The Dutch system of external quality assessment: description and experiences.

CONTEXT: Generally speaking, quality assurance in Dutch higher education consists of four parts: a self-evaluation, written by the faculty, a review committee, consisting of experts, the site visit, and a public report of the assessment outcomes. TASK OF THE REVIEW COMMITTEE: The organization, in which all universities are united, appoints a review committee for each educational program. Most educational programs are taught at different universities. Consequently, the review committee visits several universities. The task of the review committee is: to assess the overall quality of these educational programs in The Netherlands; and to assess the quality of each school separately. METHOD: The members of the review committee start their activities by formulating the evaluation criteria (standards) for the content of an educational program and for the educational process. This ends with a paper that will be used as a reference for the assessment. Then the review committee studies the self-evaluation reports. The faculties write these reports along established guidelines. In cases where the self-evaluation is not completely clear, or not sufficient, the committee formulates questions and asks for additional information. Then the committee visits the faculties. These visits take usually two days each. During these visits, the committee gets information from the dean of the faculty, the program committee, teachers, students, and from other employees of the faculty. In addition, the members of the committee inspect the facilities of the faculty, e.g. the library. RESULT: Directly after the visit, the chair of the committee gives, orally, a first impression of the findings. After visiting all faculties, the committee starts their deliberations, which result in a report of the assessment of the overall quality of the educational programs. The committee also assesses the quality of each faculty separately, often ending with recommendations. CONCLUSION: The Dutch system of quality assurance in higher education is much copied by other countries. The essence is the self-evaluation on one hand, and the site visit on the other. Committees try to act as consultants, and not as executioners. Therefore, the way the members of the committee play their role is very important.

Insulin-like growth factor-I and prostate cancer: a meta-analysis.

Some, but not all, epidemiological found have shown that high circulating levels of insulin-like growth factor-I (IGF-I) are associated with an increased risk of prostate cancer. We performed a meta-analysis on all the studies reported so far to evaluate this association. In our Medline search, 14 case-control studies were identified. A standard protocol abstracted information for each study. Hedges' standardized mean difference (HSMD) and odds ratio (OR) were used to estimate the effect of IGF-I and IGF-binding proteins (IGFBP-3). The combined data showed that circulating levels of IGF-I were significantly higher in prostate cancer patients (HSMD = 0.194). The OR for prostate cancer was 1.47 (95% confidence interval (CI) 1.23-1.77) among men with high IGF-I compared to those with low IGF-I. The OR was 1.26 (95% CI 1.03-1.54) for IGFBP-3. Circulating levels of IGF-I and IGFBP-3 are likely to be higher in prostate cancer patients than in the controls. These findings support the suggestion that high IGF-I and IGFBP-3 are associated with an increased risk of prostate cancer.

Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender.

Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine concentration was used to verify smoking status. Thirty-seven subjects (18 males, 19 females) were classified as cigarette smokers and 38 were nonsmokers (19 males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR, and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours after dosing. Plasma samples were analyzed for bupropion and its three major metabolites (hydroxybupropion and the aminoalcohol isomers, erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic parameters. Smokers and nonsmokers differed significantly (p < 0.05) in age and urinary cotinine (p < 0.01) concentration but did not differ significantly in mean weight, height, body surface area, or body mass index. The pharmacokinetic (PK) parameters for bupropion and hydroxybupropion did not differ between smokers and nonsmokers, but differences were found between male and female subjects. Mean values for area under the plasma concentration versus time curve (AUC0-->infinity), volume of distribution (Vd beta) normalized to body weight, maximum plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion were significantly (p < 0.05) greater in females than males, while clearance of bupropion normalized to body weight (CL/f) did not differ between males and females. Females also exhibited significantly (p < 0.05) larger values for hydroxybupropion mean AUC0-->infinity and Cmax than males. The mean ratio of hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which is lower than that previously reported for adults. In conclusion, smoking status does not affect the single-dose pharmacokinetics of bupropion SR in adolescents. However, females differ from males in several potentially important PK parameters for bupropion and its major metabolite, hydroxybupropion.

