Efficacy of erlotinib in patients with relapsed gliobastoma multiforme who expressed EGFRVIII and PTEN determined by immunohistochemistry.

Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.

The impact of physician compliance on screening mammography for older women.

Screening mammography is underutilized, even for women older than 50 years for whom there is a general consensus that regular annual screening is appropriate and necessary. To evaluate reasons for this underutilization, we studied a random sample of 517 women in Los Angeles, Calif who were older than 50 years. All women were found to be underscreened, especially women older than 65 years. For example, approximately 35% of women 50 to 64 years old and 47% of women aged 65 years and older never had had even one mammogram. Analyses revealed that the most important factor that predicted whether a women ever had had a mammogram was whether her physician had talked to her about mammography. Women were between four and 12 times more likely, depending on their age group, to have had a mammogram at some time if their physicians discussed it with them. The discussions did not need to be lengthy or complex. These results indicate that physicians need to know that discussing screening mammography with their patients has a major impact on breast cancer screening behaviors.

Controlled evaluation of implementing the Cytobrush technique to improve Papanicolaou smear quality.

The effect of introducing the Cytobrush Cell Collector for endocervical sampling on the quality of Papanicolaou smears was evaluated using a quasi-experimental design. Baseline evaluation of the Ayre spatula-cotton swab method in two patient groups showed that only 61.8-61.9% of smears contained endocervical cells. Replacing the cotton swab with the Cytobrush in the intervention group improved endocervical cell yields to 82.0% (P less than .001). This improvement was not due to group differences in patient factors previously related to endocervical cell yields, eg, parity, use of oral contraceptives, pregnancy, previous cervical procedures, and menopausal status. An increase in the proportion of Papanicolaou smears showing dysplasia or cancer (class III or higher) was associated with use of the Cytobrush (P less than .05). Subsequent introduction of the Cytobrush to the control group resulted in a similar significant improvement in cell yields to 82.5% (P less than .001). Greater use of methods such as the Cytobrush Cell Collector in the primary care setting can improve cervical cancer screening by reducing the number of false-negative Papanicolaou smears resulting from inadequate endocervical cell sampling.

A characterization of the imminent leadership transition in academic family medicine.

Of the 106 identified chairmen of academic departments, divisions, or sections of family medicine in the United States in 1990, 97 (92%) responded to a survey designed to characterize the current chairmen of family medicine and estimate requirements for future chairmen. Even though 43% had occupied the chair for less than five years, over half, not limited to older chairmen, intended to leave within five years. Reasons for leaving varied, including being required to leave, career choice, personal reasons, and especially dissatisfaction with the job. Only half of current chairmen identified one or more qualified applicants for chairmanship within their own departments. The formal training and experience of these potential chairmen strongly resembled the training and experience of current chairmen, especially the fact that they had little training or experience in research. In the 1990s, the demand for academic chairmen of family medicine is likely to be large, the competition for capable candidates keen, and the challenges great for new chairmen, who will probably be young, residency-trained family physicians with relatively limited academic experience.

The influence of ethnicity, socioeconomic status, and psychological barriers on use of mammography.

This study assessed the relative influence of psychological barriers, SES, and ethnic differences in mammography use for a community sample of 586 White, 227 Black, and 150 Hispanic women. Confirmatory factor analyses with latent variables indicated plausible factor structures for all groups on items related to barriers to mammography. Summed indicators of SES, fear of radiation, embarrassment, pain, anxiety, and cost concerns were correlated significantly with mammography use for the pooled group. Separate analyses by ethnicity indicated a substantial relationship between mammography use and cost concerns by White and Black women, and fear of pain by Black and Hispanic women. Use of mammography was associated more highly with SES among Hispanic women. Pooled logistic regression analyses controlling for SES and ethnicity showed that the psychological barriers, especially concern about cost, remained important independent predictors of mammography use. We explore sociocultural explanations for less mammography use by Hispanic women, especially those less acculturated.

A visit-based quantitative measure of family care.

