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Results for “Surrogate variables analysis”

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PubMed2000

A new surrogate variable for erectile dysfunction status in the Massachusetts male aging study.

Erectile dysfunction (ED) is the subject of a vast clinical literature, but little information has been gathered from random samples of the general public. The Massachusetts Male Aging Study (MMAS) addressed this important aspect of men's health. The MMAS was conducted in two waves, with baseline data collection in 1987-1989 and follow-up in 1995-1997. Subsequent to the baseline MMAS survey, a consensus developed that subjective measures are optimal for defining ED. Unfortunately, the baseline questionnaire did not ask subjects directly about their erectile functioning. Thus, we previously assigned the MMAS subjects a degree of impotence at baseline using a series of related questions, employing a discriminant formula constructed from a separate sample of urology clinic patients. At follow-up the men classified themselves directly in addition to answering the original series of related questions. In the present article, we report the results of a new discriminant function, based on the MMAS men at follow-up. We also compare the two methods and discuss our reasons for preferring the internally calibrated method.

Cross-Sectional Studies↗

PubMed2007

Predicting inadequate long-term lung development in children with congenital diaphragmatic hernia: an analysis of longitudinal changes in ventilation and perfusion.

PURPOSE: Infants born with congenital diaphragmatic hernia (CDH) demonstrate a wide variability in postnatal catch-up lung growth. The goals of this study were to assess the pulmonary development of children born with CDH using sequential ventilation-perfusion (V/Q) scintigraphy and to identify the perinatal factors that correspond to a progressive V/Q mismatch. METHODS: The records of 137 patients seen between 1990 and 2005 in a multidisciplinary CDH clinic were reviewed. Changes in the ipsilateral V/Q quotient were compared in 46 patients who had 2 or more studies with the following variables: sex, patch repair, laterality, gestational age, and use of extracorporeal membrane oxygenation. An abnormal V/Q quotient was defined as greater than 1.2 (reference range, 0.8-1.2). RESULTS: Abnormal V/Q scans were identified in 28 (61%) of the 46 patients at the time of the last V/Q study. Patients who underwent a patch repair had nearly 7 times the risk (P < .001) of developing an ipsilateral V/Q mismatch. The use of extracorporeal membrane oxygenation had a variable effect on the probability of an abnormal V/Q study finding. No other variable was significant. CONCLUSIONS: Many children with CDH develop significant and progressive V/Q mismatches. Although some perinatal variables appear to be predictive of this phenomenon, they may simply be surrogates for a greater degree of pulmonary hypoplasia present at birth. This subpopulation of CDH survivors is an identifiable group clearly at risk and thus requires long-term follow-up.

Adolescent↗

PubMedDate not supplied

Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proarrhythmic potential of drugs.

Prolongation of the QTc interval of the electrocardiogram (ECG) is used as a surrogate marker for a rare, but life threatening, ventricular arrhythmia known as torsades de pointes (TdP). However, the clear link between QTc prolongation and the arrhythmogenic risk has not been demonstrated unequivocally. In the present review article, we examine (a) the current understanding of electrophysiological and pharmacological mechanisms linking changes in action potential (AP) properties with proarrhythmia and (b) the value of the isolated, paced Langendorff-perfused female rabbit heart model (Screenit system) in predicting the torsadogenic potential of drugs in man. The Screenit system records monophasic action potentials (MAPs) from which the following parameters are evaluated: action potential duration (APD), conduction, instability (indicative of beat to beat APD variability), triangulation (indicative of changes of Phase 3 repolarization), and reverse-use dependency (indicating that the APD is more prolonged at slow heart rates). So far, over 16,000 experiments have been conducted, including approximately 300 dedicated tests to evaluate, in a blinded manner, approximately 70 clinically used drugs. The drugs tested covered a wide range of compounds from various pharmacological and chemical classes with clinical torsadogenic propensity, as well as drugs without the latter effect in clinical settings. Overall, the Screenit system and its associated analysis classified the drugs based on their effects on AP morphology and conduction and additionally identified, in a qualitative manner, drugs clinically associated with TdP. Such an identification is based on the triangulation, reverse-use dependency, and instability of the AP, as well as on the direct indexes of proarrhythmia such as early afterdepolarization (EADs), ventricular tachycardia (VT), and ventricular fibrillation (VF). Overall, drugs that readily induce arrhythmia and/or EADs and/or causes triangulation, reverse-use dependency, and/or instability and/or a chaotic Poincaré plot in a range of concentrations likely to be achieved in man is likely to cause TdP in man, eventually. Only if none of these elements is present, at concentrations well exceeding the free therapeutic plasma concentration, can one expect that the drug will probably be devoid of torsadonenicity. Therefore, this in vitro model provides detailed information on the overall profile of drug-induced electrophysiological effects. In combination with other in vitro and in vivo repolarization assays and with pharmacokinetic data in man, it is a valuable tool to establish an integrated cardiovascular risk assessment of pharmaceutical compounds.

