Baseline Characteristics Of Subjects Research Articles

Continuous Dose-Response Relationship of the LDL-Cholesterol–Lowering Effect of Phytosterol Intake

Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.

The Baseline Serum Lipoprotein Profile Is Related to Plant Stanol Induced Changes in Serum Lipoprotein Cholesterol and Triacylglycerol Concentrations

Objective: Baseline characteristics of subjects might be related to the effect of plant stanols on the serum lipoprotein profile. The aim of the study was to examine effects of subjects’ baseline characteristics (baseline serum concentrations of lipids and lipoproteins at the start of the study, lathosterol, campesterol and sitosterol; gender, age, BMI, smoking, use of oral contraceptives and menopause) on the effects of plant stanol esters on the serum lipoprotein profile. Methods: We used data of five studies performed at our Department. A random intercept model was used for statistical analysis, using serum lipid and lipoprotein concentrations after plant stanol ester consumption, as dependent variables. Results: After plant stanol ester consumption, higher baseline serum concentrations of total and LDL cholesterol resulted in larger absolute decreases in their respective serum concentrations. For the ratio of total to HDL cholesterol and triacylglycerol, higher baseline serum levels resulted in larger absolute and relative decreases in their serum levels. HDL cholesterol concentrations increased in subjects with low baseline concentrations and decreased in those with high baseline concentrations. Effects however were small. No relationships were observed with baseline serum cholesterol-standardized lathosterol and campesterol concentrations, although LDL cholesterol concentrations tended to decrease more at higher baseline sitosterol concentrations. No effects of other baseline characteristics were found. Conclusions: People with an unfavorable serum lipid and lipoprotein profile benefit even more of plant stanols than people with a more favorable profile.

Heart failure with preserved ejection fraction: Clinical characteristics of 4133 patients enrolled in the I‐PRESERVE trial

We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction - the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). 4133 patients with a mean age of 72 years (a third were 75 years or older) were randomised and 60% were women. The mean (SD) LVEF was 59 (9)% and almost 80% of patients were in NYHA Class III or IV. Approximately 80% of patients were also overweight or obese. Heart failure was reported by investigators to have a hypertensive aetiology in 64% of patients. Prior myocardial infarction was relatively uncommon (24%), as was coronary revascularisation (13%). Atrial fibrillation and diabetes each occurred in between a quarter and a third of patients. The following treatments were used at baseline: diuretic 83%, beta-blocker 59%, calcium channel blocker 40%, ACE inhibitor 25%, spironolactone 15% and digoxin 14%. Patients in I-PRESERVE are broadly representative of those seen in epidemiological studies and, because of this, the results of this trial should be generally applicable to "real world" patients with heart failure and preserved ejection fraction.

Long-Term Cost-Effectiveness Analysis of Nebivolol Compared with Standard Care in Elderly Patients with Heart Failure

The SENIORS trial demonstrated that nebivolol is effective in the treatment of heart failure in elderly patients (e.g. > or = 70 years). This analysis evaluates the cost effectiveness of nebivolol compared with standard treatment. An individual patient-simulation model based on a Markov modelling framework was developed to compare costs and outcomes for nebivolol and standard care in patients with heart failure starting treatment at the age of 70 years. Health states were defined by New York Heart Association (NYHA) class and death. At a given NYHA class and a given cycle, patients could die, be hospitalized for cardiovascular disease or remain stable. Risks for these events were derived from individual patient data from the SENIORS trial. The risk of each event in a given cycle was based on the subject's baseline characteristics and time in the current health state. The economic analysis was conducted from the UK NHS perspective with a lifetime horizon. The costs (euro; year 2006 values) considered were drug costs for nebivolol and other cardiac drugs, costs of GP visits, outpatient specialist visits and cardiovascular-related hospitalizations. Univariate and probabilistic sensitivity analysis was conducted. In the baseline analysis, the total cost per patient was euro6740 and euro9288, and QALYs were 5.194 and 5.843 for patients aged 70 years at the start of treatment for the standard treatment and nebivolol groups, respectively. The probabilistic sensitivity analysis provided an incremental cost-effectiveness ratio of euro3926 (95% CI 3731, 4159) per QALY. This analysis indicates that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care.