Expression of the translation initiation factor eIF4E in the polyp-cancer sequence in the colon.

The eukaryotic translation initiation factor 4E (eIF4E) has been shown to play a key role in cell growth, and several studies have documented an increased expression of eIF4E in a number of solid tumors, including breast, bladder, cervical, and head and neck cancers. This study was done to evaluate the potential role of eIF4E in the polyp-cancer sequence in the colorectum. Eighty-seven cases with lesions in the colorectum with a variety of histopathological diagnoses were randomly selected from the archives of the Pathology Department at Louisiana State University Health Sciences Center-Shreveport. Appropriate sections were selected for immunostaining with eIF4E. The medical records of the patients were reviewed, and demographic information was collected. All statistical analyses were performed using SAS software. A statistically significant relationship was found between the level of eIF4E expression and histological type of lesion: the lowest level of eIF4E expression was found in normal colon tissue, whereas the highest level of eIF4E expression was found in colorectal adenocarcinomas. Carcinomatous lesions were found to have a 43 times higher chance of having a high level of eIF4E expression compared with normal tissue (95% confidence interval, 8.0-213.6, P < 0.0001). In a multivariate analysis, histological type was the only variable that showed a significant relationship with eIF4E expression; no effect was found due to age, gender, race, history of polyps, and family history. The results from this study are consistent with other data from the literature and support the suggestion that eIF4E is strongly involved in colon tumorigenesis. eIF4E might be a useful intermediate biomarker for use in chemoprevention intervention studies in patients with colorectal polyps.

Smoking status, reading level, and knowledge of tobacco effects among low-income pregnant women.

BACKGROUND: Smoking during pregnancy increases the health risks of the unborn child as well as the mother. Although smoking rates for the population as a whole have declined drastically in the past generation, since 1992 there has been an increase in smoking among women, teenagers, and adults living in poverty. The purpose of this study was to assess reading level, tobacco knowledge, attitudes, and practices of tobacco use among pregnant adult and adolescent women in the public health system in north Louisiana. METHODS: A convenience sample of 600 pregnant women was interviewed in person in the Obstetrics Clinics at Louisiana State University Health Sciences Center at Shreveport and E.A. Conway in Monroe. The structured interview contained detailed questions about smoking practices, tobacco knowledge, and attitudes. Reading was assessed using the Rapid Estimate of Adult Literacy in Medicine. Smoking practices were assessed by self-report and verified by measuring urine cotinine levels. The Cochran-Mantel-Haenszel test was used to estimate the relationship between reading level and knowledge and attitude; multiple logistic regression was used to determine which variable(s) predicted current smoking practices. RESULTS: Knowledge about the effects of smoking and concern about the health effect of smoking on their baby varied significantly by reading level, with participants with higher reading levels having more knowledge and greater concern. Smoking practices did not vary by reading level even when race, age, and living with a smoker were controlled. Race was a significant determinant of smoking practices, with more white women reporting currently smoking during pregnancy than African Americans (34% vs 8%). CONCLUSIONS: Reading level was related to knowledge about health effects of smoking. Women with higher reading levels were also more concerned about the adverse health effects of smoking on themselves and their babies. However, reading level was not correlated with smoking prevalence. The most significant determinant of smoking was race (with whites smoking significantly more than African Americans).

Free insulin-like growth factor-I and breast cancer risk.

