Showing papers by "Ralph B. D'Agostino published in 2000"

The Female Sexual Function Index (FSFI): A Multidimensional Self-Report Instrument for the Assessment of Female Sexual Function

Abstract: This article presents the development of a brief, self-report measure of female sexual function. Initial face validity testing of questionnaire items, identified by an expert panel, was followed by a study aimed at further refining the questionnaire. It was administered to 131 normal controls and 128 age-matched subjects with female sexual arousal disorder (FSAD) at five research centers. Based on clinical interpretations of a principal components analysis, a 6- domain structure was identified, which included desire, subjective arousal, lubrication, orgasm, satisfaction, and pain. Overall test-retest reliability coefficients were high for each of the individual domains (r=0.79 to 0.86) and a high degree of internal consistency was observed (Cronbach’s alpha values of 0.82 and higher) Good construct validity was demonstrated by highly significant mean difference scores between the FSAD and control groups for each of the domains (p<0.001). Additionally, divergent validity with a scale of marital satisfactio...

Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study

Abstract: ContextSleep-disordered breathing (SDB) and sleep apnea have been linked to hypertension in previous studies, but most of these studies used surrogate information to define SDB (eg, snoring) and were based on small clinic populations, or both.ObjectiveTo assess the association between SDB and hypertension in a large cohort of middle-aged and older persons.Design and SettingCross-sectional analyses of participants in the Sleep Heart Health Study, a community-based multicenter study conducted between November 1995 and January 1998.ParticipantsA total of 6132 subjects recruited from ongoing population-based studies (aged ≥40 years; 52.8% female).Main Outcome MeasuresApnea-hypopnea index (AHI, the average number of apneas plus hypopneas per hour of sleep, with apnea defined as a cessation of airflow and hypopnea defined as a ≥30% reduction in airflow or thoracoabdominal excursion both of which are accompanied by a ≥4% drop in oxyhemoglobin saturation), obtained by unattended home polysomnography. Other measures include arousal index; percentage of sleep time below 90% oxygen saturation; history of snoring; and presence of hypertension, defined as resting blood pressure of at least 140/90 mm Hg or use of antihypertensive medication.ResultsMean systolic and diastolic blood pressure and prevalence of hypertension increased significantly with increasing SDB measures, although some of this association was explained by body mass index (BMI). After adjusting for demographics and anthropometric variables (including BMI, neck circumference, and waist-to-hip ratio), as well as for alcohol intake and smoking, the odds ratio for hypertension, comparing the highest category of AHI (≥30 per hour) with the lowest category (<1.5 per hour), was 1.37 (95% confidence interval [CI], 1.03-1.83; P for trend=.005). The corresponding estimate comparing the highest and lowest categories of percentage of sleep time below 90% oxygen saturation (≥12% vs <0.05%) was 1.46 (95% CI, 1.12-1.88; P for trend <.001). In stratified analyses, associations of hypertension with either measure of SDB were seen in both sexes, older and younger ages, all ethnic groups, and among normal-weight and overweight individuals. Weaker and nonsignificant associations were observed for the arousal index or self-reported history of habitual snoring.ConclusionOur findings from the largest cross-sectional study to date indicate that SDB is associated with systemic hypertension in middle-aged and older individuals of different sexes and ethnic backgrounds.

Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS)

Abstract: Background—Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects. Methods and Results—We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (SI) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of b...

The Preclinical Phase of Alzheimer Disease: A 22-Year Prospective Study of the Framingham Cohort

Abstract: Objectives To relate performance on tests of cognitive ability to the subsequent development of probable Alzheimer disease (pAD) and to identify the pattern of earliest changes in cognitive functioning associated with a diagnosis of pAD. Design From May 1975 to November 1979, a screening neuropsychological battery was administered to Framingham Study participants. They were followed up prospectively for 22 years and examined at least every 2 years for the development of pAD. Setting A community-based center for epidemiological research. Participants Subjects were 1076 participants of the Framingham Study aged 65 to 94 years who were free of dementia and stroke at baseline (initial) neuropsychological testing. Main Outcome Measure Presence or absence of pAD during a 22-year surveillance period was related to test performance at initial neuropsychological testing. Results Lower scores for measures of new learning, recall, retention, and abstract reasoning obtained during a dementia-free period were associated with the development of pAD. Lower scores for measures of abstract reasoning and retention predicted pAD after a dementia-free period of 10 years. Conclusions The "preclinical phase" of detectable lowering of cognitive functioning precedes the appearance of pAD by many years. Measures of retention of information and abstract reasoning are among the strongest predictors of pAD when the interval between initial assessment and the development of pAD is long.

