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Biomedical subjects

W E Barlow

Publications and source records attributed to W E Barlow.

At least 19 recordsLinked to original sources

Performance assessment for radiologists interpreting screening mammography.

When interpreting screening mammograms radiologists decide whether suspicious abnormalities exist that warrant the recall of the patient for further testing. Previous work has found significant differences in interpretation among radiologists; their false-positive and false-negative rates have been shown to vary widely. Performance assessments of individual radiologists have been mandated by the U.S. government, but concern exists about the adequacy of current assessment techniques. We use hierarchical modelling techniques to infer about interpretive performance of individual radiologists in screening mammography. While doing this we account for differences due to patient mix and radiologist attributes (for instance, years of experience or interpretive volume). We model at the mammogram level, and then use these models to assess radiologist performance. Our approach is demonstrated with data from mammography registries and radiologist surveys. For each mammogram, the registries record whether or not the woman was found to have breast cancer within one year of the mammogram; this criterion is used to determine whether the recall decision was correct. We model the false-positive rate and the false-negative rate separately using logistic regression on patient risk factors and radiologist random effects. The radiologist random effects are, in turn, regressed on radiologist attributes such as the number of years in practice. Using these Bayesian hierarchical models we examine several radiologist performance metrics. The first is the difference between the false-positive or false-negative rate of a particular radiologist and that of a hypothetical 'standard' radiologist with the same attributes and the same patient mix. A second metric predicts the performance of each radiologist on hypothetical mammography exams with particular combinations of patient risk factors (which we characterize as 'typical', 'high-risk', or 'low-risk'). The second metric can be used to compare one radiologist to another, while the first metric addresses how the radiologist is performing compared to an appropriate standard. Interval estimates are given for the metrics, thereby addressing uncertainty. The particular novelty in our contribution is to estimate multiple performance rates (sensitivity and specificity). One can even estimate a continuum of performance rates such as a performance curve or ROC curve using our models and we describe how this may be done. In addition to assessing radiologists in the original data set, we also show how to infer about the performance of a new radiologist with new case mix, new outcome data, and new attributes without having to refit the model.

Adult↗

The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine.

BACKGROUND: The administration of the diphtheria and tetanus toxoids and whole-cell pertussis (DTP) vaccine and measles, mumps, and rubella (MMR) vaccine has been associated with adverse neurologic events, including seizures. We studied the relation between these vaccinations and the risk of a first seizure, subsequent seizures, and neurodevelopmental disability in children. METHODS: This cohort study was conducted at four large health maintenance organizations and included reviews of the medical records of children with seizures. We calculated the relative risks of febrile and nonfebrile seizures among 679,942 children after 340,386 vaccinations with DTP vaccine, 137,457 vaccinations with MMR vaccine, or no recent vaccination. Children who had febrile seizures after vaccination were followed to identify the risk of subsequent seizures and other neurologic disabilities. RESULTS: Receipt of DTP vaccine was associated with an increased risk of febrile seizures only on the day of vaccination (adjusted relative risk, 5.70; 95 percent confidence interval, 1.98 to 16.42). Receipt of MMR vaccine was associated with an increased risk of febrile seizures 8 to 14 days after vaccination (relative risk, 2.83; 95 percent confidence interval, 1.44 to 5.55). Neither vaccination was associated with an increased risk of nonfebrile seizures. Analyses of automated data alone gave results similar to the analyses of the data from medical-record reviews. The number of febrile seizures attributable to the administration of DTP and MMR vaccines was estimated to be 6 to 9 and 25 to 34 per 100,000 children, respectively. As compared with other children with febrile seizures that were not associated with vaccination, the children who had febrile seizures after vaccination were not found to be at higher risk for subsequent seizures or neurodevelopmental disabilities. CONCLUSIONS: There are significantly elevated risks of febrile seizures on the day of receipt of DTP vaccine and 8 to 14 days after the receipt of MMR vaccine, but these risks do not appear to be associated with any long-term, adverse consequences.

Child↗

Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality.

