To study the association between a candidate gene and a complex genetic disease, Pearson'... more To study the association between a candidate gene and a complex genetic disease, Pearson's chi2 statistic can be applied to an mx2 contingency table, where the m categories correspond to m haplotypes or marker alleles. For m>2, two alternative approaches for Pearson's chi2 can be followed, which are more powerful if one haplotype or marker allele is associated. For the first approach, various 2x2 tables are formed by combining various categories and the maximum of the corresponding chi-square statistics is considered as the final statistic. The second approach takes the average over the possible associated categories by writing down an overall likelihood. For the latter approach, we propose a new score statistic, which gives more weight to haplotypes or marker alleles that are common. Since the disease allele is often not observed, the power of the various statistics depends on both the linkage disequilibrium pattern and the frequencies of the associated haplotype or marker allele in the cases and the controls. We heuristically compare various statistics within the two approaches and present the results of a simulation that compares the performance of all considered statistics. Finally, we apply the statistics to a case-control study on the association between COL2A1 gene and radiographic osteoarthritis. Our conclusion is that overall the new proposed score statistic has good power.
ABSTRACT Background In rheumatoid arthritis (RA) patients, bone marrow edema (BME)-scores are ass... more ABSTRACT Background In rheumatoid arthritis (RA) patients, bone marrow edema (BME)-scores are associated with development of erosions. However, little is known on the course and outcome of BME at bone level. Therefore this study determined the association of BME and MRI-synovitis in the same bone longitudinally. Objectives This study was aimed to determine the course of BME and MRI-synovitis at bone level. Furthermore the association between the course of BME and local synovitis and the development of erosions in the same bone was studied. Methods 1,947 bones of MCP, wrist and MTP-joints of 59 patients presenting with rheumatoid or undifferentiated arthritis were studied using 1.5T MRI at baseline, after four and twelve months. Scanning and scoring of BME, synovitis and erosions were performed according to RAMRIS. The relation of the course of BME and synovitis to erosive progression at bone level during 1-year was evaluated. Results Of the bones showing BME at baseline (n=203), BME persisted in 56%, disappeared in 39%, and disappeared-reappeared seldom (5%). Stratified analyses at baseline revealed that BME was associated with erosive progression, in presence and in absence of local synovitis (ORs 7.5 95%CI 3.8-14.9 and 6.9 95%CI 1.9-25.6). Local synovitis, however, was not associated with erosive progression (OR 2.0 95%CI 0.6-7.0 in presence of BME and 1.9 95%CI 0.8-4.1 in the absence of BME). In multivariable GEE-analyses, persistent BME was strongly associated with erosive progression (OR 60 95%CI 17-318), in contrast to persistent synovitis (OR 1.4 95%CI 0.4-5.3). Conclusions BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independent of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for the comprehension on the development of erosions in RA. Disclosure of Interest None declared
Interactive cardiovascular and thoracic surgery, 2014
Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or on... more Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or ongoing. Since randomized clinical studies to support this are lacking, it is relevant to know whether lower fibrinogen levels are associated with excessive bleeding. We performed a systematic review and meta-analysis to define the association between fibrinogen levels and blood loss after cardiac surgery. A database search (January 2013) was performed on publications assessing the association between pre- and postoperative fibrinogen levels and postoperative blood loss in adult patients undergoing cardiac surgery. Cohort studies and case-control studies were eligible for inclusion. The main outcome was the pooled correlation coefficient, calculated via Fisher's Z transformation scale, in a random-effects meta-analysis model stratified for the time point at which fibrinogen was measured. A total of 20 studies were included. The pooled correlation coefficient of studies (n = 9) concerni...
Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 2012
Heart failure is characterised as a strong risk factor for systemic failure after cardiac surgery... more Heart failure is characterised as a strong risk factor for systemic failure after cardiac surgery. However, the impact has never been substantiated. Patients with heart failure (n = 48) - scheduled for elective ventricular reconstruction or external constraint device-were compared with a one-to-one matched control group of patients without heart failure undergoing cardiac surgery between 2006 and 2009. As expected, patients with heart failure more frequently experienced complications definitely related to pump failure (p = 0.01). However, complications not related to their pump failure were also more often observed, such as prolonged mechanical ventilation, sepsis and vasoplegia (p = 0.01). Overall, organ dysfunction-circulatory, renal, and pulmonary failure-was often observed in heart failure patients, contributing to a prolonged stay in the intensive care unit (p < 0.001) as well as in hospital (p = 0.01). The adverse postoperative course in patients with heart failure is not o...
Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the pro... more Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance. A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters. In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+...
Journal of applied physiology (Bethesda, Md. : 1985), 1994
In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO... more In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO) and DLCO per liter alveolar volume (DLCO/VA) at total lung capacity (TLC) and at lung volumes below TLC in sitting position. In 55 healthy nonsmoking volunteers (20-85 yr old), we determined reference values at TLC level in which age was the only parameter. In a subgroup (n = 16) these references did not change by correction for normal variability in hemoglobin concentration. In all volunteers DLCO decreased and DLCO/VA increased with decreasing VA. The increase in DLCO/VA was linear and less in older subjects. We derived equations to calculate reference values of DLCO/VA for lung volumes at and below TLC with two methods: 1) "random coefficients linear" model, which calculates the reference values directly, and 2) a conversion method, which calculates DLCO/VA for lower VA levels from reference values at TLC. An advantage of the conversion method is the suitability of DLCO/VA...
Cortical potentials were elicited by airpuff stimulation of the L5 and S1 dermatome in a group of... more Cortical potentials were elicited by airpuff stimulation of the L5 and S1 dermatome in a group of 24 healthy volunteers. The results were compared with the SEPs obtained by conventional electrical stimulation. Both stimulus modalities produce stable and good reproducible cortical responses of similar waveform. The most stable second negative peak, labeled N2, was used in this study. Mean latencies (in msec) were: N2 L5 air = 67.1 +/- 3.3, N2 L5 electr. = 55.7 +/- 3.7 N2 S1 air = 67.2 +/- 3.9, and N2 S1 electr. = 55.1 +/- 2.9 The maximum R/L difference (mean + 3 SD) was 5.7 msec, 5.9 msec, 7.2 msec and 7.2 msec for respectively N2 L5 air, N2 L5 electrical, N2 S1 air and N2 S1 electrical. Single regression analysis showed a significant influence of height, but not age upon all latencies. Multiple regression analysis with height and age as independent variables showed a significant influence of height and age together upon the latencies of the electrical SEP (both L5 and S1). For the a...
To examine the conjugacy of lid saccades in normal subjects. Saccades of both upper eyelids were ... more To examine the conjugacy of lid saccades in normal subjects. Saccades of both upper eyelids were recorded simultaneously by means of small, lightweight, magnetic search coils, fixed on each lid. Subjects then made vertical eye saccades between fixed targets. The associated eye saccades were recorded simultaneously by means of magnetic search coils. The authors further examined whether the position of the lid coils affected the recordings. Lid saccades were not as conjugate as their associated eye saccades. Nonconjugacy of lid saccades averaged approximately 8% of the target amplitude, irrespective of saccadic direction. By contrast, nonconjugacy of the associated eye saccades averaged approximately 1% of the target amplitude. Coil position significantly (P < 0.05) affected the recordings. Lid saccades are not as conjugate as their associated eye saccades. Coil position is critical for the recordings of lid saccades.
