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Biomedical subjects

J P Vandenbroucke

Publications and source records attributed to J P Vandenbroucke.

At least 19 recordsLinked to original sources
PubMed2007

Cardiovascular risk factors after bariatric surgery: Do patients gain more than expected from their substantial weight loss?

BACKGROUND: While it has been established that even limited weight loss (5-10%) improves obesity-associated cardiovascular risk factors, it is not known if considerable weight loss following laparoscopic adjustable silicone gastric banding (LASGB) results in a cardiovascular risk profile that is comparable, worse, or even better than that of matched control subjects. METHODS: Cardiovascular risk factors were compared in three groups of 24 women each: an index group that had lost considerable weight following LASGB for morbid obesity (BMI>40 kg/m(2)), a control group with the same BMI that the index group achieved after weight loss, and a pre-weight loss group of women with a BMI above 40 kg/m(2). Anthropometric measures, fasting serum glucose, insulin, lipids, C-reactive protein, and homocysteine levels were determined and insulin sensitivity was estimated using a homeostasis model assessment index (HOMA-IR). RESULTS: After bariatric surgery, the index group had a BMI of 32.0+/-0.8 kg/m(2). This resulted in a significantly better cardiovascular risk profile than that of the pre-weight loss group (BMI 42.8+/-0.6 kg/m(2)). Unexpectedly, after weight loss, the index group had significantly lower systolic blood pressure, fasting serum insulin, and HOMA-IR than the BMI-matched (32.8+/-0.9 kg/m(2)) control group. Although not significant, diastolic blood pressure, LDL-cholesterol, and CRP levels were also lower. CONCLUSION: Considerable weight loss following bariatric surgery leads to a greater improvement in cardiovascular risk factors than might be expected from the weight loss.

Journal Article↗
PubMed2006

[The N-of-1 trial: the ideal study design that is underused].

The randomised experiment in a single patient, the N-of-1 trial, is the best study design for demonstrating causality, for example between agent and effect. Despite this, this type of study is only encountered sporadically in medical journals. One reason for this is that even this type of design cannot definitively demonstrate causality, because different points in time are compared with one another. Moreover, the design is rather inefficient, since the results correspond with those from observation without randomisation, placebo control or blinding. Even so, the N-of-1 trial is the ultimate form of verification in, for example, the individualisation of treatment. For this reason, this form of study might be used more often.

Cross-Over Studies↗
PubMed2006

[Levels of evidence are insufficient].

Medical knowledge is based on various types of research, each with its own 'indication' and 'contraindication'. Although the randomised controlled trial is highly useful to quantify small differences in treatment effects, it is not able to establish all medical knowledge needed at the bedside. In most instances of non-therapeutic research, observational data are more useful. Evaluating all medical knowledge on the basis of a single hierarchy of level of evidence is therefore seriously flawed.

Clinical Competence↗
PubMed2006

[Physicians and scientific research: slight decline of the numbers of physicians with a doctoral degree].

OBJECTIVE: To establish whether the number of physicians interested in a career in academia (i.e. research) is declining. DESIGN: Descriptive. METHOD: The researchers analysed the pre- and post-doctoral careers of PhD students at 3 university medical centres (VU Amsterdam, Nijmegen and Maastricht) in 4 separate reference years (1989, 1994, 1999 and 2003), using information from doctoral dissertations and the Dutch medical address book. The researchers recorded the gender of the students and the timing of the doctorate in relation to specialist training, university education and employment, as applicable. RESULTS: The total number of dissertations produced at the 3 medical faculties in the 4 reference years increased gradually by nearly a factor of 2 (1989: 112; 1994: 152; 1999: 198; 2003: 213). In terms of absolute numbers, the number of dissertations authored by physicians increased from 1989 to 1994 and again in 1999 (64, 90 and 105), but decreased slightly in 2003 (96). The percentage of female physicians obtaining a doctorate doubled during this period (1989: 9/64 (14); 2003: 28/96 (29)). Increasingly, physicians prepared their dissertation before or during their training as specialists or general practitioners (1989: 15/64 (23%); 2003: 51/96 (53%)). Ofthe clinical specialists who had received their doctorate, approximately half continued to work in an academic setting after obtaining their degree. This percentage remained approximately the same in all reference years (1989: 13/26 (50); 1994:19/35 (54); 1999: 21/45 (47); 2003: 21/40 (53)). CONCLUSION: Although the number of physicians performing scientific research as part of their doctoral degree project declined slightly in 2003 following an initial rise, our data indicate no cause for major concern. One reason may be increased interest in Clinical Research Fellow programmes. However, the future of medical research would look brighter if young physicians with doctorates had better career prospects within academic centres. To follow the academic careers of clinicians in The Netherlands, a national registry is needed to collect the type of data analysed in this study continually.