BACKGROUND: Hormone replacement therapy (HRT) is typically avoided for women with a history of breast cancer because of concerns that estrogen will stimulate recurrence. In this study, we sought to evaluate the impact of HRT on recurrence and mortality after a diagnosis of breast cancer. METHODS: Data were assembled from 2755 women aged 35-74 years who were diagnosed with incident invasive breast cancer while they were enrolled in a large health maintenance organization from 1977 through 1994. Pharmacy data identified 174 users of HRT after diagnosis. Each HRT user was matched to four randomly selected nonusers of HRT with similar age, disease stage, and year of diagnosis. Women in the analysis were recurrence free at HRT initiation or the equivalent time since diagnosis. Rates of recurrence and death through 1996 were calculated. Adjusted relative risks were estimated by use of the Cox regression model. All statistical tests were two-sided. RESULTS: The rate of breast cancer recurrence was 17 per 1000 person-years in women who used HRT after diagnosis and 30 per 1000 person-years in nonusers (adjusted relative risk for users compared with nonusers = 0.50; 95% confidence interval [CI] = 0.30 to 0.85). Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per 1000 person-years in nonusers (adjusted relative risk = 0.34; 95% CI = 0.13 to 0.91). Total mortality rates were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers (adjusted relative risk = 0.48; 95% CI = 0.29 to 0.78). The relatively low rates of recurrence and death were observed in women who used any type of HRT (oral only = 41% of HRT users; vaginal only = 43%; both oral and vaginal = 16%). No trend toward lower relative risks was observed with increased dose. CONCLUSION: We observed lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than in women who did not. Although residual confounding may exist, the results suggest that HRT after breast cancer has no adverse impact on recurrence and mortality.

Adult↗

Cost comparison of mastectomy versus breast-conserving therapy for early-stage breast cancer.

BACKGROUND: Choice of treatment for early-stage breast cancer depends on many factors, including the size and stage of the cancer, the woman's age, comorbid conditions, and perhaps the costs of treatment. We compared the costs of all medical care for women with early-stage breast cancer cases treated by breast-conserving therapy (BCT) or mastectomy. METHODS: A total of 1675 women 35 years old or older with incident early-stage breast cancer were identified in a large regional nonprofit health maintenance organization in the period 1990 through 1997. The women were treated with mastectomy only (n = 183), mastectomy with adjuvant hormonal therapy or chemotherapy (n = 417), BCT with radiation therapy (n = 405), or BCT with radiation therapy and adjuvant hormonal therapy or chemotherapy (n = 670). The costs of all medical care for the period 1990 through 1998 were computed for each woman, and monthly costs were analyzed by treatment, adjusting for age and cancer stage. All statistical tests were two-sided. RESULTS: At 6 months after diagnosis, the mean total medical care costs for the four groups differed statistically significantly (P:<.001), with BCT being more expensive than mastectomy. The adjusted mean costs were $12 987, $14 309, $14 963, and $15 779 for mastectomy alone, mastectomy with adjuvant therapy, BCT plus radiation therapy, and BCT plus radiation therapy with adjuvant therapy, respectively. At 1 year, the difference in costs was still statistically significant (P:<.001), but costs were influenced more by the use of adjuvant therapy than by type of surgery. The 1-year adjusted mean costs were $16 704, $18 856, $17 344, and $19 081, respectively, for the four groups. By 5 years, BCT was less expensive than mastectomy (P:<.001), with 5-year adjusted mean costs of $41 930, $45 670, $35 787, and $39 926, respectively. Costs also varied by age, with women under 65 years having higher treatment costs than older women. CONCLUSIONS: BCT may have higher short-term costs but lower long-term costs than mastectomy.

Adult↗

Bone mineral density and breast cancer risk in postmenopausal women.

