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Biomedical subjects

H Heinzl

Publications and source records attributed to H Heinzl.

At least 19 recordsLinked to original sources

A simulation study comparing properties of heterogeneity measures in meta-analyses.

The assessment of heterogeneity or between-study variance is an important issue in meta-analysis. It determines the statistical methods to be used and the interpretation of the results. Tests of heterogeneity may be misleading either due to low power for sparse data or to the detection of irrelevant amounts of heterogeneity when many studies are involved. In the former case, notable heterogeneity may remain unconsidered and an unsuitable model may be chosen and the latter case may lead to unnecessary complex analyses strategies. Measures of heterogeneity are better suited to determine appropriate analyses strategies. We review two measures with different scaling and compare them with the heterogeneity test. Estimates of the within-study variance are discussed and a new total information measure is introduced. Various properties of the quantities in question are assessed by a simulation study. Heterogeneity test and measures are not directly related to the amount of between-study variance but to the relative increase of variance due to heterogeneity. It is more favourable to base the within-study variance estimate on the squared weights of individual studies than on the sum of weights. A heterogeneity measure scaled to a fixed interval needs reference values for proper interpretation. A measure defined by the relation of between- to within-study variance has a more natural interpretation but no upper limit. Both measures are quantifications of the impact of heterogeneity on the meta-analysis result as both depend on the variance of the individual study effects and thus on the number of patients in the studies.

Biomedical Research↗

Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia.

It is currently not known which level of pentagastrin-stimulated calcitonin serum concentration indicates medullary thyroid carcinoma in patients with chronic kidney disease (CKD). We examined CKD stage 3-5 patients who had total thyroidectomy because of a pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and tested the diagnostic performance of basal and pentagastrin-stimulated calcitonin levels for differentiating medullary thyroid carcinoma and C-cell hyperplasia in this patient population. A total of 180 CKD patients presented with an elevated calcitonin level and had a pentagastrin stimulation test. Forty patients showed a maximum pentagastrin-stimulated calcitonin concentration greater than 100 pg/ml, and 22 patients had a total thyroidectomy. Seven of these 22 patients presented with a medullary thyroid carcinoma, all other patients showed C-cell hyperplasia. Patients with medullary thyroid carcinoma showed higher unstimulated (212 pg/ml (36-577) vs 42 pg/ml (17-150); P < 0.001) and higher maximum pentagastrin-stimulated calcitonin concentrations (862 pg/ml (431-2423) vs 141 pg/ml (102-471); P < 0.001) as compared to patients with C-cell hyperplasia. The sensitivity (100%) and specificity (93%) estimates suggested that a maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml indicates the presence of medullary thyroid carcinoma in patients with CKD. Receiver-operating characteristic (ROC) analysis revealed an area under the ROC plot of 0.99 for maximum pentagastrin-stimulated calcitonin concentrations. A maximum pentagastrin-stimulated calcitonin concentration greater than 400 pg/ml appears to be a clinically meaningful threshold for thyroidectomy.

Adolescent↗

Histopathological prognostic factors in medulloblastoma: high expression of survivin is related to unfavourable outcome.

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.

Adolescent↗

Comparative analysis of NeuN immunoreactivity in primary brain tumours: conclusions for rational use in diagnostic histopathology.

AIMS: NeuN is considered to be a marker of neuronal differentiation in brain tumours. Our aim was to perform, for the first time, a systematic and comparative analysis of NeuN expression in all major brain tumour subtypes to provide guidance for the rational use of NeuN immunohistochemistry in diagnostic histopathology. METHODS AND RESULTS: Anti-NeuN immunohistochemistry was performed on paraffin-embedded biopsy specimens of 106 diffuse astrocytomas, 100 pilocytic astrocytomas, 107 ependymomas, 59 1p-aberrant oligodendroglial neoplasms, 115 glioblastomas, 115 medulloblastomas, 14 gangliogliomas/gangliocytomas and 10 central neurocytomas. We found no NeuN expression in pilocytic astrocytoma, whereas all other investigated tumour subtypes showed focal or widespread expression in varying proportions of cases. Comparing NeuN expression in clear cell tumours, widespread NeuN expression had a positive predictive value of 76.9% (95% confidence interval 46.2, 95.0) for central neurocytoma. Lack of NeuN expression had a positive predictive value of 87.3% (76.5, 94.4) for oligodendroglioma. CONCLUSIONS: Immunohistochemistry can detect NeuN expression in all major brain tumour subtypes except pilocytic astrocytoma. In the individual case, assessment of NeuN expression may be helpful in the differential diagnosis of clear cell primary brain tumours but does not seem to be useful for the differential diagnosis of other brain tumour subtypes.

