Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia.

BACKGROUND: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D(2) (PGD(2)). Laropiprant (LRPT), a PGD(2) receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet. METHODS AND RESULTS: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day; i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C; 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG; -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC; -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. CONCLUSION: Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g-->2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk.

Database Conference January 27-30, 2000, Washington D.C.--Do existing databases answer clinical questions about geriatric cardiovascular disease and stroke?

EXECUTIVE SUMMARY: Most randomized, controlled trials evaluating the effectiveness of pharmaceutical, surgical, and device interventions for the prevention and treatment of cardiovascular disease have excluded patients over 75 years of age. Consequently, the use of these therapies in the older population is based on extrapolation of safety and effectiveness data obtained from younger patients. However, there are many registries and observational databases that contain large amounts of data on patients 75 years of age and older, as well as on younger patients. Although conclusions from such data are limited, it is possible to define the characteristics of patients who did well and those who did poorly. The goal of this conference was to convene the principal investigators of these databases, and others in the field of geriatric cardiology, to address questions relating to the safety and effectiveness of treatment interventions for several cardiovascular conditions in the elderly. Seven committees discussed the following topics: (I) Risk Factor Modification in the Elderly; (II) Chronic Heart Failure; (III) Chronic Coronary Artery Disease: Role of Revascularization; (IV) Acute Myocardial Infarction; (V) Valve Surgery in the Elderly; (VI) Electrophysiology, Pacemaker, and Automatic Internal Cardioverter Defibrillators Databases; (VII) Carotid Endarterectomy in the Elderly. The chairs of these committees were asked to invite principal investigators of key databases in each of these areas to discuss and prepare a written statement concerning the available safety and efficacy data regarding interventions for these conditions and to identify and prioritize areas for future study. The ultimate goal is to stimulate further collaborative outcomes research in the elderly so as to place the treatment of cardiovascular disease on a more scientific basis.

Certain cardiac risk factors predict risk factor interventions and influence communication between physicians and patients.

We assessed predictors of cardiac risk factor testing and services and the degree of concordance among patients, physicians, and the medical records for these services, and found considerable variability among different risk factors. The data suggest that baseline risk factors influence communication and performance of interventions and that physicians appear to be underestimating the importance of treating multiple risk factors simultaneously.

A comparison of self-reported function assessed before and after depression treatment among depressed geriatric inpatients.

The purpose of this study was to determine whether self-perception of function among depressed, geriatric psychiatry inpatients improved as their depression resolved. Sixty-four older adults diagnosed with major depression were asked to evaluate their function upon admission to an inpatient psychiatry unit, and then again 3 months post-discharge. Subjects' caregivers also rated the patients' function at admission and 3 months after being discharged. Self-perceptions of function improved over time, while caregivers' perceptions remained stable, suggesting that patients' perceptions of function is in part influenced by their depression. Further, correlations between patient and caregiver perceptions of function were higher at 3 months post discharge (when patients were not depressed) than they were at admission. The implication is that self-perceptions of function are more accurate when not depressed.

Smoking by patients in a smoke-free hospital: prevalence, predictors, and implications.

BACKGROUND: No-smoking policies are now mandated in all U.S. hospitals. They require hospitalized smokers to abstain temporarily from tobacco. Little is known about patients' compliance with these policies or about their effects on patients' comfort and subsequent smoking behavior. Hospitalization in a smoke-free hospital might precipitate nicotine withdrawal in smokers, but it might also offer smokers an opportunity to stop smoking. METHODS: To assess the prevalence, predictors, and implications of smoking during hospitalization, we analyzed data from a cohort of 650 adult smokers who were admitted to an urban teaching hospital and participating in a smoking intervention trial. We measured nicotine withdrawal symptoms at study entry (24-48 h after admission) and patients' self-reports of smoking while hospitalized, compliance with the hospital no-smoking policy (smoking prohibited indoors but permitted outdoors), and smoking status 1 and 6 months after discharge. RESULTS: One-quarter of smokers admitted to a smoke-free hospital reported smoking during their hospital stay, although only 4% of smokers admitted violating policy by smoking indoors. Within 48 h of admission, 55% of smokers reported cigarette cravings and 29% of smokers reported difficulty refraining from smoking. Smokers with cigarette cravings were more likely to smoke while hospitalized (OR 3.6; 95% CI: 1.9-6.7). Those with nicotine withdrawal symptoms were more likely to violate the hospital no-smoking policy (OR 6.8; 95% CI: 5.3-8.3). Abstaining from tobacco use while hospitalized was a strong independent predictor of continued abstinence after discharge (OR 3.8; 95% CI: 1.4-10.3). CONCLUSIONS: Smoking by patients in a smoke-free hospital was common. Craving for cigarettes and symptoms consistent with nicotine withdrawal occurred frequently in hospitalized smokers and were associated with smoking during hospitalization, which was itself strongly linked with continuing to smoke after discharge. Pharmacologic treatment of cigarette cravings in hospitalized smokers could potentially improve patient comfort, increase compliance with hospital no-smoking policies, and promote smoking cessation after hospital discharge. This approach deserves further study.

