Biomedical subjects

M M Brooks

Publications and source records attributed to M M Brooks.

At least 37 records · Page 2Linked to original sources

PubMed1997

Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization Investigation (BARI) Investigators.

BACKGROUND: Randomized trials comparing coronary angioplasty with bypass surgery in patients with multivessel coronary disease have shown no significant differences in overall rates of death and myocardial infarction. We compared quality of life, employment, and medical care costs during five years of follow-up among patients treated with angioplasty or bypass surgery. METHODS: A total of 934 of the 1829 patients enrolled in the randomized Bypass Angioplasty Revascularization Investigation participated in this study. Detailed data on quality of life were collected annually, and economic data were collected quarterly. RESULTS: During the first three years of follow-up, functional-status scores on the Duke Activity Status Index, which measures the ability to perform common activities of daily living, improved more in patients assigned to surgery than in those assigned to angioplasty (P<0.05). Other measures of quality of life improved equally in both groups throughout the follow-up period. Patients in the angioplasty group returned to work five weeks sooner than did patients in the surgery group (P<0.001). The initial mean cost of angioplasty was 65 percent that of surgery ($21,113 vs. $32,347, P<0.001), but after five years the total medical cost of angioplasty was 95 percent that of surgery ($56,225 vs. $58,889), a difference of $2,664 (P = 0.047). The five-year cost of angioplasty was significantly lower than that of surgery among patients with two-vessel disease ($52,930 vs. $58,498, P<0.05), but not among patients with three-vessel disease ($60,918 vs. $59,430). After five years of follow-up, surgery had an overall cost-effectiveness ratio of $26,117 per year of life added, but unacceptable ratios of $100,000 or more per year of life added could not be excluded (P=0.13). Surgery appeared particularly cost effective in treating diabetic patients because of their significantly improved survival. CONCLUSIONS: In patients with multivessel coronary disease, coronary-artery bypass surgery is associated with a better quality of life for three years than coronary angioplasty, after the initial morbidity caused by the procedure. Coronary angioplasty has a lower five-year cost than bypass surgery only in patients with two-vessel coronary disease.

Angioplasty, Balloon, Coronary↗

PubMed1997

The substrate specificity of the enzyme endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumonia.

The substrate specificity of the enzyme endo-alpha-N-acetyl-D-galactosaminidase from Diplococcus pneumonia was re-examined using bovine submaxillary mucin and remodelled antifreeze glycoprotein as substrates. Incubation with desialylated bovine submaxillary mucin, which contains six O-linked core types, indicated that the disaccharide Gal beta1-3GalNAc, which is present in very small amount, was the only glycan released, while the disaccharide GlcNAc beta1-3GalNAc, which is the major structure present, and other disaccharides, were not released. To test whether the core disaccharide Gal beta1-3GalNAc with sialic acid linked alpha2-3 to the Gal or linked alpha2-6 to the GalNAc was released, the enzyme was incubated with remodelled antifreeze glycoprotein containing (1) [3H]NeuAc alpha2-3Gal beta1-3GalNAc and (2) Gal beta1-3[[14C]NeuAc alpha2-6]GalNAc as substrates. No NeuAc-containing trisaccharide was released. These results serve to clarify the doubts of many researchers regarding the activity of this enzyme on some newly-described core types and on sialylated substrates.

Animals↗

PubMed1997

Gender differences in health-related quality of life among postmyocardial infarction patients: brief report. CAST Investigators. Cardiac Arrhythmia Suppression Trials.

Heart disease is the leading cause of death among women in the United States. The prognosis for heart disease is worse for women than for men. Also, although women are less likely than men to initially present with a myocardial infarction (MI), they are more likely to die following an MI. A number of factors have been identified that partially account for the gender difference in post-MI morbidity and mortality. However, limited data are available on the sex differences in clinical, psychosocial, and demographic factors that may combine to explain the poorer prognosis for women following an acute MI. The Cardiac Arrhythmia Suppression Trials collected detailed demographic, clinical, and psychosocial data on 2,043 men and 448 women following acute MIs. Analyses indicate that women had a worse clinical, socioeconomic, and psychosocial profile than did men. In addition, significant differences in psychosocial profiles persisted after controlling for demographic and clinical data, suggesting that women presenting with MIs have a cluster of complex factors that put them at high risk for morbidity and mortality following an MI. Future longitudinal studies that include adequate numbers of women as well as reliable assessments of both clinical and psychological variables are needed to better understand the factors that influence the poor prognosis for women with coronary heart disease.