Antigens, Nuclear↗

Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis.

BACKGROUND: Early treatment prevents progression of joint damage in rheumatoid arthritis (RA), but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria. OBJECTIVE: To study the value of rheumatoid factor (RF), anti-cyclic citrullinated peptide autoantibodies (anti-CCP), and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis. METHODS: The prospective follow up inception cohort included 200 patients with very early (<3 months) inflammatory joint disease. Autoantibodies were measured at baseline and analysed in a tree based model which aimed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone. RESULTS: RA was diagnosed in 102 patients, while 98 developed other inflammatory arthropathies. Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml, above which anti-CCP and anti-RA33 had no additional diagnostic value. Remarkably, RF >or=50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA, but overlapped considerably. Anti-RA33 was less specific and did not correlate with RF or anti-CCP. Among patients with RA, 72% showed at least one of these three autoantibodies, compared with 15% of non-RA patients. RF >or=50 U/ml and anti-CCP were predictors of erosive disease, whereas anti-RA33 was associated with mild disease. CONCLUSIONS: Stepwise autoantibody testing in early inflammatory joint disease, starting with RF, followed by anti-CCP (in patients with RF <50 U/ml), and finally anti-RA33, should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome.

Adolescent↗

Stability of coagulation factors in thawed, solvent/detergent-treated plasma during storage at 4 degrees C for 6 days.

BACKGROUND AND OBJECTIVES: Transfusion of fresh-frozen plasma is still a pillar in emergency medicine for using to prevent dilutional coagulopathy or disseminated intravascular coagulation after severe blood loss, but thawing procedures can delay its availability. On the other hand, the wastage of plasma, once thawed and not transfused within a defined time-period, represents an inefficient handling of economic resources and is contradictory to blood donor intentions. In this study we investigated the stability of coagulation factor activities and plasma protein levels during 6 days of storage of thawed solvent/detergent (S/D)-treated plasma at +4 degrees C. Our results may form the basis for reconsideration of expiry times of thawed S/D-treated plasma. MATERIALS AND METHODS: Five units of S/D-treated plasma (Octaplas) were thawed and warmed to 20 degrees C, then recooled and stored at +4 degrees C for 6 days. The activities of coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen, antithrombin (AT), protein C, protein S and von Willebrand factor antigen (vWF:Ag) were measured on days 0, 1, 2, 3 and 6. RESULTS: Except for protein S, the activities of all coagulation factors and inhibitors were at least 0.5 U/ml during storage at 4 degrees C for 6 days. The mean levels, during storage, of factors IX, X, XI and XII, vWF:Ag, fibrinogen and protein C were at least 94%, and of factors II, V and VIII, and AT at least 78%, of the levels immediately after thawing; the activity of factor VII decreased to 83% and of protein S to 43% of the baseline values. CONCLUSIONS: Thawed S/D-treated plasma stored at +4 degrees C for up to 6 days still contains sufficient coagulation activities and plasma proteins to be regarded as suitable for transfusion in the established indications.

Blood Coagulation Factors↗

Position dependent changes of cerebral blood flow velocities in premature infants.

UNLABELLED: The supine or prone positioning of infants has been a cause of much controversy. Recently it has been postulated that the position dependent hypoperfusion of the brainstem represents a possible cause of sudden infant death. To demonstrate position dependency and maturational changes of cerebral perfusion in premature newborn infants we investigated cerebral blood flow velocities (CBFV) in the main supratentorial and brainstem cerebral arteries. Measurements of CBFV were done with transfontanellar colour-coded Doppler sonography in the internal carotid artery (ICA), basilar artery (BA), and vertebral artery (VA) in the prone (head centered-baseline) and supine positions (maximal rotation to both sides) in 23 premature infants aged between 3-5 days of life. We performed follow-up measurements in 17 infants 7-10 days later and in 16 infants at the corrected age of 1 month. There was no difference in mean CBFVs between the prone and supine position at the first investigation. At the third investigation, CBFVs were significantly higher in the supine compared to the prone position. The CBFVs of the ICA were higher than in the BA and VA. This difference was not influenced by the body position but increased with post-natal age more in the VA (159%) than in the BA (129%) and ICA (128%). Position dependency was not seen in the ICA perfusion. In the prone position, five infants showed an incomplete steal effect in the contralateral VA. There was no significant side difference in the CBFVs of the ICA and VA, but in the resistance indices in the VA (left > right). CONCLUSION: in premature newborns, position dependent changes of cerebral blood flow velocity develop with maturation and are most pronounced in the vertebrobasilar system. These changes are possibly due to compression of the vertebral artery by neck movement and suggest an individual risk of brainstem perfusion deficits that may be aggravated with age and head rotation in a prone position.