Action Potentials↗

PubMed1996

Impact of donor/recipient size matching on outcomes in renal transplantation.

Interest in nonimmunologic factors affecting longterm graft survival has focused on adequacy of nephron dosing. Body surface are (BSA) is a reliable surrogate for nephron mass. In a retrospective study of 378 primary recipients of paired kidneys from 189 cadaveric donors, we assessed the impact of matching donor and recipient BSA on outcome over 7 years. BSA of donors was 1.82 +/- 0.26 m2. Initially, paired recipients of kidneys from a single donor were divided into two groups. Group 1 included the recipient with the larger BSA of the pair (1.97 +/- 0.17 m2), while group 2 consisted of smaller BSA recipients (1.69 +/- 0.19 m2). Although early function was better in group 2 patients, graft survival at 1 year (77% vs. 79%) and 5 years (54% vs. 55%) was identical between groups, as were most recent serum creatinine levels (2.0 +/- 0.1 vs. 2.1 +/- 0.1 mg/dl). A second analysis divided patients with a functioning allograft at discharge from initial transplant hospitalization (n = 345) into three groups based solely on donor to recipient BSA ratio: the ratio of group A (n = 30) was < or = 0.8, that of group B (n = 255) was between 0.81 and 1.19, and that of group C (n = 51) was > or = 1.2. Graft survival and kidney function over 5 years did not differ among groups. In multivariate analysis of 17 variables, donor:recipient BSA, independent of other risk factors, did not affect risk allograft loss. These data indicate that including nephron mass as a criterion for cadaveric organ allocation is unlikely to improve long-term results in renal transplantation.

Adult↗

PubMed1994

Geographic variability in hospital admission rates for respiratory disease among the elderly in the United States.

BACKGROUND: The elderly represent a susceptible subpopulation that experiences disproportionate levels of morbidity and mortality from respiratory disease. As a consequence, they are frequently hospitalized for these conditions. Evaluating the geographic distributions of these hospital admissions can provide useful insights concerning patterns in incidence and medical care for respiratory diseases. METHODS: All hospital admissions for pneumonia, acute respiratory infections, asthma, and chronic obstructive pulmonary disease from the United States for a 6-year period (1984 through 1989) were identified using Medicare admissions records. Age-, race-, and sex-standardized annual admission rates were calculated for each county and spatial clustering of disease specific rates was evaluated using Moran's I statistic. Ecologic analyses were conducted using multiple regression procedures with county-specific measures of average annual temperature, average income, household crowding, median educational level, population density, physicians per capita, and hospital beds per capita together with surrogate measures of cigarette consumption and occupational exposures as predictor variables. RESULTS: Hospital admission rates in the elderly for all four categories of respiratory disease showed marked regional elevations (p < 0.0001), particularly in the southeast and the northern plains states. Low median education level, low per capita income, and household crowding were all associated with elevated hospital admission rates. Surrogate measures of cigarette consumption were strongly associated with hospital admissions in all four disease groups. Hospital beds per capita demonstrated positive associations with hospital admissions, but the number of physicians per capita exhibited consistent inverse relationships with hospital admissions. CONCLUSIONS: Hospital admission rates for respiratory diseases among the elderly show marked geographic variation and are associated with regional indicators of socioeconomic status, availability of medical resources, occupational lung disease rates, and smoking.

Aged↗

PubMed2002

A limited sampling strategy for the estimation of 12-hour Neoral systemic drug exposure in heart transplant recipients.

