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Biomedical subjects

H Schouten

Publications and source records attributed to H Schouten.

At least 19 recordsLinked to original sources

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe.

The Accreditation Subcommittee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published in 1996. Haemopoietic stem cell transplantation today includes grafting with allogeneic and autologous stem cells derived from bone marrow, peripheral blood and cord blood. With reduced intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged such as autoimmune disorders and AL amyloidosis for autologous, and solid tumours for allogeneic transplants. The introduction of alternative therapies has challenged well-established indications such as imatinib for chronic myeloid leukaemia. An updated report with revised tables and operating definitions is presented here.

Europe↗

Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries.

OBJECTIVE: To assess direct costs associated with ankylosing spondylitis (AS). To determine which variables, including country, predict costs. METHODS: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year observational study and filled in bimonthly economic questionnaires. Disease related healthcare resource use was measured and direct costs were calculated from a societal perspective (true cost estimates) and from a financial perspective (country-specific tariffs). Predictors of costs were assessed using Cox's regression analysis. RESULTS: 209 patients provided sufficient data for cost analysis. Mean annual societal direct costs for each patient were euro;2640, of which 82% were direct healthcare costs. In univariate analysis costs were higher in the Netherlands than in Belgium, but this difference disappeared after adjusting for baseline differences in patients' characteristics among countries. Longer disease duration, lower education, worse physical function, and higher disease activity were predictors of costs. Mean annual direct costs from a financial perspective were euro;2122, euro;1402, and euro;941 per patient in the Netherlands, France, and Belgium, respectively. For each country, costs from a financial perspective were significantly lower than costs from a societal perspective. CONCLUSION: Direct costs for AS are substantial in three European countries but not significantly different after adjusting for baseline characteristics among countries. Worse physical function and higher disease activity are important determinants of costs, suggesting better disease control might reduce the costs of AS. The difference in costs from a societal and financial perspective emphasises the importance of an economic analysis.

Adolescent↗

Costs of ankylosing spondylitis in three European countries: the patient's perspective.

OBJECTIVE: To assess a patient's out of pocket costs, income loss, time consumption, and quality of life (QoL) due to ankylosing spondylitis (AS) in three European countries and to assess variables predicting these outcomes. METHODS: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year study. Health resource use, days absent from work, time lost, and quality of life (EuroQol) were assessed by bimonthly questionnaires. AS related healthcare and non-healthcare expenditure and income loss were calculated taking into account country-specific regulations. Predictors of costs, time consumption, and QoL were analysed by Cox's regression. RESULTS: 209 patients provided data for cost analysis. Average annual healthcare and non-healthcare expenditure was euro;431 per patient and average annual income loss was euro;1371 per patient. Healthcare costs were highest for Belgian and lowest for French patients, while non-healthcare costs were highest for Dutch patients. A patient's total costs were associated with higher age and worse physical function. On average, patients with AS needed 75 minutes additional time a day because of AS. Worse physical function and higher disease activity predicted time consumption. After adjusting for baseline confounders, QoL was worse in Belgian and French than in Dutch patients. Peripheral arthritis, worse physical function, higher disease activity, and loss of income contributed to worse QoL. CONCLUSION: AS is time consuming and associated with substantial out of pocket costs. Belgian patients incur the highest healthcare payments. Poor physical function increases patient's costs and time consumption. Loss of income is associated with lower QoL.

Adolescent↗

Work status and productivity costs due to ankylosing spondylitis: comparison of three European countries.