Hyperinsulinemia, Hyperglycemia, and Impaired Hemostasis: The Framingham Offspring Study

Abstract: ContextIncreased risk for cardiovascular disease in persons with glucose intolerance (impaired glucose tolerance and type 2 diabetes mellitus) is not fully explained by concomitant elevations in traditional atherosclerosis risk factors. Hyperinsulinemia associated with glucose intolerance may increase risk directly, or its effect could be mediated through impaired hemostatic function.ObjectiveTo evaluate associations between fasting insulin levels and hemostatic factors in subjects with normal and impaired glucose homeostasis.DesignCross-sectional analysis conducted between January 1991 and June 1995.SettingThe population-based Framingham Offspring Study.SubjectsA total of 1331 men and 1631 women aged 26 to 82 years, without diagnosed diabetes or cardiovascular disease and classified as having normal glucose tolerance (80.2%) or glucose intolerance (impaired glucose tolerance and impaired fasting glucose combined, 15.2%; previously undiagnosed diabetes, 4.7%) using an oral glucose tolerance test.Main Outcome MeasuresTrends across quintiles of fasting insulin in levels of plasminogen activator inhibitor 1 (PAI-1) antigen, tissue-type plasminogen activator (tPA) antigen, von Willebrand factor (vWF) antigen, factor VII antigen, fibrinogen, and plasma viscosity. We stratified analyses by sex and glucose tolerance status and adjusted hemostatic factor levels for obesity, lipid levels, and traditional cardiovascular disease risk factors.ResultsMean levels of all hemostatic factors (except for fibrinogen in men) increased across fasting insulin quintiles among subjects with normal glucose tolerance (P<.001 for trend). Levels of PAI-1 and tPA antigens, but not other hemostatic factors, were higher comparing subjects with glucose intolerance with those with normal glucose tolerance (P<.001). Among subjects with glucose intolerance, levels of PAI-1 and tPA antigen in men and women (P<.01 for trend) and vWF antigen in men (P<.05 for trend) increased significantly across insulin quintiles, but levels of factor VII antigen, fibrinogen, and plasma viscosity did not increase.ConclusionsElevated levels of fasting insulin are associated with impaired fibrinolysis and hypercoagulability in subjects with normal glucose tolerance. Hyperinsulinemia is associated primarily with impaired fibrinolysis in subjects with glucose intolerance. Excess risk for cardiovascular disease associated with hyperinsulinemia and glucose intolerance may be mediated in part by enhanced potential for acute thrombosis.

Association of Fibrinogen With Cardiovascular Risk Factors and Cardiovascular Disease in the Framingham Offspring Population

Abstract: Background—Fibrinogen has been identified as an independent risk factor for cardiovascular disease and associated with traditional cardiovascular risk factors Also, the role of elevated fibrinogen in thrombosis suggests that it may be on the causal pathway for certain risk factors to exert their effect These associations remain incompletely characterized Moreover, the optimal fibrinogen assay for risk stratification is uncertain Methods and Results—In 2632 subjects from cycle 5 of the Framingham Offspring Population, fibrinogen levels were determined with a newly developed immunoprecipitation test (American Biogenetic Sciences) and the functional Clauss method With the immunoprecipitation method, there were significant linear trends across fibrinogen tertiles (P<0001) for age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL cholesterol, and triglycerides in men and women The Clauss method had significant results (P<0030), except for triglycerides in men Fibrinogen levels were

Estimating and Using Propensity Scores with Partially Missing Data

Abstract: Investigators in observational studies have no control over treatment assignment. As a result, large differences can exist between the treatment and control groups on observed covariates, which can lead to badly biased estimates of treatment effects. Propensity score methods are an increasingly popular method for balancing the distribution of the covariates in the two groups to reduce this bias; for example, using matching or subclassification, sometimes in combination with model-based adjustment. To estimate propensity scores, which are the conditional probabilities of being treated given a vector of observed covariates, we must model the distribution of the treatment indicator given these observed covariates. Much work has been done in the case where covariates are fully observed. We address the problem of calculating propensity scores when covariates can have missing values. In such cases, which commonly arise in practice, the pattern of missing covariates can be prognostically important, and ...