Two recent studies have shown a woman's bone mineral density (BMD) (a composite measure of exposure to many different factors throughout one's lifetime) predicts breast cancer. In a prospective cohort study, we examined whether hip BMD was associated with breast cancer risk among 8203 postmenopausal women. During an average follow-up of 3.7 years, 131 incident breast cancer cases (102 invasive) were identified. Cox proportional hazards models were used to obtain estimates of the relative risk of breast cancer. Our results demonstrate an increase in breast cancer risk among women with higher BMD. Independent of age, geographic area, and body mass index, relative to the lowest BMD quartile the risk of breast cancer (95% confidence interval) by increasing quartile was 1.9 (1.1, 3.2), 1.5 (0.8, 2.6), and 1.5 (0.8, 2.7), respectively. An examination of other factors important in determining BMD may help explain the positive association between BMD and breast cancer.

Aged↗

Bone mineral density and endogenous hormones and risk of breast cancer in postmenopausal women (United States).

OBJECTIVE: This case-cohort study was designed to examine whether total hip bone mineral density (BMD) is independently associated with breast cancer over and above its association with other determinants, including levels of total and bioavailable estradiol and testosterone and sex-hormone binding globulin. METHODS: Our study population was selected from a cohort of 8,203 postmenopausal women who were screened for the Fracture Intervention Trial in 1992, at which time BMD was assessed, and blood samples were obtained. A total of 109 women developed breast cancer during four years of follow-up; 173 other randomly selected women from the larger cohort were also selected. Cox proportional hazards with robust variance adjustment was used for these analyses. RESULTS: Relative to women in the lower fourth of the BMD distribution, the risk associated with being in the upper fourth was 2.6 (95% confidence interval (CI) 1.1-5.8). After adjusting for serum hormone levels, the corresponding relative risk was 2.5 (95% CI 0.9-5.2). With body mass index and number of years since menopause added to the multivariate analysis, the relative risk decreased to 1.4 (95% CI 0.5-4.0). CONCLUSIONS: BMD may not influence breast cancer risk independent of its relationship with endogenous hormones and measured covariates.

Aged↗

Formal education and back pain: a review.

OBJECTIVES: To summarise the scientific evidence on the relation between educational status and measures of the frequency and the consequences of back pain and of the outcomes of interventions among back pain patients, and to outline possible mechanisms that could explain such an association if found. DESIGN: Sixty four articles published between 1966 and 2000 that documented the association of formal education with back pain were reviewed. MAIN RESULTS: Overall, the current available evidence points indirectly to a stronger association of low education with longer duration and/or higher recurrence of back pain than to an association with onset. The many reports of an association of low education with adverse consequences of back pain also suggest that the course of a back pain episode is less favourable among persons with low educational attainment. Mechanisms that could explain these associations include variations in behavioural and environmental risk factors by educational status, differences in occupational factors, compromised "health stock" among people with low education, differences in access to and utilisation of health services, and adaptation to stress. Although lower education was not associated with the outcomes of interventions in major studies, it is difficult, in light of the current limited available evidence, to draw firm conclusions on this association. CONCLUSION: Scientific evidence supports the hypothesis that less well educated people are more likely to be affected by disabling back pain. Further study of this association may help advance our understanding of back pain as well as understanding of the relation between socioeconomic status and disease as a general phenomenon.

Adolescent↗

Effects of contraceptive use on bone biochemical markers in young women.

The purpose of this study was to compare biochemical markers of bone resorption and formation in young women using different hormonal contraceptive methods. Women aged 18-39 yr who were using depot medroxyprogesterone acetate (DMPA) contraception were recruited for the study; comparison women were matched by age and clinic location. There were 116 women using DMPA, 39 using oral contraceptives containing estrogen and progestin, and 72 not currently using hormonal contraceptives. Biochemical measurements were serum calcium, PTH and osteocalcin, and urine N-telopeptide. Bone density was measured using dual-energy x-ray absorptiometry. The N-telopeptide levels, adjusted for age and other risk factors, were 42.4 +/- 2.3 nmol/mmol creatinine in the DMPA group, 26.2 +/- 3.3 nmol/mmol in the oral contraceptive group, and 35.4 +/- 2.9 nmol/mmol in the nonusers; significant differences were seen in all pairwise comparisons. Osteocalcin levels showed the same pattern, although the difference between the DMPA users and nonusers was not statistically significant. There were no differences among groups in the PTH levels. The bone density at the spine was 1.086 +/- 0.085 g/cm(2) in the DMPA group, 1.103 +/- 0.095 g/cm(2) in the oral contraceptive group, and 1.093 +/- 0.090 g/cm(2) in nonusers (P = 0.051). The results suggest that in women using DMPA bone resorption exceeded bone formation.

