Bordetella species in children with cystic fibrosis: what do we know? The role in acute exacerbations and chronic course.

Despite vaccination, pertussis is still endemic in the Netherlands. A literature search was performed to verify what is known about the role of Bordetella species in children with cystic fibrosis, with regard to the incidence of Bordetella infections, the involvement in pulmonary exacerbations and the influence on chronic course. Little is known about the frequency of Bordetella infections and the involvement of Bordetella species both in relation to the chronic course of cystic fibrosis and to pulmonary exacerbations. Since it is difficult to detect Bordetella species in cultures and few sputum cultures investigated have been obtained during an exacerbation, it is likely that the frequency of Bordetella species in CF patients is underestimated. Identification of Bordetella species in these patients may have serious consequences for the treatment of exacerbations in CF. Future research investigating the role of Bordetella species in cystic fibrosis should use specific techniques to detect Bordetella in cultures.

Dental school faculty shortages increase: an update on future dental school faculty.

The 1999 publication of the American Association of Dental Schools (AADS) President s Task Force on Future Dental School Faculty revealed a crisis in the shortages of dental school faculty. Stakeholders from around the nation have used the AADS Task Force report to address the crisis. In addressing one of the AADS Task Force recommendations, the American Dental Education Association (ADEA), formerly AADS, gathered additional data through a new survey of dental school deans to elucidate the current state of faculty shortages. Based on this research, ADEA projects that the number of unfilled budgeted faculty positions in U.S. dental schools now approaches 400. Survey respondents identified retirement as the leading reason for full-time faculty separations, while separation to enter private practice was the second most frequent reason for leaving the institution. Offering a salary competitive with that of private practice was identified as the most critical factor in recruiting future faculty. A number of short and long-range strategies to recruit and retain faculty are presented. Ultimately, the dental school faculty shortage places in jeopardy the general and oral health of the public.

Prostate specific antigen testing and digital rectal examination before and during a randomized trial of screening for prostate cancer: European randomized study of screening for prostate cancer, Rotterdam.

PURPOSE: Worldwide 2 large-scale randomized screening trials for prostate cancer have been initiated. Determining prostate specific antigen (PSA) involves a simple test that may influence the outcome of these trials if frequently done in the control arm or before study enrollment. We quantified PSA and digital rectal examination before and during the screening trial in Rotterdam, The Netherlands and in the general population. MATERIALS AND METHODS: Trial participants were administered study intake questionnaires on tests done before study participation. Data on PSA from the regional general practice laboratory were correlated with participant data. Various sources were used to quantify PSA tests and digital rectal examinations in the general population. RESULTS: Of men 55 to 74 years old 45% underwent digital rectal examination at 1 time and 13% reported that PSA was tested before trial participation. Each rate increased with age. No statistically significant effect of former PSA testing or digital rectal examination on the cancer detection rate was identified. The rate of PSA determination after initial screening and/or randomization in the control arm was 2-fold that in the screening arm (76 versus 33/1,000 person-years). PSA determination initially decreased in the screening arm but increased rapidly after some time. The number of PSA determinations in the general population was estimated to be 45/1,000 person-years at ages 55 to 69 years. CONCLUSIONS: PSA testing was moderate in the control arm but if different men undergo this test each year, the contamination rate may become rather high. In the final analysis of mortality PSA testing should be considered.

A cognitive task analysis for dental hygiene.