Evaluation of an Electronic Critical Drug Interaction Program Coupled with Active Pharmacist Intervention

Failure to detect significant drug interactions may result in adverse outcomes. While proper screening and management of drug interactions can prevent the majority of adverse events, studies indicate that current practice is suboptimal. In the last quarter of 2001, physicians and pharmacists in Kaiser Permanente Colorado, a group model health maintenance organization, developed an electronic critical drug interaction alert program (CDIX). Electronic screening was coupled with active intervention to prevent dispensing of critically interacting drug combinations. To assess the impact of CDIX on the co-dispensing of critically interacting drug combinations. A physician and team of outpatient pharmacists and clinical pharmacy staff developed a condensed list of critical drug interactions (8 drug combinations) to be included in the evaluation of CDIX. Monthly electronic outpatient pharmacy data were collected 20 months before and 37 months after CDIX implementation, with no lag period following implementation. Univariate analyses were completed to compare baseline subject characteristics of the pre- and post-CDIX groups using chi2 and Wilcoxon Rank Sum tests. Interrupted time series analysis was used to estimate changes in the rates of critical drug interactions. Three hundred sixty-seven instances of co-dispensing were observed in 348 subjects during the pre-CDIX period and 256 instances of co-dispensing were observed in 248 subjects during the post-CDIX period. Following CDIX implementation, the overall rate of co-dispensing dropped abruptly from 21.3 to 14.7 per 10,000 prescriptions, representing a relative decrease in co-dispensing of 31% from the month before CDIX implementation (p = 0.0125). Significant reductions in co-dispensing were noted for 7 of the 8 drug class combinations. Employing an intervention system that limits electronic alerts regarding drug interactions to those deemed critical but that also requires pharmacist intervention and collaboration with the prescriber decreases the number of critical drug interactions dispensed.

A Randomized Trial Comparing Continuous Subcutaneous Insulin Infusion of Insulin Aspart Versus Insulin Lispro in Children and Adolescents With Type 1 Diabetes

The safety and efficacy of insulin aspart continuous subcutaneous insulin infusion (CSII) was compared with that of insulin lispro CSII in children and adolescents with type 1 diabetes. Children and adolescents aged 4-18 years with diagnosed type 1 diabetes >or=1 year previously and treated with insulin analog in a CSII >or=3 months were randomly assigned 2:1 to 16 weeks of insulin aspart CSII (n = 198) or insulin lispro CSII (n = 100) in this open-label, parallel-group, multicenter study. Standard diabetes safety and efficacy parameters were assessed. Baseline demographics, subject characteristics, and diabetes history were similar between treatment groups. After 16 weeks of treatment, insulin aspart CSII was noninferior to insulin lispro CSII as measured by change in A1C from baseline (aspart, -0.15 +/- 0.05%; lispro, -0.05 +/- 0.07% [95% CI of the treatment difference -0.27 to 0.07]; P = 0.241). No significant differences between treatment groups were observed in fasting plasma glucose, hyperglycemia, and rates of hypoglycemic episodes. At week 16, 59.7% of subjects in the aspart group and 43.8% of subjects in the lispro groups achieved age-specific American Diabetes Association A1C goals (<8.5% for subjects aged <6 years; <8% for subjects aged 6-18 years) (P = 0.040, corrected for baseline). Daily insulin dose (units per kilogram) was significantly lower at week 16 for subjects treated with aspart compared with those treated with lispro (0.86 +/- 0.237 vs. 0.94 +/- 0.233, P = 0.018). Insulin aspart was as safe and effective as insulin lispro for use in a CSII in children and adolescents with type 1 diabetes.

Effect of Low Dose Antioxidant Vitamin and Trace Element Supplementation on the Urinary Concentrations of Thromboxane and Prostacyclin Metabolites

Objective: This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB2/2,3 dinor 6 keto PGF1α ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis.Methods: This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB2 and 2,3 dinor 6 keto PGF1α were measured.Results: Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB2/2,3 dinor 6 keto PGF1α ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB2/2,3 dinor 6 keto PGF1α ratio.Conclusions: These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.

