonoxidative ethanol metabolites that have been shown to be long term markers of ethanol intake and have been implicated as mediators of ethanol-induced cell injury. Previous studies have indicated that the fatty acid composition of the FAEE found in the plasma of human subjects after ethanol ingestion is predominantly ethyl palmitate and ethyl oleate. This raised the possibility that there is some selectivity toward the fatty acid used for FAEE to be exported from the liver into the blood. METHODS: To address the hypothesis that the fatty acid composition of FAEE secreted from organs, such as the liver and pancreas, differs from the fatty acid composition of FAEE in the organs, this study was performed using rats that received ethanol by intra-arterial infusion. RESULTS: It was found that the fatty acids in FAEE differed significantly in plasma versus liver, bile versus liver, and pancreatic secretions versus pancreas. CONCLUSIONS: These results indicate that organs selectively export certain FAEE species.


Subject(s)
Esters/analysis , Fatty Acids/analysis , Liver/chemistry , Liver/metabolism , Pancreas/chemistry , Pancreas/metabolism , Animals , Bile/chemistry , Linoleic Acids/analysis , Male , Oleic Acids/analysis , Pancreatic Juice/chemistry , Rats , Rats, Sprague-Dawley , Rats, Wistar , Stearates/analysis
20.
Ecotoxicol Environ Saf ; 46(2): 192-201, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10831333

ABSTRACT

Comparison was made of abiotic conditions, amphibian reproductive outputs, and the survival of embryonic and larval amphibians in wastewater effluent-irrigated and natural temporary ponds in an area in Centre County, Pennsylvania that has been spray-irrigated with secondarily treated, chlorinated wastewater effluent from The Pennsylvania State University for approximately 14 years. Three species of temporary pond-breeding amphibians were studied: wood frogs (Rana sylvatica LeConte), Jefferson salamanders (Ambystoma jeffersonianum Green), and spotted salamanders (A. maculatum Gravenhorst). Comparisons of physico-chemical parameters in 10 wastewater-irrigated and 10 natural temporary ponds over 19 weeks in 1997 indicated that wastewater -irrigated ponds had significantly higher median conductance, pH, ¿Na, ¿K, ¿Ca, ¿Mg, and ¿N-NO(3) and lower ¿dissolved oxygen. Many of the wastewater-irrigated ponds supported large mats of duckweed (Lemna spp.) that completely blanketed the pond's surface by mid-May. There were significantly fewer egg masses of all three species in wastewater-irrigated ponds than in natural ponds in both 1997 and 1998. In situ egg hatching success and larval survival (over a 6-day period) of all species was lower in wastewater-irrigated ponds than in natural ponds. Cumulatively, these studies suggest that wastewater effluent irrigation may impact amphibian populations by reducing the survival of amphibian eggs and larvae.


Subject(s)
Sewage , Water Pollutants, Chemical/toxicity , Ambystoma/physiology , Animals , Fresh Water , Larva/drug effects , Ranidae/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...