BACKGROUND: Therapeutic drug monitoring of cyclosporine in heart transplant patients is used to monitor therapy and prevent rejection. Of the various methods available for performing therapeutic drug monitoring of cyclosporine, the method of limited sampling strategy for area under the concentration-time curve profiling has been used most widely recently. The process of identifying sparse data points to predict area under the concentration-time curve is essentially a variable selection problem, with the variables being the drug concentrations at the various timepoints. Although fitting more variables into a model will typically allow for a better prediction of area under the concentration-time curve, improving the prediction has to be traded-off against the desirability of using as few timepoints as possible. The objective of this study was thus to formulate a model that would provide a good prediction of area under the concentration-time curve based on a limited number of sampling points. METHODS: We studied 15 stable heart transplant patients (11 Chinese and 4 Indians). All patients were receiving Neoral-based immunosuppression. Whole blood samples for area under the concentration-time curve analysis were obtained at the following timepoints: pre-dose (C(0h)) and at 1, 2, 3, 4, 6 and 12 hours (C(1h), C(2h), C(3h), C(4h), C(6h), C(12h), respectively) post-dose during the first dosing interval. The linear trapezoidal rule was used to calculate the area under the concentration-time curve (AUC) from time 0 h to 12 h. Various limited sampling strategies, as well as Keown's formula, which was derived in renal transplant patients and used C(0h) and C(2h), were compared based on their capacity for reducing total error squared. RESULTS: C(4h) was found to be the single most predictive timepoint and explained 95.3% of AUC(0-12) variation. C(0h) and C(12h) explained 60% and 75.7% of the variation in AUC(0-12), respectively. The best 2-variable model identified by stepwise selection procedures included C(1h) and C(4h) as predictors, explaining 97.3% of the variation in total area under the concentration-time curve from time 0 h to 12 h. Using Keown's algorithm, the R(2) was only 80.9%. CONCLUSION: We recommend using C(1h) and C(4h) as surrogate markers of area under the concentration-time curve from time 0 h to 12 h in our heart transplant patients. Because C(1h) and C(4h) represent timepoints within the zone of highest variability for Neoral's absorption phase, a model incorporating these timepoints would be able to explain a greater degree of variability associated with the Neoral absorption profile.

Adult↗

PubMed1995

Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis.

OBJECTIVE: To develop guidelines for therapeutic trials designed to improve the overall course of systemic sclerosis (SSc), that is, to reduce the development of significant organ damage or death. METHODS: A committee developed general guidelines for patient inclusion and exclusion criteria, randomization, blinding of patients and physicians, controls, duration of the trial, investigator training, responses, samples size, study dropouts, statistical analyses, data management, and safety monitoring. Delphi and nominal group techniques were used. RESULTS: Briefly, patients with diffuse cutaneous SSc of less than 24 months' duration should be included because they are at greatest risk for the development of severe organ damage and death. Patients should be excluded if they have other connective tissue diseases, SSc-like illnesses related to exposures or ingestions, severe existing internal organ damage, an unacceptable risk of side effects, or concurrent therapies that might independently influence the outcome. Randomized, double-blind, placebo-controlled trials are preferred. The treatment and followup period must be long enough to permit observation of any disease modification, which is likely to require 18-36 months, unless an extraordinarily effective therapy is identified. Responses selected should be quantitative, consistently and accurately reflect activity of SSc in major target organs (not solely the skin), be sensitive to change, and be standardized, with limited variability. An example of a set of responses is given. Surrogate responses are desirable, but none have been validated as correlating with organ damage. CONCLUSION: Guidelines have been established for trials of disease-modifying interventions in SSc. These guidelines will need to be altered as additional information becomes available. Any given protocol will be individualized based on the nature of the intervention and objectives of the study. Nonetheless, each study team should develop a protocol that meets the spirit of these guidelines.

Clinical Protocols↗

PubMed2000

A combined in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate target site pharmacodynamics of antibiotics in humans.

We describe a new approach to quantify in vivo anti-infective activity by simulating effect site pharmacokinetics of antibiotics in vitro. This approach is based on (i) the in vivo measurement of interstitial drug pharmacokinetics (PK) at the target site and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. To demonstrate the feasibility of this approach, individual time-concentration profiles of ciprofloxacin were measured in the interstitial space fluid of eight healthy volunteers by microdialysis following iv administration of 200 mg. Thereafter, different isolates of Pseudomonas aeruginosa were exposed in vitro to the interstitial ciprofloxacin concentration profile obtained from in vivo experiments. This led to a 1- to 3-log10 decrease in the number of viable organisms after 8 h. Significant correlations were observed between the maximal bactericidal effect and several PK surrogate parameters, notably the AUC/MIC ratio (P: = 0.0005), the C:max/MIC ratio (P: = 0.006) and the time > MIC (P: = 0.02). Furthermore, the data were analysed with an integrated PK-PD model allowing a much more detailed evaluation of the data than using MIC. The model employed an E:max relationship to link unbound ciprofloxacin concentration to bacterial kill rate. In conclusion, our experiments show that therapeutic success and failure in antimicrobial therapy may be explained by pharmacokinetic variability at the target site. Therefore, the in vivo PK-in vitro PD approach presented in our study may provide valuable guidance for drug and dose selection of antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2004

Measures of abdominal obesity assessed for visceral adiposity and relation to coronary risk.