Career Choice↗
PubMed2006

[No prior informed consent required for 'no-risk' scientific research].

Recent research has shown that prior informed consent not only leads to a lower response but also distorts the results of the study. The concern about the protection of the individual may not be given preference over the importance of participation in a study, in particular for those studies that carry a very limited or non-existent risk or that are not burdensome to the patient.

Ethics, Research↗
PubMed2005

[The investigation of gene-environment interaction using case-control comparisons].

Many chronic diseases are caused by the interaction of genes and environmental factors. Genetic epidemiologic research seeks to elucidate the role of genetic factors and their interaction with environmental factors in the occurrence of disease. Gene-environment interaction can be assessed using different types of case-control comparisons. The classic case-control design is suitable to investigate the association between multiple genes and environmental factors. Results can be presented in a two-by-four table. In a case-parents design, the genotype of each case is compared with the genotype of a fictitious control formed by the non-transmitted alleles from each parent. In a case-only design, the relationship between a genotype and an environmental factor is examined in a population of affected cases only. Both the case-parents and the case-only designs assume independence between genotype and environmental factors in the control group.

Case-Control Studies↗
PubMed2005

[The predictive value of autoantibodies in disseminating lupus erythematosus and rheumatoid arthritis].

In some conditions e.g. osteoporosis, hypertension and hypercholesterolaemia, certain phenomena precede manifestation of the disease and preventive measures can be taken long before the disease presents itself. In the same way systemic lupus erythematosus (SLE) and rheumatoid arthritis can be explored. Recently, studies have been published on healthy blood donors, who later developed SLE or rheumatoid arthritis, and in whom specific autoantibodies could be demonstrated. In SLE the autoantibodies are not specific enough to develop preventive strategies, but in rheumatoid arthritis in particular there are specific antibodies against cyclic citrullinated peptides (anti-CCP-antibodies) which are very specific. A clinical trial has been initiated in which HLA-DR4-positive people with raised autoantibody concentrations are given 1-2 intramuscular injections of dexamethasone with the aim of halving the antibody concentration and in the long term lowering the incidence of rheumatoid arthritis.

Anti-Inflammatory Agents↗
PubMed2004

[Epoetin-induced pure red-cell aplasia].

A 73-year-old man, a 73-year-old woman, and a 57-year-old man with anaemia due to renal insufficiency were treated with epoetin. After 6-12 months, the haemoglobin level decreased despite dosage increases, after which the patients became dependent on regular transfusions of concentrated erythrocytes. The older man died from peritonitis following diagnostic examination because of the anaemia. The woman died from septic shock, even though epoetin had been replaced by darbepoetin. The haemoglobin level in the younger man returned to normal after the presence of antibodies against epoetin had been demonstrated, he had stopped using the drug, and he had started on immunosuppressive therapy following kidney transplantation. Since 1998, the number of patients with epoetin resistance due to the development of antibodies against the drug (epoetin-induced pure red-cell aplasia) has increased. This complication should be considered in every patient treated with epoetin who experiences unexplained transfusion-dependent anaemia.

Aged↗
PubMed2003

[Breast cancer and the use of the hormones around the menopause].

Following the publication of the 'Million women study', commotion has broken out in the media about the relationship between hormone use around the menopause and breast cancer. In this study, women were asked about possible risk factors for breast cancer, including hormone replacement therapy, prior to breast cancer screening. After an average follow-up period of 2.6 years, it was found that breast cancer more frequently occurred among women who had recently used an oestrogen-progestagen preparation (relative risk (RR): 2.00; 95%-CI: 1.88-2.12), an oestrogen preparation (RR: 1.30; 1.21-1.40) or tibolone (RR: 1.45; 1.25-1.68) than among women who had not used either of these. Methodologically, the study contains both strengths and weaknesses. However, the findings agree with those from an earlier randomised study. Current users of hormone use were more likely than never users to die from breast cancer (RR: 1.22; 1.00-1.48). For the prescription of hormone replacement therapy, the twice as high relative risk of breast cancer together with the other potentially life-threatening side effects of hormone replacement therapy need to be weighed up against the complaints which form the indication for the prescription. Therefore, the advice for hormone replacement therapy continues to be that it should, if necessary, be made available as a treatment option for a short period (3 months) and only in the case of serious and debilitating complaints. Long-term preventative use, as happens in practice, is not indicated due to the risk of relatively serious side effects.

Breast Neoplasms↗
PubMed2003

Living with epilepsy: long-term prognosis and psychosocial outcomes.

