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T Lumley

Publications and source records attributed to T Lumley.

At least 19 recordsLinked to original sources

The differential association of conjugated equine estrogen and esterified estrogen with activated protein C resistance in postmenopausal women.

OBJECTIVES: Clinical trials have demonstrated that oral conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) increases venous thrombotic risk but this safety issue has not been investigated for other oral estrogens. Based on observational study findings that esterified estrogen (EE) was not associated with venous thrombotic risk whereas CEE was, we hypothesized that CEE users would be more resistant to activated protein C (APC), a prothrombotic phenotype, than EE users. METHODS: We conducted an observational, cross-sectional study of postmenopausal women 30-89 years old who were controls in a case-control study of venous thrombosis. Use of CEE, EE, and MPA at the time of phlebotomy was determined using computerized pharmacy records. APC resistance was measured in plasma by the endogenous thrombin potential normalized APC sensitivity ratio. Adjusted mean APC resistance values were compared across estrogen type and CEE:EE ratios are presented. RESULTS: There were 119 CEE and 92 EE users at the time of phlebotomy. Compared with EE users, CEE users had APC resistance measures that were 52% higher (1.52; 95% confidence intervals: 1.07-2.17) in adjusted analyses. Restricting to modal dose users (0.625 mg) and stratifying by MPA use did not materially change associations. CONCLUSIONS: CEE use was associated with higher levels of APC resistance when compared with EE use in postmenopausal women. These findings might provide an explanation for the higher risk of venous thromboembolism previously observed with CEE compared with EE use and, if replicated, may have safety implications for women when choosing an estrogen for symptom relief.

Activated Protein C Resistance↗

Respiratory muscle strength and the risk of incident cardiovascular events.

BACKGROUND: Maximal inspiratory pressure (MIP) is a measure of inspiratory muscle strength. The prognostic importance of MIP for cardiovascular events among elderly community dwelling individuals is unknown. Diminished forced vital capacity (FVC) is a risk factor for cardiovascular events which remains largely unexplained. METHODS: MIP was measured at the baseline examination of the Cardiovascular Health Study. Participants had to be free of prevalent congestive heart failure (CHF), myocardial infarction (MI), and stroke. RESULTS: Subjects in the lowest quintile of MIP had a 1.5-fold increased risk of MI (HR 1.48, 95% CI 1.07 to 2.06) and cardiovascular disease (CVD) death (HR 1.54, 95% CI 1.09 to 2.15) after adjustment for non-pulmonary function covariates. There was a potential inverse relationship with stroke (HR 1.36, 95% CI 0.97 to 1.90), but there was little evidence of an association between MIP and CHF (HR 1.22, 95% CI 0.93 to 1.60). The addition of FVC to models attenuated the HR associated with MIP only modestly; similarly, addition of MIP attenuated the HR associated with FVC only modestly. CONCLUSIONS: A reduced MIP is an independent risk factor for MI and CVD death, and a suggestion of an increased risk for stroke. This association with MIP appeared to be mediated through mechanisms other than inflammation.

Cardiovascular Diseases↗

Measurement of offline exhaled nitric oxide in a study of community exposure to air pollution.

As part of a large panel study in Seattle, Washington, we measured levels of exhaled nitric oxide (eNO) in children's homes and fixed-site particulate matter with aerodynamic diameters of 2.5 micro m or less (PM(2.5)) outside and inside the homes as well as personal PM(2.5) during winter and spring sessions of 2000-2001. Nineteen subjects 6-13 years of age participated; 9 of the 19 were on inhaled corticosteroid (ICS) therapy. Exhaled breath measurements were collected offline into a Mylar balloon for up to 10 consecutive days. Mean eNO values were 19.1 (SD +/- 11.4) ppb in winter sessions and 12.5 +/- 6.6 ppb in spring sessions. Fixed-site PM(2.5) mean concentrations were 10.1 +/- 5.7 microg/m(3) outside homes and 13.3 +/- 1.4 inside homes; the personal PM(2.5) mean was 13.4 +/- 3.2 microg/m(3). We used a linear mixed-effects model with random intercept and an interaction term for medications to test for within-subject-within-session associations between eNO and various PM(2.5) values. We found a 10 microg/m(3) increase in PM(2.5) from the outdoor, indoor, personal, and central-site measurements that was associated with increases in eNO in all subjects at lag day zero. The effect was 4.3 ppb [95% confidence interval (CI), 1.4-7.29] with the outdoor monitor, 4.2 ppb (95% CI, 1.02-7.4) for the indoor monitor, 4.5 ppb (95% CI, 1.02-7.9) with the personal monitor, and 3.8 ppb (95% CI, 1.2-6.4) for the central monitors. The interaction term for medication category (ICS users vs. nonusers) was significant in all analyses. These findings suggest that eNO can be used as an assessment tool in epidemiologic studies of health effects of air pollution.