AIMS: We aimed to identify by computed tomography (CT) the best suited of three anthropometric indices that reflect the visceral adipose tissue (VAT), and to discern the relationship between VAT and certain atherogenic risk factors and coronary heart disease (CHD) diagnosis in a population sample which had a high (34%) prevalence of the metabolic syndrome (MS). METHODS: A single-scan CT was performed between the fourth and fifth lumbar vertebrae in 157 unselected men and women aged 34-69 y. Total adipose tissue area, abdominal VAT area and the abdominal sagittal diameter were determined. Diagnosis of CHD was based on clinical findings and Minnesota coding of resting electrocardiograms. RESULTS: Men had significantly higher VAT than women. Linear regression analysis for correlates of abdominal VAT area, in a model comprising age, sex, waist circumference, waist-to-hip ratio (WHR) and body mass index (BMI) identified waist circumference as the only independent variable (P<0.001). Waist circumference in men and BMI in women were the independently associated parameters of sagittal diameter (P<0.001). By stepwise linear regression, it was elicited that VAT area rose significantly by a mean of 6.8 cm2 in men and 3 cm2 in women for every 1 cm increment in waist circumference, independent of WHR. Age in women and (inversely) BMI in men were further independent variables, indicating in men that a lower BMI at a given waist girth suggests the existence of a higher VAT. Apo B and HDL-cholesterol (HDL-C) in men, and the latter in women were independently associated with VAT area in linear regression models that also comprised triglycerides, fasting insulin and C-reactive protein concentrations. In the study sample comprising 13 individuals with a CHD diagnosis, the age-adjusted odds ratio of cutpoints of VAT area > vs <140 cm2 in men and > vs <120 cm2 in women was 11.3 (95% CI (1.37, 93)). CONCLUSIONS: The best surrogate of visceral adiposity across a wide age range is waist circumference, in a population in which MS prevails. Apo B and HDL-C in men, and the latter in women were independently associated with VAT area, which proved to be closely related to CHD risk. A lower BMI at a given waist girth in men suggests the existence of a higher VAT.

Abdomen↗

PubMed2001

Levodopa pharmacokinetic-pharmacodynamic modeling and 6-[18F]levodopa positron emission tomography in patients with Parkinson's disease.

OBJECTIVE: Parameters of a pharmacokinetic-pharmacodynamic (PK-PD) model of levodopa have been claimed to reflect the magnitude of the dopaminergic deficit in patients with Parkinson's disease. The aim of this study was to correlate such parameters with positron emission tomography (PET) with levodopa tagged with 6-fluorine 18, an established imaging method for striatal dopaminergic neurons. METHODS: Twenty-three patients in different disease stages (Hoehm and Yahr stage 2.5-5 [Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;4:427-42]; median duration, 12 years) were studied. PK-PD modeling followed a single oral dose of levodopa/benserazide. The sum score of the Columbia Rating Scale (CURSSigma) was used for clinical assessments. A nonparametric effect compartment approach assuming a sigmoidal E(max) model was applied to the PK-PD analysis of plasma levodopa concentrations and corresponding CURSSigma. Thereafter 6-[18F]levodopa PET was performed, and the influx rate constants (k(c)) for the putamen and the caudatus region were correlated with the median effective concentration (EC(50)) and the equilibrium half-life (T(eq)) of the PK-PD model. RESULTS: (1) A significant correlation was observed between PK-PD parameters or with k(c) putamen as the dependent variable and the duration of the disease as the independent variable, which explains 33% of the variability of the EC(50), 42% of the variability of T(eq), and 36% of the variability of k(c). (2) Significant correlations were observed between k(c) and either EC(50) or T(eq), yielding the closest correlation for the putamen region (r = -0.47, P <.05; and r = 0.55, P <.01; respectively). CONCLUSIONS: Our findings show that key parameters of a PK-PD model of levodopa were in fairly close agreement with imaging of dopaminergic neurons by 6-[18F]levodopa PET. However, although PK-PD modeling of levodopa has been proven as a useful investigation of approaches aimed to restore dopaminergic deficits or to monitor disease progression, this modeling cannot serve as a pathomorphologic surrogate for the loss of striatal dopaminergic neurons.

