As mammography use increases, are some providers omitting clinical breast examination?

OBJECTIVE: To explore use of clinical breast examination (CBE) among women receiving mammography. METHODS: A retrospective cohort analysis of 100 women aged 50 years or older with at least one bilateral mammogram. Chart review documented demographic information, severity of illness, and performance of CBE (from 1 year prior to 18 months after the mammogram). RESULTS: The mean age of the 100 women was 63 years. They were predominantly unmarried (60%), nonwhite (58%), and not currently employed (57%). Three quarters (76%) had mammography and CBE (comprehensive screening), while the remaining 24% had mammography only. Sociodemographic factors did not differ for women with and without comprehensive screening (P>.1). However, patients of female providers were more likely to receive comprehensive screening than patients of male providers. Specifically, 95% of women seen by female attending physicians or fellows had comprehensive screening vs 67% for male attending physicians or fellows and 61% for residents (P=.008). CONCLUSIONS: Mammography may be replacing CBE especially among patients of male providers. Interventions targeted to these providers could help improve the use of CBE and mammography.

Physician characteristics: do they influence the evaluation and treatment of breast cancer in older women?

BACKGROUND: To determine if physician specialty, length of time in practice, and fear of malpractice influence the diagnosis and management of breast cancer in older women. METHODS: We used a fractional factorial design that controlled for patient age (65 or 80 years), race, socioeconomic status, mobility, comorbidity, and assertive behavior through 2 videotaped scenarios (a potential breast cancer [no. 1] and a known stage IIA breast cancer [no. 2]). One hundred twenty-eight white male physicians equally divided by specialty (surgeon versus nonsurgeon) and time in practice (< or = 15 or >15 years) viewed the videotapes and made recommendations. RESULTS: The physician subjects saw 46 patients per week, 59% female, and 47% age > or = 65. Their concern over malpractice was 4.7 (on a 10-point Likert scale with a higher score indicating more concern) and did not differ by specialty or time in practice (P values > 0.7). After viewing scenario no. 1, surgeons were less likely than nonsurgeons to consider breast cancer as the principal diagnosis (odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.2 to 0.9) and to obtain a tissue diagnosis (OR = 0.3, 95% CI = 0.1 to 0.9). However, in scenario no. 2, surgeons were more likely to offer reconstruction (OR = 3.8, 95% CI = 1.4 to 10.4). Physicians in practice < or = 15 years were more likely than those in practice <15 years to obtain a tissue diagnosis in scenario no. 1 (OR = 6.1, 95% CI = 1.9 to 19.2) and to perform full primary therapy in scenario no. 2 (OR = 2.8, 95% CI = 1.2 to 6.9). Physicians who performed an extensive metastatic evaluation (bone or computer tomography [CT] scan) had greater concern over malpractice than those who did not, as did physicians who performed an axillary node dissection (OR = 2.1, 95% CI 1.3 to 3.4 and OR = 1.8, 95% CI = 1.1 to 3.0). CONCLUSIONS: With the uncertainty of how to diagnose and treat older women with breast cancer, physician specialty, length of time in practice, and concern over malpractice do influence clinical decisions.

Outcomes for older men and women with congestive heart failure.

OBJECTIVES: To describe and compare outcomes for men and women discharged alive following a hospitalization for congestive heart failure (CHF). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 519 patients, aged > or = 65, who were discharged alive after a hospitalization for CHF (DRG = 127). MEASUREMENTS: Outcomes (Activities of Daily Living (ADLs), shortness of breath when walking, perceived health, living situation, rehospitalization, and mortality) were measured at 3 times (6 weeks, 6 months, and 1 year) post-discharge. RESULTS: The 205 men were, on average, younger (77 +/- 7 vs 80 +/- 8, P < .001), wealthier (46% vs 21% earned > or = $10,000, P < .001), and more often married (50% vs 19%, P < .001). Men were more likely than women to have a previous history of CHF (71% vs 63%, P = .052). Men also had higher 1-year mortality than women (48% vs 35%, P = .009), even after adjusting for age, comorbidity, physiological severity (APACHE II APS and RAND discharge instability), radiological evidence of CHF, prior ADLs, walking ability, living situation, and perceived health. Men and women survivors at 1-year had similar and substantial impairment for all non-fatal outcomes considered (all P values > or = .489). Their adjusted mean ADL scores were consistent with complete dependence on one essential activity (range 0-6 dependencies); 35% were short of breath walking less than 1 block; 62% had fair or poor perceived health; 32% received some formal care; and 46% were rehospitalized within 1 year of discharge. CONCLUSIONS: Men with CHF have a higher mortality than women with CHF. Men and women who survive have similar and substantial impairment for all non-fatal outcomes (ADLs, shortness of breath upon walking, perceived health, living situation, and rehospitalization).