OBJECTIVE: To analyze the impact of seizures on everyday life and the long-term effects of epilepsy on health status and psychosocial outcomes. METHODS: Follow-up study was conducted of a cohort of consecutive patients newly diagnosed with epilepsy between 1953 and 1967. In 1995 (mean follow-up 34 years), a random sample of 333 patients received a questionnaire asking clinical and demographic information and validated measures for psychosocial outcomes. Comparisons were made with the general Dutch population. RESULTS: The response rate was 73% (116 men and 127 women); mean age was 49.9 years (SD 11.2 years). Mean age at epilepsy onset was 15 years (SD 11 years); mean duration was 24.4 years (SD 13.1 years). In total, 134 (55%; 72 men and 62 women) patients were seizure-free for the previous 5 years, and 81 patients still had seizures in the last year. One hundred twenty-seven patients were taking antiepileptic drugs, of which 51 were on monotherapy. Epilepsy patients have a positive health evaluation, comparable with the general Dutch population. Fewer epilepsy patients married or had children than the general Dutch population; more patients live at home with their parents or in foster homes or institutions (p < 0.001). Having epilepsy at school age has a significant negative effect on learning achievement (p < 0.01). Employment status is affected less, though more epilepsy patients are unfit to work than individuals from the general population (p < 0.05). CONCLUSIONS: Epilepsy has a marked negative impact on education and achievement in later life. Despite worse psychosocial outcomes than the Dutch population, patients with epilepsy cope well with their epilepsy, regardless of their handicaps.

Activities of Daily Living↗
PubMed2003

Renal disease in relatives of Indo-Asian Type 2 diabetic patients with end-stage diabetic nephropathy.

AIMS/HYPOTHESIS: Indo-Asian immigrants in The Hague, The Netherlands, have a nearly 40-fold higher risk of end-stage diabetic nephropathy compared to the Caucasian population. To detect a genetic susceptibility for nephropathy within the Indo-Asian population, we assessed whether familial clustering of nephropathy occurs in families of Indo-Asian Type 2 diabetic patients. METHODS: We compared nephropathy prevalence between two groups of first-degree relatives of Indo-Asian patients with Type 2 diabetes; the first group (case relatives) consisted of 169 relatives of patients with end-stage diabetic nephropathy; the second group (control relatives) consisted of 161 relatives of diabetic patients who had no nephropathy. The case and control relatives were examined for diabetes, blood pressure, renal function, microalbuminuria and urine dipstick measurements. RESULTS: The mean age was 41 years and similar in the case and control relatives. Diabetes was distributed equally in both family groups. We did not find more nephropathy in first-degree relatives of Indo-Asian Type 2 diabetic patients with end-stage diabetic nephropathy in comparison with the control-relatives. CONCLUSION/INTERPRETATION: We could not detect a genetic susceptibility for diabetic nephropathy within the Indo-Asian population. The lack of familial clustering of renal disease in Indo-Asian diabetic patients points to a general genetic or environmental susceptibility for diabetic nephropathy in this population.

Adult↗
PubMed2003

Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.

The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar high-grade osteosarcoma. Of this last group, one patient was known with Rothmund-Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88-3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.

Adolescent↗
PubMed2002

[Adverse cardiovascular effects of postmenopausal hormone replacement therapy].

The views on the effects of postmenopausal hormone-replacement therapy (HRT) on cardiovascular disease have moved from one end of the spectrum to the other over the past decades. The presumed beneficial effects of HRT on arterial cardiovascular disease were based on observational findings and have led to the widespread use of these agents. However, recent large-scale randomised, placebo-controlled trials have demonstrated that HRT in women with a history of arterial diseases initially increases the risk of recurrent disease, while offering no benefit in the long term. Healthy postmenopausal women on HRT have an increased risk of arterial cardiovascular events compared with those taking placebo (relative risk 1.29; 95% CI: 1.02-1.63). Finally, the risk of venous thrombosis and pulmonary embolism is increased with the use of HRT. These results demonstrate that bias and confounding can play an important role in observational research and underscore the importance of randomised, placebo-controlled trials when studying the efficacy of drugs.

Cardiovascular Diseases↗
PubMed2002

[The importance of case reports as compared to evidence-based medicine and molecular explanation].

Over the past few decades case reports have become a much maligned form of medical research. Does the case report still have a place in modern medical science, which is based on evidence-based medicine on the one hand and genomics on the other? The answer is an emphatic 'yes': clinical case descriptions form a necessary basis for detecting new ideas--new disease entities, new aetiological clues, side effects and new treatments. They are also necessary in medical education, and are a time-honoured cornerstone of quality assurance: the clinical pathological conference where difficult or rare cases are discussed for the benefit of all. Case reports form the basis of progress in clinical science, independent of basic subjects or epidemiological insights. They will continue to be necessary in a context of discovery. Moreover, they can also provide convincing clinical evidence. Finally, a well-written case report must clearly state what is already known and what the case report adds to this.