Adult↗

Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Thiazide may have beneficial effects on bone mineral density and may reduce risk for hip fracture. However, the existence of a causal role remains uncertain because experimental evidence is limited. OBJECTIVE: To determine the effect of hydrochlorothiazide on rates of bone loss in older adults. DESIGN: Randomized, double-blind, placebo-controlled trial with 3-year follow-up. SETTING: A large health maintenance organization in western Washington State. PARTICIPANTS: 320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age. INTERVENTION: Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo. MEASUREMENTS: Bone mineral density using dual-energy x-ray absorptiometry at the total hip, posterior-anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiographic vertebral fractures. RESULTS: 309 of 320 participants completed the 36-month visit (97%). Adherence to study medication throughout follow-up was high in all participants (81.6% to 89.7%) except men in the high-dose hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the 36-month differences in percentage change in total hip bone mineral density were 0.79 percentage point (95% CI, -0.12 to 1.71) for the 12.5-mg hydrochlorothiazide group and 0.92 percentage point (CI, -0.001 to 1.85) for the 25-mg group compared with placebo (P = 0.03). Percentage change at the posterior-anterior spine was significantly greater for the 25-mg hydrochlorothiazide group at 6 months (intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI, -0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone mineral density between the treatment groups. Treatment effects were stronger in women than in men. CONCLUSIONS: In healthy older adults, low-dose hydrochlorothiazide preserves bone mineral density at the hip and spine. The modest effects observed over 3 years, if accumulated over 10 to 20 years, may explain the one-third reduction in risk for hip fracture associated with thiazide in many epidemiologic studies.

Aged↗

Current medicolegal and confidentiality issues in large, multicenter research programs.

The convenience of fast computers and the Internet have encouraged large collaborative research efforts by allowing transfers of data from multiple sites to a single data repository; however, standards for managing data security are needed to protect the confidentiality of participants. Through Dartmouth Medical School, in 1996-1998, the authors conducted a medicolegal analysis of federal laws, state statutes, and institutional policies in eight states and three different types of health care settings, which are part of a breast cancer surveillance consortium contributing data electronically to a centralized data repository. They learned that a variety of state and federal laws are available to protect confidentiality of professional and lay research participants. The strongest protection available is the Federal Certificate of Confidentiality, which supersedes state statutory protection, has been tested in court, and extends protection from forced disclosure (in litigation) to health care providers as well as patients. This paper describes the careful planning necessary to ensure adequate legal protection and data security, which must include a comprehensive understanding of state and federal protections applicable to medical research. Researchers must also develop rules or guidelines to ensure appropriate collection, use, and sharing of data. Finally, systems for the storage of both paper and electronic records must be as secure as possible.

Confidentiality↗

Testing reminder and motivational telephone calls to increase screening mammography: a randomized study.

BACKGROUND: Prospective randomized trials have demonstrated that motivational telephone calls increase adherence to screening mammography. To better understand the effects of motivational calls and to maximize adherence, we conducted a randomized trial among women aged 50-79 years. METHODS: We created a stratified random sample of 5062 women due for mammograms within the Group Health Cooperative of Puget Sound, including 4099 women with prior mammography and 963 without it. We recruited and surveyed 3743 (74%) of the women before mailing a recommendation. After 2 months, 1765 (47%) of the 3743 women had not scheduled a mammogram and were randomly assigned to one of three intervention groups: a reminder post-card group (n = 590), a reminder telephone call group (n = 585), and a motivational telephone call addressing barriers group (n = 590). The telephone callers could schedule mammography. We used Cox proportional hazards models to estimate the hazard ratio (HR) and 95% confidence interval (CI) for documented mammography use by 1 year. RESULTS: Women who received reminder calls were more likely to get mammograms (HR = 1.9; 95% CI = 1.6-2.4) than women who were mailed postcards. The motivational and reminder calls (average length, 8.5 and 3.1 minutes, respectively) had equivalent effects (HR = 0.97; 95% CI = 0.8-1.2). After we controlled for the intervention effect, women with prior mammography (n = 1277) were much more likely to get a mammogram (HR = 3.4; 95% CI = 2.7-4.3) than women without prior use (n = 488). Higher income, but not race or more education, was associated with higher adherence. CONCLUSIONS: Reminding women to schedule an appointment was as efficacious as addressing barriers. Simple intervention groups should be included as comparison groups in randomized trials so that we better understand more complex intervention effects.