Adolescent↗

Combining components of quality of life to increase precision and evaluate trade-offs.

Methods for combining measurements on multiple dimensions of quality of life can reduce the dimensionality of the data and increase the precision of estimation. When the dimensions are weighted according to their importance to patients, the resulting estimate is clinically useful and provides a step towards a true utility estimate. We derive two such weighting methods using linear regression on a measure of overall quality of life and demonstrate their usefulness in the analysis of quality of life data from two clinical trials of cancer therapies. Procedures for transforming the quality of life measures into utility measures are demonstrated.

Antineoplastic Combined Chemotherapy Protocols↗

Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.

BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure. METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified. RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension. CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.

Aged↗

Referent selection in case-crossover analyses of acute health effects of air pollution.

The case-crossover design was proposed for the study of a transient effect of an intermittent exposure on the subsequent occurrence of a rare acute-onset disease. This design can be an alternative to Poisson time series regression for studying the health effects of fine particulate matter air pollution. Characteristics of time-series of particulate matter, including long-term time trends, seasonal trends, and short-term autocorrelations, require that referent selection in the case-crossover design be considered carefully and adapted to minimize bias. We performed simulations to evaluate the bias associated with various referent selection strategies for a proposed case-crossover study of associations between particulate matter and primary cardiac arrest. Some a priori reasonable strategies were associated with a relative bias as large as 10%, but for most strategies the relative bias was less than 2% with confidence interval coverage within 1% of the nominal level. We show that referent selection for case-crossover designs raises the same issues as selection of smoothing method for time series analyses. In addition, conditional logistic regression analysis is not strictly valid for some case-crossover designs, introducing further bias.

Acute Disease↗

A case-crossover analysis of particulate matter air pollution and out-of-hospital primary cardiac arrest.

Numerous epidemiologic studies have reported increases in the daily incidence of cardiovascular mortality and morbidity associated with increases in daily levels of particulate matter air pollution. We studied the association between the incidence of primary cardiac arrest and two daily measures of particulate matter using a case-crossover study of 362 cases of out-of-hospital cardiac arrest. All cases were attended by paramedics and had no history of clinically recognized heart disease or life-threatening comorbidities. We compared particulate matter levels at index times with particulate matter levels from referent days matched on day of week within strata defined by month and year. The estimated relative risk at a lag of 1 day for an interquartile range (IQR) change in nephelometry (0.51 x 10(-1) km(-1)) was 0.893 (95% CI = 0.779-1.024). The estimated relative risk at a lag of 1 day for an IQR change in PM10 (19.3 microg m(-3)) was 0.868 (95% CI = 0.744-1.012). Other lag periods gave similar results. We did not find evidence of confounding by carbon monoxide or sulfur dioxide. Analysis of effect modification by individual-level variables did not reveal any susceptible subgroups. These findings do no support an association between particulate matter and increased risk of primary cardiac arrest among persons without clinically recognized heart disease. The null results of this study may result from several factors, including the highly selected nature of this case series and the relatively low particulate matter levels in the Seattle metropolitan area.

Adult↗

A comparison of standard gamble, time trade-off, and adjusted time trade-off scores.

OBJECTIVE: To adjust patients' time trade-off (TTO) scores using information on their utility functions for survival time to derive a measure of health state utility equivalent to the standard gamble (SG). METHODS: A sample of 199 cardiovascular patients were asked three TTO and SG questions (to assess their own health state), and three certainty equivalent questions (to assess their utility function for survival time) in an interview. RESULTS: Patient's utility functions for time were increasingly concave, but being unable to model this successfully, a constant function with an averaged level of concavity was used. The raw TTO scores were significantly higher than SG scores, while the adjusted TTO scores were equivalent to the SG. CONCLUSIONS: Raw time trade-off scores will give biased estimates of health state utility when patients' utility functions for time are not linear, but these can be adjusted to yield true utilities. The constant proportional risk-posture assumption of the conventional QALY model, on which previous attempts to adjust time trade-offs have been based, was not supported by the data.

Cardiovascular Diseases↗

Time-dependent ROC curves for censored survival data and a diagnostic marker.