To evaluate the presence of antileukoprotease in the lung and its possible contribution to parenc... more To evaluate the presence of antileukoprotease in the lung and its possible contribution to parenchymal protection, surgically removed lungs or lobes of 41 patients were studied. Tissue slices were stained immunohistochemically for antileukoprotease. Site and number of antileukoprotease-containing cells were recorded. To measure emphysema, the mean linear intercept of each slice was determined. Antileukoprotease was observed in bronchial epithelium and glands and in at least two types of nonciliated cells and in a few basal cells of bronchiolar epithelium. No relationship existed between the frequency of antileukoprotease positive cells in membranous bronchioles and the mean linear intercept, the smoking history or lung function except for total lung capacity. These results do not support a protective activity of antileukoprotease against emphysema, but neither do they provide evidence against it.
A retrospective cohort-study with a follow-up of 6-17 years was carried out in four general pract... more A retrospective cohort-study with a follow-up of 6-17 years was carried out in four general practices in the Netherlands in the period 1967-1983. In total 317 overweight men and 565 overweight women were followed in a continuous morbidity registration, starting in the year they were diagnosed as overweight (at age 20-50 years). Incidence of illnesses in this group was compared to that in a control group (444 men and 627 women not registered overweight), matched on sex, age and calendar-year at start of follow-up. The incidence of registered morbidity in the overweight group was higher for diabetes, gout, arteriosclerotic disease, arthrosis for men and women, and also for varicose veins for women. Increasing BMI at start of follow-up was associated with increased risk for most illnesses under study. For gout and arteriosclerotic disease in men, overweight appeared to be a risk factor at lower levels of BMI than in women.
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 1988
The blood flow velocity pattern of the anterior cerebral artery (ACA) was investigated using tran... more The blood flow velocity pattern of the anterior cerebral artery (ACA) was investigated using transcutaneous Doppler technique in ten preterm infants with posthemorrhagic hydrocephalus (PHH), before and after drainage of cerebrospinal fluid. The pulsatility index of the ACA was elevated during PHH, mainly due to an increase of peak systolic flow velocity, explained by an increased compliance of the vascular wall. The end diastolic flow velocity and the area under the velocity curve were not different before and after drainage, indicating that cerebrovascular resistance was not changed and blood flow through the ACA was not affected in the studied infants during PHH.
T lymphocyte subset numbers in bone marrow grafts were correlated with the cytomegalovirus (CMV) ... more T lymphocyte subset numbers in bone marrow grafts were correlated with the cytomegalovirus (CMV) antibody status of the donors and with the occurrence of acute graft-versus-host disease (GVHD) in their recipients. We studied whether or not the (previously reported) association between donor CMV antibodies and GVHD could be explained by CMV-related changes in T cell subsets in the marrow grafts. There were no significant correlations between any of the T cell subsets in the marrow grafts and the occurrence of grades II-IV GVHD. A particular subset of CD8+ T cells carrying the HNK1 marker was significantly increased in the marrow grafts of CMV-seropositive donors. Although recipients of marrow from CMV-seropositive donors received an average of five times more CD8+ HNK1+ T cells than those with CMV-seronegative donors, that situation was not associated significantly with the development of GVHD.
The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marr... more The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marrow donors, the occurrence of active HSV infections, and the development of grades II-IV acute graft-versus-host disease (GVHD) in their HLA-A,B,C,DR-identical sibling recipients were studied. The absence of IgG-class HSV antibodies in the marrow donors was associated with a low incidence of GVHD: 38 of 53 recipients (72%) of marrow from HSV-seropositive donors developed GVHD versus only two of 15 recipients (13%) with HSV-seronegative donors (p = 0.0004). The cellular immunity to HSV was studied in vitro by evaluating the degree of lymphocyte proliferative responses to that virus and was also significantly associated with GVHD: 30 of 43 recipients (70%) of marrow from donors with a positive test developed GVHD versus 10 of 25 recipients (40%) of marrow from donors with a negative test (p = 0.03). The previously reported risk for GVHD attributed to donor CMV antibodies increased the risk ...