Impact of Baseline Covariates on the Immunogenicity of a Quadrivalent (Types 6, 11, 16, and 18) Human Papillomavirus Virus‐Like‐Particle Vaccine

The quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like-particle vaccine was 95%-100% effective in preventing cervical and genital disease related to HPV-6, -11, -16, and -18. Vaccine efficacy is thought to be mediated by humoral immunity. Here, we analyze the effect of the baseline characteristics of subjects on vaccine-induced immune responses. Immunogenicity data from 12,343 subjects 9-26 years old randomized to quadrivalent HPV vaccine or placebo in phase 2/3 studies were analyzed. Covariates examined were day 1 HPV serostatus, age, race/ethnicity, region of residence, lactation status, hormonal contraceptive usage, smoking status, Pap test diagnosis, immunosuppressant or anti-inflammatory agent use, and number of sex partners. Anti-HPV responses were summarized as serum anti-HPV-6, -11, -16, or -18 geometric mean titers 1 month after dose 3. Age at vaccination initiation was inversely proportional to the vaccine-induced anti-HPV response. Vaccination of subpopulations of subjects who were seropositive at day 1 to a vaccine HPV type resulted in more robust anti-HPV responses to that type, compared with those in subjects who were seronegative at baseline. Anti-HPV responses were comparable among the remaining demographic subgroups. The immunogenicity of quadrivalent HPV vaccine was comparable among subjects with differing baseline characteristics. These data support vaccination with quadrivalent HPV vaccine across a broad range of baseline subject characteristics.

Effects of Aerobic Exercise on Postprandial Glucose in Glucose intolerant Subjects

Exercise is recommended for the treatment of all forms of glucose intolerance (i.e. impaired fasting glucose; impaired glucose tolerance; type 2 diabetes), yet little is known about the relationship between the timing of exercise and its effects on subsequent blood glucose (BG) levels throughout the day in glucose intolerance. PURPOSE: The purpose of the ongoing study is to examine the effects of early morning exercise on postprandial metabolism in glucose intolerant (n=4; f=3; m=1) and normglycemic (n=6; f=3; m=3) subjects. METHODS: Subjects were hospitalized in the General Clinical Research Center (GCRC) on two separate occasions for participation in exercise [E] and non-exercise [NE] protocols. The E protocol began at 0800 hours following an overnight fast. During the E protocol subjects walked on the treadmill for 30 minutes at 65% V0 Max. During the NE protocol, the exercise session was replaced by a 30 minute period of rest. Blood glucose levels were monitored for 18 hours following the exercise/rest sessions, using continuous glucose monitoring sensors. Patients remained in the GCRC following exercise/rest sessions; diet and physical activity were similar during each visit. RESULTS: The baseline characteristics of subjects (glucose intolerant vs. normoglycemic) were as follows: age (48±0.8 vs. 39.8± 11.1 years [mean and SD]); BMI(34.2±3.6vs. 36.5±2.6); % body fat (35.1±3.6 vs. 36.5±2.6); V02Max(23.1±10.8 vs. 28.3±3.6 ml/kg). Mean BG levels were calculated for the 3-hour postprandial period following breakfast, lunch and dinner and the entire 18 hours following exercise/rest. As expected, there were between group differences in all mean BG levels at these times (p <0.0005). Within the glucose intolerant group, exercise was associated with significant reductions in BG levels following breakfast and lunch when compared to rest (breakfast: 10.3 ± 4.2 vs. 8.5 ± 5.5 mmol/l [p <0.04]; [rest vs. exercise]; lunch (9.2 ± 3.6 vs. 7.3 ± 3.4 mmol/l [p<0.01]). In addition, there was an overall reduction in mean BG levels for the1 8-period following exercise (9.0 ±3.7 vs. 7.6 ±2.9 mmol/l [p<0.03]) within this group. CONCLUSION: An early morning bout of exercise is associated with reduced BG at least 18 hours following exercise as compared to rest in a small sample of glucose intolerant subjects. The use of glucose sensor technology will help researchers characterize glucose dynamics following different types of exercise. Study is funded by NIH grant R01NR007760-01A2, and supported by the GCRC at the University of Illinois at Chicago (NIH grant M01-RR-13987)