Affect↗

Depressive symptoms in users and non-users of depot medroxyprogesterone acetate.

To evaluate the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception on depressive symptoms, we conducted a population-based prospective study with women aged 18-39 years old enrolled at a health maintenance organization. At baseline, 183 women used DMPA and 274 were non-users. Data on depressive symptoms and on factors potentially related to DMPA use and depression were collected by questionnaire at 6-month intervals for up to 3 years. In multivariate longitudinal analysis, we found an increased likelihood of reporting depressive symptoms among continuous DMPA users (OR = 1.44; 95% CI = 1.00-2.07) and discontinuers (OR = 1.60; 95% CI = 1.03-2.48) when compared to non-users. Women who discontinued DMPA use had elevated depressive symptoms prior to discontinuation (OR = 2.30; 95% CI = 1.42-3.70) and immediately following discontinuation (OR = 2.46; 95% CI = 1. 46-4.14), and depressive symptoms subsided at subsequent visits relative to non-users. Our prospective analyses found an association between DMPA use and depressive symptoms but further research is needed to determine whether the relationship is causal.

Adolescent↗

Identification and management of domestic violence: a randomized trial.

BACKGROUND: Diagnosis of domestic violence (DV) in primary care is low compared to its prevalence. Care for patients is deficient. Over a 1-year period, we tested the effectiveness of an intensive intervention to improve asking about DV, case finding, and management in primary care. The intervention included skill training for providers, environmental orchestration (posters in clinical areas, DV questions on health questionnaires), and measurement and feedback. METHODS: We conducted a group-randomized controlled trial in five primary care clinics of a large health maintenance organization (HMO). Outcomes were assessed at baseline and follow-up by survey, medical record review, and qualitative means. RESULTS: Improved provider self-efficacy, decreased fear of offense and safety concerns, and increased perceived asking about DV were documented at 9 months, and also at 21 months (except for perceived asking) after intervention initiation. Documented asking about DV was increased by 14.3% with a 3.9-fold relative increase at 9 months in intervention clinics compared to controls. Case finding increased 1.3-fold (95%, confidence interval 0.67-2.7). CONCLUSIONS: The intervention improved documented asking about DV in practice up to 9 months later. This was mainly because of the routine use of health questionnaires containing DV questions at physical examination visits and the placement of DV posters in clinical areas. A small increase in case finding also resulted. System changes appear to be a cost-effective method to increase DV asking and identification.

Adult↗

A comparison of pain, functional limitations, and work status indices as outcome measures in back pain research.

STUDY DESIGN: We conducted a prospective study with a 2-year follow-up. OBJECTIVE: To compare pain, functional limitations, and work status indices as measures of outcome among back pain patients. SUMMARY OF BACKGROUND DATA: Work status, pain, and functional limitations indices are often considered as interchangeable outcome measures in back pain research. This perspective has been criticized by several authors, who argue that each of these outcome measures reflects a different construct that may vary independently of the others. METHODS: The study was conducted on 720 patients, who sought care for back pain in primary care settings of a large health maintenance organization in 1989-90, and were interviewed one month and two years later. X2 analyses and receiver operating characteristic curves were used to compare the accuracy of a pain rating and a modified 16-item Roland-Morris score in classifying patients on work status and on the change in work status over time. RESULTS: Moderate agreement between the pain and functional limitations measures and work status was observed. Pain and functional limitations change scores agreed moderately with improvement in work status, but were poorly associated with decline in work status. CONCLUSIONS: Although the pain, functional limitations, and work status indices examined in this study are related, they are not equivalent and should not be regarded as interchangeable. These results argue for a clearer distinction of outcome measures in back pain research.

