Re: "Population attributable fraction estimation for established breast cancer risk factors: considering the issues of high prevalence and unmodifiability".
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Breast Neoplasms↗
Biomedical subjects
J Benichou
Publications and source records attributed to J Benichou.
Percutaneous mechanical mitral commissurotomy with a newly designed metallic valvulotome: immediate results of the initial experience in 153 patients.
BACKGROUND: Percutaneous balloon valvotomy has become a common treatment of mitral stenosis, but the cost of the procedure remains a limitation in countries with restricted financial resources, leading to a frequent reuse of the disposable catheters. To overcome this limitation, a reusable metallic valvotomy device has been developed with the goals of both improving the mitral valvotomy results and decreasing the cost of the procedure. METHODS AND RESULTS: The device consists of a detachable metallic cylinder with 2 articulated bars screwed onto the distal end of a disposable catheter whose proximal end is connected to an activating pliers. By the transseptal route, the device is advanced across the valve over a traction guidewire. Squeezing the pliers opens the bars up to a maximum extent of 40 mm. The clinical experience consisted of 153 patients with a broad spectrum of mitral valve deformities. The procedure was successful in 92% of cases and resulted in a significant increase in mitral valve area, from 0.95+/-0.2 to 2. 16+/-0.4 cm2. No increase in mitral regurgitation was noted in 80% of cases. Bilateral splitting of the commissures was observed in 87%. Complications were 2 cases of severe mitral regurgitation (1 requiring surgery), 1 pericardial tamponade, and 1 transient cerebrovascular embolic event. In this series, the maximum number of consecutive patients treated with the same device was 35. CONCLUSIONS: The results obtained with this new device are encouraging and at least comparable to those of current balloon techniques. Multiple uses after sterilization should markedly decrease the procedural cost, a major advantage in countries with limited resources and high incidence of mitral stenosis.
Adolescent↗
Designing studies to estimate the penetrance of an identified autosomal dominant mutation: cohort, case-control, and genotyped-proband designs.
One can obtain population-based estimates of the penetrance of a measurable mutation from cohort studies, from population-based case-control studies, and from genotyped-proband designs (GPD). In a GPD, we assume that representative individuals (probands) agree to be genotyped, and one then obtains information on the phenotypes of first-degree relatives. We also consider an extension of the GPD in which a relative is genotyped (GPDR design). In this paper, we give methods and tables for determining sample sizes needed to achieve desired precision for penetrance estimates from such studies. We emphasize dichotomous phenotypes, but methods for survival data are also given. In an example based on the BRCA1 gene and parameters given by Claus et al. [(1991) Am J Hum Genet 48:232-242], we find that similar large numbers of families need to be studied using the cohort, case-control, and GPD designs if the allele frequency is known, though the GPDR design requires fewer families, and, if one can study mainly probands with disease, the GPD design also requires fewer families. If the allele frequency is not known, somewhat larger sample sizes are required. Surprisingly, studies with mixtures of families of affected and non-affected probands can sometimes be more efficient than studies based exclusively on affected probands when the allele frequency is unknown. We discuss the feasibility and validity of these designs and point out that GPD and GPDR designs are more susceptible to a bias that results when the tendency for an individual to volunteer to be a proband or to be a subject in a cohort or case-control study depends on the phenotypes of his or her relatives.
Bias↗
[Interpretation of standard chest x-rays in thoracic trauma: influence of the experience of the interpreter].
OBJECTIVE: To compare the quality of interpretation of chest radiographs (CRs) by physicians of different levels of experience, with reference to data obtained from helicoidal computed tomography (HCT). STUDY DESIGN: Prospective observational study. MATERIAL: CRs of 50 thorax trauma patients as recent to HCTs as possible obtained within the 48 h following admission to the intensive therapy unit. METHOD: CRs were analyzed according to a grid by observers included in one of the four groups: residents in anaesthesiology (n = 6), residents in radiology (n = 3), senior anaesthesiologists (n = 5), and senior radiologists (n = 3). The inter-observer agreements, the specificity and sensibility of each group with reference to HCT, and their global performances were assessed. RESULTS: Inter-observer agreements were poor and sensitivities low in comparison to specificities. No group of observers performed better than another one. These data substantiate the low sensitivity of CRs in comparison to HCT and show that the quality of interpretation of CRs of thorax trauma patients is not influenced by physicians' experience.
Adult↗
[Epidemiology of precancerous lesions: from endoscopic detection to screening].
