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Biomedical subjects

A L Verbeek

Publications and source records attributed to A L Verbeek.

At least 55 records · Page 3Linked to original sources

Past and current understanding of the pathophysiology of muscle cramps: why treatment of varicose veins does not relieve leg cramps.

Historically relevant hypotheses on the pathophysiology of muscle cramps are reviewed. Psychosomatic, static, vascular, myogenic and neural theories are highlighted from a clinician's point of view. Modern neurophysiologic research leaves little doubt that muscle cramp is caused by excitation of spinal motor neurones mediated by changes in presynaptic input. Nevertheless, obsolete theories and relative treatments stubbornly persist in clinical practice.

Humans↗

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.

Age Factors↗

Mammographic breast density and risk of breast cancer: masking bias or causality?

Masking bias is hypothesized to explain associations between breast density and breast cancer risk. Tumours in dense breasts may be concealed at the initial examination, but manifest themselves in later years, suggesting an increase in breast cancer incidence. We studied the association between breast density and breast cancer risk in 0, 1-2, 3-4 and 5-6 year periods between initial examination and diagnosis. We studied 359 cases and 922 referents, identified in a breast cancer screening programme in Nijmegen, The Netherlands. Breast density was assessed at the initial examination and classified as 'dense' (if > 25% of the breast was composed of density) or 'lucent' (< or = 25% density). In women examined with mid-1970s film screen mammography, we found that at time 0 the odds ratio (OR) for women with dense breasts compared to those with lucent breasts was 1.4 (95% confidence interval (CI): 0.7-6.2). After a 3-4 year period the risk was increased to 3.3 (95% CI: 1.5-7.1). Then, the risk decreased again (OR: 1.2, 95% CI: 0.6-2.7). This rise and decline in risk are in accordance with the masking hypothesis. The observation, however, that the risk at time 0 does not appear to be lower for women with dense breasts than for those with lucent breasts, seems to be inconsistent with the masking hypothesis and may be indicative of causality. The same analysis were performed in women whose initial screening examination was done with current high-quality mammography. Due to the small size of this study group no firm conclusions could be drawn, but it seems as if masking bias could still play a role with high-quality mammography.

Adult↗

Estimating the cost of lost productivity in dyspepsia.

BACKGROUND: In the field of gastrointestinal disease, productivity costs are highly relevant because work loss is substantial in dyspeptic patients. Productivity costs are normally calculated by multiplying days absent valued by gross earnings. This, however, might lead to an overestimation. AIM: To use a conservative approach to calculating productivity costs, taking absence compensating mechanisms into account. METHODS: Patients who visited their general practitioner for the first time with dyspeptic complaints and patients who were known to have persistent dyspeptic complaints were enrolled in two studies. In total, 136 patients completed a questionnaire about their employment situation, absence from work and absence compensating mechanisms. RESULTS: Sixty-six of the respondents had a paid job, of which 25 (38%) reported absence from work during the previous 4 weeks (average 3.0 days, 1.9 days related to dyspeptic complaints). More than 50% of the employed respondents answered that absence could be compensated for by colleagues, and only in 8% of the cases was absence compensated for by overtime. Using our conservative approach, only one-quarter of the productivity costs remained, compared to the current approach of valuing each day absent as a loss of productivity. CONCLUSIONS: We suggest using both the current and the conservative approaches, analogous to the principles of sensitivity analysis, to avoid overestimation of productivity costs.

Adult↗

Randomized controlled trial of omeprazole or endoscopy in patients with persistent dyspepsia: a cost-effectiveness analysis.

BACKGROUND: Cost-effectiveness analysis, Helicobacter pylori research and the development of proton pump inhibitors are having an increasing impact on the management of dyspepsia. However, clinical trials have not always included both H. pylori diagnosis and proton pump inhibitors in their protocols. METHODS: Patients who were referred for upper gastrointestinal endoscopy by their general practitioner were randomized to either prompt endoscopy followed by directed medical treatment (conventional group, n=38), or to empirical treatment with omeprazole and, in the case of symptom relapse, serological screening for H. pylori infection followed by eradication therapy in seropositive patients (empirical group, n=42). The study lasted for up to 1 year. RESULTS: In the empirical group, only 13 patients (31%) underwent endoscopy. The average number of days for which the patients kept records of their dyspeptic symptoms was 266 (95% CI: 226-307) in the empirical group, of which 166 (95% CI: 128-204) were symptom-free. In the conventional group, 159 (95% CI: 119-198) out of 255 days (95% CI: 209-302) were recorded as symptom-free. The average medical cost in the empirical group was $284 (95% CI: 218-350) and in the conventional group $491 (95% CI: 383-600). In the empirical group, two malignancies were found, whereas in the conventional group one malignancy was found. CONCLUSIONS: The empirical drug treatment strategy in patients with persistent dyspeptic symptoms resulted in 69% fewer diagnostic endoscopies with lower medical costs and equal effectiveness in the first year, compared to prompt endoscopy followed by directed medical treatment.

Adult↗

High prevalence of abdominal aortic aneurysm in a primary care screening programme.

