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Biomedical subjects

David A Katz

Publications and source records attributed to David A Katz.

13 recordsLinked to original sources
PubMed2006

Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics.

OBJECTIVE: Our objective was to learn whether genetic polymorphisms of metabolic enzymes or transport proteins provide a mechanistic understanding of the in vivo disposition of atrasentan, a selective endothelin A receptor antagonist. METHODS: Atrasentan uptake was measured in HeLa cells transfected to express major alleles of organic anion transporting polypeptide 1B1 (OATP1B1). The results were used to classify individuals as extensive, intermediate, or poor OATP1B1 transporters according to their SLCO1B1 genotypes. Analysis of covariance including genotype, study, age, weight, sex, and ethnicity was used to identify factors influencing atrasentan single-dose (n = 44) and steady-state (n = 38) pharmacokinetic parameters. Genotypes for cytochrome P450 3A5, uridine diphosphate-glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B15, adenosine triphosphate-binding cassette subfamily B (ABCB) 1, solute carrier organic anion transporter (SLCO) 1B1, and solute carrier family 22 (SLC22) A2 were each assessed. RESULTS: Single-dose atrasentan exposure (P = .0244), steady-state atrasentan exposure (P = .0108), and maximum postdose plasma concentration (P = .0002) were associated with OATP1B1 activity classified by SLCO1B1 genotype. No other tested genotypes were observed to be associated with both single-dose and steady-state atrasentan pharmacokinetics. CONCLUSIONS: OATP1B1 is a meaningful factor for atrasentan disposition. Individuals may be classified as having extensive, intermediate, or poor OATP1B1 transport phenotypes according to SLCO1B1 genotypes. Increased exposures of OATP1B1 substrates might be expected in individuals who have the poor transporter phenotype or are treated with an OATP1B1 inhibitor.

Adult↗
PubMed2005

Emergency physicians' fear of malpractice in evaluating patients with possible acute cardiac ischemia.

STUDY OBJECTIVE: We evaluate the association between emergency physicians' fear of malpractice and the triage and evaluation patterns of patients with symptoms suggestive of acute coronary syndrome. METHODS: We surveyed 33 emergency physicians of 2 university hospitals during the preintervention phase of an implementation trial of the Agency for Health Care Policy and Research Unstable Angina guideline in 1,134 study patients. The survey included a 6-item instrument that addressed concerns about malpractice and a measure of general risk aversion. We used hierarchical logistic regression to model emergency department (ED) triage decisions and diagnostic testing as a function of fear of malpractice, with adjustment for patient characteristics, Agency for Health Care Policy and Research guideline risk group, study site, and clustering by emergency physician. RESULTS: Overall, emergency physicians in the upper tertile of malpractice fear were less likely to discharge low-risk patients compared with emergency physicians in the lower tertile (adjusted odds ratio [OR] 0.34; 95% confidence interval [CI] 0.12 to 0.99; P=.05). Patients treated by emergency physicians in this group were also more likely to be admitted to an ICU or telemetry bed (adjusted OR 1.7; 95% CI 1.2 to 2.4). In addition, emergency physicians in the upper tertile of malpractice fear were more likely to order chest radiography, as well as cardiac troponin. Malpractice fear accounted for a similar amount of variance after controlling for emergency physicians' risk aversion. CONCLUSION: Malpractice fear accounts for significant variability in ED decisionmaking and is associated with increased hospitalization of low-risk patients and increased use of diagnostic tests.

Adult↗
PubMed2004

Effectiveness of implementing the agency for healthcare research and quality smoking cessation clinical practice guideline: a randomized, controlled trial.

BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit. METHODS: We conducted a randomized, controlled trial of the effectiveness of Guideline implementation at eight community-based primary care clinics in southern Wisconsin (four test sites, four control sites) among 2163 consecutively enrolled adult patients who smoked at least one cigarette per day and presented for nonemergency care during the baseline period (June 16, 1999, to June 20, 2000) or the intervention period (from June 21, 2000, to May 3, 2001). After collecting baseline data, staff at test sites implemented the intervention over a 2-month period. The intervention included a tutorial for intake clinicians, group and individual performance feedback for intake clinicians, use of a modified vital signs stamp, an offer of free nicotine replacement therapy, and proactive telephone counseling. Staff at control sites received only general information about the AHRQ Guideline. Self-reported abstinence from smoking was determined by telephone interviews at 2- and 6-month follow-up assessments. Hierarchical logistic regression models were used to estimate the odds ratios (ORs) for treatment assignment after adjustment for patient characteristics. All statistical tests were two-sided. RESULTS: There were no statistically significant differences in smoking cessation rates between participants at test and control sites during the baseline period. Among participants treated during the intervention period, those at test sites were more likely than those at control sites to report being abstinent at the 2-month (16.4% versus 5.8%; adjusted OR = 3.3, 95% confidence interval [CI] = 1.9 to 5.6; P<.001) and 6-month (15.4% versus 9.8%; adjusted OR = 1.7, 95% CI = 1.2 to 2.6; P =.009) follow-up assessments and to report continuous abstinence, that is, abstinence at both 2 and 6 months (10.9% versus 3.8%; adjusted OR = 3.4, 95% CI = 1.8 to 6.3; P<.001). CONCLUSION: Implementation of a guideline-based smoking cessation intervention by intake clinicians in primary care is associated with higher abstinence among smokers.

Adult↗
PubMed2004

Implementing guidelines for smoking cessation: comparing the efforts of nurses and medical assistants.

BACKGROUND: It is unclear how different types of intake clinicians (registered nurses [RNs], and less costly licensed practical nurses [LPNs] and medical assistants [MAs]) compare in the performance of smoking-cessation activities recommended in the Agency for Healthcare Research and Quality (AHRQ) smoking-cessation clinical practice guideline. METHODS: A secondary analysis of data from a randomized controlled trial of guideline implementation was performed. Exit interviews of consecutive adult smokers who presented to nine primary care clinics for routine, non-emergency care were conducted during the period February 2000 to May 2001; a total of 1221 patients with adequate data were analyzed. Intake clinicians were surveyed prior to guideline training. Hierarchical logistic regression models were used to determine the association between type of intake clinician and performance of cessation counseling at the clinic visit, after adjustment for patient-level covariates, intake clinicians' characteristics, and study site. RESULTS: Performance of all guideline-recommended counseling activities were significantly greater for all intake clinicians at test versus control sites. MAs were significantly less likely to assess willingness to quit (adjusted odds ratio [AOR]=0.4, 95% confidence interval [CI]=0.2-0.8, p =0.005) and tended to offer advice and assistance in quitting less often than RNs. Similar findings were observed for LPNs (AOR=0.5, 95% CI=0.3-1.0, p =0.03, for assessing willingness to quit). Subset analysis in subjects with complete survey data revealed that being seen by a MA was no longer associated with statistically significant differences in performance, after accounting for personal beliefs, self-efficacy, and role satisfaction in cessation counseling. CONCLUSIONS: Although both MAs and LPNs showed marked improvements in performance in response to the guideline intervention, patients seen by these intake clinicians were less likely to receive guideline-recommended counseling, compared to those patients seen by RNs. Given their important role in the delivery of preventive care, MAs and LPNs should receive proper training in cessation counseling, should have strong physician and administrative support, and should be included in efforts to implement smoking-cessation guidelines in primary care.

Adolescent↗
PubMed2004

CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels.