Evaluation of Subsecond Gated Helical CT for Quantification of Coronary Artery Calcium and Comparison with Electron Beam CT

Abstract: OBJECTIVE. Since its introduction early in the 1990s, helical CT has become the predominant technology for obtaining CT images for medical applications. Recent improvements in the temporal resolution of helical CT (subsecond) and the addition of retrospective cardiac gating are combined in this report evaluating cardiac-gated helical CT for quantifying coronary artery calcium. We compare total calcium scores determined on subsecond gated helical CT with the current reference for coronary calcium evaluation, electron beam CT.MATERIALS AND METHODS. We compared total calcium scores obtained using a general purpose, unmodified helical CT scanner with scores obtained using electron beam CT in 36 individuals who were 68 ± 11 years old (age range, 41-85 years).RESULTS. Correlation coefficients ranged from 0.97 to 0.98 (Pearson's product moment) and from 0.95 to 0.96 (Spearman's rank order), depending on the coronary calcium scoring method used. Agreement in the classification of participants as “healthy” or “dis...

Association of Blood Pressure With Fibrinolytic Potential in the Framingham Offspring Population

Abstract: Background —Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study. Methods and Results —We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP ( P P =0.008) and DBP ( P =0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex. Conclusions —These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.

Associations between alcohol consumption and insulin sensitivity and cardiovascular disease risk factors: the Insulin Resistance and Atherosclerosis Study.

Abstract: OBJECTIVE: Light-to-moderate alcohol consumption has been associated with reduced cardiovascular disease (CVD) mortality, which may be explained by increased insulin sensitivity (SI) and an improved lipoprotein and blood pressure profile. Prior research has shown improved SI with light-to-moderate alcohol intake even though somewhat imprecise measures of SI were used. RESEARCH DESIGN AND METHODS: Relationships between alcohol use and SI and CVD risk factors were assessed in a cross-sectional analysis of 1,196 white, African-American, and Hispanic men and women from the Insulin Resistance and Atherosclerosis Study (IRAS). Five categories of previous-year alcohol use (never, or =3 drinks/day) and log SI + 1 (frequently sampled intravenous glucose tolerance test with Bergman minimal model analysis), log fasting insulin, log triglycerides, HDL cholesterol, and systolic/diastolic blood pressure were examined using analysis of variance. RESULTS: Univariate analysis showed an inverse U-shaped relationship between SI and alcohol intake, with a peak at the 0.5-0.99 drinks/day category. A U-shaped relationship was observed between fasting insulin and the lipid and blood pressure measures. After adjustment for demographic (clinic, sex, ethnicity, age), lifestyle (smoking, dietary energy/fat intake, physical activity), and physical (BMI, waist circumference) variables, the alcohol/insulin association was attenuated, but the association with lipids and blood pressure remained for high-intake categories. CONCLUSIONS: These data suggest that the enhanced SI associated with light-to-moderate alcohol consumption may be a function solely of a BMI and central adiposity profile more favorable to higher SI.

Computing estimates of incidence, including lifetime risk: Alzheimer's disease in the Framingham Study. The Practical Incidence Estimators (PIE) macro.

Abstract: The incidence of disease is estimated in medical and public health applications using various different techniques presented in the statistical and epidemiologic literature. Many of these methods have not yet made their way to popular statistical software packages and their application requires custom programming. We present a macro written in the SAS macro language that produces several estimates of disease incidence for use in the analysis of prospective cohort data. The development of the Practical Incidence Estimators (PIE) Macro was motivated by research in Alzheimer's Disease (AD) in the Framingham Study in which the development of AD has been prospectively assessed over an observation period of 24 years. The PIE Macro produces crude and age-specific incidence rates, overall and stratified by the levels of a grouping variable. In addition, it produces age-adjusted rates using direct standardization to the combined group. The user specifies the width of the age groups and the number of levels of the grouping variable. The PIE macro produces estimates of future risk for user-defined time periods and the remaining lifetime risk conditional on survival event-free to user-specified ages. This allows the user to investigate the impact of increasing age on the estimate of remaining lifetime risk of disease. In each case, the macro provides estimates based on traditional unadjusted cumulative incidence, and on cumulative incidence adjusted for the competing risk of death. These estimates and their respective standard errors, are provided in table form and in an output data set for graphing. The macro is designed for use with survival age as the time variable, and with age at entry into the study as the left-truncation variable; however, calendar time can be substituted for the survival time variable and the left-truncation variable can simply be set to zero. We illustrate the use of the PIE macro using Alzheimer's Disease incidence data collected in the Framingham Study.