The Adolescent and Child Health Initiative to Encourage Vision Empowerment (ACHIEVE) Study Design and Baseline Data

The purpose of this study was to describe the baseline characteristics of subjects and methods for a multicenter, randomized clinical trial to compare the effects of contact lens wear and spectacle wear on children's self-perception. Eligible subjects are randomly assigned to wear glasses or contact lenses throughout the 3-year study. Self-perceptions are measured 1 month after randomization and every 6 months using the Self-Perception Profile for Children (SPPC). Children's satisfaction with spectacles and refractive error-related visual quality of life are also measured using surveys developed for the study. Visual acuity, cycloplegic autorefraction, corneal curvature, and axial dimensions are measured annually. Five clinical sites enrolled 484 subjects with a mean (+/- standard deviation [SD]) age of 10.4 +/- 1.1 years. Approximately three-fifths of the subjects are girls, 47.1% of the subjects are white, 21.5% are black, and 21.5% are Hispanic. The mean (+/- SD) cycloplegic spherical equivalent autorefraction of the right eye is -2.38 +/- 1.04 D, and the average (+/- SD) axial length of the right eye is 24.32 +/- 0.77 mm. The average (+/- SD) Global Self-Worth score on the SPPC is 3.20 +/- 0.62 on a scale from one (low perceived competence) to 4 (high perceived competence). The average (+/- SD) spectacle satisfaction is 59.1 +/- 26.6 on a scale from zero (no satisfaction) to 100 (perfect satisfaction). The average refractive error-related quality of life score is 63.5 +/- 12.8 on a scale from zero (poor quality of life) to 100 (excellent quality of life). Subjects enrolling in the ACHIEVE Study are an ethnically diverse group of young myopic children. Ocular characteristics of the sample are consistent with data presented in other randomized clinical trials evaluating treatments for myopic children. The data reported here represent the baseline data for a 3-year randomized clinical trial to investigate the effects of contact lens vs. spectacle wear on children's self-perceptions.

Use of heated humidification during nasal CPAP titration in obstructive sleep apnoea syndrome

Nasal symptoms associated with the use of nasal continuous positive airway pressure (nCPAP) in obstructive sleep apnoea (OSA) can adversely impact on patients' tolerance, acceptance and adherence to nCPAP therapy. Regular use of heated humidification is effective in alleviating these symptoms and improve patient comfort. In a randomised, parallel, double-blinded, controlled study, the present authors examined the use of heated humidification during a single night laboratory nCPAP titration in untreated OSA patients and its effect on nasal symptoms, nasal airway resistance (NAR), effective pressure and treatment tolerability and acceptance. Baseline characteristics of subjects (n=70) receiving placebo and humidification were (mean+/-sem): age 51.2+/-2.2 versus 50.6+/-1.6 yrs; body mass index 33.6+/-0.9 versus 35.2+/-0.9 kg.m-2; Epworth Sleepiness Scale 10.8+/-1.0 versus 11.3+/-0.7; and apnoea-hypopnoea index 43.5+/-4.6 versus 44.4+/-4.1 events.h-1. Total inspiratory NAR, before (0.36+/-0.09 (placebo) versus 0.33+/-0.09 kPa.L-1.s-1) and after nCPAP (0.47+/-0.11 versus 0.29+/-0.04 kPa.L-1.s-1) were not significantly different between the groups. No difference was found in the frequency and severity of nasopharyngeal symptoms, therapeutic pressure and subjective response to nCPAP. In conclusion, heated humidification during the initial nasal continuous positive airway pressure titration offers no additional benefit in nasal physiology, symptoms or subjective response to nasal continuous positive airway pressure, and, therefore, should not be routinely recommended.

In reply to Dr Anton Wernig

Thank you for the opportunity to respond to the comments made by Dr Anton Wernig regarding our recent publication.1 It is true that the subjects in our prospective study did not, as a group, achieve the same degree of independent walking capability as reported in Wernig's retrospective studies, and it is important to identify the possible reasons for this discrepancy. It is our opinion that two of the main contributors to this apparent difference in 'effectiveness' of the therapy are differences in baseline subject characteristics and differences in training parameters.