Within the discipline of family medicine, providing family care receives varying emphasis. Studies are needed to more strongly link the process of family care to improvements in health outcomes. Such studies require validated measures with which to quantify the amount of care provided to families. This paper proposes a conceptual definition and an operational quantitative measure of family care. This family care measure, which we based on a three-dimensional operational model of family care (frequency of visits, number of family members, number of providers), translates a family's pattern of health care into an easily interpreted index.

Variations in content of care in a family medicine residency relating to types of insurance coverage.

The content of care in a family practice residency program was analyzed using a microcomputer information system. The distribution of recorded diagnoses in the training program was found to be very similar to results of two national studies of family medicine. Despite this overall similarity, important differences were found when distributions for patients with six types of insurance coverages were analyzed separately. This study demonstrates the potential effect of insurance coverage on the clinical content of family medicine. As the health care system changes, residency programs will need to remain adaptable to maintain patient bases reflecting the broad content of family medicine.

Relationship between Pap smear performance and physician ordering a mammogram.

BACKGROUND: Although Pap smear screening for cervical cancer in general has been successfully implemented, mammography screening for breast cancer remains relatively underused. Patients having one screening test are more likely to have other screening tests performed. The objective of this study was to determine whether visits by women for Pap smears serve as opportunities for physicians to order a screening mammogram. METHODS: A matched case-control design was used for this retrospective study. Eligible women included those over 50 years of age who had no history of breast cancer or mastectomy and who had made at least one visit to a family practice residency program during the 2-year study period. Cases were randomly selected from women who had mammograms performed. For each case, one control subject who did not have a mammogram was matched by age and number of visits. A chart audit was performed to collect data on the characteristics of these women and whether they completed their screening tests. RESULTS: The adjusted odds ratio (controlling for the patient's age and number of physician visits) for mammogram completion among women who had a Pap smear compared with those who did not was 6.67. This effect persisted after controlling for other confounding factors using logistic regression. CONCLUSIONS: Performing a Pap smear appears to serve as a prompt for the physician to order a screening mammogram. That physicians appear to provide screening tests, particularly Pap smears and mammograms, as a package of services should be considered when future efforts to improve implementation are made.

Who is the family doctor? Relating primary care to family care.

Many families receive care as intact family units. To determine which specialists provide this family care, a subset of families (N = 447) enrolled in the Rand Health Insurance Experiment were examined. Among families designating a single primary care physician, family physicians and general practitioners provided 65.9% to 89.7% of their family care. Internists provided 20.0% and 27.3% of family care for younger and older couples, respectively. The remaining specialties, including pediatrics and obstetrics-gynecology, each provided less than 5% of family care; these small proportions of family care may reflect the specialists' self-imposed limits in primary care roles. As family members matured, families used fewer pediatricians and obstetrician-gynecologists for primary care and concurrently increased their use of family physicians or general practitioners. Care for intact families is provided predominantly by family physicians or general practitioners, although in families without children, internists also play an important role. Self-defined limits in primary care roles by physicians in various specialties and the changing use of specialties during the family life cycle largely determined which specialties provided family care.

Physicians' attitudes and behaviors regarding hepatitis B immunization.

BACKGROUND: Hepatitis B virus (HBV) infections are a serious health problem in the United States, where approximately 18,000 cases are reported each year to the Centers for Disease Control. Even among health care providers, reported vaccination rates have ranged from 17% to 68%. The purpose of this study was to determine the important factors influencing physicians in an academic medical center to receive the HBV vaccination since the introduction of recombinant yeast-derived vaccines. METHODS: The 1282 house staff and attending physicians in a university medical center were surveyed regarding their HBV vaccination history. The characteristics of vaccinated and nonvaccinated physicians and their attitudes and concerns regarding vaccination were compared. RESULTS: Of the 813 physicians who responded, 54.0% had been vaccinated. Vaccination rates varied with level of training, from 91.9% among first- and second-year residents to 32.2% among attending physicians. Although physicians in specialties at higher risk for infection were more likely to have been vaccinated, only 40.0% of pathologists and 51.9% of obstetrician-gynecologists reported having been vaccinated. Using multivariate analysis, we found important demographic predictors of HBV vaccination included physician sex and years since graduation, as well as level of training and specialty. Physicians who had been offered the vaccine were more likely to have been vaccinated. CONCLUSIONS: These results show that many physicians in an academic medical center, particularly those at an early stage of their training, have received HBV vaccination. Our results suggest that programs offering hepatitis B vaccinations to physicians can be effective in reducing this group's risk of hepatitis B infections. Special efforts may be necessary to reach physicians who have completed their training.