Prevention Conference V Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Medical Office Assessment : Writing Group I

Abstract: Writing Group I of Prevention Conference V reviewed the role of medical office assessment in the detection of risk factors and estimation of total cardiovascular risk The primary focus was on identification of known risk factors for coronary heart disease (CHD) Population screening may identify risk factors that prompt people to seek clinical consultation Risk factors may also be identified in patients who are seeking medical treatment for other conditions Physicians have the responsibility to evaluate cardiovascular risk in all their patients Medical office assessment permits the identification of many high-risk patients without the need for noninvasive testing for atherosclerotic burden or subclinical myocardial ischemia Techniques for office assessment available to clinicians include history, physical examination, laboratory testing, and electrocardiography (ECG) Routine evaluation and testing provides most of the information needed to estimate risk and make treatment decisions The essential information required for estimating risk for CHD lies in the known risk factors for coronary disease These risk factors must first be identified and their severity determined The relationship between risk factors and development of CHD is strong but variable When a risk factor is causally and independently related to disease, the physician should make recommendations to the patient about risk factor modification When risk factors are associated with increased risk for CHD but are not directly causative, the risk factor is considered to be a marker for increased risk In the following discussion, the major risk factors and risk markers for CHD that can be detected in medical office assessment are reviewed The different categories of risk are then considered Finally, the special characteristics of each risk factor in relation to global risk assessment are reviewed Special groups, including older patients and those with diabetes, are considered, and suggestions are made for modifying the existing guidelines for risk …

Heart rate in relation to insulin sensitivity and insulin secretion in nondiabetic subjects.

Abstract: OBJECTIVE: Elevated heart rate has been predictive of cardiovascular disease and has been proposed as a global index of the autonomic nervous system influence on the heart. Hyperinsulinism has been shown to trigger sympathetic activity experimentally; however, the clinical and epidemiological data on the association of heart rate with hyperinsulinism and insulin resistance are conflicting. RESEARCH DESIGN AND METHODS: Insulin sensitivity (S(I)) and the acute insulin response (AIR) to glucose were assessed by a frequently sampled intravenous glucose tolerance test and related to resting heart rate in the tri-ethnic nondiabetic population (n = 1,000) of the Insulin Resistance Atherosclerosis Study. RESULTS: Heart rate was related to fasting insulin (r = 0.20), intact proinsulin (r = 0.15), split proinsulin (r = 0.17), and AIR (r = 0.18), and an inverse relation was found between heart rate and S(I) (r = -0.19) (all P values

Can sustained weight loss in overweight individuals reduce the risk of diabetes mellitus

Abstract: Although rates of adult-onset diabetes mellitus increase with increasing obesity, there is little evidence that weight loss in overweight individuals can reduce their risk of developing diabetes. Using data from the Framingham Study, we examined the effects of sustained and nonsustained weight loss on risk of diabetes mellitus among 618 overweight (body mass index > or =27) subjects 30-50 years of age. To separate sustained from nonsustained weight loss, we examined weight change in two consecutive 8-year periods. Subjects who had stable weight (+/- 1 lb per year) during both periods served as the referent group for all analyses. Sustained weight loss led to a 37% lower risk of diabetes [relative risk (RR) = 0.63; 95% confidence interval = 0.34-1.2], and this effect was stronger for more obese (body mass index > or =29) subjects (RR = 0.38; 95% confidence interval = 0.18-0.81). Those who lost 8.1-15 lb had a 33% reduction in diabetes risk, whereas those losing more had a 51% reduction in risk. Regardless of the amount of weight lost, those who regained the lost weight had no reduction in diabetes risk (RR = 1.1 and 1.2 for those who lost 8.1-15 and >15 lb, respectively). We conclude that a modest amount of sustained weight loss can substantially reduce the risk of diabetes mellitus in overweight individuals.

Relation of systemic blood pressure, left ventricular mass, insulin sensitivity, and coronary artery disease to QT interval duration in nondiabetic and type 2 diabetic subjects.

Abstract: A prolonged QT interval has been identified as a risk factor for cardiovascular disease; however, knowledge about etiologic factors is limited. We studied determinants of QT interval duration in the Insulin Resistance Atherosclerosis Study, a large, triethnic population (n = 1,577) with varying degrees of glucose tolerance. In particular, we sought to investigate the relation of QT interval with blood pressure (BP), left ventricular (LV) mass, estimated using electrocardiographic criteria, and insulin sensitivity, directly measured by a frequently sampled intravenous glucose tolerance test. QT interval was measured electronically on electrocardiograms at rest and corrected for heart rate using standard equations. The QT interval was related to various components of the insulin resistance syndrome, including BP and insulin sensitivity. Multivariate analyses showed that BP and LV mass were the main determinants of the QT interval in diabetic and nondiabetic subjects. Additionally, prevalent coronary artery disease was related to the QT interval in subjects with newly diagnosed diabetes. In conclusion, we found that BP and LV mass were the strongest and most consistent determinants of the QT interval in nondiabetic and diabetic subjects. Additional factors potentially contributing to QT interval prolongation in diabetic patients include insulin sensitivity and prevalent coronary artery disease.