We consider random effects meta-analysis where the outcome variable is the occurrence of some eve... more We consider random effects meta-analysis where the outcome variable is the occurrence of some event of interest. The data structures handled are where one has one or more groups in each study, and in each group either the number of subjects with and without the event, or the number of events and the total duration of follow-up is available. Traditionally, the meta-analysis follows the summary measures approach based on the estimates of the outcome measure(s) and the corresponding standard error(s). This approach assumes an approximate normal within-study likelihood and treats the standard errors as known. This approach has several potential disadvantages, such as not accounting for the standard errors being estimated, not accounting for correlation between the estimate and the standard error, the use of an (arbitrary) continuity correction in case of zero events, and the normal approximation being bad in studies with few events. We show that these problems can be overcome in most cases occurring in practice by replacing the approximate normal within-study likelihood by the appropriate exact likelihood. This leads to a generalized linear mixed model that can be fitted in standard statistical software. For instance, in the case of odds ratio meta-analysis, one can use the non-central hypergeometric distribution likelihood leading to mixed-effects conditional logistic regression. For incidence rate ratio meta-analysis, it leads to random effects logistic regression with an offset variable. We also present bivariate and multivariate extensions. We present a number of examples, especially with rare events, among which an example of network meta-analysis.
It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emph... more It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emphysema is represented by the shape of expiratory carbon dioxide tension versus volume curve. We examined the diagnostic value of this test in patients with various degrees of emphysema. The volumes between 25-50% (V25-50) and 25-75% (V25-75) of the expiratory carbon dioxide tension versus volume curve were determined in 29 emphysematous patients (20 severely obstructed and 9 moderately obstructed), 12 asthma patients in exacerbation of symptoms, and 28 healthy controls. Discriminant analysis was used to examine whether these diagnostic groups could be separated. With regard to phase 2 of the expiratory CO2 versus volume curve (mixture of anatomic deadspace and alveolar air), a plot of intercept versus slope of the relation- ships of (V25-50) and (V25-75) versus inspiratory volume (VI) from functional residual capacity (FRC), obtained during natural breathing frequency, proved to be most d...
To study the association between a candidate gene and a complex genetic disease, Pearson&#39;... more To study the association between a candidate gene and a complex genetic disease, Pearson&#39;s chi2 statistic can be applied to an mx2 contingency table, where the m categories correspond to m haplotypes or marker alleles. For m&gt;2, two alternative approaches for Pearson&#39;s chi2 can be followed, which are more powerful if one haplotype or marker allele is associated. For the first approach, various 2x2 tables are formed by combining various categories and the maximum of the corresponding chi-square statistics is considered as the final statistic. The second approach takes the average over the possible associated categories by writing down an overall likelihood. For the latter approach, we propose a new score statistic, which gives more weight to haplotypes or marker alleles that are common. Since the disease allele is often not observed, the power of the various statistics depends on both the linkage disequilibrium pattern and the frequencies of the associated haplotype or marker allele in the cases and the controls. We heuristically compare various statistics within the two approaches and present the results of a simulation that compares the performance of all considered statistics. Finally, we apply the statistics to a case-control study on the association between COL2A1 gene and radiographic osteoarthritis. Our conclusion is that overall the new proposed score statistic has good power.