BACKGROUND: The metabolizing enzyme cytochrome P450 (CYP) 3A5 is polymorphically expressed as a result of genetic variants that do not encode functional protein. Because of overlapping substrate specificity with CYP3A4 and the multidrug efflux pump P-glycoprotein, the importance of CYP3A5 genetic polymorphism for pharmacokinetics is controversial. OBJECTIVE: Our objective was to determine whether genetic polymorphisms in CYP3A5 or MDR-1 (which encodes P-glycoprotein) influence the drug levels of ABT-773, a ketolide antibiotic that is a substrate for both CYP3A and P-glycoprotein. METHODS: Healthy volunteers given 3 different oral dose levels of ABT-773 were genotyped at 2 common CYP3A5 and 7 common MDR-1 polymorphisms. Individuals were categorized as CYP3A5-positive if they carried at least 1 functional CYP3A5*1 allele and as CYP3A5-negative if they did not. Area under the plasma concentration-time curves (AUCs) from 0 to 6 hours (AUC(t)) and maximum postdose plasma concentration (C(max)) after a single dose and on day 5 of a twice-daily regimen were calculated and correlated with genotypes. RESULTS: ABT-773 AUC(t) and C(max) were, on average, higher in CYP3A5-negative subjects given 450 mg ABT-773 (n = 9) than in CYP3A5-positive subjects with identical doses (n = 8). The relationship for AUC(t) was statistically significant both after a single dose (geometric mean and 95% confidence interval [CI], 5.0 microg.h/mL [3.9-6.4 microg.h/mL] versus 2.8 microg.h/mL [1.8-4.3 microg.h/mL]; P =.03) and on the fifth day of twice-daily dosing (12.4 microg.h/mL [8.7-17.6 microg.h/mL] versus 7.4 microg.h/mL [5.5-9.8 microg.h/mL], P =.04). The relationship for C(max) was statistically significant after a single dose (1220 microg/mL [867-1167 microg/mL] versus 727 microg/mL [506-1044 microg/mL], P =.04) and showed a trend in the same direction on the fifth day of twice-daily dosing (2566 microg/mL [1813-3631 microg/mL] versus 1621 microg/mL [1122-2343 microg/mL], P =.07). In contrast, AUC(t) and C(max) were not significantly different between CYP3A5-positive and CYP3A5-negative individuals given 150 mg or 300 mg ABT-773. ABT-773 plasma levels did not trend with MDR-1 genotypes. CONCLUSIONS: These results suggest that CYP3A5 genotype may be an important determinant of in vivo drug disposition and that this effect may be dose-dependent.

Adolescent↗
PubMed2004

Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics.

This study utilized cytochrome P450 2D6 (CYP2D6) genotypes to explain variability of desipramine pharmacokinetics in a cohort of non-poor metabolizer individuals. In an interaction study utilizing desipramine as a probe, genotyping for the CYP2D6*3, *4, *5 and *6 alleles was used to screen out CYP2D6 poor metabolizers. Individuals were categorized according to these and additional alleles (CYP2D6*2, *9, *10, *17, *41 and x2). Genotypes of individuals heterozygous for two or three of *2, *17 and *41 alleles were confirmed by molecular haplotyping. Pharmacokinetic parameters of desipramine were analysed according to CYP2D6 category. Molecular haplotyping was necessary to definitively categorize four of 16 individuals. A subject who had unusually high plasma elimination half-time, exposure and metabolic ratios carried an intermediate metabolizer (IM) *9 allele in combination with a non-functional allele. This combination has a population frequency of less than 1 : 200. Individuals with *1/*1, *1/*2 and *2/*2 genotypes had lower than average plasma elimination half-time, exposure and metabolic ratios. For desipramine, additional genotyping of CYP2D6 IM alleles helped define subgroups of the CYP2D6-positive cohort. This suggests that genotyping for IM alleles will aid in interpretation of clinical trials involving CYP2D6 substrates. Due to the diversity of IM alleles, molecular haplotyping may be necessary to fully characterize CYP2D6 genotype-phenotype relationships.

Alleles↗
PubMed2002

Effectiveness of a clinic-based strategy for implementing the AHRQ Smoking Cessation Guideline in primary care.

BACKGROUND: The Agency for Healthcare Research and Quality Smoking Cessation Practice Guideline recommends systematic assessment of smoking status and counseling of smokers at every visit, but the actual effectiveness of the guideline in primary care practice is unknown. METHODS: We conducted a nonrandomized, controlled before-after trial of a guideline-derived intervention that includes routine identification and brief counseling of smokers by nurses and medical assistants, coupled with free nicotine replacement therapy (NRT) and telephone counseling of those smokers who are willing to make a quit attempt, and feedback on performance of guideline-recommended activities. The intervention was pilot tested at 1 family practice (FP) clinic over a 2-month period; patterns of usual care were observed concurrently at four control FP clinics. We obtained exit interviews of 651 consecutive adult smokers who presented for routine, nonemergency care. Abstinence (7-day point prevalence) was determined by telephone interview during 6-month follow-up. RESULTS: Concordance with guidelines was significantly greater for all recommended actions at the test site during the intervention versus baseline (P < or = 0.05). Significantly more intervention versus baseline patients at the test site reported abstinence at 2-month follow-up (21 vs. 4%, P = 0.0004), and more patients tended to be abstinent at 6-month follow-up (21 vs. 11%, P = 0.08). No significant differences in 2- or 6-month quit rates between intervention and baseline patients were observed at the control sites. CONCLUSIONS: Implementation of a guideline-driven smoking cessation intervention that focuses primarily on smokers who are interested in making a quit attempt is associated with increased abstinence in primary care practice.