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Asbestos↗
Population attributable risk of renal cell cancer in Minnesota.
A population-based case-control study of renal cell cancer was conducted in Minnesota between 1988 and 1990. It included 690 histologically confirmed incident cases identified through the state cancer surveillance system, and 707 age and sex frequency-matched controls. In this paper, the authors present estimates of the proportion of renal cell cancer cases attributable (or population attributable risk (PAR)) to 1) well-established risk factors, namely smoking, excess weight, and hypertension, and 2) more speculative risk factors, namely elevated protein intake, history of renal disease (i.e., stone, injury, or infection) and high parity among women. These estimates were based on information obtained from directly interviewed subjects (65% of cases and 100% of controls). The PARs for the three main risk factors were 21% for hypertension (defined by a reported personal history of hypertension or of treatment with antihypertensive or diuretic drugs), 21% for excess weight (defined by an elevation of the usual body mass index above the first quartile), and 18% for smoking (past and current). Overall, these three factors accounted for 49% of cases. The proportion increased to 60% when the three more speculative risk factors were considered as well. Sex-specific analyses revealed a greater impact of smoking among men mainly due to a higher prevalence of past smoking. In contrast, the impact of hypertension and excess weight was greater among women due to higher relative risks. These results suggest that 1) intervention measures aimed at reducing smoking, excess weight, and hypertension could substantially lower the overall incidence of renal cell cancer, and 2) intervention measures may have to be sex-specific. Conversely, because at least 40% of cases remain unexplained by the risk factors under study, further etiologic research is needed into renal cell cancer, an increasingly common form of cancer.
Adult↗
Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study.
OBJECTIVE: To assess both the prevalence and the characteristics of motor disorders of the small bowel in patients with systemic sclerosis (SSc) and to investigate for an association between clinical manifestations in the upper intestinal tract, capillaroscopic features, esophageal motor impairment, and manometric evidence of motor disturbances. METHODS: Fasting and postprandial motor activity of the upper intestinal tract was studied in 17 consecutive patients with SSc (6 with and 11 without clinical manifestations of small bowel involvement) and 17 age- and sex-matched healthy control subjects. RESULTS: The prevalence of manometric evidence of intestinal involvement was as high as 88% in the SSc patients; normal motor activity was present in only 2 patients. The median values for duodenal and jejunal interdigestive phase III migrating motor complex duration, amplitude, and velocity and the postprandial motility index were therefore lower in SSc patients compared with controls. Our manometric findings indicated that there are both neuropathic and myopathic stages of upper intestinal tract dysfunction in SSc. Furthermore, no association could be found between the severity of the intestinal manometric abnormalities and clinical presentation, SSc subsets, disease score, capillaroscopic findings, or esophageal manometric impairment. CONCLUSION: We suggest that manometry of the upper intestinal tract may be useful in SSc patients with clinical manifestations in the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it can be used to accurately evaluate both the nature and the severity of motor disturbances. Furthermore, this procedure can be used to assist in the selection of patients who may require octreotide therapy.
Adult↗
Treatment of uveitis with recombinant human interleukin-13.
AIM: To evaluate the anti-inflammatory cytokine interleukin-13 (IL-13) for the treatment of uveitis. METHODS: Uveitis was induced in monkeys by immunisation with human retinal S-antigen. Starting at the onset of disease, the animals were treated with IL-13 at 25 micrograms/kg, or vehicle control, injected subcutaneously once a day for 28 days. Intraocular inflammation was scored by indirect ophthalmoscopy for a period of 56 days. Circulating leucocyte levels were monitored. RESULTS: Uveitis started unilaterally in all but one animal. IL-13 inhibited inflammation both in the eyes in which the disease was present when the treatment was initiated (p = 0.0001), and in the contralateral initially negative eyes (p = 0.0001). After cessation of therapy, there was a progressive increase of inflammation in the IL-13 treated group. However, the beneficial effect of IL-13 extended into the 4 week follow up period. IL-13 produced an increase in circulating polymorphonuclear neutrophils and a decrease in lymphocytes. CONCLUSION: Administration of IL-13 appears to be a promising modality of treatment for severe uveitis.
Animals↗
Ethnicity and variation in breast cancer incidence.