ABSTRACT Background In rheumatoid arthritis (RA) patients, bone marrow edema (BME)-scores are ass... more ABSTRACT Background In rheumatoid arthritis (RA) patients, bone marrow edema (BME)-scores are associated with development of erosions. However, little is known on the course and outcome of BME at bone level. Therefore this study determined the association of BME and MRI-synovitis in the same bone longitudinally. Objectives This study was aimed to determine the course of BME and MRI-synovitis at bone level. Furthermore the association between the course of BME and local synovitis and the development of erosions in the same bone was studied. Methods 1,947 bones of MCP, wrist and MTP-joints of 59 patients presenting with rheumatoid or undifferentiated arthritis were studied using 1.5T MRI at baseline, after four and twelve months. Scanning and scoring of BME, synovitis and erosions were performed according to RAMRIS. The relation of the course of BME and synovitis to erosive progression at bone level during 1-year was evaluated. Results Of the bones showing BME at baseline (n=203), BME persisted in 56%, disappeared in 39%, and disappeared-reappeared seldom (5%). Stratified analyses at baseline revealed that BME was associated with erosive progression, in presence and in absence of local synovitis (ORs 7.5 95%CI 3.8-14.9 and 6.9 95%CI 1.9-25.6). Local synovitis, however, was not associated with erosive progression (OR 2.0 95%CI 0.6-7.0 in presence of BME and 1.9 95%CI 0.8-4.1 in the absence of BME). In multivariable GEE-analyses, persistent BME was strongly associated with erosive progression (OR 60 95%CI 17-318), in contrast to persistent synovitis (OR 1.4 95%CI 0.4-5.3). Conclusions BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independent of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for the comprehension on the development of erosions in RA. Disclosure of Interest None declared
Interactive cardiovascular and thoracic surgery, 2014
Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or on... more Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or ongoing. Since randomized clinical studies to support this are lacking, it is relevant to know whether lower fibrinogen levels are associated with excessive bleeding. We performed a systematic review and meta-analysis to define the association between fibrinogen levels and blood loss after cardiac surgery. A database search (January 2013) was performed on publications assessing the association between pre- and postoperative fibrinogen levels and postoperative blood loss in adult patients undergoing cardiac surgery. Cohort studies and case-control studies were eligible for inclusion. The main outcome was the pooled correlation coefficient, calculated via Fisher's Z transformation scale, in a random-effects meta-analysis model stratified for the time point at which fibrinogen was measured. A total of 20 studies were included. The pooled correlation coefficient of studies (n = 9) concerni...
Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 2012
Heart failure is characterised as a strong risk factor for systemic failure after cardiac surgery... more Heart failure is characterised as a strong risk factor for systemic failure after cardiac surgery. However, the impact has never been substantiated. Patients with heart failure (n = 48) - scheduled for elective ventricular reconstruction or external constraint device-were compared with a one-to-one matched control group of patients without heart failure undergoing cardiac surgery between 2006 and 2009. As expected, patients with heart failure more frequently experienced complications definitely related to pump failure (p = 0.01). However, complications not related to their pump failure were also more often observed, such as prolonged mechanical ventilation, sepsis and vasoplegia (p = 0.01). Overall, organ dysfunction-circulatory, renal, and pulmonary failure-was often observed in heart failure patients, contributing to a prolonged stay in the intensive care unit (p < 0.001) as well as in hospital (p = 0.01). The adverse postoperative course in patients with heart failure is not o...
Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the pro... more Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance. A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters. In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+...
Journal of applied physiology (Bethesda, Md. : 1985), 1994
In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO... more In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO) and DLCO per liter alveolar volume (DLCO/VA) at total lung capacity (TLC) and at lung volumes below TLC in sitting position. In 55 healthy nonsmoking volunteers (20-85 yr old), we determined reference values at TLC level in which age was the only parameter. In a subgroup (n = 16) these references did not change by correction for normal variability in hemoglobin concentration. In all volunteers DLCO decreased and DLCO/VA increased with decreasing VA. The increase in DLCO/VA was linear and less in older subjects. We derived equations to calculate reference values of DLCO/VA for lung volumes at and below TLC with two methods: 1) "random coefficients linear" model, which calculates the reference values directly, and 2) a conversion method, which calculates DLCO/VA for lower VA levels from reference values at TLC. An advantage of the conversion method is the suitability of DLCO/VA...