Clinical goals and performance measures for cholesterol management in secondary prevention of coronary heart disease.

Guidelines from the National Cholesterol Education Program (NCEP) recommend reduction of low-density lipoprotein cholesterol (LDL-C) to 100 mg/dL (2.59 mmol/L) or less in patients with established coronary heart disease (CHD). However, the National Committee for Quality Assurance (NCQA) is implementing a new performance measure as part of the Health Plan Employer and Data Information Set (HEDIS) that appears to endorse a different target. The new HEDIS measure will require managed care organizations seeking NCQA accreditation to measure and report the percentage of patients who have had major CHD events who achieve LDL-C levels less than 130 mg/dL (3.36 mmol/L) between 60 and 365 days after discharge. These different LDL-C thresholds emphasize the difference between a clinical goal for the management of individual patients (< or =100 mg/dL) and a performance measure used to evaluate the care of a population of patients (<130 mg/dL). This article discusses the rationale for each threshold and explains the use of 2 different thresholds for these 2 purposes. Both the NCQA and NCEP expect that the new HEDIS measure will encourage managed care organizations to develop systems that improve secondary prevention of CHD.

The use of nicotine-replacement therapy by hospitalized smokers.

BACKGROUND: No-smoking policies are mandatory in U.S. hospitals. Consequently, smokers who are hospitalized must temporarily stop smoking. Nicotine-replacement therapy (NRT) could help hospitalized smokers relieve nicotine withdrawal symptoms, comply with no-smoking policies, and sustain tobacco abstinence after discharge. The extent of NRT use in the hospital setting is unknown. We describe the prevalence and patterns of NRT use in hospitalized smokers. DESIGN: Prospective observational study within a randomized smoking-intervention trial. SETTING/PARTICIPANTS: Six hundred fifty adult smokers admitted to the medical and surgical services of a large urban teaching hospital that prohibits smoking in all indoor areas. Follow-up was at 6 months. MAIN OUTCOME MEASURE: Inpatient pharmacy records of nicotine patch or gum use. RESULTS: Only 34 of 650 smokers (5.2%) received NRT during their hospital stay, including only 9.6% of smokers who reported difficulty refraining from smoking while hospitalized and 9.0% of hospitalized smokers with nicotine withdrawal. NRT was more likely to be prescribed to patients with nicotine withdrawal (OR 2.23; 95% CI: 1.01, 4.90), a higher daily cigarette consumption (OR 1.04; 95% CI: 1.01, 1.06), and a longer hospitalization (OR 1.05; 95% CI: 1.00, 1.10). NRT use was independent of a patient's intention to quit smoking after discharge and was not associated with smoking cessation 1 and 6 months after discharge. CONCLUSIONS: NRT was rarely used in this hospital, even among those who could have benefited from it to treat nicotine-withdrawal symptoms. When NRT was used, relief of nicotine withdrawal, rather than assistance with smoking cessation, appeared to be the primary goal. Greater use of NRT could benefit the estimated 6.5 million smokers who are hospitalized annually by reducing nicotine withdrawal, encouraging smoking cessation, and ensuring compliance with hospital no-smoking policies.

Cisapride in the treatment of visual hallucinations caused by vision loss: the Charles Bonnet syndrome.

The authors describe the use of cisapride (Propulsid), a potent 5-HT(3) antagonist, in the treatment of visual hallucinations in two patients with vision loss (the Charles Bonnet syndrome).

Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy.

OBJECTIVE: The authors tested the hypothesis that nortriptyline and interpersonal psychotherapy, alone and in combination, are superior to placebo in achieving remission of bereavement-related major depressive episodes. METHOD: Eighty subjects, aged 50 years and older, with major depressive episodes that began within 6 months before or 12 months after the loss of a spouse or significant other were randomly assigned to a 16-week doubleblind trial of one of four treatment conditions: nortriptyline plus interpersonal psychotherapy (N = 16), nortriptyline alone in a medication clinic (N = 25), placebo plus interpersonal psychotherapy (N = 17), or placebo alone in a medication clinic (N = 22). The protocol required that the acute-phase double-blind treatment be ended after 8 weeks if Hamilton depression scale ratings had not improved by 50%. Remission was defined as a 17-item Hamilton scale score of 7 or lower for 3 consecutive weeks. RESULTS: The rate of remission for nortriptyline plus interpersonal psychotherapy was 69% (N = 11); for medication clinic, nortriptyline, 56% (N = 14); for placebo plus interpersonal psychotherapy, 29% (N = 5); and for medication clinic, placebo, 45% (N = 10). In a generalized logit model, there was a significant effect of nortriptyline over placebo but no interpersonal psychotherapy effect and no nortriptyline-by-interpersonal psychotherapy interaction. Rates of all-cause attrition were lowest in the nortriptyline plus interpersonal psychotherapy group. CONCLUSIONS: Nortriptyline was superior to placebo in achieving remission of bereavement-related major depressive episodes. The combination of medication and psychotherapy was associated with the highest rate of treatment completion. These results support the use of pharmacologic treatment of major depressive episodes in the wake of a serious life stressor such as bereavement.