A breast cancer case-control study in Atlanta and 5 counties of central New Jersey involving interviews with 960 white and 281 black cases younger than 54 years of age enabled assessment of reasons for the varying incidence rates among these 2 ethnic groups. Of interest was why rates of breast cancer are higher among older white women, a trend that is reversed among very young women (<40 years). Calculation of the prevalence of exposure to classic and speculative risk factors and associated relative risks enabled derivation of population attributable risks (PARs) for the various combinations of age and ethnic groups. A higher PAR was derived for older (40-54 years) white (62%) than black (54%) women, which appeared to account for the observed difference in incidence between the 2 ethnic groups. Most of the difference in PARs between older whites and blacks was accounted for by whites having fewer births, later ages at first birth and slightly higher risks associated with reproductive and menstrual factors. Consideration of only well-established breast cancer risk factors showed a PAR among older whites of 57%, an estimate comparable to those previously published. Slightly higher overall PARs were derived when analyses considered several speculative but modifiable risk factors, including years of use of oral contraceptives, body size and alcohol consumption. Many of the analyses among younger women (20-39 years) were limited by available numbers, but it appeared that very little disease occurrence in young black women was associated with the factors studied.
Adult↗
Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases.
We studied the efficacy and tolerance of humanized Ab interfering with the signal of the IL-2 and IL-15 receptors in a primate model of experimental autoimmune uveoretinitis. The inhibitory effects of humanized anti-Tac (HAT), an anti-IL-2R alpha-chain Ab, and HuMik beta1, an Ab directed at the beta-chain shared by the receptors of IL-2 and IL-15, were tested in culture on the proliferative response of monkey Con A-blast lymphocytes stimulated with IL-2 or IL-15. Uveitis was induced in cynomolgus monkeys by immunization with human recombinant retinal S-antigen. Treatment was initiated at the first sign of disease and consisted of HAT and HuMik beta1, alone or in combination, or vehicle control given by i.v. injection twice a week for 4 wk. Disease was evaluated by ocular funduscopy. The results in culture showed a significant dose-dependent inhibition of the IL-2-driven proliferation of lymphocytes by HAT. HuMik beta1 alone was ineffective against IL-2 stimulation, but had a marked potentiating effect in combination with HAT, independent of IL-15 signaling. IL-15-driven proliferation was inhibited by HuMik beta1, but not by HAT alone or in combination. In monkeys, experimental autoimmune uveoretinitis evolution was significantly inhibited by HAT treatment. HuMik beta1 alone had no effect on the disease. However, when used in combination, the two Ab markedly reduced the severity of ocular inflammation. The Ab were well tolerated. Only three monkeys, treated with HAT alone, made an Ab response against the injected Ab.
Animals↗
Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group.
BACKGROUND: Recently, a cluster of patients was observed in France in whom primary pulmonary hypertension developed in patients exposed to derivatives of fenfluramine in appetite suppressants (anorexic agents), which are used for weight control. We investigated the potential role of anorexic agents and other suspected risk factors for primary pulmonary hypertension. METHODS: In a case-control study, we assessed 95 patients with primary pulmonary hypertension from 35 centers in France, Belgium, the United Kingdom, and the Netherlands and 355 controls recruited from general practices and matched to the patients' sex and age. RESULTS: The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension (odds ratio with any anorexic-drug use, 6.3; 95 percent confidence interval, 3.0 to 13.2). For the use of anorexic agents in the preceding year, the odds ratio was 10.1 (95 percent confidence interval, 3.4 to 29.9). When anorexic drugs were used to a total of more than three months, the odds ratio was 23.1 (95 percent confidence interval, 6.9 to 77.7). We also confirmed an association with several previously identified risk factors: a family history of pulmonary hypertension, infection with the human immunodeficiency virus, cirrhosis, and use of cocaine or intravenous drugs. CONCLUSIONS: The use of anorexic drugs was associated with the development of primary pulmonary hypertension. Active surveillance for this disease should be considered, particularly since their use is expected to increase in the near future.
Adolescent↗
Alcohol use and prostate cancer risk in US blacks and whites.