Analysis of Variance↗

BJ: an S-Plus program to fit linear regression models to censored data using the Buckley-James method.

Most researchers are familiar with ordinary multiple regression models, most commonly fitted using the method of least squares. The method of Buckley and James (J. Buckley, I. James, Linear regression with censored data, Biometrika 66 (1979) 429-436.) is an extension of least squares for fitting multiple regression models when the response variable is right-censored as in the analysis of survival time data. The Buckley-James method has been shown to have good statistical properties under usual regularity conditions (T.L. Lai, Z. Ying, Large sample theory of a modified Buckley-James estimator for regression analysis with censored data, Ann. Stat. 19 (1991) 1370-1402.). Nevertheless, even after 20 years of its existence, it is almost never used in practice. We believe that this is mainly due to lack of software and we describe here an S-Plus program that through its inclusion in a public domain function library fully exploits the power of the S-Plus programming environment. This environment provides multiple facilities for model specification, diagnostics, statistical inference, and graphical depiction of the model fit.

Data Interpretation, Statistical↗

Extracting a statistical data matrix from electronic patient records.

This paper describes the processing and transformation of medical data from a clinical database to a statistical data matrix. Precise extraction and linking tools must be available for the desired data to be processed for statistical purposes. We show that flexible mechanisms are required for the different types of users, such as physicians and statisticians. In our retrieval tools we use logical queries based on operands and operators. The paper describes the method and appliance of the operators with which the desired matrix is created through a process of selection and linking. Examples with a Kaplan-Meier function and time-dependent covariables demonstrate how our model is useful for different user groups.

Biometry↗

Improved prediction of intraocular lens power using partial coherence interferometry.

PURPOSE: To evaluate the feasibility of using a new optical biometry technique, dual-beam partial coherence interferometry (PCI), to improve intraocular lens (IOL) power prediction in cataract surgery. SETTING: Department of Ophthalmology, Vienna General Hospital, and Institute of Medical Physics, University of Vienna, Vienna, Austria. METHODS: Preoperative axial length (AL) data obtained with PCI biometry and applanation ultrasound (US) biometry in 77 eyes of 51 patients was applied to 4 commonly used IOL power formulas. The refractive outcome and the mean absolute error (MAE) were calculated for each formula using both biometry methods. A linear multiple-regression model based on preoperative PCI biometry data was derived to predict the postoperative anterior chamber depth (ACD). The predictive power of this regression model was assessed by adding the predicted ACD to the SRK/T formula. Predicted residuals were calculated to evaluate the feasibility and stability of this modified IOL power formula. RESULTS: Using PCI instead of US biometry significantly improved the refractive outcome with all 4 IOL power formulas. The Holladay I and SRK/T formulas yielded an MAE of 0.44 diopter (D) using PCI AL data and 0.56 D and 0.57 D, respectively, using US biometry data. The SRK/T formula combined with the PCI regression model for postoperative ACD prediction performed slightly better (MAE 0.42 D) than the conventional SRK/T formula alone. Predicted residuals revealed an MAE of 0.46 D, proving the predictive performance of the new formula. CONCLUSIONS: Partial coherence interferometry biometry applied to several widely used IOL power formulas yielded significantly better IOL power prediction and therefore refractive outcome in cataract surgery than US biometry. Further improvement can be achieved by applying PCI to a modified SRK/T formula that predicts the postoperative ACD using PCI biometry data.

Biometry↗

A note on R2 measures for Poisson and logistic regression models when both models are applicable.

The aim of many epidemiological studies is the regression of a dichotomous outcome (e.g., death or affection by a certain disease) on prognostic covariables. Thereby the Poisson regression model is often used alternatively to the logistic regression model. Modelling the number of events and individual outcomes, respectively, both models lead to nearly the same results concerning the parameter estimates and their significances. However, when calculating the proportion of explained variation, quantified by an R2 measure, a large difference between both models usually occurs. We illustrate this difference by an example and explain it with theoretical arguments. We conclude, the R2 measure of the Poisson regression quantifies the predictability of event rates, but it is not adequate to quantify the predictability of the outcome of individual observations.