OBJECTIVE: To compare work disability, sick leave, and productivity costs due to ankylosing spondylitis (AS) of three European countries. METHODS: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year observational study. Employment and work disability rates at baseline were adjusted for age and sex. Productivity costs were calculated by both the friction cost method and the human capital approach. The adjusted contributions of country to employment, work disability, and having an episode of sick leave were assessed by logistic regression and the contribution of the country to days of sick leave and costs by Cox proportional hazard analysis. RESULTS: 209 patients completed the two years' follow up with sufficient data for cost analysis. Adjusted employment was 55% in the Netherlands as compared with 72% in both other countries and only in the Netherlands was it lower than expected in the general population. Adjusted work disability was 41%, 23%, and 9% in the Netherlands, France, and Belgium and in all countries was higher than expected in the general population. In those with a paid job, the mean number of days of sick leave per patient per year because of AS was 19 (range 0-130), six (range 0-77), and nine (range 0-60 ) in the Netherlands, France, and Belgium respectively. Applying the friction cost method to those with a paid job resulted in mean costs per patient per year of 1257 euros (range 0-7356), 428 euros (range 0-5979), and 476 euros (range 0-2354) in the Netherlands, France, and Belgium. Applying the human capital approach to the whole group resulted in mean costs per patient per year of 8862 euros (range 0-46 818), 3188 euros (range 0-43 550), and 3609 euros (range 0-34 320) in the three countries, respectively. After adjusting for sociodemographic and disease characteristics, living in the Netherlands, as compared with both other countries, was associated with a higher chance of being work disabled (odds ratio (OR)=3.82; 95% confidence interval (CI) 1.33 to 11.01), but not with the risk of having an episode of sick leave. Similarly, living in the Netherlands contributed independently to the number of days sick leave (OR=0.65; 95% CI 0.43 to 0.97), a higher amount of friction costs (OR=0.63; 95% CI 0.42 to 0.96), and a higher amount of human capital costs (OR=0.46; 95% CI 0.32 to 0.68). CONCLUSION: There are remarkable differences in work status and productivity costs between the three European countries. This has implications for the generalisability of health economic studies.

Adult↗

Withdrawal from labour force due to work disability in patients with ankylosing spondylitis.

OBJECTIVE: To investigate withdrawal from the labour force because of inability to work owing to ankylosing spondylitis (AS) and to determine the characteristics of patients with no job because of work disability attributable to AS. METHODS: A postal questionnaire was sent to 709 patients with AS aged 16-60 years followed up by a rheumatologist. Kaplan-Meier survival statistics were used to assess the time lapse between diagnosis and withdrawal from work. Standardised incidence ratios were calculated to compare withdrawal from the labour force in patients with AS and the general population. Determinants of withdrawal were assessed by Cox's proportional hazard regression analysis using variables assumed to be time independent. Cross sectional characteristics of patients without a job owing to disability were further analysed by simple and multiple regression analyses. RESULTS: A total of 658 patients returned the questionnaire. Of 529 patients with a paid job before diagnosis of AS, 5% had left the labour force within the first year after the diagnosis, 13% after 5 years, 21% after 10 years, 23% after 15 years, and 31% after 20 years. Age and sex adjusted risk for withdrawal was 3.1 (95% CI 2.5 to 3.7) times higher than in the general population. In patients with AS, determinants of withdrawal from work were older age at diagnosis, manual work, and coping strategies characterised by limiting or adapting activities. Patients with work disability at the time of the study were older, came from a lower social class, and were more likely to have total hip replacement, peripheral arthritis, or comorbidity. Moreover, they reported worse physical function (BAS-FI), experienced lower quality of life, and more often had extraspinal disease than those with a job. CONCLUSION: Withdrawal from work is 3.1 times higher in patients with AS than expected in the general population. Within patients, higher age at diagnosis, manual work, and unfavourable coping strategies are important determinants of withdrawal. Patients without a job experience a lower quality of life.

Adaptation, Psychological↗

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions.