Adult↗
PubMed2002

The relationship between insomnia and health-related quality of life in patients with chronic illness.

OBJECTIVES: To determine the association between insomnia and health-related quality of life (HRQOL) in patients with chronic illness after accounting for the effects of depression, anxiety, and medical comorbidities. STUDY DESIGN: We used a cross-sectional analysis of Medical Outcomes Study (MOS) data. POPULATION: The sample consisted of 3445 patients who completed a self-administered questionnaire and who were given a diagnosis of 1 or more of 5 chronic medical and psychiatric conditions by an MOS clinician. Patients were recruited from the offices of clinicians practicing family medicine, internal medicine, endocrinology, cardiology, and psychiatry in 3 US cities. OUTCOMES MEASURED: Outcomes were sleep items, health-related quality of life as measured by the Medical Outcomes Study Short Form Health Survey (SF-36), chronic medical comorbidity, depression, and anxiety. Insomnia was defined as the complaint of difficulty initiating or maintaining sleep. RESULTS: Insomnia was severe in 16% and mild in 34% of study patients. Patients with insomnia demonstrated significant global decrements in HRQOL. Differences between patients with mild insomnia versus no insomnia showed small to medium decrements across SF-36 subscales ranging from 4.1 to 9.3 points (on a scale of 0 to 100); the corresponding decrements for severe insomnia (versus no insomnia) ranged from 12.0 to 23.9 points. CONCLUSIONS: Insomnia is independently associated with worsened HRQOL to almost the same extent as chronic conditions such as congestive heart failure and clinical depression.

Adult↗
PubMedDate not supplied

From bench to bedside: a diagnostics framework for pharmacogenetics research.

Although many genetic variants have been associated with differential drug responses, a very limited number of pharmacogenetic tests have entered common clinical practice. Pharmacogenetic tests that are successful address unmet medical needs, are clinically relevant, and have sufficient sensitivity, and specificity. In this respect, pharmacogenetics is no different from other diagnostics fields. Unmet medical need, clinical relevance, sensitivity, and specificity are discussed in the context of specific pharmacogenetic associations. These parameters are useful guides for researchers interested in translating pharmacogenetic findings from the bench to the bedside.

Arachidonate 5-Lipoxygenase↗
PubMedDate not supplied

The impact of unstable angina guidelines in the triage of emergency department patients with possible acute coronary syndrome.

OBJECTIVE: The primary aim of this study is to determine whether implementing the Agency for Health Care Policy and Research (AHCPR) Unstable Angina Practice Guideline improves emergency physician's decision making in patients with symptoms of possible acute coronary syndrome (ACS), including those for whom the diagnosis of unstable angina is uncertain. METHODS: The authors conducted a prospective guideline implementation trial with pre-post design in the emergency departments of 1 university hospital and 1 university-affiliated community teaching hospital from January 2000 to May 2001. They enrolled 1140 adults who presented with chest pain or other symptoms of possible ACS. The intervention included the following: 1) physician training in use of the AHCPR risk groups, 2) algorithm for risk stratification, and 3) group feedback. To determine how accurately physicians interpreted the guideline algorithm, the authors compared their risk ratings with actual guideline risk groups. RESULTS: No significant difference in physician triage decisions was observed between baseline and intervention periods. Analysis of physician's risk ratings during the intervention period revealed low overall concordance with actual guideline risk groups (kappa = 0.31); however, physician's risk ratings showed superior discrimination in identifying patients with confirmed ACS (receiver operating characteristic [ROC] area .81 v. .74, P = 0.008). Strict adherence to guideline recommendations would have resulted in hospitalizing 9% more non-ACS patients without lowering the rate of missed ACS. CONCLUSION: Implementation of the AHCPR guideline did not improve triage decisions in emergency department patients with possible ACS. Assessing physician triage solely based on concordance with the AHCPR guideline may not accurately reflect the quality of patient care.

Adult↗