bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a multimodal anti‐emetic prophylaxis on patient satisfaction in high‐risk patients for postoperative nausea and vomiting
Authors: Eberhart L. H. J. , Mauch M. , Morin A. M. , Wulf H. , Geldner G. 
Published: March 2003

SummaryPostoperative nausea and vomiting (PONV) are frequent and unpleasant symptoms. This prospective study aimed to assess the efficacy of a multimodal approach to prevent PONV, and patient satisfaction using the willingness‐to‐pay method. Two validated risk scores were applied to forecast the individual risk for PONV in 900 consecutive patients of whom 108 were identified as high‐risk patients (predicted risk: 79–87%). High‐risk patients received multimodal anti‐emetic prophylaxis: total intravenous anaesthesia with propofol, high fractional inspired oxygen (80%), omission of nitrous oxide, dexamethasone 8 mg, haloperidol 10 µg.kg−1, and tropisetron 2 mg. Of the remaining patients with low or moderate risk for PONV, a random sample of 71 females received balanced propofol‐desflurane anaesthesia without prophylactic anti‐emetics. All patients were interviewed 2 and 24 h after surgery for occurrence of nausea and vomiting. Patient satisfaction was measured using the willingness‐to‐pay method. The incidence of PONV (95%‐confidence interval) in the control‐group was 41% (29–51%), slightly lower than predicted by the risk scores (53–57%). The multimodal anti‐emetic approach reduced the predicted risk (79–87%) in the high risk‐group to 7% (3–14%). This was associated with a high willingness‐to‐pay median (25th/75th percentile) of £84 (£33–184) in the multimodal anti‐emetic grouped compared to £14 (£4–30) in the control group. A multimodal anti‐emetic approach can considerably reduce the incidence of PONV in high‐risk patients and is associated with a high patient satisfaction as measured by the willingness‐to‐pay method.
Cooling of the Sverdrup Basin during Tertiary basin inversion: implications for hydrocarbon exploration
Authors: Arne D.C. , Grist A.M. , Zentilli M. , Collins M. , Embry A. , Gentzis T. 
Published: March 2003

ABSTRACT The regional thermal history of the north‐eastern Sverdrup Basin, Canadian Arctic Archipelago, has been assessed using apatite fission‐track thermochronology and vitrinite reflectance data. Fission‐track data for 27 samples from six wells through the Mesozoic section on Axel Heiberg and Ellesmere Islands reveal significant Palaeocene cooling associated with basin inversion during the Eurekan Orogeny. Fission‐track data for 29 outcrop samples, ranging in stratigraphic age from Cambrian to Tertiary, also reveal significant Palaeocene cooling. Vitrinite reflectance data from carbonaceous shales and coal seams in well and outcrop samples are consistent with these conclusions. The degree of Palaeocene cooling observed is greatest for well and outcrop samples in the cores of anticlines or the hanging walls of thrust faults, such as the Fosheim anticline, and faults, such as the Lake Hazen fault system, and the East Cape and Vesle Fiord thrust faults. Palaeocene cooling is largely attributed to the denudation of structures during the Eurekan Orogeny.At one locality on north‐western Ellesmere Island, which is on the northern flank of the Sverdrup Basin, the underlying Franklinian basement rocks yield Early Cretaceous fission track ages with relatively long mean track lengths. This indicates that this part of the basin was uplifted at this time and that subsequent sedimentation and subsidence in the Cretaceous and early Tertiary were modest. This locality thus appears to be on the rift shoulder, which developed along the flank of the Amerasia Basin in the Lower Cretaceous.At a locality on western Axel Heiberg Island, which is downflank from the rift shoulder, the Upper Jurassic Awingak sandstone has a Late Cretaceous fission track age. This is best explained by heating above the total annealing temperature for fission‐tracks in apatite by extensive Lower Cretaceous intrusions and subsequent heat dissipation and cooling in the Late Cretaceous followed by further substantial cooling due to Tertiary denudation.These results indicate that maximum burial temperatures occurred in the presently exposed Mesozoic section prior to basin inversion during the Eurekan Orogeny. It can therefore be inferred that peak hydrocarbon generation and primary migration predated the formation of structural traps during the Tertiary at shallow depths within the northern Sverdrup Basin.
Forebulge migration in the Cretaceous Western Interior basin of the central United States
Authors: White T. , Furlong K. , Arthur M. 
Published: March 2003