Adult↗

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.

Adult↗

A long-term review of the treatment of patients with Ewing's sarcoma in one institution.

AIMS: The treatment of patients suffering from Ewing's sarcoma has changed over the last three decades. We report the analyses, significant prognostic factors, interdisciplinary approach and development of therapy in one institution in Austria. METHODS: One hundred and forty-two patients treated for Ewing's sarcoma between 1949 and 1994 were reviewed. Median follow-up was 8.5 years. Fifty-six patients were treated between 1949 and 1980 (group 1), and 86 patients between 1981 and 1994 (group 2). Patients in group 1 were treated with polychemotherapy. Patients in group 2 were treated with a neoadjuvant CESS (Cooperative Ewing's Sarcoma Study) regimen. In group 1, 24 patients underwent biopsy only, 32 patients had a definitive operation, 48 patients received either radiation therapy only or additional radiation therapy compared with in group 2: 6, 80 and 44 cases, respectively. RESULTS: Five-year overall survival (OS) increased from 27% to 57%. Significant prognostic factors for OS were pre-operative metastases (P=0.0001), tumour location (P=0.0048), type of chemotherapy (P=0.002) and response to chemotherapy (P=0.0004). Chemotherapy (P=0.037), tumour location (P=0.0017) and metastases at diagnosis (P=0.0025) were significant. CONCLUSION: The most effective treatment of Ewing's sarcoma is chemotherapy.

Adolescent↗

Long-term followup of uncemented tumor endoprostheses for the lower extremity.

Between 1982 and 1989, 100 primary lower limb reconstructions were done using the Kotz Modular Femur Tibia Reconstruction System after resection of a malignant tumor. In 32 patients a proximal femur prosthesis was implanted, in 40 patients a distal femur prosthesis was implanted, in 19 patients a proximal tibia component was implanted, in four patients a total femur prosthesis was implanted, and in five patients a total knee prosthesis was implanted. The Kaplan-Meier estimate of the overall survival rate of the prostheses was 85% after 3 years, 79% after 5 years, and 71% after 10 years. The most common reason for implant failure was aseptic loosening in 27% of patients (11 patients; range, 10-121 months) after the initial operation. The other reasons for revision surgery were implant fracture (n 5 4) and infection (n 5 4). Early repair of prostheses-related minor complications, such as worn polyethylene bushings, resulted in a statistically significant reduction of implant failure. After a median followup of 127.5 months after the initial surgery, 51 patients had died and eight patients were lost to followup. Forty-one patients were evaluated clinically and radiologically using the Musculoskeletal Tumor Society score and the radiologic implant evaluation system of the International Symposium on Limb Salvage; these 41 patients had a mean of 80% (range, 40%-100%) of the normal functional capability.

Adult↗

The role of surgery and resection margins in the treatment of Ewing's sarcoma.

Because of the enormous progress in surgery in the treatment of patients with tumors, the current study analyzed the influence of wide surgical resection margins on the outcome of patients with Ewing's sarcoma. Between 1980 and 1994, 86 patients were treated with systemic therapy and surgery (biopsy in six patients, tumor resection in 80 patients). Forty-four patients also had radiation therapy. The 5-year overall survival was 56.8% (5-year disease-free survival, 59.4%). The 5-year overall survival after radical or wide resection was 60.2% (5-year disease-free survival, 58.2%), in comparison with 40.1% (46.7%) after marginal or intralesional resection. Two patients with inadequate resection margins had local recurrences. In addition to the influence of neoadjuvant chemotherapy for higher survival rates (5-year overall survival with a good response was 80.2% versus 41.7% with a poor response), adequate surgical margins significantly affect the outcome for patients with Ewing's sarcoma.

Adolescent↗

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma.

BACKGROUND AND PURPOSE: To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS: This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS: Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS: Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.

Adult↗

Using SAS to calculate the Kent and O'Quigley measure of dependence for Cox proportional hazards regression model.

Kent and O'Quigley (1988) apply the concept of information gain to define a measure of dependence (R-squared measure) between explanatory variables and a censored response variable within the framework of the Cox model. Two SAS macros to calculate this measure are presented. The first one is based on a Newton-Raphson search and makes use of the SAS IML procedure. The second one is a simple grid search using SAS DATA steps and Base-SAS procedures.

Data Interpretation, Statistical↗