ROC curves are a popular method for displaying sensitivity and specificity of a continuous diagnostic marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, D(t), and ROC curves that vary as a function of time may be more appropriate. A common example of a time-dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t = 0), by calculating ROC curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan-Meier estimator for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics 22, 1299-1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials.

Breast Neoplasms↗

Variation in the quality of lumbar spine MR images in Washington State.

PURPOSE: To investigate the variation in quality of lumbar spine magnetic resonance (MR) images as a function of type of ownership of the imaging center, number of studies performed per month, specialty training of the image interpreter, and field strength of the MR unit. MATERIALS AND METHODS: Data were collected from all imaging facilities in western Washington state that received reimbursement from the Washington State Health Care Authority. Three readers with expertise in spine imaging, who were blinded to center and patient identification information, rated the technical image quality of each study. All MR images of the lumbar spine (maximum of six) paid for by the health care authority were evaluated. If a center had performed more than six studies, then six were randomly selected for evaluation. RESULTS: Variation in quality scores among sites was significant (P =.001). Field strength was the strongest predictor of better quality. Poorer quality was associated with for-profit ownership, a larger number of radiologists at the site reading MR images, and a larger percentage of studies checked by a radiologist prior to the end of the examination. CONCLUSION: There was significant variation in the quality of MR images of the lumbar spine, and at least a portion of this variation was attributable to characteristics of the imaging center.

Ambulatory Care Facilities↗

Effects of ambient air pollution on symptoms of asthma in Seattle-area children enrolled in the CAMP study.

We observed a panel of 133 children (5-13 years of age) with asthma residing in the greater Seattle, Washington, area for an average of 58 days (range 28-112 days) during screening for enrollment in the Childhood Asthma Management Program (CAMP) study. Daily self-reports of asthma symptoms were obtained from study diaries and compared with ambient air pollution levels in marginal repeated measures logistic regression models. We defined days with asthma symptoms as any day a child reported at least one mild asthma episode. All analyses were controlled for subject-specific variables [age, race, sex, baseline height, and FEV(1) PC(20) concentration (methacholine provocative concentration required to produce a 20% decrease in forced expiratory volume in 1 sec)] and potential time-dependent confounders (day of week, season, and temperature). Because of variable observation periods for participants, we estimated both between- and within-subject air pollutant effects. Our primary interest was in the within-subject effects: the effect of air pollutant excursions from typical levels in each child's observation period on the odds of asthma symptoms. In single-pollutant models, the population average estimates indicated a 30% [95% confidence interval (CI), 11-52%] increase for a 1-ppm increment in carbon monoxide lagged 1 day, an 18% (95% CI, 5-33%) increase for a 10-microg/m(3) increment in same-day particulate matter < 1.0 microm (PM(1.0)), and an 11% (95% CI, 3-20%) increase for a 10-microg/m(3) increment in particulate matter < 10 microm (PM(10)) lagged 1 day. Conditional on the previous day's asthma symptoms, we estimated 25% (95% CI, 10-42%), 14% (95% CI, 4-26%), and 10% (95% CI, 3-16%) increases in the odds of asthma symptoms associated with increases in CO, PM(1.0), and PM(10), respectively. We did not find any association between sulfur dioxide (SO(2)) and the odds of asthma symptoms. In multipollutant models, the separate pollutant effects were smaller. The overall effect of an increase in both CO and PM(1. 0) was a 31% (95% CI, 11-55%) increase in the odds of symptoms of asthma. We conclude that there is an association between change in short-term air pollution levels, as indexed by PM and CO, and the occurrence of asthma symptoms among children in Seattle. Although PM effects on asthma have been found in other studies, it is likely that CO is a marker for vehicle exhaust and other combustion by-products that aggravate asthma.

Adolescent↗

Efficacy of antiseptic-impregnated central venous catheters in preventing catheter-related bloodstream infection: a meta-analysis.