ABSTRACT This study combines stratigraphic evidence with geodynamic modelling to demonstrate that a forebulge played an identifiable role in Cenomanian–Turonian erosion and sediment accumulation in the North American Western Interior basin. The early to middle Turonian forebulge migrated progressively eastwards, and by the upper middle Turonian acted as a ‘backstop’ against which barrier islands formed in the axial basin.This paper focuses on the progressive migration of an unconformity on the forebulge. The lengthwise orogen‐parallel orientation and time‐transgressive orogen‐normal migration of the forebulge unconformity are characteristics that differentiate it from unconformities developed on reactivated basement structures. We present a conceptual model in which the unconformity formed as the seafloor was uplifted by forebulge‐related flexure to a water depth at which submarine bypass and erosion occurred. A numerical model that describes forebulge migration in response to load dispersal by erosion of the orogenic front and sedimentation into the foredeep indicates that the distance from the thrust front to the forebulge is within reasonable bounds established using a flexural rigidity of 3×1024 Nm.We identify architecturally similar, coeval unconformities from Montana to New Mexico, and interpret the similar distance from the thrust front to a point where each unconformity dissipates as indicative of a uniform lithospheric flexural response along the orogenic front. Here we ascribe cratonward (west‐to‐east) forebulge migration to erosional load redistribution, whereas orogen‐parallel (north–south) stratigraphic climb of the forebulge unconformities developed in response to depocentre migration. Inherited lithospheric inhomogeneities may have allowed the forebulge in central Colorado to crest farther from the orogen than to the north and south.
Folding and faulting in coulomb materials
Authors: Waltham D. 
Published: March 2003

ABSTRACTSand in laboratory scale analogue models of folding and faulting is usually assumed to behave as a simple Coulomb material in which failure occurs along planes inclined at an angle completely determined by the internal angle of friction. This simple model has inspired use of the inclined simple shear model to explain analogue model behaviour. Unfortunately the inclined simple shear model is incapable of describing the full richness of behaviour in sand‐based analogue models since it cannot cope with rotations and it cannot satisfy general boundary conditions. A rotational simple shear description is developed in this paper which overcomes these obstacles. It is shown that this description explains high‐angle back thrusts in contractional models, that it quantitatively predicts fault throws in listric‐fault extensional models and that it provides a complete kinematic description for domino‐fault block models including the transition from uniform stretch at the model base to rigid rotation in the model upper half.
The dose–response effects of terbutaline on the variability, approximate entropy and fractal dimension of heart rate and blood pressure
Authors: Jartti Tuomas T. , Kuusela Tom A. , Kaila Timo J. , Tahvanainen Kari U. O. , Välimäki Ilkka A. T. 
Published: March 2003

Aims
To study the dose‐response effects of intravenous terbutaline on the cardiovascular and respiratory autonomic nervous regulation.
Methods
The study followed a randomized, placebo‐controlled crossover design in six healthy adult volunteers. The terbutaline dose ranged from 10 to 30 μg min−1. We continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow‐volume spirometry in supine and upright positions at baseline and during 3 h drug infusion. The periodic variability components of R‐R intervals (time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. The regularity of the time series was assessed by approximate entropy (ApEn) and the convolutedness by fractal dimension (FD).
Results
Terbutaline dose‐dependently decreased total variability of R‐R intervals, low frequency (LF) variability of R‐R intervals (10 s waves), high frequency (HF) variability of R‐R intervals (respiratory variability), total variability of SAP, HF variability of SAP, baroreflex sensitivity, plasma potassium concentration, approximate entropy of R‐R interval and of SAP as well as fractal dimension of R‐R interval. Terbutaline dose‐dependently increased heart rate, LF/HF ratios of R‐R intervals and of SAP, LF variability of SAP, minute ventilation and plasma terbutaline concentration.
Conclusions
Terbutaline infusion decreases parasympathetic cardiovascular reactivity, baroreflex sensitivity, dimensionality of heart rate and plasma potassium concentration; it increases sympathetic dominance in cardiovascular autonomic balance, minute ventilation, and the regularity of heart rate and blood pressure time series.
Tamoxifen and risk of idiopathic venous thromboembolism
Authors: Meier Christoph R. , Jick Hershel 
Published: March 2003

