Biomedical subjects

Brian B Hoffman

Publications and source records attributed to Brian B Hoffman.

8 recordsLinked to original sources

PubMed2005

Improving adherence to guidelines for hypertension drug prescribing: cluster-randomized controlled trial of general versus patient-specific recommendations.

OBJECTIVE: To determine whether an intervention focusing clinician attention on drug choice for hypertension treatment improves concordance between drug regimens and guidelines. STUDY DESIGN: Cluster-randomized controlled trial comparing an individualized intervention with a general guideline implementation in geographically diverse primary care clinics of a university-affiliated Department of Veterans Affairs healthcare system. METHODS: Participants were 36 attending physicians and nurse practitioners (16 in the general group and 20 in the individualized group), with findings based on 4500 hypertensive patients. A general guideline implementation for all clinicians, including education about guideline-based drug recommendations and goals for adequacy of blood pressure control, was compared with addition of a printed individualized advisory sent to clinicians at each patient visit, indicating whether or not the patient's antihypertensive drug regimen was guideline concordant. We measured change from baseline to end point in the proportion of clinicians' patients whose drug therapy was guideline concordant. RESULTS: The individualized intervention resulted in an improvement in guideline concordance more than twice that observed for the general intervention (10.9% vs 3.8%, t = 2.796, P = .008). Bootstrap analysis showed that being in the individualized group increased the odds of concordance 1.5-fold (P = .025). The proportion of patients with adequate blood pressure control increased within each study group; however, the difference between groups was not significant. CONCLUSION: An individualized advisory regarding drug therapy for hypertension given to the clinician at each patient visit was more effective in changing clinician prescribing behavior than implementation of a general guideline.

Aged↗

PubMed2004

Clinician awareness of adherence to hypertension guidelines.

PURPOSE: Little is known about how well clinicians are aware of their own adherence to clinical guidelines, an important indicator of quality. We compared clinicians' beliefs about their adherence to hypertension guidelines with data on their actual performance. METHODS: We surveyed 139 primary care clinicians at three Veterans Affairs medical centers, asking them to assess their own adherence to hypertension guidelines. We then extracted data from the centers' clinical databases on guideline-concordant medication use and blood pressure control for patients cared for by these providers during a 6-month period. Data were collected for patients with hypertension and diabetes, hypertension and coronary disease, or hypertension with neither of these comorbid conditions. RESULTS: Eighty-six clinicians (62%) completed the survey. Each clinician saw a median of 94 patients with hypertension (mean age, 65 years). Patients were treated with an average of 1.6 antihypertensive medications. Overall, clinicians overestimated the proportion of their patients who were prescribed guideline-concordant medications (75% perceived vs. 67% actual, P <0.001) and who had blood pressure levels <140/90 mm Hg on their last visit (68% perceived vs. 43% actual, P <0.001). Among individual clinicians, there were no significant correlations between perceived and actual guideline adherence (r = 0.18 for medications, r = 0.14 for blood pressure control; P > or =0.10 for both). Clinicians with relatively low actual guideline performance were most likely to overestimate their adherence to medication recommendations and blood pressure targets. CONCLUSION: Clinicians appear to overestimate their adherence to hypertension guidelines, particularly with regards to the proportion of their patients with controlled blood pressure. This limited awareness may represent a barrier to successful implementation of guidelines, and could be addressed through the use of provider profiles and point-of-service feedback to clinicians.

Aged↗

PubMed2004

Translating research into practice: organizational issues in implementing automated decision support for hypertension in three medical centers.

Information technology can support the implementation of clinical research findings in practice settings. Technology can address the quality gap in health care by providing automated decision support to clinicians that integrates guideline knowledge with electronic patient data to present real-time, patient-specific recommendations. However, technical success in implementing decision support systems may not translate directly into system use by clinicians. Successful technology integration into clinical work settings requires explicit attention to the organizational context. We describe the application of a "sociotechnical" approach to integration of ATHENA DSS, a decision support system for the treatment of hypertension, into geographically dispersed primary care clinics. We applied an iterative technical design in response to organizational input and obtained ongoing endorsements of the project by the organization's administrative and clinical leadership. Conscious attention to organizational context at the time of development, deployment, and maintenance of the system was associated with extensive clinician use of the system.