Insulin-like growth factor-I (IGF-I) has mitogenic and anti-apoptotic effects on breast cancer cells. Epidemiologic studies have shown that high plasma levels of IGF-I and low levels of IGF binding protein (BP)-3 are associated with increased risk of breast cancer in premenopausal women. The actions of IGF-I are mediated through the IGF-I receptor (IGF-IR) and are regulated by IGFBPs. In circulation, most of the IGF-I binds to IGFBP-3, and binding of IGF-I to IGFBP-3 inhibits the actions of IGF-I. Since free IGF-I, which does not bind to IGFBPs, can readily cross the endothelial barrier to interact with IGF-IR, circulating free IGF-I is thought to be more relevant to the biologic activity of IGF-I. To examine the association of free IGF-I with breast cancer, we compared free IGF-I levels between 40 newly diagnosed breast cancer patients and 40 age- and race-matched healthy controls. Plasma levels of free IGF-I, total IGF-I and IGF-II, as well as total, intact and fragment IGFBP-3, were measured using commercial immunoassay kits. The association between IGF-I and breast cancer was examined using the conditional logistic regression analysis. Analysis of correlation (Spearman) showed that free IGF-I was correlated with total IGF-I and IGFBP-3 but not with IGF-II. The odds ratios for breast cancer patients having high plasma IGF-I (> or = median) after adjusting for menopausal status and IGFBP-3 were 2.00 (p < o r = 0.376) for total IGF-I and 6.31 (p < or = 0.047) for free IGF-I. A high ratio of IGF-I to IGFBP-3 was also associated with breast cancer (p < 0.05). No association was found for IGF-II, nor for total, intact and fragment IGFBP-3. The findings of this study suggest that measuring free IGF-I in circulation is more useful than measuring total IGF-I with respect to evaluation of an association between IGF-I and breast cancer risk.

Levels of insulin-like growth factor I (IGF-I) and IGF binding proteins 2 and 3 in serial postoperative serum samples and risk of prostate cancer recurrence.

OBJECTIVES: To determine changes of insulin-like growth factor I (IGF-I), IGF binding protein-2 (IGFBP-2), and IGFBP-3 levels in serial postoperative serum samples from prostate cancer patients with and without relapse and to evaluate the prognostic value of these molecules in the recurrence of prostate cancer. METHODS: From a group of patients with prostate cancer who had been followed for disease recurrence for almost 5 years after radical prostatectomy, we selected 38 patients (cases) who developed recurrent disease and 40 patients (controls) who were in remission. Of these patients, 70 had 4 and 8 had 3 serial postoperative serum samples collected. The median times for serum collection after surgery were 1.5 years for the first serial samples, 2.6 years for the second, 3.5 years for the third, and 4.5 years for the fourth. Serum levels of IGFBP-2, IGFBP-3, and IGF-I were measured, using commercial immunoassay kits. RESULTS: The study showed lower serum levels of IGFBP-2 and IGFBP-3 in the cases than in controls(P <0.05) but no difference in IGF-I levels between the two groups (P = 0.277). In the sequential samples, IGFBP-2 levels increased over time in the controls (P = 0.014) but did not change in the cases (P = 0.528). There were no increasing or decreasing trends for IGF-I and IGFBP-3 in either case or control group(P >0.05). CONCLUSIONS: The study suggests that IGFBP-2 may play a role in the progression of prostate cancer, but serum levels of IGFBP-2 as well as IGF-I and IGFBP-3 have no predictive values in the prognosis of prostate cancer.

Polymorphic CA repeats in the IGF-I gene and breast cancer.

Insulin-like growth factor (IGF)-I is a potent mitogen for breast cancer cells and may play a role in the disease. Although the involvement of IGF-I phenotype in breast cancer has been studied extensively, little is known about IGF-I genotype in relation to the disease. The IGF-I gene contains a polymorphic region composed of multiple cytosine-adenine dinucleotides (CA repeats). Studies of other genes indicate that the CA-repeat region in the promoter of a gene may affect transcription activity and that the length of the repeat is inversely correlated with transactivation. To examine if the IGF-I polymorphism is associated with breast cancer, we compared the length of CA repeats in the IGF-I gene between 53 breast cancer patients and 53 controls. Genomic DNA extracted from peripheral blood was used to determine the number of CA repeats through PCR amplification and DNA sequencing. Associations between CA repeats and breast cancer were assessed using unconditional logistic regression analysis. The results showed that the median number of CA repeats was 19, ranging from 15 to 23, and that compared to women without 19 CA repeats, women with 19 CA repeats were more likely to be breast cancer patients (OR = 2.87, 95%CI: 1.16-7.06) after adjusting for age, race, menopausal status, age at menopause, and alcohol use. The study also suggested possible synergistic interplay between IGF-I genotype and phenotype as women with 19 CA repeats and high plasma IGF-I had a much higher odds ratio for breast cancer (OR = 5.12, 95%CI: 1.42-18.5) than those with only one of the conditions. If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility.