Adult↗

PubMed1996

Chronobiology of acute myocardial infarction: cardiac arrhythmia suppression trial (CAST) experience.

The onset of acute myocardial infarction (AMI) has been shown to occur in a reproducible pattern with a peak in mid-morning and a secondary peak in late afternoon and early evening. More detailed information on the timing of this catastrophic event may provide important pathophysiologic information. Using the database from the Holter Registry of the Cardiac Arrhythmia Suppression Trial (CAST) (n = 22,516), the day of the week, the month, and season of the onset of AMI was obtained and correlated with demographic characteristics. The pattern of the day of onset for the entire population was significantly nonuniform (p <0.0001) with a Monday peak and a weekend nadir. This pattern was observed in most of the examined subgroups. Analysis of seasonal data revealed nonuniform distribution (p <0.001) with a peak in winter and autumn. We conclude that AMI is not a random event but occurs in definite patterns related to the day of the week and the season of the year. These patterns were observed in a wide variety of patient subgroups and appear related to climate, occupation, and other factors.

Arrhythmias, Cardiac↗

PubMed1996

Logrank, play the winner, power and ethics.

We show by simulation and numerical integration techniques that power is largely unaffected by play the winner strategies in a typical chronic disease mortality trial utilizing the logrank test. This raises the issue of the ethics of equal allocation in such a setting.

Anti-Arrhythmia Agents↗

PubMed1996

Adherence and arrhythmic mortality in the cardiac arrhythmia suppression trial (CAST).

Patient adherence to therapy is essential to assess treatment efficacy, particularly in clinical trials. Active treatment usually is expected to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medication and overall concern for health, explains the improved survival of more adherent patients in both active and placebo medication groups of several clinical trials. The Cardiac Arrhythmia Suppression Trial (CAST), a placebo-controlled double-blind clinical trial of post-myocardial infarction (MI) patients with asymptomatic ventricular arrhythmias, in which active medication (encainide or flecainide) led to increased mortality, provided an opportunity to examine the relationship of adherence to survival from a different perspective. We consider whether adherence to active treatment was related to arrhythmic mortality and whether a healthy adherer effect might counteract the effect of treatment on mortality among patients taking active medication. Adherence (average pill count) at the first follow-up visit did not differ in the active treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional hazard regression model, medication adherence predicted arrhythmic mortality among the active (P < 0.0062) but not the placebo medication group. The effect of adherence on arrhythmic mortality was significant beyond the effects of ejection fraction, race, spouse, smoking status, diuretic medication, and history of MI. A 10% increase in adherence led to more than a threefold increase of risk of arrhythmic death. The design of the CAST, which included a titration phase, may have tended to select relatively adherent patients since only those whose arrhythmias were suppressed with active medication were randomized into the trial. The data do not support a strong healthy adherer effect in the CAST. There was no evidence in this study that a healthy adherer effect counterbalanced the effect of the active medication.

Anti-Arrhythmia Agents↗

PubMed1995

Smoking cessation and arrhythmic death: the CAST experience. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators.

OBJECTIVES: This study was performed to assess the effect of cigarette smoking cessation on overall mortality and the incidence of arrhythmic death in the population of the Cardiac Arrhythmia Suppression Trial (CAST). BACKGROUND: Cigarette smoking is a known risk factor for sudden cardiac death. Some of the adverse effects of smoking have been shown to dissipate with smoking cessation, but the time frame over which these changes occur and the population that stands to benefit have not been well delineated. CAST was a multicenter double-blind placebo-controlled study to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs in patients with left ventricular dysfunction after acute myocardial infarction would reduce the incidence of arrhythmic death. METHODS: Of 2,752 patients randomized to blinded therapy, 1,026 were smoking at the time of their baseline examination and completed a 4-month follow-up visit. Of these, 517 stopped smoking by the time of this visit ("quitters") and 509 continued to smoke ("smokers"). RESULTS: Over a mean follow-up period of slightly < 16 months, there were 17 arrhythmic deaths and 32 total deaths among the quitters versus 30 and 45, respectively, among the smokers; these differences were of marginal statistical significance. Most of the fatal events occurred in a group at high risk of ongoing ischemia: the 558 patients who did not have thrombolysis or undergo revascularization after their qualifying myocardial infarction. In this high risk cohort, smoking cessation greatly reduced the incidence of arrhythmic death and was associated with a statistically significant benefit in survival. CONCLUSIONS: Smoking cessation was accompanied by a marked reduction in arrhythmic death and overall mortality that achieved statistical significance in a high risk cohort. These data imply that smoking cessation is important in risk factor reduction in patients with advanced ischemic heart disease.