Academic Medical Centers↗

PubMed2004

Activation of alpha2 adrenergic receptors suppresses fear conditioning: expression of c-Fos and phosphorylated CREB in mouse amygdala.

alpha(2) adrenergic agonists such as dexmedetomidine generally suppress noradrenergic transmission and have sedative, analgesic, and antihypertensive properties. Considering the importance of the neurotransmitter norepinephrine in forming memories for fearful events, we have investigated the acute and chronic effects of dexmedetomidine on discrete cue and contextual fear conditioning in mice. When administered before training, dexmedetomidine (10-20 microg/kg, i.p.) selectively suppressed discrete cue fear conditioning without affecting contextual memory. This behavioral change was associated with a decrease in memory retrieval-induced expression of c-Fos and P-CREB in the lateral, basolateral, and central nuclei of the amygdala. Dexmedetomidine's action on discrete cue memory did not occur in alpha(2A) adrenoceptor knockout (KO) mice. When dexmedetomidine was administered after training, it suppressed contextual memory, an effect that did not occur in alpha(2A) adrenoceptor KO mice. We conclude that dexmedetomidine, acting at alpha(2A) adrenoceptors, must be present during the encoding process to decrease discrete cue fear memory; however, its ability to suppress contextual memory is likely the result of blocking the consolidation process. The ability of alpha(2) agonists to suppress fear memory may be a valuable property clinically in order to suppress the formation of memories during stressful situations.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed2003

Augmentation of the noradrenergic system in alpha-2 adrenergic receptor deficient mice: anatomical changes associated with enhanced fear memory.

We have investigated sensitivity to the conditioned fear procedure of mice is influenced by the genetic deletion of alpha2A adrenoceptors (ARs). We observed a heightened freezing response in the discrete cue memory test in alpha2A AR knockout (alpha2A AR KO) mice and in D79N mice, a transgenic mouse strain with functionally impaired alpha2A ARs. No significant differences in contextual memory were observed between control and alpha2A AR KO or D79N mice suggesting a minimal role for the noradrenergic system in contextual memory. We speculated that the increased freezing response of the alpha2A AR KO and D79N mice in the discrete cue setting was due to increased release of norepinephrine evoked by the unconditioned footshock stimulus. In alpha2A AR KO mice we measured a doubling in the number of noradrenergic neurons in the locus coeruleus (LC) and a large increase in the cell volume of tyrosine hydroxylase positive neurons, likely due to selective preservation of large, multipolar neurons in the subcoeruleus. Hyperplasia of the noradrenergic neurons in the nucleus tractus solitarius, A5 and A7, was also observed. Alpha2A AR KO mice exhibit greater c-Fos expression in the LC compared to wild type mice suggesting that the LC neurons in the alpha2A AR KO mice were spontaneously more active. This study suggests that alpha2A ARs are involved in the development of the central noradrenergic system and raises the possibility that alterations in alpha2A AR expression may contribute to variations in fear and stress responses.

Animals↗

PubMed2002

Beta-adrenergic receptor activation inhibits keratinocyte migration via a cyclic adenosine monophosphate-independent mechanism.

There is increasing evidence that G-protein-coupled receptors cross-talk with growth factor receptor-mediated signal transduction in a variety of cell types. We have investigated mechanisms by which the activation of beta-adrenergic receptors, classically GTP-binding proteins coupled receptors, influence the migration of cultured human keratinocytes. We found that iso-proterenol, a beta-adrenergic receptor-selective agonist, inhibited cell migration stimulated by either epidermal growth factor, or extracellular Ca2+ in a concentration-dependent manner. This was prevented by pretreatment of the cells with the beta-adrenergic receptor-selective antagonist timolol. Interestingly, isoproterenol, at a concentration of 1 nm, did not measurably increase intracellular cyclic adenosine monophosphate concentrations yet inhibited cell migration by 50%. To test further if isoproterenol's actions were mediated via activation of adenylyl cyclase, two inhibitors of its activity, 2'5'-dideoxyadenosine and SQ22536, were used. Both compounds significantly diminished iso-proterenol-induced increases in intracellular cyclic adenosine monophosphate concentrations but did not attenuate isoproterenol-induced inhibition of cell migration. Also, forskolin (1 microm) markedly increased intracellular cyclic adenosine monophosphate concentrations but did not significantly inhibit cell migration. As mitogen-activated protein kinases are known to signal growth factor-stimulated cell migration, we examined whether beta-adrenergic receptor-mediated inhibition of keratinocyte migration might occur via inactivation of mitogen-activated protein kinases. We found that isoproterenol inhibited phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration-dependent manner but had no effect on the phosphorylation of the stress mitogen-activated protein kinases c-jun N-terminal kinase and stress-activated protein kinase-2. Neither forskolin nor a membrane permeable cyclic adenosine monophosphate analog inhibited phosphorylation of any of these mitogen-activated protein kinases. These findings suggest that beta-adrenergic receptor-induced inhibition of keratinocyte migration is mediated through inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase signaling in a cyclic adenosine monophosphate-independent manner.