Intervention to increase mammography utilization in a public hospital.

OBJECTIVE: To study the effects of three approaches to increasing utilization of screening mammography in a public hospital setting in Northwest Louisiana. DESIGN: Randomized intervention study. POPULATION: Four hundred forty-five women aged 40 years and over, predominantly low-income and with low literacy skills, who had not had a mammogram in the preceding year. INTERVENTION: All interventions were chosen to motivate women to get a mammogram. Group 1 received a personal recommendation from one of the investigators. Group 2 received the recommendation plus an easy-to-read National Cancer Institute (NCI) brochure. Group 3 received the recommendation, the brochure, and a 12-minute interactive educational and motivational program, including a soap-opera-style video, developed in collaboration with women from the target population. MEASUREMENTS AND MAIN RESULTS: Mammography utilization was determined at 6 months and 2 years after intervention. A significant increase (p = .05) in mammography utilization was observed after the intervention designed in collaboration with patients (29%) as compared with recommendation alone (21%) or recommendation with brochure (18%) at 6 months. However, at 2 years the difference favoring the custom-made intervention was no longer significant. CONCLUSIONS: At 6 months there was at least a 30% increase in the mammography utilization rate in the group receiving the intervention designed in collaboration with patients as compared with those receiving the recommendation alone or recommendation with brochure. Giving patients an easy-to-read NCI brochure and a personal recommendation was no more effective than giving them a recommendation alone, suggesting that simply providing women in a public hospital with a low-literacy-level, culturally appropriate brochure is not sufficient to increase screening mammography rates. In a multivariate analysis, the only significant predictor of mammography use at 6 months was the custom-made intervention.

Informed consent for clinical trials: a comparative study of standard versus simplified forms.

BACKGROUND: A high level of reading skill and comprehension is necessary to understand and complete most consent forms that are required for participation in clinical research studies. This study was conducted to test the hypothesis that a simplified consent form would be less intimidating and more easily understood by individuals with low-to-marginal reading skills. METHODS: During July 1996, 183 adults (53 patients with cancer or another medical condition and 130 apparently healthy participants) were tested for reading ability and then asked to read either the standard Southwestern Oncology Group (SWOG) consent form (16th grade level) or a simplified form (7th grade level) developed at Louisiana State University Medical Center-Shreveport (LSU). Participants were interviewed to assess their attitudes toward and comprehension of the form read. Then they were given the alternate consent form and asked which one they preferred and why. RESULTS: Overall, participants preferred the LSU form (62%; 95% confidence interval [CI] = 54.8%-69.2%) over the SWOG form (38%; 95% CI = 30.8%-45.2%) (P = .0033). Nearly all participants thought that the LSU form was easier to read (97%; 95% CI = 93.1%-99.9%) than the SWOG form (75%; 95% CI = 65.1%-85.7%) (P<.0001). However, the degree to which the participants understood the forms was essentially the same for the LSU form (58%; 95% CI = 48.6%-67.0%) and the SWOG form (56%; 95% CI = 43.8%-66.8%). IMPLICATIONS: These findings raise serious questions regarding the adequacy of the design of written informed consent documents for the substantial proportion of Americans with low-to-marginal literacy skills.

Knowledge and attitude on screening mammography among low-literate, low-income women.