Adult↗

Hypertension, antihypertensive medication use, and risk of renal cell carcinoma.

To investigate whether diuretic medication use increases risk of renal cell carcinoma (RCC), the authors conducted a case-control study of health maintenance organization members in western Washington State. Cases (n = 238) diagnosed between January 1980 and June 1995 were compared with controls (n = 616) selected from health maintenance organization membership files. The computerized health maintenance organization pharmacy database provided information on medications prescribed after March 1977. Additional exposure information was collected from medical records. For women, use of diuretics was associated with increased risk of RCC (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.0-3.1), but the association was not independent of a diagnosis of hypertension (adjusted for hypertension, OR = 1.1, 95% CI 0.5-2.1). Similarly, nondiuretic antihypertensive use was associated with increased risk, but only when unadjusted for hypertension. For men, neither diuretic nor nondiuretic antihypertensive use was associated with risk of RCC. A diagnosis of hypertension was clearly associated with RCC risk for women (OR = 2.5, 95% CI 1.2-5.1), but not men (OR = 1.3, 95% CI 0.7-2.5). High systolic and diastolic blood pressures were associated with increased risk in both sexes. These results do not support the hypothesis that use of diuretic medication increases RCC risk; they are more consistent with an association between RCC and high blood pressure.

Adolescent↗

Bone mineral density in women using depot medroxyprogesterone acetate for contraception.

OBJECTIVE: To evaluate the possible effects of depot medroxyprogesterone acetate injectable contraception on bone mineral density in reproductive-age women. METHODS: We conducted a population-based cross-sectional comparison of bone mineral density levels in women using depot medroxyprogesterone acetate contraception and in women of similar age not using this method. The study recruited 457 nonpregnant women aged 18-39 years who were enrollees of a Washington state health maintenance organization. One hundred eighty-three women were receiving injections and 274 were not. Bone mineral density at several anatomic sites (spine, femoral neck, greater trochanter, and whole body) was measured using dual-energy x-ray absorptiometry. Data on other factors potentially related to bone density were collected through questionnaire and examination. RESULTS: Overall, age-adjusted mean bone density levels were lower for users of this method than for nonusers at all anatomic sites: The mean difference was 2.5% for the spine (P = .03) and 2.2% for the femoral neck (P = .12). Exposure to depot medroxyprogesterone acetate continued to be significantly (P < .01) associated with decreased bone density at the femoral neck, spine, and trochanter after multivariate adjustment for other risk factors related to bone density. Age-specific comparisons indicated that the major differences in bone density between users and nonusers occurred in the youngest age group (women 18-21 years); the mean femoral neck bone density was 10.5% lower (P < .01) for the exposed women, and differences were consistent (P < .01) across all anatomic sites. We also noted a significant dose-response relation between longer use of depot medroxyprogesterone acetate and decreased bone density levels in this age group (P < .01 for all sites). CONCLUSION: These results provide evidence that contraception with depot medroxyprogesterone acetate, particularly long-term use, may adversely affect bone mineral density levels in young women aged 18-21 years. The implications for future bone health need further study.

Absorptiometry, Photon↗

Analysis of case-cohort designs.

The case-cohort design is most useful in analyzing time to failure in a large cohort in which failure is rare. Covariate information is collected from all failures and a representative sample of censored observations. Sampling is done without respect to time or disease status, and, therefore, the design is more flexible than a nested case-control design. Despite the efficiency of the methods, case-cohort designs are not often used because of perceived analytic complexity. In this article, we illustrate computation of a simple variance estimator and discuss model fitting techniques in SAS. Three different weighting methods are considered. Model fitting is demonstrated in an occupational exposure study of nickel refinery workers. The design is compared to a nested case-control design with respect to analysis and efficiency in a small simulation. In this example, case-cohort sampling from the full cohort was more efficient than using a comparable nested case-control design.

Case-Control Studies↗