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Biomedical subjects

A L Verbeek

Publications and source records attributed to A L Verbeek.

At least 37 records · Page 2Linked to original sources

A prognostic index as diagnostic strategy in children suspected of mitochondriocytopathy.

The aim of this study was to assess an optimal screening for paediatric patients suspected of mitochondriocytopathy to justify a muscle biopsy. Forty-five patients were included. Medical history, physical examination, cardiac and ophthalmologic evaluation, clinical chemical investigations, in vivo function tests, neuroimaging and a skeletal muscle biopsy were performed in all patients. The results of the biochemical muscle studies were compared with the results of the other investigations. First, parameters with a statistical relationship with the result in muscle, normal or deficient, were selected. Secondly, a prognostic index was constructed using these parameters. Five parameters were selected: age <4 years, elevated fasting lactate to pyruvate ratio, elevated thrombocyte count, elevated lactate, and elevated alanine. Each parameter was scored 0 (not present) or 1 (present). The chance of a normal biopsy with a given value of this index (sum of the scores) was calculated: logit (Pr) = alpha + beta x index; alpha: -0.8167 and beta: 0.8331. (Pr: probability of normal biopsy.) The chance of a normal biopsy with an index value of 5 is 0.03, 4 is 0.07, 3 is 0.16, 2 is 0.30, 1 is 0.50 and 0 is 0.69. This prognostic index is a valuable instrument in deciding whether the suspicion of mitochondriocytopathy is strong enough to merit a muscle biopsy.

Adolescent↗

Parity and mammographic breast density in relation to breast cancer risk: indication of interaction.

We examined whether the harmful influence of nulliparity on breast cancer risk could be mediated by high mammographic density. Another possibility is that mammographic density and nulliparity act independently or perhaps synergistically on breast cancer risk. Our study population consisted of 129 cases and 517 controls who had been participants in the Nijmegen breast cancer screening programme for 10 years. Breast density was classified with a fully automated technique on digitized mammograms from the screening examination 10 years before diagnosis. Classification was based on the proportion of the breast that was composed of high density: < 5%, 5-25% or > 25%. Data on parity and potential confounders were obtained using a questionnaire, administered at the same examination. We found that nulliparae with low breast density (< 5%) were not at increased risk compared to parous women with low density: OR 1.1 (95% CI 0.2-5.8). Parous women with < 5% density formed the reference category throughout all analyses. The risks for parous women with 5-25% or > 25% density were 2.7 (95% CI 1.3-5.6) and 3.6 (95% CI 1.7-7.7) fold increased, respectively. However, when both factors were present (nulliparity and > or = 5% density), breast cancer risk was 7.1 times higher (95% CI 3.2-15.9). This could indicate that nulliparity and high breast density might work synergistically and that breast density is not just an explanatory factor in the influence of nulliparity on breast cancer risk. It is hypothesized that high breast density (reflecting fibro-glandular tissue with increased epithelial cell proliferation) is more susceptible to carcinogenic effects in the undifferentiated epithelial breast tissue of nulliparae than in the differentiated tissue of parous women. Since there were few data, no firm conclusions can be drawn. If these findings can be confirmed in a larger study population, however, they may have important implications for the prevention and early detection of breast cancer.

Adult↗

A blind review and an informed review of interval breast cancer cases in the Limburg screening programme, the Netherlands.

OBJECTIVE: To investigate the proportion of interval breast cancers that could have been detected at the previous screening examination, and to gain more insight into the characteristics of these tumours. SETTING: Breast cancer screening programme in mid- and southern Limburg, the Netherlands. METHOD: Firstly, previous screening mammograms of 92 interval cancer cases were blindly reread by the radiologists from two different units as part of their daily screening workload. Secondly, a separate informed review was conducted, in which all of the cases (except for two) were subclassified into four categories: screening error; minimal signs; radiologically occult both at previous screening and at diagnosis; or radiologically occult at previous screening. Trends in recall rates and false and true positive rates were calculated to study potential changes during and after the blind review. RESULTS: In the blind review, 15% of the interval cancers were detected in both rereadings and 21% in one rereading. In the informed review, 25% were classified as a screening error and 24% as minimal signs present; 74% of the cases classified as a screening error had been recalled at least once in the blind review. Recall rates and false positive rates in daily screening practice increased significantly during and after the study period. CONCLUSIONS: About one third of the interval cancers could have been detected in the previous screening round. In order to diminish the number of avoidable interval cancers, review and classification of interval cancers is an important tool for continuing the education of screening radiologists. Therefore, further development of review training procedures is necessary.