Adult↗

PubMed1998

Antigen mimicry by an anti-idiotypic antibody single chain variable fragment.

For the therapy of cancer patients whose disease is positive for Carcinoembryonic Antigen (CEA), we developed an active specific immunotherapy based on the idiotypic network. The anti-idiotype monoclonal antibody (mAb), 3H1 was generated by immunization of mice with the anti-CEA mAb, 8019. 3H1 mimics CEA both functionally and structurally and acts as a surrogate for CEA. To define the minimum structural requirements for antigen mimicry by 3H1, we constructed plasmid vectors for expression of single chain Fv (scFv) variants of 3H1 in Escherichia coli. Variable heavy (VH) and variable light (VL) chain domains of 3H1 were linked by a 15 amino acid linker (Ln), (Gly4Ser)3 in two constructs, VH-Ln-VL and VL-LnVH. Ln was omitted in two constructs, VH-VL and VL-VH. Each of the scFv constructs has a tag of six His [(His)6 tag] for purification by metal chelate affinity chromatography and detection by enzyme-linked immunoabsorbent assay (ELISA). Comparisons of the binding of 8019 to purified scFv proteins by ELISA and immunoblot experiments showed that only VH-Ln-VL had significant activity. VH-Ln-VL also showed maximum inhibition of binding of 8019 to CEA. Immunization of mice with naked VH-Ln-VL and VH-Ln-VL conjugated to keyhole limpet hemocyanin induced anti-CEA antibodies in mouse sera. Sera from immunized mice inhibited the binding of 8019 to 3H1 as well as CEA. Induction of anti-CEA antibodies in the immunized mice was confirmed by flow cytometric analysis using CEA positive MC-38cea cells. These results demonstrate that for antigen mimicry of 3H1 scFv, the presence of Ln is necessary and the domain order should be VH followed by VL.

Animals↗

PubMed1997

Cardiac baroreceptor sensitivity is impaired after acute stroke.

BACKGROUND AND PURPOSE: The blood pressure (BP) fall and increased BP variability after acute stroke have been previously described. The underlying pathophysiological mechanisms producing these findings are unclear but may include abnormalities of cardiac baroreceptor reflex arc and/or changes in sympathetic nervous system activity. To date, evidence of impaired cardiac baroreceptor sensitivity (BRS) after stroke is limited to patients with chronic disease as determined by invasive methodology. Therefore, it was proposed to assess cardiac BRS and sympathovagal balance with the use of novel noninvasive techniques after acute stroke. METHODS: Thirty-seven acute stroke patients underwent simultaneous surface electrocardiographic and noninvasive beat-to-beat BP recording. Cardiac BRS was assessed by power spectral analysis techniques, and sympathovagal balance was determined from the ratio of the low- to high-frequency powers for pulse interval variability. The responses were compared with a control group matched for age, sex, and BP. RESULTS: Median cardiac BRS was significantly lower in stroke patients than in control subjects (high-frequency alpha-index, 4.89 versus 6.50 ms/mm Hg; P = .007; combined alpha-index, 4.65 versus 5.46 ms/mm Hg; P = .02). Median normalized high- but not low-frequency power of systolic BP variability was significantly greater in stroke patients (11.0 versus 6.7 normalized units; P < .001), probably reflecting differences in the mechanical effects of respiration on BP in stroke patients. No significant differences were observed in the power spectrum of pulse interval variability between stroke patients and control subjects. Patients with tight hemisphere strokes, however, had a significant reduction in median high-frequency pulse interval power compared with patients with left hemisphere strokes (8 versus 20 normalized units; P = .03), which may reflect a change in sympathovagal balance in favor of increased sympathetic tone in this group. CONCLUSIONS: The impairment of cardiac BRS may be important in explaining the increased BP variability after stroke. There was no significant difference in surrogate measures of sympathovagal activity between acute stroke patients and control subjects, but right hemisphere stroke patients had a significant alteration in the sympathovagal balance of pulse interval variability compared with left hemisphere stroke patients. This sympathetic predominance in right hemisphere strokes may be important in the development of cardiac arrhythmias after stroke. The prognostic implications of these findings need to be further explored.