It is unknown whether and to what extent changes in various endothelial functions and adrenergic responsiveness are related to the development of microvascular complications in type 1 diabetes. Therefore, endothelium-dependent and endothelium-independent vasodilatation, endothelium-dependent hemostatic factors, and one and two adrenergic vasoconstrictor responses were determined in type 1 patients with and without microvascular complications. A total of 34 patients with type 1 diabetes were studied under euglycemic conditions on two occasions (11 without microangiopathy, 10 with proliferative and preproliferative retinopathy previously treated by laser coagulation, 13 with microalbuminuria, and 12 healthy volunteers also were studied). Forearm vascular responses to brachial artery infusions of N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, acetylcholine (ACh), clonidine, and phenylephrine were determined. The ACh infusions were repeated during coinfusion of L-arginine. Furthermore, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator antigen levels, von Willebrand factor antigen levels, tissue factor pathway inhibitor (TFPI) activity, and endothelin-1 levels were measured. No differences in endothelium-dependent or endothelium-independent vasodilatation or adrenergic constriction were observed between the diabetic patients and the healthy volunteers. In comparison to the first ACh infusion, the maximal response to repeated ACh during L-arginine administration was reduced in the diabetic patients, except in the patients with proliferative and preproliferative retinopathy previously treated by laser coagulation. In these patients, the combined infusion of L-arginine and ACh resulted in an enhanced response. TFPI activity was elevated, and PAI-1 activity was reduced in the type 1 diabetic patients. Furthermore, PAI-1 activity was positively correlated with urinary albumin excretion (r = 0.48, P < 0.01) and inversely correlated with the vasodilatory response to the highest ACh dose (r = -0.37, P < 0.05). The response to the highest ACh and L-NMMA dose were positively correlated with mean arterial blood pressure (r = 0.32, P < 0.01; r = 0.41, P < 0.01, respectively). Forearm endothelium-dependent and endothelium-independent vasodilatation and adrenergic responsiveness were unaltered in type 1 diabetic patients with and without microvascular complications. Relative to healthy control subjects, endothelium-dependent vasodilatation was depressed during a repeated ACh challenge (with L-arginine coinfusion) in the diabetic patients without complications or with microalbuminuria. In contrast, this vasodilatation was enhanced in the patients with retinopathy. Elevation of TFPI was the most consistent marker of endothelial damage of all the endothelial markers measured.

Adrenergic alpha-Agonists↗

Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group.

We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were randomized to either receive daunomycin-cytosine arabinoside with GM-CSF or daunomycin-cytosine arabinoside (control arm). Based on the rationale that GM-CSF might sensitize the leukemic cells to the cytotoxicity of chemotherapy as well as enhance white blood cell regeneration, GM-CSF was given during chemotherapy as well as after chemotherapy. Patients were treated with one, and in case of a partial response, with two remission induction cycles. When a complete remission was attained they received one additional cycle of consolidation therapy. Of 318 evaluable patients with a median age of 68 years, 157 were randomized to receive GM-CSF and 161 were assigned to control therapy. The effect of GM-CSF on treatment was evaluated according to intention-to-treat. Complete remission was achieved in 56% of the patients in the GM-CSF group and 55% of the control patients (P = .98). Recovery of neutrophils was significantly faster in GM-CSF-treated patients. The median time of recovery of neutrophils towards 0.5 x 10(9)/L was 23 days in the GM-CSF group versus 25 days in the control group (P = .0002) with the percentages of patients who recovered being 81% and 71%, respectively. With a median follow-up of 36 months, the probabilities of survival at 2 years after randomization were estimated at 22% for individuals assigned to the GM-CSF treatment as well as for control patients (P = .55). Disease-free survival at 2 years compared 15% and 19% for the two treatment groups (P = .69). The number of nights spent in the hospital, number of transfusions, and frequencies and types of hemorrhages and infections did not differ either. The cytogenetic results at diagnosis of this study in elderly AML shows that there is a relatively high numerical representation of patients with abnormal cytogenetics (55% of documented cases), who showed significantly inferior response rates and survival duration. We conclude that, except for a faster neutrophil recovery, GM-CSF during and after induction chemotherapy does not improve the clinical outcome of elderly patients with AML.

Acute Disease↗

Helicobacter pylori and non-Helicobacter pylori bacterial flora in gastric mucosal and tumour specimens of patients with primary gastric lymphoma.

