Unprincipled QALYs: a response to Harris.
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Biomedical subjects
Publications and source records attributed to J Cubbon.
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This paper presents a case for allocating health care resources so as to maximise Quality Adjusted Life Years (QALYs). Throughout parallels are drawn with the grounds for adopting utilitarianism. QALYs are desirable because they are essential for human flourishing and goal-attainment. In conditions of scarcity the principle of QALY maximisation may involve unequal treatment of different groups of people; and it is argued that this is not objectionable. Doctors in their dealings with patients should not be continually consulting the principle (though it can sometimes be useful); instead by following existing ethical codes more QALYs will be produced overall. In the formulation of policy, however, the principle should be applied in a thoroughgoing way and, if it is, it will not have some of the counterintuitive consequences it may have in interpersonal situations.
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The hemodynamic effects of dilevalol, a nonselective beta-adrenergic blocking agent with vasodilating properties, were evaluated in 34 hypertensive patients and compared with those of the "cardioselective" beta blockers atenolol and metoprolol in 21 patients. Hemodynamic measurements were obtained at baseline, after acute treatment (first dose) with dilevalol (400 mg) and atenolol (50 mg) or metoprolol (100 mg), and again after subchronic treatment with these agents. After both acute and subchronic treatment (mean daily dose 1,042 mg), dilevalol significantly reduced mean arterial pressure (MAP, p less than 0.0001), by significantly reducing systemic vascular resistance index (SVRI, p less than 0.001), and by not significantly altering cardiac index (CI). In contrast, atenolol and metoprolol significantly reduced MAP (p less than 0.002) by significantly reducing CI (p less than 0.0001), with a concomitant increase in SVRI (p less than 0.007). Heart rate (HR) was reduced significantly less (p less than 0.006) with dilevalol than with the cardioselective agents. Correlation of the decrease in MAP with other hemodynamic parameters revealed that the effects on MAP of acute treatment with the cardioselective drugs are related to a decrease in HR (r = 0.63, p = 0.002), whereas those of subchronic treatment are correlated to a decrease in CI (r = 0.59, p = 0.01). The decrease in MAP after acute and subchronic dilevalol treatment is correlated primarily with SVRI (r = 0.46 to 0.49, p less than 0.01) and only secondarily with HR (r = 0.34, p less than 0.05). Therefore, the main mechanism of antihypertensive action for dilevalol is vasodilation, in contrast to the cardioselective agents, which is beta blockade.
Dilevalol is a new antihypertensive agent that is both a vasodilator, through its beta 2-agonist action, and a nonselective beta antagonist. Two multicenter, double-blind studies were performed: study 1 compared dilevalol administered once-daily with either dilevalol or propranolol every 12 hours; study 2 compared dilevalol administered once daily with placebo. Both studies had a placebo run-in period to establish that the baseline supine diastolic blood pressures were consistent in the mild to moderate severity range (95 to 115 mm Hg) at 2 consecutive visits for study 1 and in the mild severity range (95 to 105 mm Hg) in study 2. Patients then were randomized to the double-blind titration phase, during which doses were titrated over a 9-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg and a decrease from baseline of greater than or equal to 10 mm Hg. Patients were then maintained on a fixed dose for 2 months (study 1) or for 1 month (study 2). Dilevalol given once daily was as effective in reducing supine diastolic blood pressure as dilevalol every 12 hours and propranolol every 12 hours (study 1) and was superior to placebo (p less than 0.001) (study 2). In both studies, dilevalol given once daily was effective and well tolerated. The side-effect profile of dilevalol was similar to that of placebo and different from that of propranolol. Treatment with dilevalol resulted in significantly less fatigue (p less than 0.05), bradycardia (less than 50 beats/minute) and mental depression than with propranolol, but significantly (p less than 0.05) more diarrhea/loose stools.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic and left ventricular function parameters were measured in patients with mild to moderate hypertension and compromised left ventricular function who were given dilevalol, an antihypertensive agent with selective beta 2-agonism and nonselective beta-antagonist activity. After a 2- to 3-week placebo washout period, 9 patients were given dilevalol titrated upward from 100 to 600 mg twice daily over a 7-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg with a decrease of greater than or equal to 10 mm Hg from baseline. Multigated radionuclide ventriculography and systolic and diastolic time intervals were performed after the pretreatment placebo washout, at the end of 2 weeks' maintenance dosing, and after a 7- to 10-day post-treatment discontinuation and placebo washout period. At an average daily dose of dilevalol, 444 mg, heart rate at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. Systolic and diastolic blood pressures at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. At maximal exercise, changes in blood pressure and heart rate were significantly blunted (p less than 0.05) during treatment. Ejection fraction at rest increased significantly (p less than 0.01) during treatment, with no significant change occurring during exercise, and decreased during post-treatment placebo. Preejection period decreased significantly during treatment (p less than 0.005) and increased during post-treatment placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
The antihypertensive effects of oral dilevalol, a beta-blocking agent with vasodialating properties were compared with placebo in 128 mildly hypertensive patients (supine diastolic blood pressure 95 to 105 mm Hg) in a multicenter, double-blind, parallel group study. Following a 4-week placebo phase, 63 patients were randomly assigned to receive dilevalol and 65 to receive placebo. A titration phase followed during which the dose of dilevalol was increased every other week from 100 mg to 800 mg to achieve a supine diastolic blood pressure (SDBP) less than 90 mm Hg and decreased by 10 mm Hg or more from baseline. A matching number of placebo capsules for each dose level of dilevalol was dispensed for blinding purposes. Patients who had at least a 5 mm Hg reduction in SDBP entered a 1-month maintenance phase. Blood pressure and heart rate were measured weekly 20 to 24 hours after a dose. This study demonstrated that the minimally effective dose of dilevalol was 100 mg, which was shown to result in a significantly (P less than or equal to 0.05) greater reduction in systolic BP. A once-daily dose of 200 mg was superior to placebo in both systolic and diastolic BP effects (P less than 0.001 and less than 0.001, respectively), and this superiority was seen again at both the end of titration and the end of the study. The BP reduction was accompanied by a small (5 bpm) decrease in heart rate. The side effect profile of dilevalol was not different from placebo. Dilevalol appears to have no adverse effect on plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the safety of labetalol in the treatment of hypertension in patients with heart failure, sixteen hypertensive patients with a history of congestive heart failure and an ejection fraction at rest less than 45%, had measurements of ejection fraction and cardiac output by first pass radionuclide angiography at baseline, at the end of 2 weeks maintenance with labetalol (titrated to the effective antihypertensive dose of 200-1600 mg daily), and in the post-treatment placebo period. On labetalol, heart rate and blood pressure were significantly lower than placebo at rest and the ejection fraction was higher (30 vs 25%) (p less than 0.05). At maximal exercise on labetalol the heart rate and blood pressure were lower than at placebo maximal exercise (p less than 0.05) and the ejection fraction was higher (32 vs 27%) (p less than 0.01). Exercise tolerance was not changed by labetalol. No patient was discontinued from the study because of worsening heart failure. Dizziness was reported in 5 of 16 patients usually at one visit. Dyspnea that was reported in 4 of 16 patients improved with minor adjustments in digitalis or diuretic dose. In conclusion, labetalol reduces blood pressure in hypertensive patients with left ventricular dysfunction without reducing cardiac performance.
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