BACKGROUND: Low-income women utilize screening mammography less frequently, present at more advanced stages of disease, and have higher breast cancer mortality rates then women with higher incomes. The purpose of this study was to examine the relationship of reading ability to the knowledge and attitudes that low-income women have regarding screening mammography. METHODS: A convenience sample of 445 women were interviewed for this study. These women, age 40 years and older, had not had a mammogram in the past year. They were waiting to see a doctor in one of two outpatient clinics at Louisiana State University Medical Center in Shreveport when they were interviewed. A structured questionnaire assessed mammography knowledge and attitudes. Each patient's reading ability was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM). RESULTS: The women interviewed had a mean age of 56 years. Sixty-nine percent were African American, and 97% lived in households with annual incomes of less than $20,000. On the average, the highest grade completed in school was tenth grade. The average reading level was fourth to sixth grade, with 76% reading below a 9th-grade level. Lower reading ability correlated significantly with less mammography knowledge (P < 0.0001). A lack of accurate information about mammography was prevalent among low-level readers. Thirty-nine percent of women reading at or below a third-grade level did not know why women are given mammograms, compared with 12% of those reading at or above a ninth-grade level. Cost was a great concern in general, but cost concerns did not vary by reading level; 41% of all participants were very concerned about cost. CONCLUSIONS: Limited literacy skills and lack of knowledge about screening mammography may contribute considerably to the underutilization of screening mammograms in low-income women. Screening for reading level may identify a subset of low-income patients who could benefit from specialized education. These results could help guide effective educational interventions and better provider-patient communication about screening mammography for low-literate, low-income women.

Cancer screening: overview and prospects.

In Table 4, current "state-of-the-art" screening for various cancers is summarized. It is fair to say that, unfortunately, only a minority of the tumors do have proven screening methods that lead to a lower disease-specific mortality. Given the relative lack of improvement in survival rates over the last few decades, this area should be a priority for research endeavors.

Progress against cancer...?!

Data from the population based cancer registry in Alberta, Canada as well as from the National Canadian Cancer registry were used to evaluate the outcome of oncologic treatment over the past 25 years. Age standardized incidence rates for all cancers combined, and for most individual cancer sites separately, show a continuous increase over time. Overall, the mortality rates have been increasing as well. Age specific trends in incidence and mortality show that, despite an increase in incidence rate, only in childhood cancers does a decrease in mortality exist. However, in patients aged 50 years or more at the time of the cancer diagnosis an increase in mortality was noted which actually exceeded the increase in incidence. Site specific analysis showed a decreasing trend in mortality for Hodgkin's disease, testicular cancer, stomach cancer, and melanoma (in females). A disturbingly increasing trend, specifically in women, existed for lung cancer mortality. It is projected that in women in Alberta mortality from lung cancer will surpass breast cancer mortality to become the number one cancer killer in women within the next few years. The overall 1-year, 2-year, and 5-year relative survival for all cancers combined remained constant over the 25-year period covered in this study. In conclusion, when analyzing the three indicators (incidence, mortality, and survival rates) of success in the fight against cancer no objective signs of progress could be found. Exceptions are the childhood cancers and relatively infrequent tumors such as Hodgkin's disease and testicular cancer. A plea is made for a shift in funding towards an increased emphasis on applied prevention programs and research.

Nonsteroidal anti-inflammatory drugs for the prevention of colon cancer.

OBJECTIVE: To summarize the results of animal and human studies of the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on neoplastic growth in the colon and to outline the possible mechanisms involved. DATA SOURCES: Research articles published in English before June 1992 were identified from MEDLINE. STUDY SELECTION: Nine articles on the polyp-cancer sequence were reviewed, 8 on the apparent pathophysiologic aspects of tumour inhibition by NSAIDs and 22 on animal and human research into the effect of NSAIDs on colon carcinogenesis. RESULTS: The results of animal and human research into the anticarcinogenic effect of NSAIDs suggest that the drugs are effective in preventing tumour growth in the colon. CONCLUSIONS: Intervention studies in humans are necessary to elucidate the therapeutic possibilities of NSAIDs, particularly in populations at increased risk for the development of colon cancer.