Biomedical subjects

H Putter

Publications and source records attributed to H Putter.

At least 19 recordsLinked to original sources

PubMed2007

Tutorial in biostatistics: competing risks and multi-state models.

Standard survival data measure the time span from some time origin until the occurrence of one type of event. If several types of events occur, a model describing progression to each of these competing risks is needed. Multi-state models generalize competing risks models by also describing transitions to intermediate events. Methods to analyze such models have been developed over the last two decades. Fortunately, most of the analyzes can be performed within the standard statistical packages, but may require some extra effort with respect to data preparation and programming. This tutorial aims to review statistical methods for the analysis of competing risks and multi-state models. Although some conceptual issues are covered, the emphasis is on practical issues like data preparation, estimation of the effect of covariates, and estimation of cumulative incidence functions and state and transition probabilities. Examples of analysis with standard software are shown.

Biometry↗

PubMed2006

The impact of the implementation of a rehabilitation tool on the contents of the communication during multidisciplinary team conferences in rheumatology.

OBJECTIVE: Problems with multidisciplinary team conferences in health care include the exchange of too much (discipline-specific) information. The aim of this study was to investigate the effect of the implementation of a rehabilitation tool on the contents of communication during multidisciplinary team conferences in a rheumatology setting. METHODS: All initial and follow-up team conferences of 25 consecutive patients with rheumatoid arthritis admitted to a day patient care ward were videotaped during a period before (period I) and after (period II) the introduction of a rehabilitation tool. The aims of the rehabilitation tool were to enhance discussions on the co-ordination of care rather than merely exchange of information. This was achieved by providing a framework for the setting and evaluation of common treatment goals and management strategies as well as accompanying electronic and printed records. For every team conference, the duration of time spent on three types of communication was recorded: (1) grounding regarding the patient's health status, (2) the making of practical arrangements by no more than two health professionals, and (3) the co-ordination of common treatment goals or management strategies. Comparisons of the proportions of time spent on the different types of communication between the two periods were done by means of the Mann-Whitney U-test. RESULTS: Apart from the 25 initial team conferences in both periods, 86 and 71 follow-up team conferences were available in periods I and II, respectively. Regarding the initial team conferences, the proportion of time spent on grounding and practical arrangements was significantly smaller in period II than in period I. In addition, the proportion of time spent on common goals or management strategies was significantly greater in period II than in period I. For the follow-up team conferences, the proportion of time spent on practical arrangements was significantly smaller in period II, than in period I. Moreover, the proportions of time spent on the other types of communication did not differ significantly between the two periods. CONCLUSION: The implementation of a rehabilitation tool including a computer application increased the proportion of time spent on the discussion of common treatment goals or management strategies during initial but not during follow-up team conferences in a day patient rheumatology clinic.

Cohort Studies↗

PubMed2006

The effect of polyethylene glycol and butyrate on anastomotic healing in the rat colon.

BACKGROUND: The use of mechanical bowel preparation is much debated. METHODS: We evaluated the effects of polyethylene glycol (PEG), with or without a single dose of 3.0 mmol butyrate (BUT), on the bursting pressure (BP) of an intact colon segment and a colon anastomosis in rats. Also, histopathologic damage was studied. RESULTS: In rats without colectomy, the mean BP was 159.2 mmHg (SD=18.9) after PEG treatment and 116.7 mmHg (SD=27.5) in controls (p=0.001). In rats with colectomy, the mean BP was 90.4 mmHg (SD=45.9) in the PEG group, 108.0 mmHg (SD=31.9) in the BUT group, and 102.7 mmHg (SD=44.7) in controls (p=0.44). No significant differences in histopathologic scores were observed between rats treated with PEG and controls. CONCLUSIONS: PEG does not interfere with anastomotic healing in rats as measured by BP. No benefit of a single dose of butyrate was observed.

Administration, Oral↗

PubMed2006

[Right-ventricular dysfunction and the pulmonary vascular obstruction index: predictable variables of the clinical course over 3 months in patients with acute lung emboli].