Aged↗

PubMed1995

A simulation study used to design the sequential monitoring plan for a clinical trial.

In designing a sequential monitoring plan for the AVID (Antiarrhythmics Versus Implantable Defibrillators) study, a multi-centred clinical trial, we completed a simulation study to help ourselves and the Data Safety Monitoring Board understand the implications of various monitoring plans. In particular, we compared three test statistics and three use functions. Simulation was based on approximate trial parameters and two plausible but distinct alternative hypotheses. The power to detect a difference between the two treatment arms was computed as a function of time. The simulated results illuminate several of the important statistical and ethical issues involved in selecting a sequential monitoring plan and illustrate how one can use simulations to design a clinical trial.

Amiodarone↗

PubMed1995

Effect of age on postmyocardial infarction ventricular arrhythmias (Holter Registry data from CAST I and CAST II). Cardiovascular Arrhythmia Suppression Trials.

Holter data from the 17,609 postmyocardial infarction patients in the CAST Registry were analyzed to study the effect of age on VPC and VT incidence and frequency. Multivariable analysis demonstrated that age is an important independent predictor of increased ventricular ectopy, with the median rate of VPCs/hour increasing from 0.4 (patients aged < 50 years) to 4.0 (patients aged 75 to 80 years), and the prevalence of VT increasing from 7.3% (patients aged < 50 years) to 15.3% (patients aged 75 to 80 years).

Age Factors↗

PubMed1995

Association between ease of suppression of ventricular arrhythmia and survival.

BACKGROUND: We tested the hypothesis that patients whose ventricular arrhythmias are easy to suppress have a lower rate of arrhythmic death, defined as arrhythmic death and nonfatal cardiac arrest, the primary end point in the Cardiac Arrhythmia Suppression Trials (CAST-I and CAST-II), than patients whose ventricular arrhythmias are hard to suppress. In addition, we evaluated the association between ease of suppression of ventricular arrhythmias and mortality of all causes. METHODS AND RESULTS: CAST-I investigated the effect on arrhythmic death of ventricular premature depolarization (VPD) suppression achieved by three drugs, encainide, flecainide, and moricizine, at two different dose levels; CAST-II investigated the same effect, using moricizine alone at three dose levels. If suppression was achieved, patients were randomized to the effective active drug or corresponding placebo. To examine the independence of easily suppressed ventricular arrhythmias as a predictor of arrhythmic death, we adjusted statistically for other variables that were related both to ease of suppression and arrhythmic death. Patients with ventricular arrhythmias (n = 1778) that were easy to suppress had fewer arrhythmic deaths during follow-up than those with ventricular arrhythmias that were hard to suppress (n = 1173) (relative risk, .59; P = .003). Patients whose VPDs were easily suppressed were older and had a lower frequency of prior history of heart failure and myocardial infarction. They also had a higher incidence of anterior myocardial infarction, VPD frequency, and average ejection fraction. After adjusting for these variables, we found that easily suppressed ventricular arrhythmias were still significant predictors of arrhythmic death (relative risk, .66; P = .013). CONCLUSIONS: This study shows that the ease of VPD suppression identifies a subgroup of postmyocardial infarction patients who have low risk of arrhythmic death.

Aged↗

PubMed1994

Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial. CAST Investigators.

The Cardiac Arrhythmia Suppression Trial (CAST) showed antiarrhythmic drug suppression of asymptomatic or mildly symptomatic ventricular arrhythmias in survivors of myocardial infarction to be harmful. This study retrospectively searched the CAST results for evidence of mortality and morbidity reduction in patients receiving optional beta-blocker therapy. All enrolled (n = 2,611) and suppressed main study (n = 1,735) CAST patients with an ejection fraction of < or = 40% were examined using univariate analysis, Kaplan-Meier curves, and a Cox proportional-hazards multivariate analysis with respect to optional beta-blocker therapy prescribed at baseline. CAST patients receiving beta-blocker therapy had significantly enhanced survival at 30 days, and at 1 and 2 years of follow-up against all-cause and arrhythmic death or nonfatal cardiac arrest. Multivariate analysis showed beta-blocker therapy to be independently associated with a one-third reduction in arrhythmic death or cardiac arrest (p = 0.036). In CAST patients with a history of congestive heart failure, beta-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p = 0.015). This study supports the secondary preventive benefit of beta-blocker therapy in high-risk post-myocardial infarction patients, and calls attention to the possible preventive benefit of beta-blocker therapy against proarrhythmic events experienced in the CAST.