Prostate cancer is the most common malignancy in US men (more than 165,000 cases per annum) and occurs substantially more frequently in blacks than in whites. The causes of this disease are, however, poorly understood. Alcohol consumption, which has been clearly related to malignancies of the upper aerodigestive tract, may also increase risk of cancer at other sites, including the prostate. The authors investigated alcohol use as a risk factor for prostate cancer among US blacks and whites. A population-based, case-control study was carried out among 981 men (479 blacks and 502 whites) with pathologically confirmed prostate cancer diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 blacks and 721 whites) who resided in Atlanta, Georgia; Detroit, Michigan; and 10 counties in New Jersey, geographic areas covered by three population-based cancer registries. In-person interviews elicited information on alcohol use and other factors possibly related to prostate cancer. Compared with never-users, risk for prostate cancer increased with amount of alcohol drunk (chi2 (trend), p < 0.001), with significantly elevated risks seen for those who had 22-56 drinks per week (odds ratio = 1.4; 95% confidence interval 1.0-1.8) and 57 or more drinks per week (odds ratio = 1.9; 95% confidence interval 1.3-2.7). The finding was consistent among blacks (chi2 (trend), p < 0.01) and whites (chi2 (trend), p < 0.05), and among young and old subjects; it was not restricted to a specific type of alcoholic beverage. In this first large study among US blacks and whites, increased risk for prostate cancer was associated with increased alcohol use. The risk was similar for whites and blacks and could not be attributed to tobacco use or to a number of other potential confounders.
Adult↗
Software for attributable risk and confidence interval estimation in case-control studies.
The increasing interest in obtaining model-based estimates of attributable risk (AR) and corresponding confidence intervals, in particular when more than one risk factor and/or several confounding factors are jointly considered, led us to develop a program based on the procedure described by Benichou and Gail for case-control data. This program is structured as an SAS-macro. It is suited to analysis of the relationship between risk factors and disease in case-control studies with simple random sampling of controls, in terms of relative risks and ARs, by means of unconditional logistic regression analysis. The variance of the AR is obtained by the delta method and is based on three components, namely, (i) the variance-covariance matrix of the vector of the estimated probabilities of belonging to joint levels of the exposure and confounding factors conditional on being a case, (ii) the variance-covariance matrix of the odds ratio parameter estimates from the logistic model, and (iii) the covariances between these probability and parameter estimates. Only a limited number of commands is requested from the user (i.e., the name of the work file and the names of the variables considered). The estimated relative risks for all the factors included in the model, the attributable risk for the exposure factor under consideration, and the corresponding 95% confidence intervals are given as outputs by the macro. Computational problems, if any, may arise for large numbers of covariates because of the resulting large size of vectors and matrices. The macro was tested for reliability and consistency on published data sets of case-control studies.
Age Factors↗
Estimating the effect of dietary fat on the risk of lung cancer in nonsmoking women.
In 1992, approximately 13 000 lung cancers occurred in nonsmoking U.S. women but the cause of these highly fatal tumors is not well understood. As the rate of smoking declines in many developed countries, the interest in identifying lung cancer risk factors other than tobacco smoking is increasing. A population-based, case-control study of incident lung cancer among nonsmoking women in Missouri was conducted between 1986 and 1992 to assess the effect of a comprehensive list of potential risk factors. Dietary information on 429 case subjects and 1021 control subjects was obtained by personal interview, or next-of-kin interviews (36% and 64%, respectively) and the relationship of diet to lung cancer risk is the focus of this investigation. Odds ratios and population attributable risks (PAR) for dietary fat and dietary saturated fat were computed among lifetime nonsmokers and long-term ex-smokers. The mean age at lung cancer diagnosis was 71 years old, and nearly 50% of the lung cancers were histologically confirmed adenocarcinomas. Dietary intake of saturated fat was the leading identified cause of lung cancer among lifetime nonsmokers and former smokers in Missouri. The etiologic link between dietary saturated fat and lung cancer has not been examined in many other studies and the studies published to date are not completely consistent with the hypothesis so a cautious interpretation of the population attributable risks for these exposures is warranted. Nonetheless, a growing number of studies arising from around the world purport to show a link between fat, saturated fat and/or cholesterol or food groups containing relatively high amounts of these macronutrients (i.e. dairy products, eggs and/or red meat consumption) and lung cancer, and these recent studies add support to this hypothesis. If the results from Missouri are valid and applicable to other Americans, 23% of lung cancer cases among lifetime nonsmokers in the United States could be prevented if the saturated fat consumption of the upper half of saturated fat intake continuum could be reduced to the level consumed by the lower half. Even greater reductions in risk could be achieved if saturated fat consumption were reduced to even lower levels (i.e. 20th percentile of consumption as shown in this paper). However, additional etiologic research and evaluation is needed before specific dietary recommendations concerning fat and saturated fat and lung cancer prevention can be made.