Acute Disease↗

PubMed2002

Underdiagnosis of chronic obstructive pulmonary disease in Northern Sweden.

OBJECTIVE: To assess underdiagnosis of chronic obstructive pulmonary disease. MATERIAL AND METHODS: Two cross-sectional studies of respiratory symptoms and diseases in two population samples of the same age living in the same areas in northern Sweden were performed 6 years apart. In 1986, 5698 (86%) out of 6610 subjects aged 35-36, 50-51 and 65-66 years responded to a postal questionnaire. In 1992 an identical study was performed, and 5617 subjects (87%) out of 6434 responded. Lung function measurements were performed in stratified samples. RESULTS: Of the subjects diagnosed with chronic bronchitis only 25% in 1986 and 23% in 1992 had been diagnosed prior to the study as having chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD). Chronic airflow limitation (CAL), used as a surrogate variable for COPD and defined as FEV1/VC <70% and FEV1 <80% of predicted value, was found in 171 subjects in 1986-1987 (12% of the examined subjects), and 166 subjects in 1993-1994 (11%). In 1986-1987, 26% of the subjects with CAL had been diagnosed as having chronic bronchitis or emphysema prior to the survey, while a diagnosis of either asthma, chronic bronchitis or emphysema, or use of asthma medicines, was found in 58%. The corresponding figures in 1993-1994 were 31% and 63%, respectively. The great majority of the subjects with CAL had recurrent wheeze, dyspnoea and chronic productive cough. CONCLUSION: Approximately 60% of the subjects with chronic airflow limitation had been diagnosed prior to the survey as having asthma, chronic bronchitis or emphysema, or were using asthma medicines. The results were similar in 1986-1987 and 1993-1994.

Adult↗

PubMed2003

Are children of military parents more physically fit than children of civilian parents?

BACKGROUND AND OBJECTIVES: It is not known whether parental activity levels influence children's physical fitness. Members of the military are required to maintain standards of physical fitness, whereas the civilian population is not. We conducted this study to compare fitness levels of children in military and civilian families. METHODS: This was a prospective cohort study of third-grade students from two public schools in San Diego County, Calif. Attendees of one school included children of enlisted service personnel. Attendees of the other school included officers' children. Civilian students attended both schools. Students' physical fitness was tested with several standard instruments, including time on a 1-mile run. Independent variables included whether students had civilian or military parents, television viewing habits, and parental military status (enlisted personnel versus officer) as a surrogate marker for socioeconomic status. RESULTS: A total of 170 of 246 (70%) eligible students completed the study. Children of military parents had lower scores on the mile run and lower scores on other measures of fitness than did children of civilian parents. Socioeconomic status (ie, child of officer versus enlisted personnel) was the strongest predictor of poor fitness, with children of enlisted service members scoring lower on all measures of physical fitness than officers' children. More television viewing was associated with lower levels of fitness. CONCLUSIONS: Children of military parents did not have a higher fitness level than children of civilian parents. Lower socioeconomic status and more television viewing are associated with lower levels of fitness.

Analysis of Variance↗

PubMed2001

Peripheral blood cells among community residents living near nuclear power plants.

Information about hematopoieses as a result of exposure to very low levels of radiation is scarce. To investigate the human hematopoietic effect of very low level radiation exposure, measurements of peripheral blood components were performed among 3602 men and women, aged 35 and above, living in a community near two nuclear power installations in Chinshan, Taiwan. The radiation level that each individual was exposed to was represented by a surrogate level, '1/D2(1i) + 1/D2(2i)', a transformed distance from each individual's residence to the two power plants D1 and D2. In addition to comparing average hematology measurements, multiple regression analyses were done to include age, gender, smoking, drinking status and the surrogate radiation exposure level as independent variables. Univariate and bivariate analyses showed that the hematology measurements had significant associations with age, gender, smoking or drinking. The multiple regression analyses revealed that significant positive associations with '1/D2(1i) + 1/D2(2i)' were found for hemoglobin, hematocrit, platelet, white blood cell and red blood cell. The platelet count might increase for 208.7 x 10(3)/microl if the exposure from the nuclear plants increased by one exposure unit. This type of association implies that those who lived closer to the nuclear power installation had a higher blood cell count; we suspect that this could be a type of radiation hormesis.

