Biomedical subjects

J A Hanley

Publications and source records attributed to J A Hanley.

At least 19 recordsLinked to original sources

PubMed2000

GEE analysis of negatively correlated binary responses: a caution.

The method of generalized estimating equations has become almost standard for analysing longitudinal and other correlated response data. However, we have found that if binary responses have less than binomial variation over clusters, and are modelled using exchangeable correlations, prevailing software implementations may give unreliable results. Bounding the negative correlation away from its theoretical minimum may not always be a satisfactory solution. In such instances, using the independence working correlation structure and robust SEs is a more trustworthy alternative.

Binomial Distribution↗

PubMed2000

Bootstrap confidence intervals for the sensitivity of a quantitative diagnostic test.

We examine bootstrap approaches to the analysis of the sensitivity of quantitative diagnostic test data. Methods exist for inference concerning the sensitivity of one or more tests for fixed levels of specificity, taking into account the variability in the sensitivity due to variability in the test values for normal subjects. However, parametric methods do not adequately account for error, particularly when the data are non-normally distributed, and non-parametric methods have low power. We implement bootstrap methods for confidence limits for the sensitivity of a test for a fixed specificity and demonstrate that under certain circumstances the bootstrap method gives more accurate confidence intervals than do other methods, while it performs at least as well as other methods in many standard situations.

Algorithms↗

PubMed2000

Exposure to environmental tobacco smoke and the risk of lung cancer: a meta-analysis.

A meta-analysis was carried out to calculate a pooled estimate of relative risk of lung cancer following exposure to environmental tobacco smoke (ETS) and to determine whether there was any heterogeneity in the pooled estimates according to selected characteristics of the studies. A total of 35 case-control and five cohort studies providing quantitative estimates of the association between lung cancer and exposure to ETS published between January 1981 and March 1999 were identified. Using fixed- and random-effects models, we calculated pooled estimates of relative risk for exposure to ETS from subjects' parents (during childhood), spouses, and coworkers. As well, we investigated whether the pooled estimates of relative risk varied by study location, degree of control of potential confounding variables, proportion of cases confirmed histologically, proportion of surrogate respondents, nonresponse rates, and year of publication. The relative risk of lung cancer among non smoking women ever exposed to ETS from their husbands' smoking was 1.20 (95% confidence interval (CI): 1.12-1.29). The pooled relative risk was 1.19 (95% CI: 1.10-1.29) for case-control studies and 1.29 (95% CI: 1.04-1.62) for cohort studies. In various subgroup and meta-regression analyses, we found no statistically significant differences by selected characteristics of the studies. In addition, we found that the risk of lung cancer increased consistently with increasing levels of exposure. The 11 studies reporting relative risks among male non smokers yielded a pooled relative risk of 1.48 (95% CI: 1.13-1.92) for ever exposed to ETS, and the relative risk of lung cancer for ever being exposed to ETS at work was a 1.16 (95% CI: 1.05-1.28). These results are consistent with the hypothesis that exposure to ETS increases the risk of lung cancer. While there may be alternative explanations to the data, it is more likely that the observed association is not an artifact and that ETS causes lung cancer in non smokers.

Adult↗

PubMed2000

Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage.

We carried out a nested case-control study to measure the rate ratio (RR) for invasive female breast cancer in relation to non-steroidal anti-inflammatory drug (NSAID) use. The source population consisted of the female beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970. Four controls/case, matched on age and sampling time, were randomly selected. Dispensing rates during successive time periods characterized NSAID exposure. RRs associated with exposure during each period were adjusted for exposure during the others. Confounding by other determinants was studied in analyses adjusted with data obtained by interviewing samples of subjects accrued from mid-1991 to mid-1995. We accrued 5882 cases and 23,517 controls. Increasing NSAID exposure 2-5 years preceding diagnosis was associated with a trend towards a decreasing RR (P-trend = 0.003); for the highest exposure level RR = 0.76, 95% confidence interval 0.63-0.92. This protective effect could not be attributed to confounding by other determinants. In analyses involving only the cases, NSAID exposure 2-5 and 6-10 years preceding diagnosis was associated with significantly reduced risks of presenting with a large tumour (> 5 cm diameter) or distant metastasis, but not regional lymph node metastasis. The use of NSAIDs may retard the growth of breast cancers and prevent distant metastasis.

Adult↗

PubMed2000

A comparison of cause of death determination in men previously diagnosed with prostate cancer who died in 1985 or 1995.