Cortical potentials were elicited by airpuff stimulation of the L5 and S1 dermatome in a group of... more Cortical potentials were elicited by airpuff stimulation of the L5 and S1 dermatome in a group of 24 healthy volunteers. The results were compared with the SEPs obtained by conventional electrical stimulation. Both stimulus modalities produce stable and good reproducible cortical responses of similar waveform. The most stable second negative peak, labeled N2, was used in this study. Mean latencies (in msec) were: N2 L5 air = 67.1 +/- 3.3, N2 L5 electr. = 55.7 +/- 3.7 N2 S1 air = 67.2 +/- 3.9, and N2 S1 electr. = 55.1 +/- 2.9 The maximum R/L difference (mean + 3 SD) was 5.7 msec, 5.9 msec, 7.2 msec and 7.2 msec for respectively N2 L5 air, N2 L5 electrical, N2 S1 air and N2 S1 electrical. Single regression analysis showed a significant influence of height, but not age upon all latencies. Multiple regression analysis with height and age as independent variables showed a significant influence of height and age together upon the latencies of the electrical SEP (both L5 and S1). For the a...
To examine the conjugacy of lid saccades in normal subjects. Saccades of both upper eyelids were ... more To examine the conjugacy of lid saccades in normal subjects. Saccades of both upper eyelids were recorded simultaneously by means of small, lightweight, magnetic search coils, fixed on each lid. Subjects then made vertical eye saccades between fixed targets. The associated eye saccades were recorded simultaneously by means of magnetic search coils. The authors further examined whether the position of the lid coils affected the recordings. Lid saccades were not as conjugate as their associated eye saccades. Nonconjugacy of lid saccades averaged approximately 8% of the target amplitude, irrespective of saccadic direction. By contrast, nonconjugacy of the associated eye saccades averaged approximately 1% of the target amplitude. Coil position significantly (P < 0.05) affected the recordings. Lid saccades are not as conjugate as their associated eye saccades. Coil position is critical for the recordings of lid saccades.
To evaluate the presence of antileukoprotease in the lung and its possible contribution to parenc... more To evaluate the presence of antileukoprotease in the lung and its possible contribution to parenchymal protection, surgically removed lungs or lobes of 41 patients were studied. Tissue slices were stained immunohistochemically for antileukoprotease. Site and number of antileukoprotease-containing cells were recorded. To measure emphysema, the mean linear intercept of each slice was determined. Antileukoprotease was observed in bronchial epithelium and glands and in at least two types of nonciliated cells and in a few basal cells of bronchiolar epithelium. No relationship existed between the frequency of antileukoprotease positive cells in membranous bronchioles and the mean linear intercept, the smoking history or lung function except for total lung capacity. These results do not support a protective activity of antileukoprotease against emphysema, but neither do they provide evidence against it.
A retrospective cohort-study with a follow-up of 6-17 years was carried out in four general pract... more A retrospective cohort-study with a follow-up of 6-17 years was carried out in four general practices in the Netherlands in the period 1967-1983. In total 317 overweight men and 565 overweight women were followed in a continuous morbidity registration, starting in the year they were diagnosed as overweight (at age 20-50 years). Incidence of illnesses in this group was compared to that in a control group (444 men and 627 women not registered overweight), matched on sex, age and calendar-year at start of follow-up. The incidence of registered morbidity in the overweight group was higher for diabetes, gout, arteriosclerotic disease, arthrosis for men and women, and also for varicose veins for women. Increasing BMI at start of follow-up was associated with increased risk for most illnesses under study. For gout and arteriosclerotic disease in men, overweight appeared to be a risk factor at lower levels of BMI than in women.
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 1988
The blood flow velocity pattern of the anterior cerebral artery (ACA) was investigated using tran... more The blood flow velocity pattern of the anterior cerebral artery (ACA) was investigated using transcutaneous Doppler technique in ten preterm infants with posthemorrhagic hydrocephalus (PHH), before and after drainage of cerebrospinal fluid. The pulsatility index of the ACA was elevated during PHH, mainly due to an increase of peak systolic flow velocity, explained by an increased compliance of the vascular wall. The end diastolic flow velocity and the area under the velocity curve were not different before and after drainage, indicating that cerebrovascular resistance was not changed and blood flow through the ACA was not affected in the studied infants during PHH.