Mammography use, breast cancer stage at diagnosis, and survival among older women.

BACKGROUND: Women age 65 years and older account for most newly diagnosed breast cancers and deaths from breast cancer. Yet, older women are least likely to undergo mammography, perhaps because mammography's value is less well demonstrated in older women. OBJECTIVE: To investigate the relationship between prior mammography use, cancer stage at diagnosis, and breast cancer mortality among older women with breast cancer. DESIGN: Retrospective cohort study using the Linked Medicare-Tumor Registry Database. SETTING: Population-based data from three geographic areas included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. PARTICIPANTS: Women aged 67 and older diagnosed with a first primary breast cancer, from 1987 to 1993, residing in Connecticut, metropolitan Atlanta, Georgia, or Seattle-Puget Sound, Washington. MEASUREMENTS: Medicare claims were reviewed and women were classified according to their mammography use during the 2 years before diagnosis: nonusers (no prior mammograms), regular users (at least two mammograms at least 10 months apart), or peri-diagnosis users (only mammogram(s) within 3 months before diagnosis). Mammography utilization was linked with SEER data to determine stage at diagnosis and cause of death. Our main outcome variables were (1) stage at diagnosis, classified as early (in situ/Stage I) or late (Stage II or greater), and (2) breast cancer mortality, measured from diagnosis until death from breast cancer or end of the follow-up period (December 31, 1994). RESULTS: Older women who were nonusers of mammography were diagnosed with breast cancer at Stage II or greater more often than regular users (adjusted odds ratio (OR), 3.12; 95% confidence interval (CI), 2.74-3.58). This association was present within each age group studied. Nonusers of mammography were at significantly greater risk of dying from their breast cancer than regular users for all women (adjusted hazard ratio (HR), 3.38; 95% CI, 2.65-4.32) and for women within each age group. Even assuming a lead time of 1.25 years, nonusers of mammography continued to be at increased risk of dying from breast cancer. Our findings remained significant for all women and for the two youngest age groups (67-74 years, 75-85 years), although the benefit was no longer statistically significant for the oldest women (85 years and older). CONCLUSIONS: Older women who undergo regular mammography are diagnosed with an earlier stage of disease and are less likely to die from their disease. These data support the use of regular mammography in older women and suggest that mammography can reduce breast cancer mortality in older women, even for women age 85 and older.

Variability in mammography use among older women.

OBJECTIVE: To determine rates of and explore factors associated with mammography use among older women. DESIGN: Retrospective review of part B (physician) bills submitted to Medicare during 1990. SETTING: Health Care Financing Administration (HCFA) data, including sociodemographic information and part B physician bills for all services delivered to Medicare-eligible women in 1990. PATIENTS/PARTICIPANTS: Women age 65 or older as of January 1, 1990, residing in one of 10 states with part B coverage through December 31, 1990. MEASUREMENTS AND MAIN RESULTS: The outcome was receipt of a mammogram (yes/no). We explored factors associated with mammography use within three age groups: 65 to 74, 75 to 84, and 85+. The factors considered were race, state, median income of ZIP Code of residence (from the 1990 US Census, and used to divide the population into quintiles within each state), and number of primary care visits (0, 1, 2, and 3+). Overall, 15% of women had a mammogram: 20% of women age 65 to 74, 12% of women age 75 to 84, and 4% of women age 85 and older. Mammography use was lowest in Oklahoma and highest in Washington. However, in each state the older the age category, the less the mammography use (e.g., 9% vs 5% vs 2% in Oklahoma and 25% vs 16% vs 5% in Washington for women 65-74, 75-84, and 85+, respectively). Mammography use was lower for black than for white women age 65 to 74 (14% vs 21%, P < .001) and 75 to 84 (9% vs 12%, P < .001). Women in each of these two age groups had lower mammography use if they resided in the lowest income quintile and highest if they resided in the highest income quintile (17% vs 23% 65-74, and 10% vs 13% 75-84, P values < .001). Among the oldest women (those 85+), mammography use was low (4%) and varied minimally by race and income (P = .907 and .003, respectively). In all age groups, mammography use was lowest among women who did not have a primary care visit, was greater among women who had at least one visit, and continued to rise with increasing numbers of visits (all P values < .001). For example, among women age 75 to 84, mammography use increased from 5% to 10%, 14%, and 17% for those with 0, 1, 2, and 3+ visits. CONCLUSIONS: We found that mammography use was less for women who were older, of black race, who did not visit a primary care provider, and who lived in areas with lower median income and certain geographic locations (states). Similar factors influenced mammography use in women age 65 to 74, where there is greater consensus as to who should receive a mammogram, and women age 75 to 84, where there is neither consensus nor data. Surprisingly, neither race nor income had much influence on mammography use among women age 85 or older.