Adrenergic beta-Antagonists↗

PubMed1994

Prognostic significance of left ventricular aneurysm in the Cardiac Arrhythmia Suppression Trial (CAST) population.

Left ventricular aneurysm has been associated with increased mortality rates. The Cardiac Arrhythmia Suppression Trial (CAST) database was used prospectively to assess (1) the prognostic significance of left ventricular (LV) aneurysm after myocardial infarction on mortality rates and (2) the relation of LV aneurysm to ventricular arrhythmias and their suppressibility. All patients in the CAST study were enrolled after myocardial infarction. They had > or = 6 ventricular premature depolarizations (VPDs) per hour and ejection fraction < or = 55%; they were enrolled in the study an average of 96 days after the index myocardial infarction. Of 2494 patients with wall motion data, 164 had LV aneurysm, 600 had only dyskinesis, 913 had only akinesis, and 817 had none of these. Radionuclide scan was used in 39%, two-dimensional echocardiography in 30%, and LV angiogram in 31%. Baseline VPDs and nonsustained ventricular tachycardia were similar in all groups. LV aneurysm patients were more frequently eliminated during open-label titration. The incidence of sustained VT during follow-up was only 2.8% for aneurysm patients, a rate that was similar to the other groups. Patients with LV aneurysm had significantly lower survival rates (82% vs 91%) at 16 months after study entry than those without these wall motion abnormalities (p < 0.005). When survival rates were adjusted for ejection fraction there was still a moderately large hazard ratio (1.34) of LV aneurysm that was not statistically significant (p = 0.18). We conclude that (1) the presence of LV aneurysm does not independently worsen prognosis, and (2) older concepts of LV aneurysm and ventricular arrhythmias must be reevaluated.

Arrhythmias, Cardiac↗

PubMed1994

Moricizine and quality of life in the Cardiac Arrhythmia Suppression Trial II (CAST II).

The Cardiac Arrhythmia Suppression Trial II (CAST II) was a double-masked placebo-controlled randomized trial that compared the survival effects of moricizine to placebo in postmyocardial infarction arrhythmia patients. The quality-of-life outcome measures were designed prospectively for CAST and were previously shown to have high reliability and clinical discriminative validity. The CAST quality-of-life instrument detected significant differences between moricizine and placebo. In particular, moricizine was most strongly associated with inferior social activity and satisfaction scores (p = .014) and lower scores for overall contentment with life (p = .007). Moreover, the quality-of-life measures improved significantly for both the moricizine and placebo treatment groups after entry into the clinical trial. These results indicate that the CAST quality-of-life instrument is sensitive for assessing pharmacological therapies in the treatment of heart disease.

Aged↗

PubMed1994

Circadian pattern of arrhythmic death in patients receiving encainide, flecainide or moricizine in the Cardiac Arrhythmia Suppression Trial (CAST).

OBJECTIVES: The purpose of this study was to assess the effect of antiarrhythmic drugs on the timing of arrhythmic death. BACKGROUND: Sudden cardiac death remains a problem of epidemic proportions. Delineating its pathophysiology is an important step in devising preventive measures. Previous studies have shown a circadian pattern of onset of sudden cardiac death. The effect of antiarrhythmic drugs on this pattern has not been systematically studied. METHODS: The Cardiac Arrhythmia Suppression Trial (CAST) was a multicenter double-blind, placebo-controlled study designed to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs (encainide, flecainide or moricizine) after acute myocardial infarction would reduce the incidence of arrhythmic death. RESULTS: The trial was terminated prematurely because of an unexpectedly high mortality rate in the active treatment group. The onset of arrhythmic death in this group (in patients not receiving beta-adrenergic blocking agents) displayed a bimodal variation, with significant peaks in midmorning and late afternoon/early evening. More than half of the symptomatic events were accompanied by anginalike symptoms. Approximately 30% of all events occurred within 2 h of awakening. CONCLUSIONS: Our data suggest the possibility of a complex interaction among antiarrhythmic drugs, sympathetic nervous system activation and acute myocardial ischemia. Planning of future antiarrhythmic drug trials will need to take this information into account.

Aged↗

PubMed1993

Psychosocial predictors of mortality in the Cardiac Arrhythmia Suppression Trial-1 (CAST-1).