Aims
To evaluate a possible positive association between tamoxifen treatment and the risk of developing idiopathic venous thromboembolism (VTE) in women with breast cancer in the absence of clinical risk factors for venous thromboembolism other than breast cancer itself.
Methods
Using information from the large UK‐based General Practice Research Database, we identified, within a cohort of more than 10 000 women with breast cancer, all women who developed a first‐time diagnosis of deep vein thrombosis or pulmonary embolism of uncertain cause between January 1, 1991 and December 31, 1996. In a case‐control analysis, we compared their tamoxifen exposure experience prior to the thromboembolic event with that of a randomly selected group of control women with breast cancer who were matched to cases on age, year of the breast cancer diagnosis and calendar time.
Results
We identified 25 cases of idiopathic VTE and 172 controls, all of whom had breast cancer, but were otherwise free from other risk factors for VTE. Past tamoxifen exposure was not materially associated with an elevated risk of developing VTE, and we therefore combined never and past users as reference group. The relative risk estimate of VTE for current tamoxifen exposure, as compared with never and past use combined, was 7.1 (95% CI 1.5–33), adjusted for body mass index, smoking status and hysterectomy status. High body mass index was an independent predictor of VTE itself.
Conclusions
Our study provides evidence that current use of tamoxifen increases the risk of idiopathic venous thromboembolism.
Population pharmacokinetics of ondansetron: a covariate analysis
Authors: De Alwis D. P. , Aarons L. , Palmer J. L. 
Published: March 2003

Aims
To construct a population model to account for the variability in ondansetron pharmacokinetics and to evaluate methods for the efficient development of population models.
Methods
Population models were developed using 99 subjects consisting of paediatric patients, young, elderly and aged volunteers. A two compartment pharmacokinetic model with a zero order input was used to describe the pharmacokinetics of ondansetron. Three stepwise methods were proposed and used alongside a three step approach to develop population models with both rich and sparse data sets. The stepwise methods were based on obtaining empirical Bayes posterior estimates of pharmacokinetic parameters within a nonlinear mixed effect modelling (NONMEM) program. The parameters were then regressed against covariates in a stepwise procedure. Variance parameters were obtained by fitting the proposed population model to the data in one further NONMEM run. The population model was validated against a test data set of 54 subjects, including children, young and elderly patients and volunteers.
Results
The population model adequately described the differences in ondansetron pharmacokinetics between paediatric patients, young, elderly and aged volunteers. Different covariates were identified by the various methods. Weight was found to have a strong positive linear relationship with all four pharmacokinetic parameters. Clearance showed a weak negative relationship with age. Males were found to have a greater clearance than females after weight adjustment.
Conclusions
The stepwise search procedures potentially are capable of considerably reducing the time required to develop population pharmacokinetic models. The model developed for ondansetron gave accurate predictions of both the concentration‐time profile and variability in an independent data set.
Possible association between ocular chloramphenicol and aplastic anaemia—the absolute risk is very low
Authors: Laporte Joan‐Ramon , Vidal Xavier , Ballarín Elena , Ibáñez Luisa 
Published: March 2003