T lymphocyte subset numbers in bone marrow grafts were correlated with the cytomegalovirus (CMV) ... more T lymphocyte subset numbers in bone marrow grafts were correlated with the cytomegalovirus (CMV) antibody status of the donors and with the occurrence of acute graft-versus-host disease (GVHD) in their recipients. We studied whether or not the (previously reported) association between donor CMV antibodies and GVHD could be explained by CMV-related changes in T cell subsets in the marrow grafts. There were no significant correlations between any of the T cell subsets in the marrow grafts and the occurrence of grades II-IV GVHD. A particular subset of CD8+ T cells carrying the HNK1 marker was significantly increased in the marrow grafts of CMV-seropositive donors. Although recipients of marrow from CMV-seropositive donors received an average of five times more CD8+ HNK1+ T cells than those with CMV-seronegative donors, that situation was not associated significantly with the development of GVHD.
The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marr... more The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marrow donors, the occurrence of active HSV infections, and the development of grades II-IV acute graft-versus-host disease (GVHD) in their HLA-A,B,C,DR-identical sibling recipients were studied. The absence of IgG-class HSV antibodies in the marrow donors was associated with a low incidence of GVHD: 38 of 53 recipients (72%) of marrow from HSV-seropositive donors developed GVHD versus only two of 15 recipients (13%) with HSV-seronegative donors (p = 0.0004). The cellular immunity to HSV was studied in vitro by evaluating the degree of lymphocyte proliferative responses to that virus and was also significantly associated with GVHD: 30 of 43 recipients (70%) of marrow from donors with a positive test developed GVHD versus 10 of 25 recipients (40%) of marrow from donors with a negative test (p = 0.03). The previously reported risk for GVHD attributed to donor CMV antibodies increased the risk ...
We consider random effects meta-analysis where the outcome variable is the occurrence of some eve... more We consider random effects meta-analysis where the outcome variable is the occurrence of some event of interest. The data structures handled are where one has one or more groups in each study, and in each group either the number of subjects with and without the event, or the number of events and the total duration of follow-up is available. Traditionally, the meta-analysis follows the summary measures approach based on the estimates of the outcome measure(s) and the corresponding standard error(s). This approach assumes an approximate normal within-study likelihood and treats the standard errors as known. This approach has several potential disadvantages, such as not accounting for the standard errors being estimated, not accounting for correlation between the estimate and the standard error, the use of an (arbitrary) continuity correction in case of zero events, and the normal approximation being bad in studies with few events. We show that these problems can be overcome in most cases occurring in practice by replacing the approximate normal within-study likelihood by the appropriate exact likelihood. This leads to a generalized linear mixed model that can be fitted in standard statistical software. For instance, in the case of odds ratio meta-analysis, one can use the non-central hypergeometric distribution likelihood leading to mixed-effects conditional logistic regression. For incidence rate ratio meta-analysis, it leads to random effects logistic regression with an offset variable. We also present bivariate and multivariate extensions. We present a number of examples, especially with rare events, among which an example of network meta-analysis.
It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emph... more It has been postulated that serial inhomogeneity of ventilation in the peripheral airways in emphysema is represented by the shape of expiratory carbon dioxide tension versus volume curve. We examined the diagnostic value of this test in patients with various degrees of emphysema. The volumes between 25-50% (V25-50) and 25-75% (V25-75) of the expiratory carbon dioxide tension versus volume curve were determined in 29 emphysematous patients (20 severely obstructed and 9 moderately obstructed), 12 asthma patients in exacerbation of symptoms, and 28 healthy controls. Discriminant analysis was used to examine whether these diagnostic groups could be separated. With regard to phase 2 of the expiratory CO2 versus volume curve (mixture of anatomic deadspace and alveolar air), a plot of intercept versus slope of the relation- ships of (V25-50) and (V25-75) versus inspiratory volume (VI) from functional residual capacity (FRC), obtained during natural breathing frequency, proved to be most d...
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Papers by T. Stijnen