There is an association between Helicobacter pylori (H. pylori) and gastric mucosa-associated lymphoid tissue (MALT) and MALT lymphoma. Histologically, mainly non-specific stains are used to detect H. pylori, such as haematoxylin-eosin (HE) or modified Giemsa (MG). In this study, both a MG and a specific immunohistochemical stain (IMM) for H. pylori (Dako B471) were performed on sequential slides of resected material containing tumour and non-tumorous gastric mucosa from patients with primary gastric lymphoma (n = 52). Special attention was paid to the presence of non-H. pylori bacterial flora diagnosed by a positive MG (according to form and localization) and a subsequently negative IMM. On all slides, bacterial density was scored semiquantitatively (grades 0, 1, 2, 3). In total, 32 (61.5%) patients were H. pylori positive using IMM and 34 (65.4%) were non-H. pylori positive using MG. In 24 out of the 34 patients, the non-H. pylori flora consisted mainly of cocci in combination with rods in 15 patients, mostly in minor quantities; in another 10 patients, high numbers of both cocci and different types of rods were present. Most non-H. pylori bacteria were localized superficially, although in 22 patients minor quantities of non-H. pylori were also seen in the glandular lumina. After all of the patients had been analysed, no differences in the density of H. pylori and of non-H. pylori flora were found. Only when comparing patients who had a small-cell lymphoma with those who had a large-cell lymphoma was a significantly higher density of H. pylori found in the corpus mucosa of large-cell lymphomas and a higher prevalence of non-H. pylori was found in tumours, in antrum or corpus, of patients with large-cell lymphomas. In conclusion, with joint evaluation using MG and a H. pylori-specific immunohistochemical stains, the proportion of H. pylori-positive gastric lymphoma patients was lower than in most previous studies but other bacteria were found in a relatively high proportion. The role of the non-H. pylori intragastric bacterial flora identified in this study has to be further elucidated in the aetiopathogenesis of primary gastric lymphoma.

Adult↗

Cotinine concentrations in plasma of smoking pregnant women and their infants.

In the Netherlands 30% of all women of reproductive age are habitual smokers. One third of these women continue to smoke during pregnancy. Tobacco smoke consists of more than 3600 different compounds. One of its chief pharmacologically active ingredients is nicotine of which 60% is metabolized to cotinine. Cotinine is the best available biochemical marker of nicotine consumption because it is specific for tobacco smoke exposure and it has a relatively long mean t1/2 of 15 hours. In the present study nicotine and cotinine concentrations were measured in 25 smoking and 25 non-smoking healthy pregnant women. In all 25 non-smoking pregnant women nicotine and cotinine levels were < 10 mg/l. Light smokers (< 10 cigarettes/day) were found to have nicotine blood concentrations < 10 mg/l and cotinine levels varying between 40 and 99 mg/l. Heavy smokers (> or = 10 cigarettes/day) had nicotine concentrations < 10 mg/l, but high cotinine levels varying from 115 to 199 mg/l. Cotinine was also determined in 25 neonates of non-smoking mothers and in 34 neonates of smoking mothers. In 9 of these 34 newborns the relationship between maternal and neonatal cotinine concentrations was investigated. Cotinine levels in neonates born to non-smokers and to women who smoked less than 10 cigarettes/day were below the detection limit of 10 mg/l. Cotinine values in neonates whose mothers smoked > or = 10 cigarettes/day were significantly higher than in those whose mothers smoked < 10 cigarettes/day, but significantly lower than in their mothers. The results of this study confirm that cotinine is more useful than nicotine in discriminating non-smokers, light and heavy smokers. Cotinine concentrations were significantly lower in the neonates than in their mothers, but there was a strong positive linear relationship between maternal and neonatal cotinine concentrations.

Cotinine↗

Are four duplicate remeasurements sufficient for diagnosing mild hypertension?

The aim of this study was to investigate if four duplicate blood pressure (BP) remeasurements are sufficient for diagnosing hypertension in potentially hypertensive subjects. The subjects were 99 outpatients who were included on the basis of elevated diastolic (95 < or = DBP < or = 115 mm Hg) or systolic (160 < or = SBP < or = 200 mm Hg) BP. After inclusion all patients underwent nine subsequent duplicate BP measurements over a period of 7 months. None of the patients received hypotensive drug treatment during the study. Between the first (initial) and second measurements there were significant reductions in systolic (161.0-152.5 mm Hg) and diastolic (101.5-97.1 mm Hg) BPs (P < 0.01). Differences between the subsequent measurements were not statistically significant. A linear regression analysis proved that the "conceptual average BP' (the average of the last five visits) which was chosen as the reference value was stable. The decline of standard deviations of differences between two, three and four duplicate remeasurements on one hand, and the reference value on the other was found to be strikingly small. After four duplicate remeasurements, there was misclassification in 56% (systolic) and 38% (diastolic). We conclude that the numbers of two, three or four BP measurements recommended by international guidelines for diagnosing hypertension are too low. Even after four duplicate remeasurements a considerable amount of misclassification remains.

Adult↗

Increased buffer pH enhances sensitivity and specificity of human papillomavirus detection using consensus primer based PCR.