To be an effective assessment tool, a simulation-based examination must be able to evoke and interpret observable evidence about targeted knowledge, strategies, and skills in a manner that is logical and defensible. Dental Interactive Simulations Corporation's first assessment effort is the development of a scoring algorithm for a simulation-based dental hygiene initial licensure examination. The first phase in developing a scoring system is the completion of a cognitive task analysis (CTA) of the dental hygiene domain. In the first step of the CTA, a specifications map was generated to provide a framework of the tasks and knowledge that are important to the practice of dental hygiene. Using this framework, broad classes of behaviors that would tend to distinguish along the dental hygiene expert-novice continuum were identified. Nine paper-based cases were then designed with the expectation that the solutions of expert, competent, and novice dental hygienists would differ. Interviews were conducted with thirty-one dental hygiene students/practitioners to capture solutions to the paper-based cases. Transcripts of the interviews were analyzed to identify performance features that distinguish among the interviewees on the basis of their expertise. These features were more detailed and empirically grounded than the originating broad classes and better serve to ground the design of a scoring system. The resulting performance features were collapsed into nine major categories: 1) gathering and using information, 2) formulating problems and investigating hypotheses, 3) communication and language, 4) scripting behavior, 5) ethics, 6) patient assessment, 7) treatment planning, 8) treatment, and 9) evaluation. The results of the CTA provide critical information for defining the necessary elements of a simulation-based dental hygiene examination.

Issues of academic integrity in U.S. dental schools.

Evidence of violations of academic integrity can be identified at all levels of education. A survey on academic integrity was mailed in 1998 to the academic deans of all fifty-five U.S. dental schools, with a response rate of 84 percent. This survey showed that reported incidents of academic dishonesty occur in most dental schools, with the average school dealing with one or two cases a year. The most common incidents of dishonest behavior involved copying or aiding another student during a written examinations; the second most common involved writing an untrue patient record entry or signing a faculty member's name in a patient chart. Respondents indicated the major reason for failure to report academic dishonesty was fear of involvement because of time and procedural hassles and fear of repercussions from students and peers.

Interval cancers in the Dutch breast cancer screening programme.

The nationwide breast cancer screening programme in The Netherlands for women aged 50-69 started in 1989. In our study we assessed the occurrence and stage distribution of interval cancers in women screened during 1990-1993. Records of 0.84 million screened women were linked to the regional cancer registries yielding a follow-up of at least 2.5 years. Age-adjusted incidence rates and relative (proportionate) incidences per tumour size including ductal carcinoma in-situ were calculated for screen-detected and interval cancers, and cancers in not (yet) screened women, comparing them with published data from the UK regions North West and East Anglia. In total 1527 interval cancers were identified: 0.95 and 0.99 per 1000 woman-years of follow-up in the 2-year interval after initial and subsequent screens respectively. In the first year after initial screening interval cancers amounted to 27% (26% after subsequent screens) of underlying incidence, and in the second year to 52% (55%). Generally, interval cancers had a more favourable tumour size distribution than breast cancer in not (yet) screened women. The Dutch programme detected relatively less (favourable) invasive cancers in initial screens than the UK programme, whereas the number of interval cancers confirms UK findings. Measures should be considered to improve the detection of small invasive cancers and to reduce false-negative rates, even if this will lead to increasing referral rates.

Mammography requests in general practice during the introduction of nationwide breast cancer screening, 1988-1995.

Introducing an organised breast cancer screening programme for certain age groups in a population might induce opportunistic screening in adjacent (non-invited) age groups and influence health behaviour in the target population. We analysed the effect of the start of the Dutch national screening programme on the number of mammographies requested by 43-45 general practices for the age groups 30-39, 40-49, 50-69 and 70+ years, using logistic regression analysis. In all age groups an immediate increase was observed in the number of mammography requests after the start of the screening, which was largest and statistically significant in the target population of the screening programme (age 50-69 years). More than 2 years after the start of screening, the number of mammography requests in all age groups had decreased to the level before the start and in the age group 50-69 years the number of mammographies was significantly lower than before the screening started. The unexpected increase in mammographies after the start of the breast cancer screening programme might be related to registry problems or to the process of building up the screening programme. Eventually there was a decrease in the number of mammographies in the target population, probably an effect of the introduction of the national screening programme. Opportunistic screening was not clearly demonstrated in adjacent age groups.

Advanced prostate cancer: course, care, and cost implications.