APACC, a French prospective study on aspirin efficacy in reducing colorectal adenoma recurrence: design and baseline findings

Colorectal cancer is the second most frequent cause of death from cancer in western countries. Many lines of evidence suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may offer chemoprevention against colorectal cancer. A multicentre, double-blind, randomized, controlled trial is underway to determine the efficacy of regular aspirin intake (160 or 300 mg/day) in reducing colorectal adenoma recurrence. We now report the baseline characteristics of subjects enrolled into the trial. A total of 618 polyps were excised from 274 patients at the baseline colonoscopy. Men had on average (+/-SD) 2.5 +/- 1.8 polyps per subject and women had 1.7 +/- 1.2. Ninety-one (33.7%) had three or more adenomas and 183 (67.8%) had more than one adenoma measuring 10 mm or more in diameter. The mean (+/-SD) age of the subjects was 57.7 (+/- 9.4) years. Sixty-seven (24.9%) reported that they had previously had adenoma(s), 95 (35.2%) reported a family history of colorectal cancer and 41 (15.2%) a family history of colorectal adenomas. All subjects will undergo a one-year clearance colonoscopy by February 2001. Clinical, molecular biological and dietary data will enable us to investigate other factors influencing the recurrence of adenomas in this group of high-risk subjects.

Systematic review concerning the age of introduction of complementary foods to the healthy full-term infant

To evaluate existing data from published studies investigating outcomes (growth, nutritional status and morbidity) in relation to the age of introduction of complementary foods to the healthy full-term infant. To assess the methodological quality of current scientific evidence on which infant feeding recommendations are based. A database was created following a search of electronic databases MEDLINE and BIDS, a handsearch of relevant journals and consultation with international experts in infant feeding practices. The search was conducted during a 6-month period and encompassed the years 1982-1998. Randomised/non-randomised controlled trials and cohort studies investigating the relationship to the health of full-term infants of the introduction of complementary foods to childhood health. Assessment of studies for inclusion and their compliance with methodological criteria was undertaken independently by two reviewers and discrepancies were resolved by discussion. From over 400 published papers identified, 33 met specific inclusion criteria. Significant differences in baseline characteristics of subjects in included studies meant that data were not amenable to meta-analysis. The consensus of the authors was that, of the 33 included publications, 13 contained data supporting the current WHO recommendations which attempt to accommodate all infants, including those whose nutritional requirements are not met by exclusive breast-feeding for 6 months. An equal number contained data that would support a recommendation for delaying the introduction of complementary foods until 6 months of age within the study population. The remaining seven were unable to provide evidence to support a change from the current WHO infant feeding recommendations which state that 'infants should be fed exclusively on breast milk from birth to 4-6 months of age'. None of the studies met all the methodological criteria. This review has shown that there is a lack of clear evidence to either support or refute a change to the current recommendations for the age of introduction of complementary foods to the breast milk or formula fed infant. Whilst exclusive breast feeding for the first 6 months of life can support growth and development in some infants, sub-groups have been identified within certain populations who may require complementary feeding prior to this age.

Energy Balance in Women With Breast During Adjuvant Treatment

Objective To compare weight, body composition, and major determinants of energy balance of women treated with adjuvant chemotherapy (n=8) using Adriamycin and cyclophosphamide (AC), or radiation therapy (n=10). Design The study used a nonrandomized prospective design. Pretreatment and posttreatment measurements, obtained at baseline and 12 weeks, respectively, included weight, body composition (determined using dual-energy x-ray absorptiometry), energy intake (determined using 3-day food records), resting energy expenditure (determined in indirect calorimetry), and physical activity (determined using 3-day physical activity records). Poststudy follow-up weights were obtained for 13 women. Subjects/setting Eighteen premenopausal women with breast cancer in the early stage, recruited from outpatient clinics, participated in and completed the study. Statistical analyses performed Unpaired Student t tests or χ 2 tests were used to test for differences in baseline subject characteristics, and repeated measures analysis of variance was used to compare groups before and after treatment. Results Body weight was unchanged in both treatment groups during the study, although poststudy follow-up weights (n=13) suggested a tendency for weight gain in both groups. Significant changes in body composition for both groups included a mean loss of 0.8 kg total lean body mass (LBM), a mean loss of 0.4 kg LBM in the leg region, and a mean 1.3% increase in percent body fat, from 40.0% to 41.3%. Overall, no between-group differences were observed in any factors associated with energy balance. Applications In this short-term study, AC chemotherapy using fewer antineoplastic agents and number of treatments than most chemotherapy protocols for breast cancer, did not result in weight gain during treatment. Regardless of weight gain, changes in body composition may occur in women with breast cancer during or after treatment. These potential changes have important implications for preventive nutrition counseling. J Am Diet Assoc. 1999;99:1222–1227.

