Patient Perceptions of Care as Influenced by a Large Institutional Pharmacogenomic Implementation Program.

Despite growing clinical use of genomic information, patient perceptions of genomic-based care are poorly understood. We prospectively studied patient-physician pairs who participated in an institutional pharmacogenomic implementation program. Trust/privacy/empathy/medical decision-making (MDM)/personalized care dimensions were assessed through patient surveys after clinic visits at which physicians had access to preemptive pharmacogenomic results (Likert scale, 1 = minimum/5 = maximum; mean [SD]). From 2012-2015, 1,261 surveys were issued to 507 patients, with 792 (62.8%) returned. Privacy, empathy, MDM, and personalized care scores were significantly higher after visits when physicians considered pharmacogenomic results. Importantly, personalized care scores were significantly higher after physicians used pharmacogenomic information to guide medication changes (4.0 [1.4] vs. 3.0 [1.6]; P < 0.001) compared with prescribing visits without genomic guidance. Multivariable modeling controlling for clinical factors confirmed personalized care scores were more favorable after visits with genomic-influenced prescribing (odds ratio [OR] = 3.26; 95% confidence interval [CI] = (1.31-8.14); P < 0.05). Physicians seem to individualize care when utilizing pharmacogenomic results and this decision-making augmentation is perceived positively by patients.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine.

Plasma lipoprotein (a) protein concentration and coronary artery disease in black patients compared with white patients.

PURPOSE: This study examines the relation between lipoprotein (a) protein levels and other lipid parameters and coronary artery disease in white and black patients. PATIENTS AND METHODS: Plasma lipoprotein (a) protein levels were measured prior to coronary angiography in a population of 127 white and 111 black patients. Each angiogram was given a total coronary artery disease score based on the number and severity of atherosclerotic coronary lesions. RESULTS: White and black patients exhibited no differences in total plasma cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Black patients had higher lipoprotein (a) protein levels than white patients (8.6 versus 4.0 mg/dL; p < 0.0001). The extent and severity of coronary artery disease was the same in white and black patients. White and black patients with coronary artery disease had higher lipoprotein (a) levels than patients without coronary lesions (4.37 versus 1.99 mg/dL, p = 0.027 for white; 9.23 versus 6.87 mg/dL, p = 0.072 for black). In both groups of patients, there was a weak but significant positive correlation between lipoprotein (a) protein levels and coronary artery disease score. CONCLUSION: Lipoprotein (a) is higher in patients with coronary artery disease. Black patients have higher plasma lipoprotein (a) protein levels than white patients and a comparable degree of coronary artery disease. It follows that the cardiovascular pathogenicity of lipoprotein (a) is not significantly greater in black patients despite higher lipoprotein (a) levels.

Left ventricular outflow tract obstruction as a cause for hypotension and symptoms during dobutamine stress echocardiography.

BACKGROUND: Hypotension has been found to occur in more than one-third of patients during DBSE. Unlike traditional treadmill exercise stress testing, hypotension does not appear to be associated with significant coronary artery disease or left ventricular (LV) dysfunction. Several ischemic and nonischemic mechanisms such as dynamic LV intracavitary obstruction have been implicated in the pathogenesis of hypotension and the induction of symptoms during DBSE. HYPOTHESIS: The purpose of this study was the prospective evaluation of patients referred for dobutamine stress echocardiography (DBSE) to determine (1) the frequency of hypotension during DBSE, (2) the underlying mechanisms responsible for the induction of hypotension, and (3) to describe the cardiac chamber sizes and mass of patients in whom hypotension occurs. METHODS: Seventy-eight consecutive patients were studied during DBSE. Pulsed and continuous-wave Doppler echocardiography were performed at baseline and at each dobutamine infusion stage. Maximum velocities were recorded. Cardiac output was determined noninvasively at each stage in patients who developed an outflow tract gradient. Echocardiography was used to characterize LV dimensions and mass. RESULTS: During dobutamine infusion, 14 of 78 (18%) patients developed a left ventricular outflow tract (LVOT) velocity > or = 2.5 m/s. Pulsed Doppler echocardiography verified that the maximal velocity originated in the LVOT. Of the patients who developed an LVOT gradient, 57% had a concomitant hypotensive response to dobutamine compared with 33% of patients without a gradient (not significant). Four of nine patients had a simultaneous fall in cardiac output. Patients who developed an LVOT gradient had smaller LV dimensions and increased wall thicknesses compared with those who did not develop a gradient. CONCLUSIONS: Dobutamine stress echocardiography precipitates LVOT obstruction in certain patients. The development of a gradient corresponded with a fall in blood pressure and a decline in cardiac output in nearly half of the patients. These findings suggest that stress-induced LVOT obstruction may be responsible in part for the hemodynamic changes and symptoms experienced by these patients during exercise.