Aged↗

Polymorphisms in the vitamin D receptor gene and the androgen receptor gene and the risk of benign prostatic hyperplasia.

OBJECTIVE: Little is known about risk factors for the development of benign prostatic hyperplasia (BPH). Recently, associations were observed between prostate cancer (CaP) risk and polymorphisms in the vitamin D receptor (VDR) gene and the androgen receptor (AR) gene. Since both receptors are relevant for prostate growth, the VDR and AR are also expected to be involved in the development of BPH. The objective of this study is to establish the relationship between the risk of BPH and a polymorphism in the number of CAG repeats in the AR gene and a TaqI restriction enzyme polymorphism in the VDR gene. METHODS: For this study, 98 patients who had been treated for BPH-related complaints and 61 convenience controls (predominantly bladder cancer patients) were recruited from the outpatient clinic. DNA was isolated from peripheral blood, and genotyping was performed with PCR-based methods. Means as well as odds ratios (ORs) with 95% confidence intervals (CI) were calculated using SPSS software. RESULTS: The mean number of CAG repeats in the AR gene in patients and controls was found to be similar: 21.8 (SD = 2.8) and 21.9 (SD = 2.9), respectively. In the subgroup of patients with a prostate volume of at least 50 cm(3), the mean number of repeats was 21.5 (SD = 2.6). The OR for BPH for individuals with homozygous presence of the VDR TaqI restriction fragment length polymorphism (RFLP) (tt) versus individuals with homozygous absence (TT) or heterozygotes (Tt) was found to be 1.0 (95% CI 0.4-2.4). For individuals with a prostate volume of at least 50 cm(3), the OR was 1.2 (95% CI 0.5-3. 2). CONCLUSION: Unlike earlier observations in prostate cancer, we did not find an association between the CAG repeat polymorphism in the AR gene and the TaqI RFLP polymorphism in the VDR gene and the risk of BPH.

Aged↗

Shortening the duration of treatment for cervical tuberculous lymphadenitis.

The aim of the study was to determine the optimal duration of treatment for patients with tuberculous lymphadenitis. The Medline database was searched for relevant articles published between 1978-1997. Inclusion criteria were study populations of patients with predominantly cervical tuberculous lymphadenitis in whom the diagnosis had been confirmed bacteriologically and/or histologically, or was made probable by using clinical and laboratory markers. Treatment management had to include at least isoniazid, rifampicin and pyrazinamide and a follow-up of at least 12 months after the end of treatment. Patients with resistance to rifampicin and pyrazinamide and previous treatment for tuberculosis were excluded. The number of patients who relapsed after treatment was calculated. The study population in eight out of the 35 articles retrieved were suitable for analysis. Some concerned comparative studies. There were eight treatment schedules of 6 months' duration and three schedules of 9 months' duration. Treatment for 6 months resulted in a tuberculous lymphadenitis relapse rate of 13/422=3.3% (95% confidence interval: 1.7-5.5), with a mean follow-up of 31 months after completion of treatment. Treatment for 9 months resulted in a relapse rate of 3/112=2.7% (95% confidence interval: 0.6-7.8), with a mean follow-up of 20 months. Despite the limitations of the literature available, 6 months of therapy is probably sufficient for patients with tuberculous lymphadenitis.

Antitubercular Agents↗

Prediction of bladder outlet obstruction in men with lower urinary tract symptoms using artificial neural networks.

PURPOSE: To evaluate the performance of a backpropagation artificial neural network (ANN) in the diagnosis of men with lower urinary tract symptoms (LUTS) and to compare its performance to that of a traditional linear regression model. MATERIALS AND METHODS: 1903 LUTS patients referred to the University Hospital Nijmegen between 1992 and 1998 received routine investigation, consisting of transrectal ultrasonography of the prostate, serum PSA measurement, assessment of symptoms and quality of life by the International Prostate Symptom Score (IPSS), urinary flowmetry with determination of maximum flow rate (Qmax), voided volume and post-void residual urine and full pressure flow studies (PFS). Using a three-layered backpropagation ANN with three hidden nodes, the outcome of PFS, quantified by the Abrams-Griffiths number (AG-number), was estimated based on all available non-invasive diagnostic test results plus patient age. The performance of the network was quantified using sensitivity, specificity and the area under the ROC-curve (AUC). The results of the neural network approach were compared to those of a linear regression analysis. RESULTS: Prostate volume, Qmax, voided volume and post void residual urine showed substantial predictive value concerning the outcome of PFS. Patient age, PSA-level, IPSS and Quality of life did not add to that prediction. Using a cut-off value in predicted and true AG-numbers of 40 cm. H2O, the neural network approach yielded sensitivity and specificity of 71% and 69%, respectively. The AUC of the network was 0.75 (standard error = 0.01). A linear regression model produced identical results. CONCLUSIONS: This study shows that at an individual level, the outcome of PFS cannot be predicted accurately by the available non-invasive tests. The use of ANNs, which are better able than traditional regression models to identify non-linear relations and complex interactions between variables, did not improve the prediction of BOO. Thus, if precise urodynamic information is considered important in the diagnosis of men with LUTS, PFS must be carried out. Both neural networks and regression analysis appear promising to identify patients who should undergo PFS, and those in whom PFS can safely be omitted. Furthermore, the ability of ANNs and regression models to predict treatment result should be evaluated.