Gas-chromatographic analysis of busulfan for therapeutic drug monitoring.

The development and validation of a gas chromatographic assay method for determination of total and free busulfan concentrations in human plasma for pharmacokinetic studies is reported. 1,6-Bis(methanesulfonyloxy)hexane, the internal standard, and a potential metabolite, 3-hydroxysulfolane, were synthesized. Plasma and plasma ultrafiltrate samples containing busulfan and internal standard were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determination. The 63Ni electron-capture detector provided a limit of detection of 0.0600 microgram/ml with a limit of quantitation of 0.100 microgram/ml busulfan in biological samples. Calibration curves were linear from 0.100 to 3.00 micrograms/ml in plasma (500 microliters) and 0.100 to 2.00 micrograms/ml in plasma ultrafiltrate (100 microliters). Extraction and derivatization yields ranged from 78.4% to 89.6% and 56.0% to 71.3%, respectively. Specificity of this assay for busulfan in the presence of its potential metabolites was demonstrated. Also, plasma samples containing co-administered drugs gave no response under these conditions. Clinical samples obtained following administration of a 1 mg/kg oral busulfan dose demonstrate the applicability of this method to analysis of total and free plasma concentrations.

Nonmedical influences on medical decision making: an experimental technique using videotapes, factorial design, and survey sampling.

OBJECTIVE: To study nonmedical influences on the doctor-patient interaction. A technique using simulated patients and "real" doctors is described. DATA SOURCES: A random sample of physicians, stratified on such characteristics as demographics, specialty, or experience, and selected from commercial and professional listings. STUDY DESIGN: A medical appointment is depicted on videotape by professional actors. The patient's presenting complaint (e.g., chest pain) allows a range of valid interpretation. Several alternative versions are taped, featuring the same script with patient-actors of different age, sex, race, or other characteristics. Fractional factorial design is used to select a balanced subset of patient characteristics, reducing costs without biasing the outcome. DATA COLLECTION: Each physician is shown one version of the videotape appointment and is asked to describe how he or she would diagnose or treat such a patient. PRINCIPAL FINDINGS: Two studies using this technique have been completed to date, one involving chest pain and dyspnea and the other involving breast cancer. The factorial design provided sufficient power, despite limited sample size, to demonstrate with statistical significance various influences of the experimental and stratification variables, including the patient's gender and age and the physician's experience. Persistent recruitment produced a high response rate, minimizing selection bias and enhancing validity. CONCLUSION: These techniques permit us to determine, with a degree of control unattainable in observational studies, whether medical decisions as described by actual physicians and drawn from a demographic or professional group of interest, are influenced by a prescribed set of nonmedical factors.

Patient assertiveness and physician decision-making among older breast cancer patients.

The objective of this study was to determine whether assertive patient behavior influences physician decision-making in the treatment of older breast cancer patients. One hundred and twenty-eight physicians saw videotapes depicting women seeking care for breast cancer and then recommended evaluation and treatment plans. Identical scripts were used, but the age, race, socioeconomic status, mobility, general health, and assertive behavior of the patients were experimentally varied along with the physician's specialty and length of practice. No direct effects of assertive patient behavior were seen. However, black, comorbid, and lower SES women were more likely to have full staging of their tumors ordered when they made an assertive request. Treatment recommendations also showed an interaction of assertiveness with patient's age and social class as well as physicians' specialty. The results indicate that a moderately assertive patient request may change provider behavior, although the effects of assertiveness vary most by what type of patient demonstrates this behavior. In particular, assertiveness led to more careful diagnostic testing for patients who came from groups that are "disadvantaged."

A gas-chromatographic assay method for busulfan with sensitivity for test dose therapeutic monitoring.

A gas-chromatographic assay method was developed and validated for determination of busulfan in human plasma for test dose therapeutic drug monitoring. Busulfan and the internal standard (1,6-bis-(methanesulfonyloxy)hexane) were extracted from plasma samples and derivatized with 2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determination. The 63Ni electron-capture detector provided a limit of quantitation of 0.0100 micrograms ml-1 busulfan in plasma with a linear response over the concentration range 0.0100-0.400 micrograms ml-1. Extraction and derivatization yields were 85.3%-91.0% and greater than 95%, respectively. Assay specificity for busulfan in the presence of potential metabolites was demonstrated. Potentially co-administered drugs gave no response under the sample preparation and chromatographic conditions described for quantification of busulfan. The applicability of this assay to the individualization of busulfan therapy based on a 2 mg test dose is discussed.