Arterial thrombosis in a previously healthy woman.

Antiphospholipid antibodies can develop in otherwise healthy people, and their presence substantially increases the risk of thrombotic complications. Patients who have a thrombotic episode for no clear reason need to be tested for the presence of antiphospholipid antibodies. Patients with positive test results benefit from long-term anticoagulation therapy.

Cholesterol reduction to prevent CAD. What do the data show?

Primary prevention of heart disease should be an important goal of every primary care physician. All patients should undergo careful assessment of future risk and should be counseled about lifestyle modification. Patients at high risk can further benefit from cautious use of lipid-lowering drugs, which have been shown to be effective in preventing cardiac events without substantially increasing risk of noncardiac morbidity and mortality.

Drug therapy for congestive heart failure. Appropriate choices can prolong life.

The goals of therapy for congestive heart failure (CHF) are to improve quality of life and to prolong it. Improvement in patients with CHF can only be realized, however, if a multidisciplinary healthcare team can provide effective management in both the inpatient and outpatient settings. Inhibition of compensatory mechanisms that perpetuate CHF is the first step in achieving treatment goals. Combination therapy with diuretics, digoxin (Lanoxicaps, Lanoxin), and vasodilators is used for patients with symptomatic heart failure and volume overload. Because angiotensin-converting enzyme inhibitors improve survival rates more than other vasodilators, they are preferred in patients with systolic dysfunction.

Turning up the heat on hypertension. It's time to be more aggressive in finding and treating this silent killer.

Treatment of high blood pressure can be challenging. Most patients have no symptoms and are unlikely to appreciate the value of antihypertensive medications. Unless acute target organ involvement is already present, there are no compelling reasons to lower blood pressure quickly. Instead, beginning with relatively low doses of medications and slowly bringing the blood pressure to goal helps avoid troublesome medication side effects. This is especially important in elderly patients with isolated systolic hypertension who are susceptible to orthostatic hypotension, dizziness, and confusion, despite little change in blood pressure. Use of long-acting agents and combination medications may improve compliance with the medical regimen.

Mitral valve prolapse. Avoiding complications of a progressive disease.

Mitral valve prolapse is a common disorder, but it carries low morbidity and mortality. Patients require close follow-up, however, to prevent development of serious complications. In addition, patients with thickened mitral valve leaflets or mitral regurgitation require antibiotic prophylaxis against infective endocarditis. Family members of patients with primary mitral valve prolapse should be screened for the disease, because it often is asymptomatic.

Does hypertriglyceridemia increase risk for CAD? Growing evidence suggests it plays a role.

High triglyceride levels are associated with several risk factors that substantially increase the risk of CAD. The metabolic syndrome is a constellation of signs and symptoms (e.g., postprandial hypertriglyceridemia, low LDL cholesterol levels, insulin resistance) that has been linked to a high incidence of heart disease. Treatment of hypertriglyceridemia begins with an aggressive lifestyle modification program. Dietary restriction of alcohol and carbohydrates can significantly lower triglyceride levels in many patients. Pharmacotherapy should be considered for patients at high risk of cardiac disease.