Attitudes toward and experience in research among family medicine chairs.

BACKGROUND: Productive research environments are important for the development of academic family medicine, yet many of the current family medicine chairs have had little research training or experience and have rated research skills as a low priority for themselves. The younger chairs, however, representing the next generation of academic leadership, may have more traditional academic values, including the promotion of research. METHODS: The 106 active and interim chairs of family medicine academic units were surveyed by mail to determine their characteristics and attitudes toward their work responsibilities. We compared chairs 50 years of age or younger with those over 50 years of age. RESULTS: Before attaining their positions, younger chairs, in general, were more likely than older chairs to have received formal training in management, patient care, and academic skills, but they shared similar work experiences. Specifically, younger chairs were more likely to have had formal research training but did not have a great deal more research experience. Younger chairs were more likely to consider research skills to be essential in their present work activities and to identify faculty with formal training and extensive experience in research as potential chair replacements. CONCLUSIONS: Younger chairs appear to have a greater appreciation for the importance of research, having received more formal training and valuing research skills in themselves and potential replacements. With the impending large turnover in family medicine leadership, there will be an opportunity to recruit chair replacements with similar viewpoints toward research, thus improving the outlook for research in academic family medicine.

Do families get family care?

To determine the prevalence of family care, we measured the extent to which a subset of 732 families, from those enrolled in the Rand Health Insurance Experiment, perceive and use a single primary care physician. Although only 16.7% of these families had all members with a majority of their visits to the same physician, 45.4% identified a single primary care physician for all family members. (For older couples, this percentage reached 73.5%). An intermediate proportion of families had visits by all family members to a single physician. Children received less family care, but as families matured, family care increased for both children and parents. Our results suggest an inverse relationship between family care and education level. The availability of general-family practitioners, family income, insurance coverage, and population size were not significant determinants of family care. We conclude that family members share the perception of having a single "family physician," which is reflected in their patterns of utilization.

Demographic, clinical, and financial factors relating to the completion rate of screening mammography.

A retrospective analysis of the UCLA Family Health Center Research Data Base was performed to determine the relationship between completion rates of screening mammography and various patient demographic, clinical, and financial factors. Data from a 16-month period, from July 1984 through October 1985, were analyzed. Eight hundred twenty-seven women over 50 years of age were seen in the UCLA Family Health Center at least once during the study period. One hundred thirty-six (16.4%) of these women had screening mammography performed. Health insurance coverage was an important determinant of mammography completion. Patients covered by a health maintenance organization were 2.5 (P less than .05) times more likely to receive screening mammography. Uninsured patients were only 0.5 times as likely to have this procedure performed. The completion rate for screening mammography increased significantly with increasing number of visits during the study period (P less than .001). The age groups analyzed were significantly associated with completion rate. Marital status had a significant relationship to completion rate, but this was due to a lower completion rate in the group of patients whose marital status could not be determined. The employment status could not be evaluated due to the high rate of missing data. Race, smoking status, alcohol consumption, and the sex and training level of the primary provider were not found to be significantly associated with screening mammogram completion rates.

Tuberculosis screening.

In view of the decreasing prevalence of tuberculosis, it is important to be aware of the factors influencing the sensitivity, specificity and predictive value of tuberculin testing. The small predictive value of tuberculin testing in a low-risk population makes it an ineffective means for screening. Even in high-risk populations, factors such as geographic location, reaction size, previous skin testing and BCG vaccination significantly influence interpretation of the skin test.