BACKGROUND: The mortality rate associated with ruptured abdominal aortic aneurysm (AAA) remains high. The objective of this study was to assess the feasibility of population screening for AAA. METHODS: In an area with a mixed rural and industrialized population of 60000 inhabitants, all 23 general practitioners (GPs) participated. The GPs selected from their patient lists men aged 60-80 years. Men whose condition was suitable for aortic surgery were invited for screening by a single postal letter. All men responding had aortic ultrasonography in or close to the GP surgery. Diagnosis of AAA was established when the aortic diameter was 30 mm or greater. Referral for surgery was advised for an aortic diameter of 50 mm or greater. RESULTS: Of 2914 invitations, 2419 men had ultrasonography, resulting in an attendance rate of 83.0 per cent. A total of 2416 aortic measurements were made; 196 aortic aneurysms were diagnosed (prevalence 8.1 per cent). In 40 men the aortic diameter was over 50 mm. CONCLUSION: Ultrasonographic screening for AAA is feasible in a primary care setting.

Age Distribution↗

External validation of prognostic models for ongoing pregnancy after in-vitro fertilization.

This study aimed to validate prognostic models for predicting ongoing pregnancy after the first and second in-vitro fertilization cycles. Models were developed using data from the University Hospital, Nijmegen, 1991-1994 and tested using more recent data from the same centre and data from two other centres. Although the variables included in the models seemed plausible, the predictions of the models were unsatisfactory. The models did not discriminate between women who had achieved pregnancy and women who did not achieve pregnancy; neither could they indicate which women had a (very) low probability of ongoing pregnancy. Taking into account the success rate of a specific clinic or the success rate during a specific period did not show any advantage. The predictions were even inaccurate in the same hospital during another period. It is obvious that these prognostic models should not be used. This study shows the importance of validating prognostic models before their implementation in clinical practice.

Adult↗

Short-term follow-up by serology of patients given antibiotic treatment for Helicobacter pylori infection.

Helicobacter pylori serology and in particular enzyme-linked immunosorbent assays for the measurement of immunoglobulin G (IgG) antibody titers form an accurate means of diagnosing H. pylori infection in patients before treatment. H. pylori serology is of limited value in monitoring treatment because of the slow decline in antibody titers. In the present study we aimed to measure the most suitable moment after antibiotic treatment at which serology should be used to monitor treatment. Sixty-four patients who had nonulcer dyspepsia and H. pylori infection and who underwent upper gastrointestinal endoscopy because of persistent dyspeptic symptoms were included in the study. H. pylori cure was confirmed by histology and culture 5 weeks after the completion of the antibiotic treatment. Serological examination was performed before therapy and at 5 weeks, 10 weeks, and 1 year after the completion of antibiotic treatment. Diagnostic performance was assessed by receiver-operating characteristic analysis. The areas under the receiver-operating characteristic curves of the H. pylori antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment were 0.53 (95% confidence interval [CI], 0.36 to 0.69), 0.60 (95% CI, 0.43 to 0.76), and 0.78 (95% CI, 0.63 to 0.93), respectively. The areas under the receiver-operating characteristic curves of the changes in H. pylori IgG antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment in comparison with the pretreatment titers were 0.85 (95% CI, 0.72 to 0.97), 0.96 (95% CI, 0.89 to 1.0), and 1.0 (95% CI, not estimable), respectively. We conclude that serology forms a useful means of monitoring treatment in patients with nonulcer dyspepsia and H. pylori infection as early as 10 weeks and maybe even sooner after the completion of treatment for the infection.

Anti-Bacterial Agents↗

Effect of mammographic breast density on breast cancer screening performance: a study in Nijmegen, The Netherlands.

STUDY OBJECTIVE: To study the implications of breast density on mammographic screening performance. DESIGN: Screening outcomes of women with dense breast patterns were compared with those of women with lucent breast patterns (dense > 25% densities, lucent < or = 25% densities); the women were screened in different periods (before/after improvement of the mammographic technique in 1982). SETTING: Nijmegen, the Netherlands, 1977-1994. PARTICIPANTS: Between 1977 and 1994, 73,525 repeat screenings were performed in 19,152 participants (aged 50-69 years) in the Nijmegen breast cancer screening programme (repeat screenings were defined as mammographic examinations that were preceded by an examination in the previous screening round). Participants were screened biennially with mammography. There were 258 screen detected and 145 interval cancers. MAIN RESULTS: Before 1982 (rounds 2-4) the predictive value of a positive screening test (PV+) was lower in women with dense breasts than in those with lucent breasts (dense 29% v lucent 52%, p = 0.003). Also, the ratio of screen detected cancers to the total number of screen detected plus interval cancers (as a proxy for sensitivity) was lower in this group (based on a one year interval: dense 63% v lucent 92%, p = 0.001 and based on a two year interval: dense 41% v lucent 68%, p = 0.002). Moreover, the survival rate was less favourable for those with dense breasts (p = 0.07). In rounds 5-10, there were no important differences with respect to PV+ (dense 66% v lucent 62%, p = 0.57) or survival (p = 0.48). Moreover, sensitivity based on a one year interval was nearly as high in women with dense breasts as in those with lucent breasts (85% v 86%, p = 0.75). However, based on a two year interval sensitivity was lower (dense 59% v lucent 72%, p = 0.04). CONCLUSIONS: In the early screening years (rounds 2-4) high breast density had an unfavourable effect on screening performance. Nowadays, the situation has improved with respect to PV+, survival and detecting tumours in dense breasts with a lead time of up to one year, but little improvement has occurred in the detection of tumours with a lead time greater than one year.