Factor VII Gene Polymorphism, Factor VII Levels, and Prevalent Cardiovascular Disease The Framingham Heart Study

Abstract: Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100. 5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.

Debate: The slippery slope of surrogate outcomes.

Abstract: Surrogate outcomes are frequently used in cardiovascular disease research. A concern is that changes in surrogate markers may not reflect changes in disease outcomes. Two recent clinical trials (Heart and Estrogen/Progestin Replacement Study [HERS], and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]) underscore this problem since their results contradicted what was expected based on the surrogate outcomes. The current regulatory policy to allow new therapies to be introduced onto the market based solely on surrogate outcomes may need to be reviewed.

Controlling alpha in a clinical trial: the case for secondary endpoints.

Abstract: Regardless of whether a statistician believes in letting a data set speak for itself through nominal p-values or believes in strict alpha conservation, the interpretation of experiments which are negative for the primary endpoint but positive for secondary endpoints is the source of some angst. The purpose of this paper is to apply the notion of prospective alpha allocation in clinical trials to this difficult circumstance. An argument is presented for differentiating between the alpha for the experiment ('experimental alpha' or α E ) and the alpha for the primary endpoint (primary alpha, or α P ) and notation is presented which succinctly describes the findings of a clinical trial in terms of its conclusions. Capping α E at 0.10 and α P at 0.05 conserves sample size and preserves consistency with the strength of evidence for the primary endpoint of clinical trials. In addition, a case is presented for the well defined circumstances in which a trial which did not reject the null hypothesis for the primary endpoint but does reject the null hypothesis for at least one of the secondary endpoints may be considered positive in a manner consistent with conservative alpha management.

Lipoprotein concentrations and carotid atherosclerosis by diabetes status: results from the Insulin Resistance Atherosclerosis Study.

Abstract: OBJECTIVE: Lipoprotein concentrations are associated with the development of atherosclerosis in people with and without diabetes. The relative strength of these associations could differ by diabetes status as a result of diabetes-related lipoprotein modifications. RESEARCH DESIGN AND METHODS: The associations between lipoprotein concentrations and internal and common carotid artery intimal-medial thickness (IMT) assessed by B-mode ultrasonography were examined by diabetes status in a cross-sectional analysis among 1,391 participants in the Insulin Resistance Atherosclerosis Study. Participants included 442 individuals with type 2 diabetes, 308 with impaired glucose tolerance, and 641 with normal glucose tolerance. RESULTS: The differences in internal and common carotid IMT between the highest and lowest tertiles of LDL were 58.1 microm (P = 0.054) and 51.0 microm (P < 0.001), respectively. The differences in internal and common carotid IMT between the lowest and highest tertiles of HDL were 56.2 microm (P = 0.07) and 37.8 microm (P = 0.003), respectively Triglycerides and VLDL were not associated with IMT. These associations did not differ significantly because of diabetes status. CONCLUSIONS: These results support the importance of dyslipidemia as a major risk factor for atherosclerosis in people with diabetes. Future research in humans should measure lipoprotein oxidizability, glycation, size, and composition directly in people of differing glucose tolerance status to address the importance of diabetes-related lipoprotein modifications more conclusively.

In vitro zones of inhibition of coated vascular catheters predict efficacy in preventing catheter infection with Staphylococcus aureus in vivo.

Abstract: This report summarizes data from 35 rabbit model experiments investigating the relationship between in vitro anti-infective catheter coating zones of inhibition and in vivo efficacy. The rabbit model studies involving 15 anti-infective coatings demonstrate an inverse correlation between the sizes of zones of inhibition of Staphylococcus aureus and both the quantity of Staphylococcus aureus removed from the catheter and the risk of a purulent infection. The review of seven previously published clinical trials reveals that the use of anti-infective coated catheters, efficacious in the rabbit model, was associated with a higher success rate than the use of uncoated catheters in preventing both Staphylococcus aureus catheter colonization (odds ratio: 1.28; 95% confidence interval: 0.84-1.93) and Staphylococcus aureus catheter-related bloodstream infection (odds ratio: 3.07; 95% confidence interval: 0.98-9.60) in humans. These findings strongly suggest a correlation between zones of inhibition and in vivo efficacy. In vitro zones of inhibition may serve as a useful screening test for evaluating new anti-infective coatings.