Humans↗

[Roaming through methodology. XIII. Matching as a rule is not useful].

In applied medical research matching is a technique used to control confounding in the design stage of a study. With matching, particular subjects are selected in such a way that the potential prognostic confounders are distributed equally among the comparison groups. A major disadvantage of matching is that it can be inefficient. With the so-called stratified data analysis control of confounding is achieved equally well. Therefore, from the validity and efficiency points of view matching is no longer desirable.

Case-Control Studies↗

Low reproducibility of maximum urinary flow rate determined by portable flowmetry.

To evaluate the reproducibility in maximum urinary flow rate (Qmax) in men with lower urinary tract symptoms (LUTSs) and to determine the number of flows needed to obtain a specified reliability in mean Qmax, 212 patients with LUTSs (mean age, 62 years) referred to the University Hospital Nijmegen, with various degrees of obstruction on pressure-flow studies, used a portable home-based uroflowmeter with 12 disposable beakers. Voided volume and maximum flow rate were recorded continuously during micturition. Flows with voided volumes of at least 100 ml and without possible artifacts were included. All analyses were repeated while excluding flows with voided volumes <150 ml. A coefficient of variation (CV) was calculated for each patient. The CV represents the standard deviation relative to the mean. All individual CVs were subsequently pooled into a population mean CV. This parameter was used to estimate the number of flows required to obtain a mean Qmax with specified reliability for an individual patient. All analyses were repeated, while successively excluding the first, the first two, and the first three flows, to assess a possible learning curve. A total of 1,854 flows was available for analyses, yielding an average of nine flows per patient. Mean Qmax was 13.2 ml/sec; the mean CV was 24%. To allow, for instance, a 10% deviation from the true mean Qmax (e.g., 15 ml/s +/- 1.5 ml/s), approximately 25 flows are necessary. The actual number of flows needed is in fact even higher due to the presence of small and artifactual flows. Using a 150 ml volume cutoff point, somewhat fewer flows are required, but the total number of flows needed (that is, valid, small, and artifactual flows) increases. There was no evidence of a learning curve. The boundaries of a confidence interval around a single Qmax measurement that is likely to contain the true mean Qmax, lie approximately 50% below or above that single Qmax measurement. To reduce this proportion down to 10%, approximately 25 flows are needed. Thus, to obtain reliable mean Qmax values, considerably more flows are required than are normally performed in urologic practice.

Analysis of Variance↗

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.

Aged↗

Evaluation of treatment regimens to cure Helicobacter pylori infection--a meta-analysis.

OBJECTIVE: To assess effectiveness of treatment to cure Helicobacter pylori infection. DATA SYNTHESIS: Meta-analysis of 666 manuscripts (full papers, abstracts, letters to the editor) identified through Medline and a manual search (1986 to January 1998). Data were overviewed by regression analysis with weighted random effects models. SUBJECTS: 53 228 patients with H. pylori infection. INTERVENTIONS: Patients were treated with 132 different medication combinations. MAIN OUTCOME MEASURE: Cure of H. pylori infection per protocol and intention-to-treat basis at least 28 days after treatment. RESULTS: The nationality of the patients and therapeutic regimen have a significant impact on the results, after correction for the heterogeneity in the precision of the cure rate caused by different study sizes and random effect for study. On the basis of the original sample size, cure rates of 80-85% were achieved using combinations of a proton-pump inhibitor or ranitidine bismuth citrate with two antibiotics including clarithromycin, amoxycillin and metronidazole or tinidazole. Comparable cure rates were also achieved using a combination of a proton-pump inhibitor or H2-receptor antagonist with bismuth subcitrate or tripotassium dicitrato bismuthate, metronidazole and tetracycline. The dose of clarithromycin influenced cure rates. Treatment duration did not influence the outcome. CONCLUSION: Several therapeutic regimens are eligible to cure H. pylori infection. However, none of the medication combinations were able to cure H. pylori infection in more than 85% of the patients assessed by intention-to-treat. The countries in which the studies were performed also had a significant impact on eradication rates.