BACKGROUND: If prostate cancer screening proves to be effective, some cases will be prevented from reaching the advanced stage. In order to evaluate screening programs thoroughly, it is important to quantify course, care, and accompanying costs of advanced disease. METHODS: We studied 70 files of patients in two hospitals, who had received a diagnosis of distant metastases of prostate cancer and who had died in the years 1994-1998. The total healthcare received by these patients, including symptoms and complaints, was recorded. RESULTS: The most frequently reported symptoms were pain (42%), urogenital symptoms (25%), and malaise (20%). Eighty-nine percent of all patients were hormonally treated (either by orchidectomy and/or chemical castration), and 47% received one or more series of radiation therapy. Sixty-nine percent of all patients were treated with pain medication. The average duration of advanced disease in all patients was 24 months. Average costs of advanced disease were estimated at $11,182 over the total period: $1,547 (14%) was allocated to assessment and outpatient care, and $9,635 (86%) to treatment and costs of hospital stay. Almost half of the total costs were determined by hospital stay. CONCLUSIONS: These data give a better understanding of the course, care, and costs of advanced prostate cancer. These estimates, together with the effects of advanced prostate cancer on quality of life, will be used for the evaluation of prostate cancer screening.

Changing role of 3 screening modalities in the European randomized study of screening for prostate cancer (Rotterdam).

A randomized screening trial was started in Europe to show the effect of early detection and treatment of prostate cancer on mortality (European Study on Screening of Prostate Cancer). In one centre (Rotterdam), the screening protocol initially consisted of 3 screening tests for all men: prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasonography (TRUS). A PSA value of >/=4 ng/ml and/or an abnormality on DRE and/or TRUS were taken to indicate that biopsy was required. In this study, we examined the possibilities for a more efficient screening protocol. A logistic-regression model was used to predict the number of cancers for PSA < 4 ng/ml if all men were biopsied (predictive index, PI). Effects of a change in PSA cut-off on the screening results were explored. Weights were applied to procedures and cancers to explore the possibility of expressing differences between protocols in one overall figure. Biopsies in men with PSA < 1 ng/ml and a positive DRE or TRUS were very inefficient. Applying DRE and TRUS only in the PSA ranges 1.5 to 3.9 and 2 to 3.9 ng/ml to determine whether a biopsy was required would result in a decrease of 29 to 36% in biopsies and a decrease of 5 to 8% in cancers. However, the results of DRE and TRUS could not be duplicated entirely. A protocol with only PSA >/= 3 ng/ml as a direct biopsy indicator resulted in a decrease of detected cancers by 7.6% and of biopsies by 12%, also a much simpler screening procedure. Use of the PI would give more efficient protocols, but this should be viewed as a preliminary finding, with the disadvantage of necessitating many additional screening visits. Since the results of DRE and TRUS could not be duplicated, a change in protocol towards PSA >/= 3 ng/ml appears acceptable. If this proves effective, a final judgement about the optimal combination of screening tests may be made. Int. J. Cancer (Pred. Oncol.) 84:437-441, 1999.

Predictors for biopsy outcome in the European Randomized Study of Screening for Prostate Cancer (Rotterdam region).

BACKGROUND: In the European Randomized Study of Screening for Prostate Cancer (ERSPC, Rotterdam region), men aged 55-74 years are screened for prostate cancer by prostate-specific antigen (PSA) sampling, digital rectal examination (DRE), and transrectal ultrasound investigation (TRUS). All men with a PSA > or =4 ng/ml and/or a suspicious DRE and/or a suspicious TRUS are biopsied. METHODS: Logistic regression analysis was applied to derive a predictive index that equals the chance to find prostate cancer in a biopsy given the outcomes of the screening tests. This model was used to assess the number of cancers that could have been detected if all men had been biopsied (extrapolation). Furthermore, the model was used to study the possibilities for improvement of the current screening protocol. RESULTS: PSA was the dominant predictor for prostate cancer in a biopsy, followed by prostate volume, DRE, and TRUS result. It is assessed that 69% (95% CI, 52-86%) of cancers that could be identified if all men were biopsied are currently detected. Application of the same methods to screening data obtained in Göteborg (the Swedish ERSPC partner) yielded almost identical results. It was found that, in the Rotterdam protocol, a considerable number of men were biopsied according to the screening protocol with an assessed lower chance to have prostate cancer than men who were not biopsied according to the protocol. CONCLUSIONS: The chance to detect prostate cancer in a biopsy can be modeled quite accurately as a function of serum PSA, prostate volume, DRE, and TRUS results. Important improvements in the screening protocol can be achieved by the application of the predictive index.

Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: The utility of digital rectal examination (DRE) as a screening test for early detection of prostate cancer has not been established. Therefore, we evaluated the usefulness of DRE as a stand-alone screening test and in conjunction with measured serum prostate-specific antigen (PSA) levels of 0-3.9 ng/mL and transrectal ultrasonography (TRUS). METHODS: Our study population consisted of 10,523 men aged 54-76 years who were randomly assigned to the screening arm of the Rotterdam, The Netherlands, section of the European Randomized Study of Screening for Prostate Cancer. The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test. Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed (and missed) by DRE. RESULTS: The overall detection rate for prostate cancer in this population when serum PSA measurement, DRE, and TRUS were used was 4.5%, and the detection rate with DRE alone was 2.5%. The positive predictive value of DRE ranged from 4% to 11% in men with PSA levels of 0-2.9 ng/mL and from 33% to 83% in men with PSA levels of 3.0-9.9 ng/mL or more. Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small (mean volumes = 0.24-0.83 mL), and most were well differentiated (Gleason scores of 6 or less). Minimal, moderate, and advanced cancers were seen in 42%, 42%, and 16% of men, respectively, with a PSA level of 4.0 ng/mL or less. DRE alone allowed detection of 264 (55.8%) of 473 cancers; 82 (17.3%) of the 473 cancers would have remained undetected by PSA-based screening alone (i.e., no follow-up procedures for PSA values of 0-3.9 ng/mL). CONCLUSIONS: For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges.

Radiation risk of mammography related to benefit in screening programmes: a favourable balance?

OBJECTIVES: To estimate the number of breast cancer deaths induced by low dose radiation in breast cancer screening programmes compared with numbers prevented. METHODS: A computer simulation model on the natural history of breast cancer was combined with a model from BEIR-V on induced breast cancer mortality from low levels of radiation. The improvement in prognosis resulting from screening was based on the results of the Swedish overview of the randomised screening trials for breast cancer and the performance of screening in the Netherlands. Different scenarios (ages and intervals) were used to explore the objectives. Sensitivity analyses were carried out for latency period, dose of mammography, sensitivity of the screening test, early detection by screening of induced breast tumours, and new 1996 risk estimates by Howe and McLaughlin. RESULTS: For a screening programme, age group 50-69, two year interval, 2 mGy per view, the balance between the number of deaths induced versus those prevented was favourable: 1:242. When screening is expanded to the age group 40-49 with a one or two year interval the results may be less favourable, that is, 1:66 and 1:97. According to these scenarios and with the Dutch scenario as reference, one breast cancer death from radiation may be expected to occur to save eight extra deaths from breast cancer. If screening was equally effective in young women as in women aged 50-69, the marginal value was 1:+/- 30. Assuming detection of induced cancers by screening could influence the ratios by about 30%, but did not substantially change the conclusions. The new risk estimates by Howe and McLaughlin resulted in five times to eight times favourable ratios breast cancer deaths induced to prevented. Besides age group of screening, dose of mammography is the other determinant of risk. CONCLUSIONS: For screening under the age of 50, the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seem less favourable. Credibility intervals were however wide, because of many uncertainties of radiation risk at very low doses.

Anticipating the consequences for the primary therapy of breast cancer after introducing screening. A more global picture for health care policy making.

A breast cancer screening program mainly aims at reducing mortality. However, it also has an effect, often not assessed, on the utilization of health care resources that is relevant to health care policy making. Using a simulation model, this paper forecasts the impact of introducing a breast cancer screening program on the utilization of resources for the primary therapy of breast cancer. The most important consequences from a health care point of view will be an increased use of breast-conserving therapy and an increased need for postoperative radiotherapy; there will also be a higher number of women diagnosed with noninvasive breast cancer. The results of this study could provide support for health care decision making by showing the consequences of policy decisions on the introduction of screening programs for health care utilization.