PURPOSE: We quantified the agreement between the underlying cause of death determination from information in hospital medical records and on death certificates, and determined whether the frequency of assigning death from prostate cancer had changed since the introduction of testing for prostate specific antigen. MATERIALS AND METHODS: We retrospectively reviewed and analyzed the information in hospital medical records and on death certificates for men previously diagnosed with prostate cancer who died in 1985 or 1995. RESULTS: The underlying cause of death determinations from a review of 201 hospital medical records agreed with those from information on part 1 of the death certificate in 87% of cases and with those using the International Classification of Diseases-9 system coding rules in 80%. Agreement was higher in men who were older than those who were younger at the time of death, and higher in those diagnosed with prostate cancer several years before death than in those diagnosed shortly before death. CONCLUSIONS: There was a high level of agreement concerning the underlying cause of death after a review of the information in hospital medical records and on death certificates for men with prostate cancer when cause of death was viewed as a dichotomous variable. The International Classification of Diseases-9 coding rules concerning the underlying cause of death favor overreporting rather than underreporting prostate cancer deaths compared with a review of hospital medical records. Cause of death determination does not appear to have changed after the introduction of prostate specific antigen testing.

Age Distribution↗

PubMed2000

The positive yield of imaging studies in the evaluation of men with newly diagnosed prostate cancer: a population based analysis.

PURPOSE: We determine the positive yield of imaging studies performed on men with newly diagnosed prostate cancer. MATERIALS AND METHODS: A prospective, population based survey was conducted on 3,690 men with prostate cancer diagnosed between October 1, 1994 and October 31, 1995. Cases were identified by the rapid case ascertainment systems used in 6 geographic regions participating in the Surveillance, Epidemiology and End Results Program. Based on information captured in primary medical record reviews we estimated the positive yield of bone scans, computerized tomography (CT) and magnetic resonance imaging. RESULTS: The positive yield of bone scan and CT was less than 5% and 12%, respectively, for all men with prostate specific antigen (PSA) 4 to 20 ng./ml., and less than 2% and 9%, respectively, for those who also had a Gleason score of 6 or less. Only men with PSA greater than 50 ng./ml. and those with Gleason scores 8 to 10 and PSA greater than 20 ng./ml. had positive yields greater than 10% and 20% for bone scan and CT, respectively. CONCLUSIONS: Imaging studies designed to identify metastases and/or extracapsular extension in men with newly diagnosed prostate cancer frequently have a low positive yield. Wide variations exist in the use of imaging studies and are associated with tumor factors, such as Gleason score and serum PSA, and nontumor factors, such as state of residence. More extensive cost-effectiveness analyses are needed to define appropriate guidelines for ordering imaging studies to optimize the positive yield among men with newly diagnosed prostate cancer.

Aged↗

PubMed2000

Agreement in measuring socio-economic status: area-based versus individual measures.

Area-based socio-economic status (SES) measures are frequently used in epidemiology. Such an approach assumes socio-economic homogeneity within an area. To quantify the agreement between area-based SES measures and SES assessed at the individual level, we conducted a cross-sectional study of 943 children who resided in 155 small enumeration areas and 117 census tracts from 18 schools in Montreal, Quebec. We used street address information together with 1986 census data and parental occupation to establish area-based and individual level SES indicators, respectively. As compared with the SES score determined at the level of the individual, 13 different area-based SES indices classified the children within the same quintile 28.7% (+/- 2.8%) of the time. The discrepancy was within one quintile in 35.3% (+/- 2.3%) of cases, two quintiles in 20.6% (+/- 3.6%), three quintiles in 11.3% (+/- 4.2%) and four quintiles in 4.1% (+/- 0.2%). In conclusion, we observed a substantial discrepancy between area- based SES measures and SES assessed at the individual level. Caution should therefore be used in designing or interpreting the results of studies in which area-based SES measures are used to test hypotheses or control for confounding.

Bias↗

PubMed1999

Risk of developing lung cancer in relation to exposure to fumes from Chinese-style cooking.

In an evaluation of the association between exposure to indoor air pollution from Chinese-style cooking and the risk of lung cancer, epidemiologic and experimental studies were reviewed. The 9 case-referent studies that were identified showed consistent positive associations between the risk of lung cancer and a variety of indices of exposure to indoor air pollution arising from Chinese-style cooking. Three experimental studies showed that volatile emissions from oils heated in woks are mutagenic in several in vitro short-term test systems. Several toxic agents, including some accepted or suspected carcinogens, have been detected in the emissions of the heated cooking oils. While experimental data support the epidemiologic data, it may be premature to conclude that the association is causal. However, simple precautions can be taken to reduce the risk in the event that exposure to indoor air pollution arising from Chinese-style cooking is indeed a cause of lung cancer.