Education, Medical↗
PubMed2002

[Financing medical research in the Netherlands: start taking care of the future now].

Less money is spent on medical research in the Netherlands than in other industrialised countries, even though Dutch science, and certainly Dutch medical science, scores qualitatively among the best in the world. Part of the explanation is that a relatively large part of scientific research in the Netherlands is financed directly by the government. As a result of several rounds of cutbacks in government spending, that were executed each time by cutting research that performed less well, the remaining research groups are at high qualitative level and highly competitive. In countries that surpass the Netherlands, there is an important second stream of government funding via Medical and Health Research Councils. In the same countries, the pharmaceutical industry also provides more money for medical research. The other side of the coin is that medical research in those countries seems more or less 'for sale'. Too heavy dependence on market oriented research leads to doubts regarding the independence of medical research. International observers judged that the direct financing of research by government in the Netherlands was an enormous bonus since it leads to flexibility to start new topics and at the same time stability of positions. However, a major concern for Dutch science is that there are too few possibilities to attract and hold promising young people. It is especially difficult to keep promising young women; though this is true for all industrialised countries, the Netherlands lags behind its major competitors as far as the position of women in the higher ranks of science is concerned. These problems will have to be solved by stimulation programmes for young researchers and flexibility of the higher echelons. The educational system must not be directed only at the production of more doctors for medical practice, but also at sufficient scientific training for these doctors so that they will be able to comprehend new developments. The ordinary daily practice of medical science is to verify the usefulness of new developments--which is just as important as breakthroughs at the top. This means that there should be new investments, not only for top ranking scientists in fashionable areas, but also to maintain sufficient numbers of medical scientists at all levels. It cannot be foreseen where the next new developments will arise, and even in a small country, active research should be ongoing in many areas to maintain contact with the international research community. New investments should primarily be in direct government financing and in augmentation of streams of money via Medical and Health Research Councils.

Education, Medical↗
PubMed2002

Female hormones and thrombosis.

Exogenous hormones are used by more than a hundred million women worldwide as oral contraceptives or for postmenopausal hormone replacement. Oral contraceptives increase the risk of venous thrombosis, of myocardial infarction, and of stroke. The risk is highest during the first year of use. The venous thrombotic risk of oral contraceptives is high among women with coagulation abnormalities and with so-called third-generation contraceptives (containing desogestrel or gestodene). The risk of myocardial infarction does not appear to depend on coagulation abnormalities or the type of oral contraceptive. Hormone replacement therapy increases the risk of venous thrombosis. This risk is also highest in the first year of use and among women with coagulation abnormalities. The risk becomes very high in women with a previous venous thrombosis. Randomized trials have not confirmed a beneficial effect of postmenopausal hormones on the occurrence of myocardial infarction.

Contraceptives, Oral, Hormonal↗
PubMed2002

Increased end-stage diabetic nephropathy in Indo-Asian immigrants living in the Netherlands.

AIMS/HYPOTHESIS: We aimed to investigate the risk of end-stage diabetic nephropathy due to Type II (non-insulin-dependent) diabetes mellitus in Indo-Asian immigrants from Surinam. METHODS: A demographically based case-control study was carried out in Surinamese Indo-Asian immigrants and Dutch Caucasian subjects. All patients with end-stage diabetic nephropathy who had started dialysis between 1990 and 1998 were identified through a national registry of all patients entering a renal replacement program in the Netherlands. The general population of native Dutch and Surinamese Indo-Asians were considered the control subjects. RESULTS: Among Indo-Asian immigrants, the age adjusted relative risk of end-stage diabetic nephropathy was 38 (95 % CI 16 to 91) compared with the native Dutch population. The duration of diabetes until the start of dialysis treatment was similar in both ethnic groups, about 17 years. CONCLUSION/INTERPRETATION: The Indo-Asian subjects had a nearly 40-fold increase in the risk for end-stage diabetic nephropathy due to Type II diabetes, compared with the native Dutch population. This was higher than expected on the basis of the eightfold higher prevalence of diabetes in the Indo-Asian population. The similar duration of diabetes until the start of dialysis treatment in both ethnic groups supports the hypothesis of a higher incidence of diabetic nephropathy in the Indo-Asian diabetic population. Early and frequent screening for diabetes and microalbuminuria is recommended in Indo-Asian subjects.

Age of Onset↗