Nation-wide breast cancer screening in The Netherlands: results of initial and subsequent screening 1990-1995. National Evaluation Team for Breast Cancer Screening.

Based on an extensive cost-effectiveness analysis, the Dutch nation-wide breast cancer screening programme started in 1990, providing a biennial screen examination to women aged 50 to 69 years. The programme is monitored by the National Evaluation Team, which annually collects tabulated regional evaluation data to determine performance indicators. This study presents (trends in) the outcomes of initial and subsequent screening rounds, 1990-1995, and compares them to the predictions of the cost-effectiveness-analysis. Up to 1996, 88% of the target population was covered by the programme and more than 2.4 x 10(6) women were invited. The overall attendance rate was 77.5% with little differences between screening rounds and age groups; the highest rate was found in non-urbanised areas (82.4%). Of 1,000 initially (and 2 years thereafter) screened women, 13.4 (6.6) were referred for further investigation, 9.7 (4.4) were biopsied and 6.4 (3.4) had breast cancer. The positive predictive values of screen test and biopsy were 47% (51%) and 66% (78%), respectively. DCIS was diagnosed in 0.9 (0.5) and invasive cancers < or = 10 mm in 1.5 (1.0) per 1,000 screens. Lymph node metastases were found in 28% (24%) of the invasive cancers. Except the increasing attendance, which was much higher than expected, the results were fairly constant over the years. Contrary to initial screens, the results of subsequent screens did not fulfil expectations with regard to breast cancer detection and tumour size distribution. We conclude that the nation-wide screening programme is being implemented successfully. Given the results, the programme should contribute to a substantial breast cancer mortality reduction in the future. The discrepancy between observed and expected results in subsequent screens has to be watched carefully.

A comparison of disease specific survival of patients who died of and who had newly diagnosed prostate cancer.

PURPOSE: We investigated the validity of calculating prostate specific survival from a population of deaths occurring during a given period. MATERIALS AND METHODS: Stochastic simulation was used to generate a large number of life histories of men with prostate cancer. RESULTS: The investigated method of calculating survival can lead to different outcomes compared to the standard method. In an example with a Dutch population structure the investigated method leads to strong underestimation of 25 years of survival. CONCLUSIONS: The method of calculating survival studied is theoretically not valid. Several probable changes in the population can produce results that are different from the standard method of calculating survival.

Quantitative estimates of the impact of sensitivity and specificity in mammographic screening in Germany.

STUDY OBJECTIVE: To estimate quantitatively the impact of the quality of mammographic screening (in terms of sensitivity and specificity) on the effects and costs of nationwide breast cancer screening. DESIGN: Three plausible "quality" scenarios for a biennial breast cancer screening programme for women aged 50-69 in Germany were analysed in terms of costs and effects using the Microsimulation Screening Analysis model on breast cancer screening and the natural history of breast cancer. Firstly, sensitivity and specificity in the expected situation (or "baseline" scenario) were estimated from a model based analysis of empirical data from 35,000 screening examinations in two German pilot projects. In the second "high quality" scenario, these properties were based on the more favourable diagnostic results from breast cancer screening projects and the nationwide programme in The Netherlands. Thirdly, a worst case, "low quality" hypothetical scenario with a 25% lower sensitivity than that experienced in The Netherlands was analysed. SETTING: The epidemiological and social situation in Germany in relation to mass screening for breast cancer. RESULTS: In the "baseline" scenario, an 11% reduction in breast cancer mortality was expected in the total German female population, ie 2100 breast cancer deaths would be prevented per year. It was estimated that the "high quality" scenario, based on Dutch experience, would lead to the prevention of an additional 200 deaths per year and would also cut the number of false positive biopsy results by half. The cost per life year gained varied from Deutsche mark (DM) 15,000 on the "high quality" scenario to DM 21,000 in the "low quality" setting. CONCLUSIONS: Up to 20% of the total costs of a screening programme can be spent on quality improvement in order to achieve a substantially higher reduction in mortality and reduce undesirable side effects while retaining the same cost effectiveness ratio as that estimated from the German data.