Mammography usage and the health belief model.

Regular screening mammograms for asymptomatic women are the most effective method for early detection of breast cancer. This study assessed the relative influence of Health Belief Model (HBM) constructs on prior mammography usage and the intention to obtain mammograms with data from a sample of 1,057 women over the age of 35 years residing in an urban community in the United States. Covariance structure analysis with latent variables was used initially to perform a confirmatory factor analysis of indicators of Socioeconomic Status (SES), Perceived Susceptibility, Perceived Barriers, Perceived Benefits, Cues to Action, Prior Mammography, and Future Intentions. Once a plausible factor structure was confirmed, a predictive path model was tested with Future Intentions and Prior Mammography as the outcome variables. Cues to Action, operationalized as a physician influence variable, particularly impacted Prior Mammography, and Perceived Susceptibility was the most powerful predictor of Future Intentions. SES only related significantly to Perceived Barriers, and Cues to Action, and did not directly influence Prior Mammography and Future Intentions. HBM predictor variables alone accounted for the relationship between previous mammography experience and intentions to obtain mammograms in the future. Health education implications and an applied outreach program are discussed.

Effects of Dai-kenchu-to, a herbal medicine, on uterine and intestinal motility.

The effects of both Dai-kenchu-to and PGF(2alpha) on intestinal and uterine motility were studied in anaesthetized rabbits with force transducers implanted in the jejunum, ileum and uterus. A single intraduodenal administration of Dai-kenchu-to (300 mg/kg) enhanced the intestinal motility but not the uterine motility. However, intravenous administration of PGF(2alpha) (20 microg/kg) enhanced both intestinal and uterine motility. The effects of Dai-kenchu-to on the spontaneous contraction and contractile response of the isolated rat uterine strips to oxytocin, PGF(2alpha) or ACh were also studied. Oral administration of Dai-kenchu-to at 300 mg/kg for one week had no effect on either the spontaneous contraction or the contractile response of the uterus. These results indicate that Dai-kenchu-to may exert stimulatory effects on intestinal motility, as PGF(2alpha), but has no effect on the uterine motility, suggesting a selective effect on the gastrointestinal tract. Hence, Dai-kenchu-to may be safer than PGF(2alpha) in the treatment of postoperative adhesive ileus in women. However, more studies are needed to determine whether Dai-kenchu-to could be administered to pregnant women.

Dai-kenchu-to enhances accelerated small intestinal movement.

The present study was conducted to clarify the effects of Dai-kenchu-to on accelerated small intestinal movement. We evaluated the effects of Dai-kenchu-to and its constituent herbs (dried ginger root, ginseng, zanthoxylum fruit, and malt sugar) on carbachol-accelerated mouse small intestinal transit, and contractions induced by low-frequency electrostimulation (ESC), KCl, or acetylcholine (ACh) using isolated guinea pig ileum. Dai-kenchu-to (10-300 mg/kg, p.o.) significantly improved carbachol-accelerated small intestinal transit in a dose-dependent manner. Using a concentration with the compounded rate for Dai-kenchu-to 300 mg/kg, carbachol-accelerated small intestinal transit was also significantly improved with a single dose of dried ginger root or ginseng. At a concentration of 3 x 10(-5) g/ml or less, Dai-kenchu-to, dried ginger root, and ginseng all inhibited ESC but not KCl- or ACh-induced contractions. However, at a higher concentration of Dai-kenchu-to (10(-4) g/ml) or zanthoxylum fruit (10(-5) g/ml or more) the ESC were enhanced. Both Dai-kenchu-to and dried ginger root at 10(-3) g/ml remarkably inhibited the KCl-induced contractions. These results indicate that Dai-kenchu-to improves accelerated small intestinal movement and that dried ginger root and ginseng may be involved in this effect. It is also thought that the mechanisms mainly involve the direct inhibition of smooth muscle but with a contribution from neural inhibition.