Antacids↗

The prognostic value of gastrointestinal morbidity for gastric cancer.

OBJECTIVE: A history of gastrointestinal disease is a risk factor for organic gastrointestinal disorders overall. We conducted a retrospective case-control study to explore whether a history of gastrointestinal disease is of prognostic value for gastric cancer. METHODS: Forty-six patients with gastric cancer were identified from a dynamic population of approximately 12,000 patients followed since 1971 in four general practices. The control subjects without gastric cancer were matched one-on-one according to age, general practice, sex and observation period. Data on gastrointestinal morbidity in the period before gastric cancer was diagnosed were obtained from the Continuous Morbidity Registration. RESULTS: The mean observation period between the date of enrolment in the registration and the first diagnosis of gastric carcinoma was 12 years. Although every patient with gastric cancer ultimately will develop gastrointestinal complaints, 28 of these patients had no previous gastrointestinal morbidity, in comparison with 26 control subjects. Furthermore, patients who developed gastric cancer did not have more frequent gastrointestinal morbidity in their past than the control subjects (odds ratio 0.80, 95% CI 0.32-2.03). CONCLUSIONS: Our results suggest that a history of gastrointestinal morbidity is not of prognostic value for gastric cancer. Focusing attention on patients with a past history of gastrointestinal symptoms to detect gastric cancer may be of little value.

Aged↗

Mortality trend from cancer of the gastric cardia in The Netherlands, 1969-1994.

BACKGROUND: Time trends of cancer of the gastric cardia differ between populations and the reasons are not fully understood. The object of this study was to investigate the occurrence of cancer of the gastric cardia in descriptive relation to age at death, calendar period, birth cohort and gender in the Netherlands between 1969 and 1994. METHODS: Data on the number of people with cancer of the gastric cardia as the underlying cause of death from 1969 to 1994 were obtained from annual publications by the National Causes of Death Registry of Statistics Netherlands. To estimate the separate effects of age, calendar period and birth cohort on the trend in mortality, a simultaneous analysis of these factors was performed using a log-linear Poisson model. RESULTS: In 1969, the mortality rates from cancer of the gastric cardia for males and females per 100,000 people were 2.1 and 1.1; in 1994 the mortality rates were 1.5 and 0.7, respectively. Examination of the time trend suggested that mortality for cancer of the gastric cardia may reflect a period phenomenon, although a cohort effect may have also contributed to the observed time trend. Furthermore, more males than females died from cancer of the gastric cardia. The difference was most striking in the younger age categories. CONCLUSION: In this Dutch population, the age-period-cohort-gender analysis indicated that the mortality rates decreased after the period 1975-1979 which might be explained by a decrease in exposure to risk factor(s) or an increase in exposure to protective factor(s).

Adult↗

Changes in mammographic breast density and concomitant changes in breast cancer risk.

Among participants of the biennial Nijmegen breast cancer screening programme, we examined whether diminution of mammographic breast density lowered breast cancer risk. Post-menopausal breast cancer cases (n = 108), who had to have participated in all the five screening rounds prior to their diagnosis, were matched to 400 controls on year of birth and screening history. Controls had to be free of breast cancer at the time of the case's diagnosis. Changes in breast density were measured over a 10-year period, by a fully computerized method. Women in whom 5-25% or >25% of the breast was composed of fibro-glandular density showed a threefold increased 10-year risk compared to women with <5% density. In women with 5-25% density initially, we observed a trend of decreasing risk with diminishing density: when women with <5% density throughout the whole period formed the reference category, the odds ratio (OR) for those who decreased from 5-25% to <5% density was 1.9 [95% confidence interval (CI) = 0.6-6.1] in contrast to the OR of 5.7 (95% CI = 2.2-15.2) for those with persisting 5-25% density. In women who increased from 5-25% density to >25% density the OR was 6.9 (95% CI = 2.1-22.9). In women with >25% density initially, diminishing density was not clearly associated with lowering risk, which may be partly explained by the low number of women who decreased to <5% (n = 12). Due to the limited size of the study these results have to be interpreted with caution. Although the results are not conclusive, they could indicate a trend of decreasing risk with diminishing breast density. Should this effect be real, it may have great implications for the primary prevention of breast cancer or for the identification of high-risk groups who would benefit by more frequent screening. Therefore, large-scale, long-term follow-up studies on the effects of changes in breast density are needed.