Raloxifene effects on vasomotor and other climacteric symptoms in postmenopausal women

Introduction and Objectives: Raloxifene, a novel selective estrogen receptor modulator (SERM), is under investigation for the prevention of osteoporosis in postmenopausal women. Like traditional estrogen replacement therapy, raloxifene has beneficial effects on bone and on serum lipids whereas, in contrast to estrogen’s adverse effects in the breast and uterus, raloxifene is an estrogen antagonist in the breast and is nonstimulatory in the uterus. This study examines the effects of raloxifene 60 mg/day compared with placebo on: 1) the incidence of vasomotor symptoms: hot flashes (flushing) and sweating (including night sweats), 2) the severity and time course of hot flashes, and 3) the relation of hot flashes to baseline subject characteristics and study discontinuations. Additionally, the study explores the effects of raloxifene 60 mg/day compared with placebo on other climacteric symptoms that affect the quality of life of postmenopausal women, such as depression, insomnia, mood lability and genitourinary complaints. Methods: Integrated data from five randomized, placebo-controlled studies involving 1,165 healthy, postmenopausal women, with up to 30 months of study drug exposure, were analyzed. The incidence and severity of hot flashes and other climacteric symptoms were compared in patients treated with placebo or raloxifene (60 mg/day) via open-ended, non-directed subject self-assessment questionnaires. Data were analyzed for subgroup-by-therapy interactions using many baseline subject characteristics such as age, body mass index, smoking, alcohol, and years post-menopause, as well as preexisting conditions such as hot flashes, sweating, insomnia, depression, and history of hysterectomy. The overall incidence of other climacteric symptoms were reported as adverse events. Results: The increase in overall incidence of hot flashes in raloxifene-treated (24.6%) and placebo-treated (18.3%) subjects was modest, but statistically significant. However, this difference was significant only during the first 6 months of therapy, raloxifene (20.1%) compared with placebo (14.4%). After 6 months of treatment, there was no statistically significant difference in the incidence of hot flashes between the two treatment groups. The majority of hot flashes in raloxifene-treated subjects were subject-assessed as “mild-to-moderate” in severity (89%). The incidence of hot flashes reported as “severe” did not differ significantly in raloxifene- or placebo-treated subjects. Subgroup analyses revealed the overall incidence of hot flashes to be highest for both raloxifene and placebo-treated subjects, in younger (age < 55 years) women ( P = .004), in women who had previously experienced hot flashes ( P = .031), and in women having had hysterectomies ( P < .001). Within each of these subgroups, there was no statistical difference in the incidence of hot flashes between the raloxifene and placebo groups. Between the two treatment groups, there was no difference in the overall incidence of subject discontinuations from study due to hot flashes. The occurrence of the other common vasomotor symptom, sweating (which includes night sweats), was not statistically different for the raloxifene- or placebo-treated subjects. Genitourinary complaints are often symptoms related to vaginal dryness, such as dyspareunia and decreased libido, as well as other symptoms of vaginitis and leukorrhea. No statistically significant differences occurred for raloxifene- or placebo-treated subjects in reports of these genitourinary symptoms. Similarly, for the other common climacteric symptoms; depression, insomnia, and mood lability, no significant differences in incidence between the raloxifene and placebo treatment groups were observed. Conclusions: Raloxifene (60 mg/day) treatment modestly increased the incidence of hot flashes compared with placebo, however, this difference was only statistically significant during the first 6 months of treatment. There were no differences in the severity of hot flashes between treatment groups, and this symptom did not adversely affect subjects’ study participation. In both the raloxifene and placebo treatment groups, young postmenopausal women (age < 55), those with baseline hot flashes, and those with histories of hysterectomy were most likely to experience hot flashes. Raloxifene therapy did not affect the occurrence of other climacteric symptoms commonly affecting the quality of life of women after menopause.