OBJECTIVE: To quantify right-ventricular dysfunction and the pulmonary artery obstruction index, in patients with acute pulmonary embolism, using helical CT, and to assess the prognostic value of these parameters. DESIGN: Prospective. METHOD: In 120 consecutive patients with proven acute pulmonary embolism, the extent of right-ventricular dysfunction was assessed by quantifying the ratios of the right to left-ventricular short-axis diameters (RV/LV ratio) and the extent ofobstruction ofthe pulmonary-artery circulation by using helical CT images. Regression analysis was used to correlate these parameters with patient outcome. RESULTS: Right-ventricular dysfunction (RV/LV ratio > 1.0) was seen in 69 patients (57.5%). Seven patients died as a direct result of pulmonary embolism. Both the RV/LV ratio and the obstruction index were significant risk factors for mortality within three months (p = 0.04 and 0.01 respectively). The positive predictive value for pulmonary embolism-related mortality of an RV/LV ratio > 1.0 was 10.1% (95% CI: 2.9-17.4). The negative predictive value for an uneventful outcome of an RV/LV ratio < or = 1.0 was 100% (95% CI: 94.3-100). There was a 11.2-fold risk of dying of pulmonary embolism in patients with an obstruction index > or = 40% (95% CI: 1.3-93.6). CONCLUSION: Markers of right-ventricular dysfunction and pulmonary vascular obstruction, assessed by helical CT-examination at baseline, help to predict mortality during follow-up of patients with acute pulmonary embolism.

Acute Disease↗

PubMed2006

Potential bias in Generalized Estimating Equations linkage methods under incomplete information.

The mean identity-by-descent (IBD) specification used in the Generalized Estimating Equations (GEE) methodology for linkage is only valid, strictly speaking, under the assumption of fully polymorphic markers. In practice, markers often provide only partial IBD information, which can potentially result in inconsistency of the locus location and gene effect estimates obtained by the GEE method. Using both simulations and theory, we identify some realistic conditions about marker information under which the validity of the GEE linkage methods may be arguable. Namely, researchers should not trust the GEE parameters' estimates and their associated confidence intervals in areas of the genome where IBD information is sparse or when this information changes abruptly. We show that properly standardized statistics based on IBD sharing provide a valid alternative.

Alleles↗

PubMed2006

Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD.

BACKGROUND: von Willebrand disease (VWD) type 1 is a congenital bleeding disorder caused by genetic defects in the von Willebrand factor (VWF) gene and characterized by a reduction of structurally normal VWF. The diagnosis of type 1 VWD is difficult because of clinical and laboratory variability. Furthermore, inconsistency of linkage between type 1 VWD and the VWF locus has been reported. OBJECTIVES: To estimate the proportion of type 1 VWD that is linked to the VWF gene. PATIENTS AND METHODS: Type 1 VWD families and healthy control individuals were recruited. An extensive questionnaire on bleeding symptoms was completed and phenotypic tests were performed. Linkage between VWF gene haplotypes and the diagnosis of type 1 VWD, the plasma levels of VWF and the severity of bleeding symptoms was analyzed. RESULTS: Segregation analysis in 143 families diagnosed with type 1 VWD fitted a model of autosomal dominant inheritance. Linkage analysis under heterogeneity resulted in a summed lod score of 23.2 with an estimated proportion of linkage of 0.70. After exclusion of families with abnormal multimer patterns the linkage proportion was 0.46. LOD scores and linkage proportions were higher in families with more severe phenotypes and with phenotypes suggestive of qualitative VWF defects. About 40% of the total variation of VWF antigen could be attributed to the VWF gene. CONCLUSIONS: We conclude that the diagnosis of type 1 VWD is linked to the VWF gene in about 70% of families, however after exclusion of qualitative defects this is about 50%.

Adolescent↗

PubMed2005

Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conserving therapy: long-term results of European Organisation for Research and Treatment of Cancer studies.

The aim of this study was to evaluate prognostic factors for isolated loco-regional recurrence in patients treated for invasive stage I or II breast cancer. The study population comprised 3602 women who had undergone primary surgery for early stage breast cancer, who were enrolled in European Organisation for Research and Treatment of Cancer (EORTC) trials 10801, 10854, or 10902, by breast conservation (55%) and mastectomy (45%). The median follow-up time varied from 5.3 (range: 0.6-9.5) to 11.9 years (range: 0.6-17.4). Main outcome was the occurrence of isolated loco-regional recurrence. The results of multivariate analysis showed that younger age and breast conservation were risk factors for isolated loco-regional recurrence (breast cancer under 35 years of age versus over 50 years of age: hazard ratio 2.80 (95% CI 1.41-5.60)); breast cancer age 35-50 years versus over 50 years: hazard ratio 1.72 (95% CI 1.17-2.54); breast conservation (hazard ratio: 1.82 (95% CI 1.17-2.86)). After perioperative chemotherapy, less isolated loco-regional recurrences were observed (hazard ratio 0.63 (95% CI 0.44-0.91)). No significant interaction effects were observed. It is concluded that young age and breast conserving therapy are both independent predictors for isolated loco-regional recurrence. As an isolated loco-regional recurrence is a potentially curable condition, women treated with breast conservation or diagnosed with breast cancer at a young age should be monitored closely to detect local recurrence at an early stage.