Air Pollution, Indoor↗

PubMed1999

Statistical considerations when assessing outcomes following treatment for prostate cancer.

PURPOSE: We explore the impact of study designs, biases, outcome variables and statistical techniques when interpreting studies concerning prostate cancer management. MATERIALS AND METHODS: Examples from the current literature and a recently assembled population based sample of patients 55 to 75 years old at diagnosis identified by the Connecticut Tumor Registry as having newly diagnosed localized prostate cancer between 1971 and 1984 are provided to assist the reader to understand the principles discussed. RESULTS: Most reports concerning prostate cancer outcomes suffer from obvious and subtle biases that confound the reader's understanding of the impact of different treatment alternatives. CONCLUSIONS: By remaining vigilant to these confounding issues, clinicians and patients can gain greater insights into the medical literature and can make individual interpretations concerning the potential impact of treatment interventions on men with prostate cancer.

Aged↗

PubMed1999

The repeatability of three methods for measuring prospective patients' values in the context of treatment choice for end-stage renal disease.

In the context of the choice of treatment for end-stage renal disease (ESRD), three approaches to value assessment were examined for their repeatability over time within subjects. If formal decision analyses are to be used to advise patients about treatment choice, then repeatable value assessment methods, an essential component of such analyses, are needed. The methods assessed were standard gamble (SG), time trade-off (TTO), and visual analogue (VA). Sixty-six nephrology clinic patients were interviewed on two occasions, 10 days apart, by one of two interviewers. An information session was conducted 1 week before the first interview. Subjects were taught about the treatments using an information package developed expressly for the study and a video produced by a pharmaceutical company for use in this decision context. Patients differed widely in the values provided for the various treatments of ESRD, with responses that ranged across the entire scale (0 to 100). The repeatability of the three methods was poor, with the coefficients of repeatability (95% range of differences from one occasion to the next) observed as +/- 27.4 for SG, +/- 38.4 for TTO, and +/- 36.5 for VA. When subsets defined by characteristics that may have improved the repeatability were analyzed, the magnitude of the error did not vary substantially. The poor repeatability of these methods raises questions about their use for decision analyses applied to the individual context.

Adult↗

PubMed1999

Coding accuracy of hospital discharge data for elderly survivors of myocardial infarction.

OBJECTIVE: To assess the coding accuracy of primary and secondary discharge diagnoses in the Quebec hospital discharge database for elderly persons with myocardial infarction (MI). DESIGN: Retrospective chart review in a convenience sample of six Montreal hospitals. The diagnoses listed in the medical chart were compared with those listed in the hospital discharge database. For each subject, the Charlson comorbidity index was calculated twice, once based on the medical chart and again based on the hospital discharge database. PATIENTS: Subjects aged 65 years and over who had an MI coded as the primary discharge diagnosis in the hospital discharge database and who were discharged alive. MAIN RESULTS: For 234 MI survivors, the positive predictive value (ie, probability that a patient with MI reported in the hospital discharge database had an MI diagnosed by the discharging physician) for coding MI was 0.96 (95% CI 0.94, 0.98). Comorbid medical conditions and complications of the MI were under-reported in the hospital discharge database, which meant that the Charlson index based on the hospital discharge database was an average of 0.71 units lower than the Charlson index based on the medical chart. CONCLUSIONS: When studying survivors of MI by using hospital discharge databases, the advantages must be weighed against potential drawbacks in the quality of the information. Hospital discharge databases are almost as reliable as medical charts for identifying MI patients, but there is substantial under-reporting of comorbid medical conditions.

Aged↗

PubMed1998

Screening for prostate cancer: estimating the magnitude of overdetection.