Histological and immunological studies on the fowl lacrimal gland following surgical excision of Harder's gland.

Surgical removal of the Harderian gland of the domestic fowl resulted in increased secretory activity in the lacrimal gland and also in an increase in goblet cell numbers along the length of the lacrimal gland duct. Plasma cells were more numerous in the lacrimal glands of operated birds and they were capable of antibody responses to both systemically and topically applied bovine serum albumin (BSA). Gel diffusion studies showed the presence of anti-BSA activity in the tears and serum of fowls stimulated after surgical removal of the Harderian gland.

Histology and immunology of Peyer's patches in the domestic fowl (Gallus domesticus).

Peyer's patches (PP) were identified in the small intestine of the domestic fowl by their thickened villi, flattened epithelium which lacked goblet cells and by the accumulations of lymphocytes in the form of encapsulated germinal centres (GC) and diffuse lymphoid tissue (DLT). Particles of orally administered carbon were seen in GC and DLT, in macrophages and within epithelial cells (M cells). Faults in the PP epithelium, which was positive for alkaline phosphatase, allowed the extrusion of lymphocytes into the intestinal lumen. Immunofluorescence detected more lymphoid cells with cytoplasmic IgG than IgA or IgM. Specific antibody production was seen in cells of GC ad DLT in PP from fowls that had received multiple injections of horse serum.

The structure of the lachrymal glands of the domestic fowl and of the duck.

The histology of the lachrymal glands of the duck and fowl is similar. In both birds the gland is a compound tubulo-acinar structure, lobulated and invested by a thin connective tissue capsule. Foci of lymphocytes, but few plasma cells, are found in the glands. Moderately acidic mucosubstances predominate in the gland of the fowl whereas sialomucins are found in that of the duck. Neutral lipids were detected only in the gland of the fowl.

Experimental stimulation of eosinophil production in the domestic fowl (Gallus gallus domesticus).

A method has been devised to produce eosinophilia in birds experimentally. Multiple intraperitoneal injections of bovine serum albumin (BSA) produced a greater response than horse serum in young adult fowls, and injections of 2 ml BSA were more effective than injections of 0.2 ml. The highest eosinophilic responses were obtained with injections of BSA together with aluminium hydroxide. Thymectomy had little effect on eosinophil numbers following horse serum injections but irradiation produced a depressed response. Horse serum that had been heated to 56 degrees C for 30 minutes to inactivate complement and to denature proteins, including possible horse IgE, induced an eosinophilic response in 50 per cent of birds compared with only 14 per cent with unheated horse serum. Furthermore, when the former birds were reinjected after a rest period of 13 weeks, the eosinophilic response followed a similar curve as before but a higher proportion of birds responded. Birds aged over two years did not give a good eosinophilic response after horse serum stimulation. There was no consistent correlation between raised IgE levels and eosinophil numbers. Tolerance to horse serum was detected in some birds using a radial immunodiffusion technique. Analyses of blood plasma from birds with eosinophilia showed a significant increase in total amino acids compared with normal birds.

Ochratoxicosis A in young Khaki Campbell ducklings.

Ochratoxin A (OA), a potent nephrotoxic mycotoxin, was fed at 2 ppm in the diet to Khaki Campbell ducklings from hatch to 18 days old. It caused retarded growth, enlargement of the kidneys and liver and regression of the thymus. Light and electron microscopical changes seen in the liver included an accumulation of glycogen and the presence of mis-shapen mitochondria in the hepatocytes. OA caused thickening of the glomerular basement membrane and in infiltration of lymphoid cells into the kidney. There was an increased deposition of IgG in the glomeruli. OA-fed ducklings had normal levels of circulating IgG in their sera and there was a subepithelial migration of IgG-positive cells in the bursa of Fabricius. In general, OA-induced changes seen in ducklings, both with the light and electron microscopes, were similar to, but less pronounced than those seen in the fowl and turkey.

Pathology of ochratoxicosis A in young broiler chicks.