Adult↗

PubMed2002

Alcohol consumption alters insulin secretion and cardiac autonomic activity.

BACKGROUND: Alcohol may have a cardioprotective effect. One possible mechanism is by modifying insulin resistance/secretion. The aims of this study were: (i) to examine the effect of short-term alcohol consumption on the metabolic control of glucose tolerance; (ii) to study the influence of short-term alcohol consumption on cardiac autonomic activity using spectral analysis of heart rate variability. METHODS: Twenty-one healthy subjects, in a randomized crossover design, either received three units of ethanol daily for 1 week or abstained from ethanol. The control of glucose tolerance was assessed using the intravenous glucose tolerance test with minimal modelling. RESULTS: There was no difference in fasting glucose, fasting insulin or insulin sensitivity between the two groups. Alcohol showed a lower insulin first phase insulin response (no alcohol 659.0 +/- 394.1 SD, alcohol 535.2 +/- 309.1) pmol L-1 min-1, P = 0.027). There was no difference in heart rate or blood pressure but a significant difference in the ratio of high to low frequency spectral power of heart rate variability; (no alcohol 4.55 +/- 3.78, alcohol 8.16 +/- 6.77, P = 0.033). This suggests decreased sympathetic and/or increased vagal modulation of heart rate in the alcohol group. CONCLUSION: The finding of no difference in insulin sensitivity between the two groups contrasts with, but does not entirely contradict, the results of previous epidemiological studies--perhaps suggesting that longer term changes such as liver enzyme induction may be important. The difference in insulin secretion questions the validity of previous studies of the influence of alcohol on insulin sensitivity, where insulin levels were used as a surrogate for insulin resistance.

Adult↗

PubMed2005

Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model.

The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SI(Clamp)) that is better than that of many other surrogate indexes. However, correlation between a surrogate and reference standard may improve as variability between subjects in a cohort increases (i.e., with an increased range of values). Correlation may be excellent even when prediction of reference values by the surrogate is poor. Thus, it is important to evaluate the ability of QUICKI to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In the present study, we used a calibration model to compare the ability of QUICKI and other simple surrogates to predict SI(Clamp). Predictive accuracy was evaluated by both root mean squared error of prediction as well as a more robust leave-one-out cross-validation-type root mean squared error of prediction (CVPE). Based on data from 116 glucose clamps obtained from nonobese, obese, type 2 diabetic, and hypertensive subjects, we found that QUICKI and log (homeostasis model assessment [HOMA]) were both excellent at predicting SI(Clamp) (CVPE = 1.45 and 1.51, respectively) and significantly better than HOMA, 1/HOMA, and fasting insulin (CVPE = 3.17, P < 0.001; 1.67, P < 0.02; and 2.85, P < 0.001, respectively). QUICKI and log(HOMA) also had the narrowest distribution of residuals (measured SI(Clamp) - predicted SI(Clamp)). In a subset of subjects (n = 78) who also underwent a frequently sampled intravenous glucose tolerance test with minimal model analysis, QUICKI was significantly better than the minimal model index of insulin sensitivity (SI(MM)) at predicting SI(Clamp) (CVPE = 1.54 vs. 1.98, P = 0.001). We conclude that QUICKI and log(HOMA) are among the most accurate surrogate indexes for determining insulin sensitivity in humans.

Adult↗

PubMed2004

Improved outcomes of carotid endarterectomy: the critical role of vascular surgeons.

Improved outcomes after carotid endarterectomy (CEA) have been related to preoperative, intraoperative, and postoperative patient and procedural variables. Outcomes after CEA have also been related to other factors that are not clearly related to the patient or the procedure, such as performance of the procedure in high volume hospitals, by high volume surgeons, and by surgeons specializing in vascular surgery. These overlapping surrogate markers of "quality" have been widely quoted and may be used by external parties to limit access to vascular care; however, these markers have unclear significance when examined systematically. Some of the confounding variables that preclude easy interpretation of these markers include interest of the surgeon in the care of vascular patients, surgical talent, surgical judgment, recognition of patients at higher risk for complications, and routine or selective use of adjunctive medications such as beta-blockers, statins, and anti-platelet agents. The practices of vascular surgeons with excellent outcomes after CEA need to be examined critically for these underlying factors that affect not only procedural results but also long-term stroke-free survival.

Aged↗