Aged↗

Evaluation of the effect of breast cancer screening by record linkage with the cancer registry, The Netherlands.

OBJECTIVE: To evaluate the effect of a breast cancer screening programme by record linkage with the cancer registry. SETTING: Breast cancer screening programme in mid- and southern Limburg, the Netherlands. METHODS: The data files of the breast cancer screening programme and the Maastricht Cancer Registry were linked in order to evaluate the effect of breast cancer screening. Only the first primary breast tumour was included in the evaluation. RESULTS: From 1990 until 1995 90 001 women participated in the first round of the breast cancer screening programme and 64 637 in subsequent rounds. After the introduction of screening the annual number of breast cancer diagnoses increased by almost 50%. The incidence decreased to previous levels after completion of the first screening round. Record linkage detected 219 interval cancers (within two and a half years of a screening), a proportionate incidence of 31% in the first year and 60% in the second year of the two-year interval between screenings. The incidence of node positive breast cancer was 1% lower in 1994 and 15% lower in 1995 than the incidence in the period 1987-90. CONCLUSIONS: Evaluation of the effect of breast cancer screening in the Netherlands can be performed using routinely available cancer registry data. The results of this evaluation seem promising, but further studies are necessary to find ways to reduce the incidence of interval cancer.

Adult↗

Quantitation of IgG and IgM human anti-mouse antibodies (HAMA) interference in CA 125 measurements using affinity chromatography.

Currently no available immunoassay system offers complete protection against spuriously elevated or lowered results due to interference by Human Anti-Mouse Antibodies (HAMA). Although routine use of chromatography procedures is not an acceptable option because of the extra cost and workload involved, such a procedure would be highly desirable to ensure accurate immunoassay results. The present report describes a relatively simple affinity chromatography procedure using a HiTrap Protein G column to isolate immunoglobulin G (IgG) HAMA, followed by a HiTrap N-hydroxy-succinimide (NHS)-activated column coupled to goat-anti human immunoglobulin M (IgM) to bind IgM HAMA. To examine the usefulness of this purification procedure we determined CA 125 in forty serum samples prior to and following chromatography. Pre- and post-injection samples were obtained from 20 patients injected with 1 mg of 111In-labelled murine OC 125 F(ab')2 fragments in an immunoscintigraphy study. It is shown that this analytical procedure provides a technique to determine the extent and the nature of the existing HAMA interference in samples of patients after in vivo use of monoclonal antibodies for diagnostic or therapeutic purposes. The procedure can also contribute to the clarification of clinically discordant CA 125 results. Finally, the availability of such a procedure in the clinical laboratory provides an opportunity to test the robustness of newly developed immunoassay systems towards HAMA interference.

Animals↗

Randomised controlled trial of hydroquinine in muscle cramps.

BACKGROUND: Although quinine and hydroquinine are commonly prescribed for muscle cramps, controlled clinical trials of these drugs have reported mixed findings about efficacy. We investigated hydroquinine therapy in otherwise healthy adults who had frequent, ordinary muscle cramps. METHODS: This randomised, double-blind, placebo-controlled, parallel-group trial consisted of three consecutive 2-week periods: qualification, treatment, and washout, 68 women and 44 men who had at least three muscle cramps per week were enrolled. During the treatment period, participants were randomly assigned 300 mg daily dose of hydroquinine hydrobromide dihydrate (54 participants) or placebo (58). The frequency, severity (1-10), duration, and location of muscle cramps, as well as any side-effects, were recorded by participant in daily diaries. The primary outcome measures were the number of muscle cramps and the number of days during which the participants had muscle cramps (cramp-days). FINDINGS: We excluded five participants from both groups from the analysis. Thus, data from 49 hydroquinine-group participants and 53 placebo-group participants were analysed. In both groups the total number of muscle cramps and the number of cramp-days decreased during the treatment period compared with the qualification period. However, these improvements were greater in the hydroquinine group than in the placebo group. The hydroquinine-group participants reported a median of 8 (95% CI 7-12) fewer cramps and median of 3 (1-4) fewer cramp-days, whereas those on placebo reported only 3 (0-5) fewer cramps and 1 (0-5) fewer cramp-days. 32 (65%) of participants in the hydroquinine group had a 50% or greater reduction in the number of muscle cramps. After the onset of cramps, hydroquinine did not reduce the severity or duration of cramps. We also found a sustained effect after treatment had stopped. Hydroquinine was well tolerated, and resulted in only mild side-effects. INTERPRETATION: In our study, 300 mg hydroquinine was safe to take in the short-term and significantly more effective than placebo in the prevention of frequent, ordinary muscle cramps. This therapeutic effect outlasted the duration of treatment.

Administration, Oral↗