Ochratoxin A (OA), a potent nephrotoxin, was fed in the diet in sublethal concentrations (2 and 4 ppm) to broiler chicks for 20 days from hatch. Its effects on growth, relative organ size and histology of the liver, kidney and lymphoid organs were investigated. In young broiler chicks, OA caused a significant enlargement of the kidney, liver and proventriculus, whereas the thymus and bursa of Fabricius were reduced in size. It principally affected the proximal convoluted tubules of the kidney causing severe distension, enlargement and hypertrophy, and it also resulted in thickening of the glomerular basement membrane. In the liver, vacuolation and glycogen accumulation in the hepatocytes were seen. The toxin also caused regression of and a drastic reduction in the lymphoid cell population in the immunological organs. The toxicity of OA was found to be dose related.

Effect of ochratoxin A on immunoglobulins in broiler chicks.

The effect of ochratoxin A (OA) on the immune system was investigated in broiler chicks fed graded dietary levels of OA up to 4 ppm for 20 days from hatch. Immunofluorescent demonstration of IgG, IgA and IgM in sections of liver, kidney and lymphoid tissues was used to assess immune competence. Serum immunoglobulin levels were measured by radial immunodiffusion. Ochratoxin caused a significant depression in immunoglobulin-containing cells in all the lymphoid organs studied. Correspondingly, total immunoglobulin levels were also reduced in the sera from OA fed birds, immunosuppression being similar at both the 2 and 4 ppm OA levels. Deposition of immunoglobulins, especially IgG, in the glomerular basement membrane was seen with greater frequency in kidneys from OA fed fowls. Immunoglobulin-containing lymphoid cells occurred more frequently in the kidney parenchyma of these birds.

Blood eosinophilia in adult bantams naturally infected with Trichostrongylus tenuis.

Blood eosinophilia was seen in 36 per cent of 115 adult bantams naturally infested with Trichostrongylus tenuis; the maximum individual count was 56 per cent eosinophils. There were no measurable levels of IgE in the plasma samples and no foci of eosinophils were found in the tissues.

Ultrastructural study of ochratoxicosis in quail (Coturnix coturnix japonica).

Ultrathin sections of liver and kidney from 11-week-old quail fed, from day-old, ochratoxin A (OA) (mixed in the diet at levels of 4 and 8 ppm) were examined in the electron microscope. Pathological changes in the kidneys were limited to the proximal convoluted tubules (PCT) and glomeruli. In the PCTs, abnormal mitochondria and excessive numbers of lipid droplets were the principal findings with glomeruli showing thickened basement membranes. Swollen mitochondria and variable glycogen deposition were the chief features present in the livers. It is suggested that OA is more hepatotoxic in quail than in broilers, as well as being nephrotoxic.

Skeletal changes in broiler chicks and turkey poults fed diets containing ochratoxin A.

Broiler chicks and turkey poults were divided at hatching into experimental and control groups. Experimental birds were fed a diet contaminated with 4 ppm ochratoxin A, whereas the ration of control birds was confirmed to be mycotoxin free. Birds were killed at fortnightly intervals up to 10 weeks old and skeletal changes were investigated. Almost all experimental birds developed generalised skeletal osteopenia with disturbed endochondral and intramembranous bone formation. Histological changes in diaphyseal cortices could account for the reduced breaking strength of bones from birds fed mycotoxin, which have been reported by others. One bird showed changes consistent with a diagnosis of hypophosphataemic rickets. In others, however, osteoid formation was defective and changes were interpreted as osteoporosis. Although it might be tempting to suggest that osteoporosis is a result of a direct toxic effect of ochratoxin on osteoblasts, the effect of inanition, inactivity and general debility may be equally important.

Ultrastructural study of the liver and kidney in ochratoxicosis A in young broiler chicks.

Ultrastructural changes are reported in the kidney and liver of 20-day-old broiler chicks fed ochratoxin A (OA), incorporated in the diet at levels of 2 and 4 ppm. Changes in the kidney included the presence of abnormally shaped mitochondria in the proximal convoluted tubules. There was an increase in the size and number of mitochondrial dense granules and cytoplasmic peroxisomes. Intranuclear and cytoplasmic lipid droplets and electron dense round bodies in the dilated smooth endoplasmic reticulum were also noted. Regional thickening and degeneration of the glomerular basement membrane was observed in some cases. In the liver from OA fed birds there was an increased accumulation of cytoplasmic glycogen in the hepatocytes. Abnormal mitochondrial ring forms in the kidney and the accumulation of glycogen in the liver are considered to be of diagnostic significance in ochratoxicosis of young broiler chicks. The severity of the changes was found to be dose related. These results suggest that the mitochondria in the proximal convoluted tubules of kidney were most sensitive to OA toxicity.