Adult↗

High mammographic breast density and its implications for the early detection of breast cancer.

OBJECTIVES: Women with high mammographic breast density are at increased risk of breast cancer. This study explores whether these women should receive intensified screening (more frequent screening or screening with alternative techniques that increase the length of the preclinical detectable phase) to reduce further breast cancer mortality. METHODS: Mathematical models were used to estimate the effects of intensified screening in women with high breast density. The effects were expressed as a reduction in the number of interval cancers. RESULTS: If women with > 25% breast density (comprising about one fifth of all women) are screened annually instead of biennially, an 18% reduction in the total number of interval cancers can be expected. Screening these women with alternative screening techniques biennially may produce the same reduction, provided that these techniques double the mean lead time. CONCLUSIONS: By screening women with dense breasts more intensively, many more breast cancers can theoretically be detected at an early stage. The results provide an early indication of what may be expected from screening strategies. Next, cost-benefit analyses are needed.

Breast Neoplasms↗

Prevalence of "syndrome X" features in parents of type 1 diabetic patients with or without nephropathy.

OBJECTIVE: To compare the prevalence of "syndrome X"-related parameters in parents of type 1 diabetic patients with diabetic nephropathy (DNP) to those in parents of diabetic patients without DNP. RESEARCH DESIGN AND METHODS: In this cross-sectional study, we included 50 parents of type 1 diabetic patients with DNP and 50 parents of diabetic patients without DNP. All parents were investigated in a fasting state for serum lipids including nonesterified fatty acids (NEFAs), glucose, HbA1c, plasma uric acid, fasting insulin levels, and albuminuria. Blood pressure was recorded in the supine position using an automatic device; ankle/brachial index was measured with Doppler ultrasound. Presence of cardiovascular disease was determined by a standardized questionnaire and electrocardiogram registration. Subjects without known diabetes underwent a 2-h oral glucose tolerance test. Anthropometric parameters such as BMI, waist-to-hip ratio, and percentage of body fat were measured. In addition to univariate analysis, a syndrome X score (SXS) was formulated, comprising a number of syndrome X-related biochemical, physiological, and/or anthropometric parameters. RESULTS: Univariate analysis revealed no significant differences in syndrome X parameters between parents of type 1 diabetic patients with or without DNP. Also, the composite SXS was similar in both groups. CONCLUSIONS: In this study, no differences were found in the prevalence of syndrome X features between parents of type 1 diabetic patients with DNP and parents of patients without DNP.

Adult↗

Optimizing diagnostic test sequences: the probability modifying plot.

The problem of deciding the optimal sequence of diagnostic tests can be structured in decision trees, but unmanageable bushy decision trees result when the sequence of two or more tests is investigated. Most modelling techniques include tests on the basis of gain in certainty. The aim of this study was to explore a model for optimizing the sequence of diagnostic tests based on efficiency criteria. The probability modifying plot shows, when in a specific test sequence further testing is redundant and which costs are involved. In this way different sequences can be compared. The model is illustrated with data on urinary tract infection. The sequence of diagnostic tests was optimized on the basis of efficiency, which was either defined as the test sequence with the least number of tests or the least total cost for testing. Further research on the model is needed to handle current limitations.

Decision Support Techniques↗

A multistate Kalman filter for neonatal clotting time prediction and early detection of coagulation disturbances.

The multistate Kalman filter was applied to develop a heparin dose proposal system and to detect coagulation disturbances during neonatal extracorporeal membrane oxygenation (ECMO). A system containing this filter was based on the activated clotting time (ACT) values and the heparin doses administered every hour during ECMO. If the ACT value can be predicted accurately from the previous heparin dose, a heparin dose proposal can be given to achieve or maintain the required ACT level. The analysis was done on 6,356 ACT level measurements in 44 ECMO neonates. The multistate Kalman filter technique showed an unbiased prediction of ACT, with a standard deviation of 23 seconds. Two out of three cases of disseminated intravascular coagulation (DIC) were detected. ACT values were predicted sufficiently accurately by the multistate Kalman filter technique to justify a prospective study on the performance of the heparin dose proposal system and its ability to detect DIC.

Drug Therapy, Computer-Assisted↗