Adult↗

PubMed2005

Long-term survival with non-proportional hazards: results from the Dutch Gastric Cancer Trial.

Randomized clinical trials with long-term survival data comparing two treatments often show Kaplan-Meier plots with crossing survival curves. Such behaviour implies a violation of the proportional hazards assumption for treatment. The Cox proportional hazards regression model with treatment as a fixed effect can therefore not be used to assess the influence of treatment of survival. In this paper we analyse long-term follow-up data from the Dutch Gastric Cancer Trial, a randomized study comparing limited (D1) lymph node dissection with extended (D2) lymph node dissection. We illustrate a number of ways of dealing with survival data that do not obey the proportional hazards assumption, each of which can be easily implemented in standard statistical packages.

Aged↗

PubMed2005

Reduced rank proportional hazards model for competing risks.

Competing events concerning individual subjects are of interest in many medical studies. For example, leukemia-free patients surviving a bone marrow transplant are at risk of developing acute or chronic graft-versus-host disease, or they might develop infections. In this situation, competing risks models provide a natural framework to describe the disease. When incorporating covariates influencing the transition intensities, an obvious approach is to use Cox's proportional hazards model for each of the transitions separately. A practical problem then is how to deal with the abundance of regression parameters. Our objective is to describe the competing risks model in fewer parameters, both in order to avoid imprecise estimation in transitions with rare events and in order to facilitate interpretation of these estimates. Suppose that the regression parameters are gathered into a p x K matrix B, with p and K as the number of covariates and transitions, respectively. We propose the use of reduced rank models, where B is required to be of lower rank R, smaller than both p and K. One way to achieve this is to write B = AGamma(intercal) with A and Gamma matrices of dimensions p x R and K x R, respectively. We shall outline an algorithm to obtain estimates and their standard errors in a reduced rank proportional hazards model for competing risks and illustrate the approach on a competing risks model applied to 8966 leukemia patients from the European Group for Blood and Marrow Transplantation.

Biometry↗

PubMed2005

Missing forms and dropout in the TME quality of life substudy.

OBJECTIVE: Missing forms may pose problems in health related quality of life (QOL) studies, because the absence of a QOL measure may be related to the patient's health and hence to the patient's QOL itself. Studying patterns of missingness, dropout, and the possible impact of missing data on QOL measures is an important step in reporting outcomes of QOL studies. We study patterns of dropout and evaluate the impact of missing forms in the TME QOL substudy. METHODS: Patients with rectal cancer, randomized to receive either radiotherapy plus total mesorectal excision (TME) or TME only were included in the TME trial. QOL was evaluated in 1302 Dutch patients, before treatment, and 3, 6, 12, 18 and 24 months after surgery. Here only the visual analogue score (VAS) was studied. RESULTS: At baseline, differences between VAS scores were found with respect to whether the QOL forms were dated before or after radiotherapy and surgery. Differences were small between different statistical methods accounting for dropout; only a cross-sectional analysis gave biased results. CONCLUSION: The results of the sensitivity analysis indicated that a linear mixed model analysis is a reliable and attractive approach for this study.

Analysis of Variance↗

PubMed2005

Pilot study of the development of a theory-based instrument to evaluate the communication process during multidisciplinary team conferences in rheumatology.