Quantitative interpretation of age-specific mortality reductions from the Swedish breast cancer-screening trials.

BACKGROUND: Results from five Swedish randomized trials may provide the most conclusive evidence on the effect of mammographic screening and have been used to forecast the expected reduction in breast cancer mortality in other programs. However, those trials demonstrated different degrees of reduction. The interpretation of observed mortality reduction after long follow-up for women aged 40-49 years at trial entry is both important and controversial. PURPOSE: We estimated what percentage of the observed mortality reduction for women aged 40-49 years at entry into the five Swedish screening trials might be attributable to screening these women at 50 years of age or older. Moreover, we calculated the most likely percentage mortality reduction for specific screening programs if the Swedish results were generalized and analyzed whether characteristics of each trial might at least partly explain the observed differences in reductions among the trials. METHODS: Each Swedish trial was simulated with one underlying computer simulation model (MISCAN--MIcrosimulation SCreening ANalysis) of the natural history of the disease and the performance of screening, taking into account nine important trial characteristics. Improvement in prognosis for screen-detected case patients was estimated with age-specific reduction for all trials and each trial design as a reference. RESULTS: An expected 7% reduction in breast cancer mortality for women aged 40-49 years at trial entry (relative risk [RR] = 0.93) was determined by computer modeling, assuming no improvement in prognosis for cancers that are screen detected before 50 years of age. This result indicates that, of the overall 10% observed reduction (RR = 0.90) in the five Swedish trials analyzed, most (70%) of this reduction might be attributable to screening these women in later rounds after their 50th birthday. Using additional trial information, predictions of breast cancer mortality reduction in women 50 years or older might be 11% larger than previously expected, assuming that high-quality mammographic screening can be achieved in nationwide programs. For women aged 50-69 years at trial entry, the differences in expected versus observed mortality reduction among the trials are estimated to be relatively small. (Expected mortality reductions range from 24% to 32%). CONCLUSIONS: Results from the Swedish randomized breast cancer-screening trials should be seen as more favorable regarding the effect of mammographic screening in reducing breast cancer mortality for women aged 50-69 years than was estimated earlier. Our analyses also suggest that the improvement in prognosis due to screening for women aged 40-49 years is much smaller than that for women aged 50 years or older. Approximately, 70% of the 10% observed reduction in breast cancer mortality (i.e., 7%) for women aged 40-49 years at trial entry might be attributable to a reduction due to screening these women after they reach age 50. IMPLICATIONS: Detailed screening data for the 40- to 49-year age group of all Swedish trials should be analyzed to specifically estimate the natural history and performance of screening in this age group.

Prediction of the effects and costs of breast-cancer screening in Germany.

Although breast-cancer screening programmes are now being introduced it is still debated whether this is an appropriate policy for all European countries. Taking into account empirical data from 2 regional pilot screening projects, this study has evaluated the effects and costs of a nationwide breast-cancer screening programme in Germany. Special attention was paid to the decentralized German health-care system and to the influence of attendance, interval and age group. The recent results of the analysis of the Swedish randomized screening trials were used to estimate the improvement in prognosis after early detection of breast cancer. Our analysis shows that a programme providing for the screening of women aged 50-69 at 2-year intervals might be expected to result in a decrease in mortality from breast cancer estimated at 11% for the total German population, representing 2,100 deaths from breast cancer prevented each year. The cost per life-year gained was assessed at between DM 18,800 and DM 25,300 for this scenario; 2 to 3 times less favourable than in the UK and The Netherlands. The sensitivity of mammography was estimated to be 12% lower than in The Netherlands and the attendance rate was calculated at 47% on average. A greater effort to ensure the quality of the screening programme and to improve the invitation system might finally lead to much better results. The mortality reduction might be as much as 18% if the attendance and the sensitivity of the screening could be improved to the Dutch level.