BACKGROUND: No randomized controlled trial of prostate cancer screening has been reported and none is likely to be completed in the near future. In the absence of direct evidence, the decision to screen must therefore be based on estimates of benefits and risks. The main risk of screening is overdetection--the detection of cancer that, if left untreated, would not cause death. In this study the authors estimate the level of overdetection that might result from annual screening of men aged 50-70. METHODS: The annual rate of lethal screen-detectable cancer (detectable cancer that would prove fatal before age 85 if left untreated) was calculated from the observed prostate cancer mortality rate in Quebec; the annual rate of all cases of screen-detectable prostate cancer was calculated from 2 recent screening studies. RESULTS: The annual rate of lethal screen-detectable prostate cancer was estimated to be 1.3 per 1000 men. The annual rate of all cases of screen-detectable prostate cancer was estimated to be 8.0 per 1000 men. The estimated case-fatality rate among men up to 85 years of age was 16% (1.3/8.0) (sensitivity analysis 13% to 22%). INTERPRETATION: Of every 100 men with screen-detected prostate cancer, only 16 on average (13 to 22) could have their lives extended by surgery, since the prostate cancer would not cause death before age 85 in the remaining 84 (78 to 87).

Aged↗

PubMed1998

Erythrocytosis after renal transplantation represents an abnormality of insulin-like growth factor-I and its binding proteins.

BACKGROUND: Secondary erythrocytosis is classically defined by an increase in erythropoietin (EPO) production. Despite increased levels of EPO often seen in secondary erythrocytosis, some of these forms such as that seen after renal transplantation remain undefined. Our group has recently investigated the in vivo function of insulin-like growth factor-I (IGF-I) in erythropoiesis both in humans and in a murine model of chronic renal failure. These data, and the recently recognized role of IGF-I in polycythemia vera, suggested that IGF-I might be involved in secondary erythrocytosis. METHODS: Renal transplant recipients who developed erythrocytosis after transplantation were compared to normal individuals and to renal transplant recipients without erythrocytosis. We measured fasting serum EPO and IGF-I in all three groups. Because binding proteins may modify IGF-I function, IGF-I-binding proteins (IGFBP) 1 and 3, major binding proteins of IGF-I, were also measured. RESULTS: Renal transplant recipients have significantly elevated serum of IGF-I and IGFBP3 compared to normal individuals. When transplant recipients with and without posttransplant erythrocytosis were compared, similar levels of IGF-I were found; however, the group with erythrocytosis had significantly elevated IGFBP1 and IGFBP3. No other significant differences including EPO levels were found between the groups. CONCLUSIONS: Erythrocytosis after renal transplantation represents an anomaly of both IGF-I and its major binding proteins. Further studies are under way to better define this dysregulation and determine whether IGF-I can play a more generalized role in secondary forms of erythropoiesis.

Adult↗

PubMed1998

Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer.

CONTEXT: The appropriate therapy for men with localized prostate cancer is uncertain. Until results of clinical trials are available, men and their physicians need guidance. OBJECTIVE: To estimate survival based on a competing risk analysis stratified by age at diagnosis and histologic findings for men diagnosed as having clinically localized prostate cancer and who were managed conservatively. DESIGN: Retrospective cohort study. SETTING: Connecticut Tumor Registry. PATIENTS: A total of 767 men with localized prostate cancer diagnosed between 1971 and 1984, aged 55 to 74 years at diagnosis, either not treated or treated with immediate or delayed hormonal therapy, and followed up for 10 to 20 years after diagnosis. MAIN OUTCOME MEASURES: Estimates of the probability of dying from prostate cancer or other competing hazards. RESULTS: Men with tumors that have Gleason scores of 2 to 4, 5, 6, 7, and 8 to 10 face a 4% to 7%, 6% to 11%, 18% to 30%, 42% to 70%, and 60% to 87% chance, respectively, of dying from prostate cancer within 15 years of diagnosis depending on their age at diagnosis. CONCLUSIONS: Men whose prostate biopsy specimens show Gleason score 2 to 4 disease face a minimal risk of death from prostate cancer within 15 years of diagnosis. Conversely, men whose biopsy specimens show Gleason score 7 to 10 disease face a high risk of death from prostate cancer when treated conservatively, even when cancer is diagnosed as late as age 74 years. Men with Gleason score 5 or 6 tumors face a modest risk of death from prostate cancer that increases slowly over at least 15 years of follow-up.

Aged↗

PubMed1998

Three-dimensional computer-assisted analysis of sector biopsy of the prostate.