CONTEXT: Central venous catheters impregnated with chlorhexidine and silver sulfadiazine have recently been introduced for the prevention of catheter-related infections. However, there remains some uncertainty regarding the efficacy of these catheters because of conflicting reports in the literature. OBJECTIVE: To evaluate the efficacy of chlorhexidine-silver sulfadiazine-impregnated central venous catheters in the prevention of catheter-related bloodstream infection. DATA SOURCES: Studies identified from a computerized search of the MEDLINE database from January 1966 to January 1998, reference lists of identified articles, and queries of principal investigators and the catheter manufacturer. STUDY SELECTION: Randomized trials comparing chlorhexidine-silver sulfadiazine-impregnated central venous catheters with nonimpregnated catheters were included. The outcomes assessed were catheter colonization and catheter-related bloodstream infection confirmed by catheter culture. DATA EXTRACTION: Twelve studies met the inclusion criteria for catheter colonization and included a total of 2611 catheters. Eleven studies with a total of 2603 catheters met the inclusion criteria for catheter-related bloodstream infection. Most patients in these studies were from groups considered to be at high risk for catheter-related infections. Summary statistics were calculated using Mantel-Haenszel methods under a fixed-effects model. DATA SYNTHESIS: The summary odds ratio for catheter colonization was 0.44 (95% confidence interval [CI], 0.36-0.54; P<.001), indicating a significant decrease in catheter colonization associated with impregnated catheters. The studies examining the outcome of primary interest, catheter-related bloodstream infection, had a summary odds ratio of 0.56 (95% CI, 0.37-0.84; P = .005). CONCLUSIONS: Central venous catheters impregnated with a combination of chlorhexidine and silver sulfadiazine appear to be effective in reducing the incidence of both catheter colonization and catheter-related bloodstream infection in patients at high risk for catheter-related infections.

Anti-Infective Agents, Local↗

Predicting patients' utilities from quality of life items: an improved scoring system for the UBQ-H.

The Utility-based Quality of Life--Heart Questionnaire (UBQ-H) is a cardiovascular extension of the Health Measurement Questionnaire. It is a multidimensional instrument that can be scored to yield a utility estimate using the Rosser Index and a classification algorithm developed for the Health Measurement Questionnaire. The aim of this study was to employ a statistical modelling approach to devise an improved scoring system. A sample of 201 cardiovascular patients completed the UBQ-H and assessed the utility of their own health state using standard gamble and time trade-off questions in an interview. Two new scoring methods were devised by regressing the UBQ-H data against patients' self-assessed utilities. The new methods gave utility estimates that correlated with angina/dyspnoea grades, life satisfaction scores and General Health Questionnaire (GHQ) scores. In a second sample of 1,112 cardiovascular patients, the UBQ-H utilities were able to distinguish between patients who had/had not experienced an adverse event (e.g. myocardial infarction) and were responsive to changes in health over time. The new scoring methods were not particularly more sensitive to quality of life effects than the original method based on the Rosser Index. However, they produced significantly lower estimates and more accurately reflected patients' self-assessed utilities.

Cardiovascular Diseases↗

A comparison of dressings in the management of surgical abdominal wounds.

This prospective randomised trial compared the performance of three dressing protocols in the management of 36 dehisced surgical abdominal wounds: a standard alginate; a gauze moistened with sodium hypochlorite (0.05%); and a combine dressing pad. Outcomes assessed were: healing time (cm2 per day and cm3 per day), patient comfort (pain and satisfaction) and cost. There were no statistically significant differences in healing rates between the three groups but there was a trend for the combine dressing pad protocol to produce a greater reduction in wound area. The combine dressing pad protocol performed well when compared with the calcium alginate in terms of healing time, patient comfort and cost. Maximum pain was significantly greater (p = 0.011) and satisfaction significantly lower among patients who received the sodium hypochlorite protocol. Costs during the in-patient phase were also substantially higher for the sodium hypochlorite protocol. Trial results support the view that sodium hypochlorite dressing protocols for surgical wounds should be abandoned.

Aged↗

First- and second-year effects in trials of calcium supplementation on the loss of bone density in postmenopausal women.

The analysis of clinical trials investigating the effect of calcium on the loss of bone mass or density has been based on the assumption that the effects are the same for all years of follow-up. Hence the average annual rate of loss is calculated and compared in the calcium and control groups. In this metaanalysis, we investigated this assumption and found that it is not tenable in the groups randomized to calcium for most sites that have been measured. The rate of bone loss was significantly less in the first year after randomization than in the second year. By contrast, the rate of loss in the control groups was less in the second year than the first, although this was not significant. At the spine, femoral neck, trochanter, intertrochanter, midtibia, and ultratibia, the effect of calcium in reducing bone loss was statistically significant compared with control only in the first year after randomization; there was no difference in rates between the groups in the second year. The effect of calcium compared to control in two arm sites and Ward's triangle was of a similar magnitude but was not statistically significant. We recommend that analysis and metaanalysis of trials should always consider the effects on a year-by-year basis.

Bone Density↗

Improved quality of life with megestrol acetate in patients with endocrine-insensitive advanced cancer: a randomised placebo-controlled trial. Australasian Megestrol Acetate Cooperative Study Group.