Beta blockers for CHF. Adrenergic blockade dramatically reduces morbidity and mortality.

Several large clinical trials have shown that beta blockers can reduce morbidity and mortality in patients with CHF. Therefore, current guidelines for treatment of CHF now include beta blockers as standard therapy for patients with left ventricular systolic dysfunction (ejection fraction < or = 40%) and mild to moderate heart failure. Beta-blocker therapy for CHF should be started cautiously and increased gradually to avoid exacerbating symptoms of heart failure. At this time, data for therapy in patients with NYHA class I or IV symptoms are limited, and it is unclear whether all beta blockers confer benefit or whether some are better than others. Several trials are under way to answer these questions. Until more evidence is available, only those agents that have proved beneficial in mortality trials should be used to manage CHF.

Causes of congestive heart failure. Prompt diagnosis may affect prognosis.

Congestive heart failure (CHF) is a progressive disease with multiple possible causes. Systolic heart failure, defined as contractile failure of the myocardium leading to a reduced ejection fraction, is the most common type. Systolic heart failure may result from coronary artery disease, hypertension, a metabolic disorder, infection, or an infiltrative or other disease, or it may be idiopathic. Recognition of CHF can be difficult, especially in elderly patients with several medical conditions. An early clinical sign may be dyspnea on exertion. The extent of workup needed is often indicated by findings on history taking and physical examination. In all patients suspected of having new-onset CHF, a chest film, an electrocardiogram, and left ventricular ejection fraction should be obtained and a search for complicating and causative factors undertaken. Early treatment may halt the otherwise inevitable decline in cardiac function and improve prognosis.

Echocardiographic determination of myocardial mass: a review.

Studies have shown that hypertensive patients with increased left ventricular wall mass are at higher risk for cardiovascular complications than are patients with normal left ventricular wall mass. Echocardiographic determination of myocardial mass is a more sensitive predictor of left ventricular hypertrophy (LVH) than are electrocardiographic or chest X-ray studies. Two-dimensional echocardiographic methods used to determine left ventricular mass have been shown to be a sensitive indicator of assessing left ventricular muscle mass. Left ventricular mass estimates can be used to determine prognosis and cardiovascular risk and to assess the efficacy of therapy in a number of different heart diseases in which LVH is present.

Hypothalamo-adenohypophyseal-thyroid interrelationships in the chick embryo. IV. Immunocytochemical demonstration of TSH in the hypophyseal pars distalis.

The cells that synthesize thyroid-stimulating hormone (TSH) in the pars distalis of the chick embryo were identified immunocytochemically (immunoperoxidase and immunofluorescence) using anti-bovine TSH-beta and anti-human TSH-beta sera. TSH cells are first demonstrable on Day 6.5 of incubation. By Day 11.5, when the two lobes (rostral and caudal) of the pars distalis are easily recognized, TSH cells are confined exclusively to the rostral lobe. TSH cells identified by means of immunofluorescence were stained with the periodic acid-Schiff component of the performic acid-Alcian blue periodic acid-Schiff's Orange G stain. Immunoreactive TSH cells in the pares distales of Day 13.5 chick embryos, injected at 5.5 days of incubation with thiourea, were more intensively stained than their normal counterparts. The marked change in immunocytochemically demonstrable TSH on Day 11.5 corresponds with physiological and morphological events occurring within the hypothalamus, adenohypophysis, and the thyroid gland of the developing chick during this midincubational (midgestational) period. The data suggest that not only is hypophyseal TSH present in greater quantities after Day 10.5, but that adenohypophyseal synthesis and secretion of TSH may be stimulated by another factor (hypothalamic TRH) at this time, signaling functional maturation of the hypothalamo-adenohypophyseal-thyroid axis.

Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.