OBJECTIVES: To assess the relationship between tumor volume, gland volume, number of sectors submitted to biopsy, and prostatic biopsy detection rate. METHODS: Using a three-dimensional mathematical model of the prostate, we assessed detection rates achieved with 4-, 6-, 8-, 10-, and 12-sector biopsies for glands ranging from 20 to 100 cc and peripheral zone tumors ranging from 0.3 to 1.4 cc. RESULTS: Quadrant and sextant biopsy approaches only yielded from 6.2% to 13.4% and 8.6% to 18.3%, respectively, of lesions in a 40-cc gland. Conversely, 10- and 12-sector approaches yielded, respectively, from 19.8% to 48.8% and 25.4% to 62% of lesions for the same gland size. When assessed according to the density of sampling, one biopsy core used for every 1 .5 to 3.5 cc of prostatic tissue detected 42.5% of 0.5-cc lesions. For the same lesion size, the density of sampling per biopsy core was then decreased to intervals extending from 3.6 to 7.5 cc, 7.6 to 12.5 cc, and 12.6 to 25 cc. These sampling density intervals yielded, respectively, 25.0%, 15.8%, and 9.8% detection rates. CONCLUSIONS: On the basis of our results, a gland volume-based biopsy algorithm is likely to result in improved detection of clinically significant prostate cancer.

Biopsy↗

PubMed1998

Aeroallergens and work-related respiratory symptoms among office workers.

OBJECTIVE: We sought to determine the association between office workers' respiratory tract symptoms and immediate skin test reactions with exposure to fungal and house dust mite aeroallergens at their work sites. METHODS: An initial prevalence survey was conducted among 1102 full-time workers in six mechanically ventilated, air-conditioned, nonindustrial buildings in downtown Montreal. Detailed environmental measures of 214 subjects' work sites were determined. Half of the workers reported frequent work-related respiratory tract symptoms on the initial survey. Participants simultaneously underwent allergy skin prick testing and completed a second self-administered questionnaire. RESULTS: Contaminant levels were low and not associated with symptoms in the great majority of workers. For approximately 17% of workers, symptoms were associated with exposure to total concentrations of house dust mite allergen greater than 1 microg/gm floor dust (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.3, 19.5]) or to detectable airborne Alternaria allergens in their offices (OR, 3.3; 95% CI, 1.2, 9.4 and in the ventilation system supplying their offices (OR, 3.9; 95% CI, 1.6, 9.6). Workers with positive skin test reactions to Alternaria extract were exposed at their work site to airborne Alternaria allergen (OR, 4.4; 95% CI, 1.4, 14.5) and cited significantly more respiratory symptoms on both questionnaires. Detection of airborne Alternaria allergen at work sites was significantly associated with detection in the ventilation system (OR, 4.0; 95% CI, 1.4,10.9); this was in turn associated with lower efficiency filters. CONCLUSIONS: Potentially avoidable exposure to aeroallergens accounted for symptoms in a small subgroup of office workers with frequent work-related respiratory tract symptoms.

Adult↗

PubMed1997

Use of physician services among family caregivers of elderly persons with dementia.

It is well known that there is an excess of physical and psychological health problems among family caregivers of elderly persons with Alzheimer's disease and other dementias. The objective of this study was to determine whether the higher level of morbidity translates into a higher level of medical care utilization. Data from a previously completed longitudinal study of caregivers for elderly persons with dementia were merged with data on physician visits obtained from the computerized records of the Quebec Health Insurance Board. Utilization of physician care (adjusted for age, sex, number of chronic diseases, and depression) was no higher for family caregivers of elderly patients with Alzheimer's disease and other dementias than for comparable family members of older persons without dementia. The annual cost of physician care was almost identical among caregivers and noncaregivers. However, the pattern of utilization for the two groups was somewhat different: there was a significantly higher frequency of physician utilization among caregivers for services billed by psychiatrists and internal medicine specialists. In multivariate analysis, physician utilization was significantly associated with having more than one chronic condition and with increased age. Future studies should focus on determining whether caregivers neglect their own health care needs as a result of the exigencies of the caregiving role.

Adult↗

PubMed1997

Extension of receiver operating characteristic analysis to data concerning multiple signal detection tasks.

RATIONALE AND OBJECTIVES: When receiver operating characteristic (ROC) studies involve multiple detection tasks in the same patient, the correlations among the within-patient interpretations and the shortage of patients raise several analytic challenges. The authors propose methods for both parametric and nonparametric analysis of this type of data. METHODS: First, they computed one accuracy statistic for each task. Then one jackknife "pseudovalue" was calculated for each task and each patient. Then, they formed a summary index from the accuracy statistics and calculated the standard error of this summary index on the basis of the observed correlations among the jackknife pseudovalues. The method was extended to comparisons of two diagnostic systems and illustrated by using data from a clinical study. RESULTS AND CONCLUSION: This approach can be used with rating or quantitative data and with any index of accuracy, whether calculated parametrically or nonparametrically.

Angiography↗