PURPOSE: To investigate the effect of two doses of megestrol acetate (MA) compared with placebo on quality of life (QoL) and nutritional status (NS) in patients with advanced endocrine-insensitive cancer. PATIENTS AND METHODS: Two hundred forty patients were randomised to double-blind MA 480 mg/day, MA 160 mg/day, or matching placebo for 12 weeks. Nutritional status (including weight, skinfold thickness and midarm circumference) and QoL (using 6 linear analogue self-assessment (LASA) scales) were assessed at randomisation and after four, eight and 12 weeks. A QoL ranking incorporating QoL and death was also used ranging from 1 = dead to 5 = much better QoL. RESULTS: One hundred seventy-four patients were assessable at week four, 136 at week eight and 103 patients at week 12. Patients receiving MA reported substantially better appetite (P = 0.001), mood (P = 0.001) and overall quality of life (P < 0.001), and possibly less nausea and vomiting (P = 0.08) than patients receiving placebo, based on a test for trend. A larger benefit was seen with the higher dose which (unlike the lower dose) was significantly better in pairwise comparisons with placebo for appetite, mood and overall QoL (each P < or = 0.001). Despite some missing data on QoL scores, QoL ranking was available on 227 (95%) of patients with significantly higher QoL ranking associated with MA (P = 0.002). Improvements in QoL occurred early within four weeks and were sustained. No statistically significant differences were observed in NS measurements, including weight (P = 0.29). Side effects of therapy were minor and did not differ significantly across treatments. CONCLUSION: Megestrol acetate given at 480 mg/day is useful palliation in patients with endocrine-insensitive advanced cancer. It improves appetite, mood and overall quality of life in these patients, although not through a direct effect on nutritional status.

Aged↗

Angiographic severity of coronary narrowing is a surrogate marker for the extent of coronary atherosclerosis.

Most acute coronary events occur because of narrowings at sites of angiographically minor plaque. Despite this, angiograms are reported in terms of the number of coronary arteries with severe narrowings. Disease severity is correlated with prognosis, but this may simply be due to a strong positive correlation between the severity and extent of coronary atheroma. We therefore aimed to assess the relation between the severity and the extent of coronary atherosclerosis. Coronary angiograms of 350 consecutive patients referred for elective cardiac catheterization were analyzed. Two independent observers calculated the number of arteries with > or = 70% stenosis, a disease severity score, and an extent score (percentage of the coronary artery length with any luminal irregularity). There were no obstructive stenoses in 123 patients (35%); 91 (26%) had 1-vessel disease, 81 (23%) had 2-vessel disease, and 55 (16%) had 3-vessel coronary artery disease. The median severity score was 1 (lower, upper quartile 0, 3; range 0 to 8), and the median extent score was 66% (lower, upper quartile 32, 83; range 0% to 100%). There was a strong linear relation between severity score and extent score (r = 0.62, p < 0.001); however, the data were better described by 2 intersecting straight lines, with a steeper increase in disease severity when the extent score was between 80% and 90% (F1;121 = 6.9, p = 0.001). The severity of coronary disease is therefore significantly correlated with disease extent. This may explain the observed relation between the number of arteries with obstructive stenoses and subsequent risk, even though most events occur at sites of minor plaque.

Adult↗

In vitro and in vivo assessment of urethral warming catheters for the transperineal cryoablation of prostatic carcinoma.

OBJECTIVE: To evaluate the two most common urethral warming catheters currently available for their effectiveness in preventing urethral injury in an animal model and thus during transperineal cryosurgery for the treatment of prostate cancer. PATIENTS, MATERIALS AND METHODS: The warming efficiency of the variable-diameter thin latex-balloon catheter (Cook, Australia) and the fixed-diameter PVC catheter (Candela, USA) were evaluated in a water-bath. A sheep model was then used for subsequent experiments to further evaluate the better catheter. The technique used for the insertion of the Cook catheter in a series of 33 patients treated with prostate cryosurgery is also described. RESULTS: In vitro, the Cook catheter was more effective (P < 0.01) than the Candela catheter in preventing localized cooling. In vivo, results in five animals showed that the urethral epithelium was viable in all sections that had been protected by the catheter and focally denuded or necrotic in those sections not protected, with each animal used as its own control (P < 0.01 Fisher's exact test). The 33 patients treated while using the Cook catheter had no subsequent complications. CONCLUSION: The urethral warming catheter currently in use for prostatic cryosurgery in Australia is more effective in vitro than its competitor and is effective in preventing urethral injury in vivo.

Catheterization↗