Adrenergic beta-Agonists↗

PubMed2002

Angiotensin II increases expression of cyclooxygenase-2: implications for the function of vascular smooth muscle cells.

In vascular smooth muscle, increased expression of cyclooxygenase-2 (COX-2) has emerged as an important mechanism for regulation of prostanoid synthesis influenced by vessel injury, cytokines, and growth factors. We have investigated how COX-2 participates in angiotensin II (ANG II)-mediated cell responses in cultured human vascular smooth muscle cells (VSMCs). ANG II type 1 (AT1) receptors induce increased accumulation of COX-2, both at the mRNA and protein levels. ANG II increased transcription of the COX-2 gene; also, nuclear extracts from stimulated cells had increased NF-kappa B binding to its DNA consensus sequence. ANG II-induced COX-2 expression was markedly blunted by inhibition of mitogen-activated protein kinase. Furthermore, the ANG II-induced increase in COX-2 protein abundance was attenuated by both the peroxisome proliferator-activated receptor alpha (PPARalpha) activator Wy-14,643 [pyrinixic acid; 4-chloro-6-(2,3-xylidino)-2-pyrimidinyl) thioacetic acid] and the PPARgamma activator 15d-PGJ2 (15-deoxy-Delta(12-14)-prostaglandin J2). Not only did ANG II increase COX-2 expression and prostaglandin synthesis, ANG II-stimulated DNA synthesis and cell migration were dependent on COX-2 activity. PPARalpha and PPARgamma activators inhibited ANG II-stimulated DNA synthesis and cell migration. These results suggest that ANG II enhances COX-2 expression at the transcription level; also, COX-2 activity plays an important role in mediating ANG II- induced proliferation and migration of VSMCs, suggesting the possibility of magnification of ANG II effects over time due to the induction of COX-2 expression. These results also demonstrate that both the alpha and gamma type of PPAR activators inhibit COX-2 expression induced by angiotensin II in VSMCs which may have therapeutic significance in vascular diseases.

Angiotensin II↗

PubMed2002

Accuracy of computerized outpatient diagnoses in a Veterans Affairs general medicine clinic.

BACKGROUND: Electronically available data, both administrative, such as outpatient encounter diagnostic data, and clinical, such as problem lists, are being used increasingly for outcome and quality assessment, risk adjustment, and clinical reminder systems. OBJECTIVE: To determine the accuracy of outpatient primary care diagnostic information recorded in administrative and clinical files in a Veterans Affairs VISTA (Veterans Health Information Systems and Technology Architecture) database compared with medical chart notes. STUDY DESIGN: Cross-sectional medical chart review of 148 patients attending a general medicine clinic at a university-affiliated Veterans Affairs hospital for 9 diagnoses relevant to the choice of drug therapy for hypertension. PATIENTS AND METHODS: An administrative file of encounter diagnoses, for a 2-year period, and a clinical file of the problem list maintained by the clinician were the sources of electronic diagnoses. We compared these sources with diagnoses abstracted by medical chart review. We estimated the sensitivity and specificity of each electronic data source for detecting medical chart note diagnoses. RESULTS: The sensitivity for 8 of the 9 study diagnoses was greater than 80% in the administrative file and 49% in the clinical problem list. The specificity was good for the administrative file (91% to 100%) and even better for the clinical file (98% to 100%). CONCLUSIONS: Outpatient encounter diagnoses relevant to hypertension recorded as electronic data had high specificity, and some codes had high sensitivity when collected over multiple visits. The administrative file was more sensitive but less specific than the clinical file. Administrative vs clinical files can be selected to minimize either the false-negative or the false-positive designations, respectively, as dictated by the needs of the quality assessment review.

California↗