Adult↗
Graphs to estimate an individualized risk of breast cancer.
PURPOSE: Clinicians who counsel women about their risk for developing breast cancer need a rapid method to estimate individualized risk (absolute risk), as well as the confidence limits around that point. The Breast Cancer Detection Demonstration Project (BCDDP) model (sometimes called the Gail model) assumes no genetic model and simultaneously incorporates five risk factors, but involves cumbersome calculations and interpolations. This report provides graphs to estimate the absolute risk of breast cancer from the BCDDP model. PATIENTS AND METHODS: The BCDDP recruited 280,000 women from 1973 to 1980 who were monitored for 5 years. From this cohort, 2,852 white women developed breast cancer and 3,146 controls were selected, all with complete risk-factor information. The BCDDP model, previously developed from these data, was used to prepare graphs that relate a specific summary relative-risk estimate to the absolute risk of developing breast cancer over intervals of 10, 20, and 30 years. RESULTS: Once a summary relative risk is calculated, the appropriate graph is chosen that shows the 10-, 20-, or 30-year absolute risk of developing breast cancer. A separate graph gives the 95% confidence limits around the point estimate of absolute risk. Once a clinician rules out a single gene trait that predisposes to breast cancer and elicits information on age and four risk factors, the tables and figures permit an estimation of a women's absolute risk of developing breast cancer in the next three decades. CONCLUSION: These results are intended to be applied to women who undergo regular screening. They should be used only in a formal counseling program to maximize a woman's understanding of the estimates and the proper use of them.
Adult↗
[Mesenteric panniculitis simulating Crohn disease].
Mesenteric panniculitis is a rare disease involving the adipose tissue of the mesentery. We report a case of a 27-year-old woman with mesenteric panniculitis, who presented clinical and radiological features mimicking Crohn's disease. In the outcome, she presented a small bowel perforation, unusual in this pathology, and an annexial involvement. This case reminds us of the role of sepsis and repeated abdominal surgery in relation to the pathogenesis of mesenteric panniculitis. We report the first case of mesenteric panniculitis mimicking Crohn's disease.
Adult↗
Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica.
Human T-cell lymphotropic virus type I (HTLV-I) has been etiologically associated with a neurologic syndrome called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-I infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-I-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-I seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-I seropositive compared with two (4.0%) of the controls with other neurologic diseases. Given HTLV-I seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual confidence interval 1.29-12.46 for individuals aged < or = 15; odds ratio = 4.26, 95% confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95% confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse or the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-I infection, whereas adult T-cell leukemia/lymphoma is not.
Adolescent↗
Proportion of breast cancer cases in the United States explained by well-established risk factors.
BACKGROUND: Few estimates of the fraction of cases of breast cancer attributable to recognized risk factors have been published. All estimates are based on selected groups, making their generalizability to the U.S. population uncertain. PURPOSE: Our goal was to estimate the fraction of breast cancer cases in the United States attributable to well-established risk factors (i.e., later age at first birth, nulliparity, higher family income, and first-degree family history of breast cancer), using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study (NHEFS), the survey and follow-up of a probability sample of the U.S. population. METHODS: From a cohort of 7508 female participants surveyed in the early 1970s, and followed up between 1982 and 1984 and again in 1987, 193 breast cancer cases were accrued for study. We calculated incidence rates, relative risks (RRs), and population attributable risks (PARs) for breast cancer risk factors and extended our results to the U.S. female population by using sample weights from the NHANES I survey. RESULTS: Our PAR estimates suggest that later age at first birth and nulliparity accounted for a large fraction of U.S. breast cancer cases, 29.5% (95% confidence interval [CI] = 5.6%-53.3%); higher income contributed 18.9% (95% CI = -4.3% to 42.1%), and family history of breast cancer accounted for 9.1% (95% CI = 3.0%-15.2%). Taken together, these well-established risk factors accounted for approximately 47% (95% CI = 17%-77%) of breast cancer cases in the NHEFS cohort and about 41% (95% CI = 2%-80%) in the U.S. population. CONCLUSIONS: The RRs for most of these risk factors were modest, but their prevalence as a group was high, leading to estimates that suggest that a substantial proportion of breast cancer cases in the United States are explained by well-established risk factors. IMPLICATIONS: Elucidation of the determinants underlying recognized factors and study of other factors that may confer risk or protection are needed in efforts to advance understanding of breast cancer etiology and to aid in devising strategies for prevention.
Adult↗