BACKGROUND: Coordinated teams with multidisciplinary team conferences are generally seen as a solution to the management of complex health conditions. However, problems regarding the process of communication during team conferences are reported, such as the absence of a common language or viewpoint and the exchange of irrelevant or repeated information. To determine the outcome of interventions aimed at improving communication during team conferences, a reliable and valid assessment method is needed. AIM: To investigate the feasibility of a theory-based measurement instrument for assessing the process of the communication during multidisciplinary team conferences in rheumatology. METHOD: An observation instrument was developed based on communication theory. The instrument distinguishes three types of communication: (I) grounding activities, (II) coordination of non-team activities, and (III) coordination of team activities. To assess the process of communication during team conferences in a rheumatology clinic with inpatient and day patient facilities, team conferences were videotaped. To determine the inter-rater reliability, in 20 conferences concerning 10 patients with rheumatoid arthritis admitted to the inpatient unit, the instrument was applied by two investigators independently. Content validity was determined by analysing and comparing the results of initial and follow-up team conferences of 25 consecutive patients with rheumatoid arthritis admitted to the day patient unit (Wilcoxon signed rank test). RESULTS: The inter-rater reliability was excellent with the intra-class correlation coefficients being >0.98 for both types I and III communications in 10 initial and 10 follow-up conferences (type II was not observed). An analysis of an additional 25 initial and 86 follow-up team conferences showed that time spent on grounding (type I) made up the greater part of the contents of communication (87% S.D. 14 and 60% S.D. 29 in initial and follow-up conferences, respectively), which is significantly more compared to time spent on co-ordination (p<0.001 and 0.02 for categories II and III, respectively). Moreover, significantly less time spent was spent on grounding in follow-up as compared to initial team conferences, whereas the time spent on coordination (type III) increased (both p-values<0.001). CONCLUSION: This theory-based measurement instrument for describing and evaluating the communication process during team conferences proved to be reliable and valid in this pilot study. Its usefulness to detect changes in the communication process, e.g. after implementing systems for re-structuring team conferences mediated by ICT applications, should be further examined.

Communication↗

PubMed2005

Cutaneous side-effects of transdermal iontophoresis with and without surfactant pretreatment: a single-blinded, randomized controlled trial.

BACKGROUND: Iontophoresis, a method that facilitates drug transport across skin by an external electrical field, offers the possibility for long-term transdermal delivery of compounds in a well-controlled manner. In general, the literature supports the contention that iontophoresis is a safe procedure. However, there are important medical issues concerning the epidermal and dermal effects of iontophoresis that have not been extensively investigated. Specific and strictly controlled studies on the dermal effect of iontophoresis are scarce. OBJECTIVES: The aim of this study was to investigate the cutaneous side-effects of transdermal iontophoresis application in healthy human volunteers. METHODS: This was a single-blinded, randomized and parallel design study. In one group (n=12) subjects were treated nonocclusively with a surfactant formulation followed by iontophoresis (3-h application at a current density of 250 microA cm(-2)). In another group (n=12) iontophoresis alone was performed. No drug was included in these studies. The corresponding passive treatments served as controls. Noninvasive methods including sensation record, transepidermal water loss (TEWL), skin colour and the visual scoring were used to assess cutaneous effects. RESULTS: Tingling and itching were commonly experienced in the first 30 min of the current application. Iontophoresis in combination with the pretreatment induced significant increases in TEWL values and in skin redness, and resulted in slight to mild erythema and oedema compared with the control. Compared with the iontophoresis alone, the presence of surfactant pretreatment caused slightly more skin irritation (erythema and oedema) but did not further disturb the skin barrier function. CONCLUSIONS: The transdermal iontophoresis challenges the skin barrier function and induces transient mild skin irritation, but does not cause any permanent damage to the skin when applied for 3 h at a current density of 0.25 mA cm(-2).

Adult↗

PubMed2005

Effect of mechanical bowel preparation with polyethyleneglycol on bacterial contamination and wound infection in patients undergoing elective open colon surgery.

Mechanical bowel preparation is common practice in elective colon surgery. In order to verify the effect of mechanical bowel preparation on the colonic flora, this study followed 185 patients undergoing elective open colon surgery, 90 of whom were assigned randomly to receive mechanical bowel preparation with polyethyleneglycol. Swabs of the anastomosis and the subcutis were taken during surgery. Further swabs were taken of any subsequent wound infections. Mechanical bowel preparation did not reduce contamination of the peritoneal cavity or the subcutis during surgery, and there appeared to be more sterile subcutaneous swabs in the control group.

Bacteria↗

PubMed2004

Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.

PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.

Adenocarcinoma↗

PubMed2004

Score test for detecting linkage to complex traits in selected samples.

We present a unified approach to selection and linkage analysis of selected samples, for both quantitative and dichotomous complex traits. It is based on the score test for the variance attributable to the trait locus and applies to general pedigrees. The method is equivalent to regressing excess IBD sharing on a function of the traits. It is shown that when population parameters for the trait are known, such inversion does not entail any loss of information. For dichotomous traits, pairs of pedigree members of different phenotypic nature (e.g., affected sib pairs and discordant sib pairs) can easily be combined as well as populations with different trait prevalences.

Analysis of Variance↗

PubMed2004

Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the Dutch randomised FAMTX trial.