Reaching Midlife and Older Smokers: Tailored Interventions for Routine Medical Care

Background.Although older adults can achieve significant health benefits from smoking cessation, few programs have specifically targeted this population. This study tested the effectiveness of an office-based smoking cessation program tailored to midlife and older smokers.Methods.This paper describes a randomized controlled trial comparing usual care with physician-delivered brief quit-smoking advice and counseling for midlife and older smokers (ages 50–74). Outpatient medical practices assigned to the Immediate Intervention (experimental) condition were trained to deliver brief quit-smoking advice and counseling. Delayed Intervention (control) practices followed usual care procedures. Thirty-nine practices accruing five or more patients per practice were included in the analyses.Results.Using a conservative measure of quitting, self-reported quit rates at 6-month follow-up were 15.41% for the Immediate Intervention group versus 8.16% of subjects in the Delayed Intervention group (P< 0.005). Baseline subject (N= 659) characteristics related to 6-month abstinence included number of previous quit attempts, quitting for 24 hr in the past year, desire to quit, confidence in quitting, perceived health benefits, and lower nicotine dependence.Conclusions.Smoking abstinence was significantly increased by training physicians and key office and clinical staff to intervene with older smokers. Brief interventions tailored to this age cohort can be successfully and efficaciously integrated into routine care.

Baseline characteristics of subjects in the lipoprotein and coronary atherosclerosis study (LCAS) with fluvastatin

A total of 429 subjects (79 women and 350 men), aged 35–75 years, have been enrolled in a randomized clinical trial of fluvastatin therapy for hypercholesterolemia. The progression and regression of atherosclerotic lesions will be assessed by quantitative angiography and positron emission tomography (PET) after 2.5 years of treatment. Patients were included in the trial if they had angiographically documented lesions that occluded 30–75% of the diameter of a major coronary vessel. Of the 429 subjects, 99 were also studied by PET at rest and during static exercise of sustained handgrip combined with administration of dipyridamole. All subjects were instructed in an American Heart Association/ National Cholesterol Education Program (AHA/ NCEP) Step I or Step II diet. Of the total, 107 subjects (25%) had low density lipoprotein cholesterol (LDL-C) ≥160 mg/dL and were given cholestyramine, 8 g/day. All subjects were randomized to placebo or fluvastatin, the newest 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor to be introduced into the U.S. market. Fluvastatin is entirely synthetic and is similar in efficacy to the other available HMGCoA reductase inhibitors. Its pharmaceutical profile (i.e., low systemic exposure) makes fluvastatin a good candidate for use in combination lipid-lowering therapy. The majority of subjects were recruited through a community campaign and the remainder through cardiac catheterization laboratories and the medical records of hospitals in the Texas Medical Center. Approximately 8,500 prospects from the community campaign were screened and 272 were randomized, a conversion rate of approximately 3%. Approximately 42,000 prospects from hospital sources were screened and 157 were randomized, a conversion rate of approximately 0.4%. The number of qualified lesions of a major coronary artery (30–75% diameter stenosis) in each subject averaged 2.8 (mode, 2; range, 1–9), and 247 subjects (48% of the women and 60% of the men) had at least 1 lesion of moderate severity (50–75% diameter stenosis). Of the subjects, 196 (49% of the men and 30% of the women) had undergone percutaneous transluminal coronary angioplasty or had 100% occlusion of one coronary artery, or had both in the same major coronary artery. Men had more severe disease according to history of angioplasty or presence of 100% occlusion in 1 major coronary artery. This relation was seen best in subjects who were not eligible for cholestyramine treatment. No association was seen between sex and number of qualified lesions. Moreover, there were no differences in the severity of coronary artery disease in relation to age. Male sex was related to amount of obstruction rather than number of qualified lesions.