Polymerase chain reaction (PCR) buffers were optimized for the specific detection of human papillomavirus (HPV) sequences. The effect of pH, potassium chloride concentration and magnesium chloride concentration of three different consensus primers were examined. Several phylogenetically distinct HPVs (HPV1, HPV2, HPV6, HPV8, HPV16, HPV18, and HPV20) were used to determine the optimal buffer components. Genital types were less sensitive to changes in pH than cutaneous types. Higher buffer pH, with a few exceptions, led to increased sensitivity and specificity of HPV detection.

Base Sequence↗

Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy.

PURPOSE AND METHODS: A prospective, randomized, multicenter phase III trial was performed to investigate the feasibility of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in elderly patients ( > or = 60 years) with advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy, and to compare the tolerance and efficacy of doxorubicin versus mitoxantrone (CHOP v CNOP). RESULTS: Of 157 enrolled patients, 148 were eligible and 145 were assessable for response. Thirty-one percent of CNOP and 45% of CHOP patients completed six cycles without dose reduction. The cumulative normalized dose-intensity (NDI) was 92% with CHOP and 90% with CNOP after six cycles. The overall complete response (CR) rates were 49% and 31% in CHOP- and CNOP-treated patients, respectively (P = .03). Survival with CNOP was significantly worse as compared with CHOP (P = .03). Lymphoma-specific survival was significantly better in CHOP-treated patients (P = .034) At 3 years, 42% of CHOP and 26% of CNOP patients were alive. Additional unfavorable prognostic factors at diagnosis were high serum lactate dehydrogenase (LDH) level, bulky mass, and low performance status, but not age. The median disease-free intervals of complete responders were 27 (CHOP) and 15 (CNOP) months, respectively. Considering the complete group of patients, at 3 years 17% of CHOP and 13% of CNOP patients were alive and disease-free (P = .12). Common toxicity criteria (CTC) grade > or = 2 with CNOP and CHOP was not different. CONCLUSION: CHOP is well tolerated in elderly patients with advanced intermediate- or high-grade NHL and its NDI is not seriously impaired. Treatment with CHOP (doxorubicin) results in better CR and survival rates than CNOP (mitoxantrone). CHOP should be recommended for elderly patients with high-risk NHL.

Aged↗

Does feedback improve the quality of cervical smears? A randomized controlled trial.

In a randomized controlled trial three methods of feedback of increasing intensity, directed at 183 doctors taking cervical smears, were compared with respect to their effects on the sampling quality of smears. Overall, feedback was found to have no influence on quality criteria in the crude data analysis. However, a significantly larger decrease in the percentage of smears lacking endocervical cells was found in the groups receiving monthly overviews of their results with peer comparison, when compared with the groups not receiving this type of feedback (odds ratio 0.75). Moreover, feedback appeared to have a clear effect on the presence of endocervical cells among doctors submitting a substantial number of smears in the intervention period, as opposed to those who submitted fewer smears. A positive correlation was also observed between the increase in the group mean of the proportions of smears containing pathological cells and the intensity of the feedback. However, this increase did not reach statistical significance. This study suggests that monthly feedback with peer comparison may have a positive relationship with some aspects of quality improvement in cervical screening.

Adult↗

Peripheral arterial occlusive disease in general practice: the reproducibility of the ankle-arm systolic pressure ratio.

One of the non-invasive techniques used in the diagnosis of patients with peripheral arterial occlusive disease is the measurement of the Ankle-Arm Systolic Pressure Ratio ("AA-Ratio"). The magnitude of different sources of measurement variation, relevant to clinical practice as well as multi-observer studies, was estimated from a random effects analysis of variance model. Thirty-five GPs and 24 practice assistants performed 503 AA-Ratio measurements on nine patients over a period of nine weeks, using pocket Doppler devices. When the AA-Ratio is used for diagnostic purposes, a 95% prediction interval consisting of the measured value +/- 15-20% AA-Ratio has to be taken into account. Furthermore, when the AA-Ratio is used in the follow-up of a patient with vascular disease, the difference between two subsequent measurements has to be at least 15.6-19.0% AA-Ratio to have an 80% certainty that this difference is not due to (intra-observer) measurement error.

Aged↗