Psychosocial variables predict the recurrence of clinical events in symptomatic patients, controlling for measures of disease severity. The Cardiac Arrhythmia Suppression Trial-1, a pharmacologic test of the arrhythmia suppression and mortality hypothesis among postmyocardial infarction patients, allowed a prospective test of the relationship of distress, perceived support, social interaction, life stress, and other variables, to mortality, adjusting statistically for ejection fraction, arrhythmia rates, and other known risk factors for coronary heart disease. Results indicated that the treatment medications, encainide and flecainide, were powerful predictors of mortality. Although the psychosocial variables were significant as univariate predictors, these variables were not significant as predictors in a multivariate model that included drug treatment. When the data analysis was restricted to patients randomized to placebo, thereby eliminating the antiarrhythmic drug effect, the level of perceived social support was a significant multivariate predictor of mortality, adjusting for measures of disease severity. The adjusted hazards ratio for a 1-point decrease in the perceived support score is equal to 1.46, based on the multivariate model.

Arrhythmias, Cardiac↗

PubMed1993

Identification of a secondary peak in myocardial infarction onset 11 to 12 hours after awakening: the Cardiac Arrhythmia Suppression Trial (CAST) experience.

OBJECTIVES: The purpose of this study was to assess the relation between the time of awakening and the time of onset of acute myocardial infarction. BACKGROUND: Previous investigation has shown the onset of symptoms of acute myocardial infarction to have a primary peak 1 to 2 h after awakening. In studies not corrected for time of awakening, there appears to be a late afternoon/early evening peak, but data correlating the onset of symptoms with awakening have been limited by small numbers of patients, perhaps precluding identification of a secondary peak. METHODS: In the Cardiac Arrhythmia Suppression Trial (CAST), 3,549 patients had a documented myocardial infarction and entered antiarrhythmic drug titration. Of these, 3,309 had data on the onset of symptoms relative to the time of awakening and form the basis of this report. RESULTS: A total of 870 patients (26.3%) were awakened by symptoms. Of the remaining 2,439 patients who were not awakened by symptoms, 798 (32.7%) experienced the onset of symptoms in the 1st 4 h after awakening (with the highest number in the 1st h), after which the incidence of symptom onset decreased in a linear fashion, with a secondary peak 11 to 12 h after awakening. Both peaks are statistically significant. A similar pattern was seen in most of the subgroups examined (based on age, gender and various other demographic characteristics). CONCLUSIONS: Analysis of the very large CAST data base confirms the relation between awakening and onset of symptoms of myocardial infarction, suggesting involvement of the morning catecholamine surge. A secondary peak in symptom onset, occurring 11 to 12 h after awakening, is a new observation and may relate to ingestion of the evening meal or other trigger factors concentrated in those hours.

Aged↗

PubMed1992

The stereochemical course of reactions catalysed by the cellobiohydrolases produced by Talaromyces emersonii.

Three forms of exocellobiohydrolase (EC 3.2.1.91), CBH IA, CBH IB and CBH II, were isolated to apparent homogeneity from culture filtrates of the aerobic fungus Talaromyces emersonii. CBH IA and CBH II appear to be native forms of these enzymes, while CBH IB may represent a proteolytic degradation product of the CBH IA enzyme. The hydrolysis of beta-cellobiosyl fluoride by each form was monitored by 1H-n.m.r. spectroscopy. The reactions catalysed by CBH IA and CBH IB proceed with retention of the anomeric configuration, whereas that catalysed by CBH II is one of inversion. Thus one may deduce that CBH IA (or CBH IB) and CBH II operate double and single displacement reactions respectively during catalysis of substrate. On the basis of these findings and the observed substrate specificities of the various forms, one may conclude that CBH IA (and CBH IB) is a family C enzyme, while CBH II belongs to family B [Henrissat, Claeyssens, Tomme, Lemesle & Mornon (1989) Gene 81, 83-95].

Ascomycota↗

PubMed1991

Artifactual elevation of thyroid-stimulating hormone.

A clinically euthyroid patient was found to have a normal serum thyroxine level and an elevated plasma thyrotropin (TSH) level measured by fluoroimmunoassay. Thyroid hormone therapy failed to suppress the TSH level. The TSH level was unresponsive to thyrotropin-releasing hormone (TRH) administration, alpha-subunits of pituitary glycoproteins were undetectable in her plasma, and imaging of the pituitary-hypothalamic region was normal. Measurement of TSH with an assay containing sheep antibody to TSH failed to reveal TSH in the patient's plasma. Addition of mouse IgG to the TSH fluoroimmunoassay reduced the patient's TSH to an undetectable level. These observations are consistent with a spurious elevation of TSH due to the presence of an anti-mouse antibody. Artifactual elevations of TSH have not been identified commonly, but this possibility should be considered when the TSH level is inappropriate for the apparent state of thyroid function.

Adult↗