AIMS: Gastric cancer in Western countries is often diagnosed in an advanced stage and prognosis is poor. We performed a randomised trial with pre-operative FAMTX vs. surgery alone in order to evaluate the effect of pre-operative chemotherapy on resectability and survival. METHODS: Patients with proven adenocarcinoma of the stomach were randomised to receive four courses of chemotherapy using 5-Fluorouracil, doxorubicin and methotrexate (FAMTX) prior to surgery or to undergo surgery alone. RESULTS: Fifty-nine patients were randomised; 29 patients were allocated to the FAMTX regimen prior to surgery and 30 patients had surgery alone. Resectability rates were equal for both groups. Complete or partial response was registered in 32% of the FAMTX group. With a median follow-up of 83 months the median survival since randomisation is 18 months in the FAMTX group vs. 30 months in the surgery alone group (p=0.17). CONCLUSIONS: This trial could not show a beneficial effect of pre-operative FAMTX. Until large randomised studies prove otherwise, adequate surgery without delay is the best treatment for operable gastric cancer.

Adenocarcinoma↗

PubMed2004

Incidence of cervical carcinoma in a high-risk, non-screened area results of a retrospective analysis on the Dutch Caribbean Antilles from 1983 to 1998.

Cancer of the uterine cervix is one of the most common malignancies worldwide. The average annual incidence of cervical cancer varies widely per geographical area. Some of the highest rates have been reported in Latin American and Caribbean countries. Previous research into the frequency of cervical carcinoma in Curaçao, the main island of the Dutch Caribbean, has reported predominantly far-advanced stages of the disease. The objectives of this study were to determine: whether there are indications of changes in the incidence of cervical carcinoma, whether these changes are a result of increased clinical attention paid by general practioners (GPs) and gynaecologists, and whether less advanced stages of cervical cancer were found, indicating earlier diagnosis. Data on patients with cervical carcinoma, obtained from records kept in the Department of Pathological Anatomy at the St Elisabeth Hospital in Curaçao were retrospectively analyzed for the period 1983 to 1998. To study the incidence rate over time, cumulative and incidence rates, standardized to the World Standard Population, were calculated and compared to the rates in other Latin American and Caribbean countries. The age-standardized incidence rate for Curaçao was 14.3 per 100 000 women. The cumulative rate up to 74-years-of-age was 1.6%. Sub-division into the three groups showed a trend towards a decrease in the incidence and cumulative rates. A comparison of clinical staging International Federation of Obstetrics and Gynaecology (FIGO) showed a trend towards an increase in time of almost 48% to 59% in stage IA (ie less severe cases). A significant increase (p < 0.0001) was found in the numbers of smears performed in the complete period of 1983-1998, compared to a previously examined period of 1972-1982. The incidence of cervical cancer in Curaçao appears to be decreasing, and is lower than in other areas in the region. The number of smears GPs performed over time increased However the incidence is still relatively high compared to western countries and cases are still presenting in relatively advanced stages of the disease. Although the introduction of a screening programme might not influence the actual incidence of cervical cancer dramatically, nonetheless it may contribute to earlier diagnosis of cervical carcinoma.

Carcinoma, Squamous Cell↗

PubMed2003

[Diagnostic surplus value of echography in children with acute abdominal pain].

OBJECTIVE: To assess the role of echography in the diagnosis of acute abdominal symptoms in children. DESIGN: Prospective, descriptive. METHOD: During one year (1 June 1999-31 May 2000), abdominal ultrasonography was performed in all children with abdominal pain less than 2 weeks, who were referred to the emergency department of the Red Cross Hospital in The Hague (the Netherlands). An initial clinical diagnosis was made on the basis of the medical history, a physical examination and the results of laboratory tests. Subsequently, ultrasonography was performed by a radiologist who was unaware of the clinical diagnosis. A working hypothesis was reached on the basis of the clinical findings and the results of echography. The final diagnosis was made on the basis of either a histologic investigation after surgery or the condition at discharge. RESULTS: The study included 112 patients. The mean age was 9 years and 54% were boys. Acute appendicitis was ascertained in 48 children. The sensitivity of the clinical findings was 88% and the specificity 70%. The sensitivity of the clinical findings together with ultrasonography was 88% and the specificity 91%. The positive predictive value of the clinical findings alone was 69% and of the clinical findings together with ultrasonography 88%. CONCLUSION: Echography has added value in the diagnosis of acute abdominal pain in children; it increases the specificity of the physical examination. The number of negative laparotomies was decreased by the use of ultrasonography.

Abdomen, Acute↗