Aims
To determine whether topical ocular chloramphenicol increases the risk of aplastic anaemia and to estimate the magnitude of this risk, if any.
Methods
Population‐based prospective case‐control surveillance of aplastic anaemia in a community of 4.2 million inhabitants from 1980 to 1995 (67.2 million person‐years) plus case‐population estimate of the risk, based on sales figures of ocular chloramphenicol in the study area during the study period.
Results
One hundred and forty‐five patients with aplastic anaemia and 1,226 controls were included in the analysis. Three cases (2.1%) and 5 controls (0.4%) had been exposed to ocular chloramphenicol during the relevant etiological period. The adjusted odds ratio was 3.77 (95% confidence interval, 0.84–16.90). Two cases had also been exposed to other known causes of aplastic anaemia. The incidence of aplastic anaemia among users of ocular chloramphenicol was 0.36 cases per million weeks of treatment. The incidence among non users was 0.04 cases per million weeks.
Conclusions
An association between ocular chloramphenicol and aplastic anaemia cannot be excluded. However, the risk is less than one per million treatment courses.
Metabolism and elimination of 14C‐donepezil in healthy volunteers: a single‐dose study
Authors: Tiseo  , Perdomo  , Friedhoff  
Published: March 2003

Aim The aim of this study was to investigate the metabolism and elimination of donepezil HCl in humans, following the administration of a single 5 mg (liquid) oral dose containing a mixture of unlabelled and 14C‐labelled donepezil.

Methods This was an open‐label, non‐randomized study in healthy male volunteers (n=8). Characterization of donepezil metabolism and elimination was performed by analysing blood, urine and faecal samples collected over a 10‐day period following drug administration. Each collected sample was assayed for total radioactivity, and aliquots from specified time‐points and/or pooled samples were assayed for the presence of donepezil metabolites by thin‐layer chromatography (TLC). Donepezil concentrations in plasma were determined by HPLC.

Results Recovery of radioactivity in subject samples averaged 72% of the administered dose. Recovery of the administered dose in urine (57%) was significantly greater than that recovered in faeces (15%). Unchanged donepezil accounted for the largest component of the recovered dose in each matrix. Three metabolic pathways were identified: (i) O‐dealkylation and hydroxylation to metabolites M1 and M2, with subsequent glucuronidation to metabolites M11 and M12; (ii) hydrolysis to metabolite M4; and (iii) N‐oxidation to metabolite M6.In plasma, the parent compound accounted for about 25% of the dose recovered during each sampling period, as well as of the cumulative dose recovered. The recovered residue showed higher levels of the hydroxylated metabolites M1 and M2 than of their glucuronide conjugates M11 and M12, respectively. In urine, the parent compound accounted for 17%, on average, of the dose recovered from each pooled sample, as well as of the total recovered dose. The major metabolite was the hydrolysis product M4, followed by the glucuronidated conjugates M11 and M12. In faeces, the parent compound also predominated, although it accounted for only 1% of the recovered dose. A large percentage of the radioactivity in faeces consisted of unidentified very polar metabolites, which were retained at the TLC origin. Of the extracted metabolites, the hydroxylation products M1 and M2 were the most abundant, followed by the hydrolysis product M4 and the N‐oxidation product M6.

Conclusions Donepezil is hepatically metabolized and the predominant route for the elimination of both parent drug and its metabolites is renal, as 79% of the recovered dose was found in the urine with the remaining 21% found in the faeces. Moreover, the parent compound, donepezil, is the predominant elimination product in urine. The major metabolites of donepezil include M1 and M2 (via O‐dealkylation and hydroxylation), M11 and M12 (via glucuronidation of M1 and M2, respectively), M4 (via hydrolysis) and M6 (via N‐oxidation).
Population pharmacokinetics of methadone in opiate users: characterization of time‐dependent changes
Authors: Rostami‐Hodjegan Amin , Wolff Kim , Hay Alastair W. M. , Raistrick Duncan , Calvert Robert , Tucker Geoffrey T. 
Published: March 2003

Aims Although methadone is widely used to treat opiate dependence, guidelines for its dosage are poorly defined. There is increasing evidence to suggest that a strategy based on plasma drug monitoring may be useful to detect non‐compliance. Therefore, we have developed a population‐based pharmacokinetic (POP‐PK) model that characterises adaptive changes in methadone kinetics.Methods Sparse plasma rac‐methadone concentrations measured in 35 opiate‐users were assessed using the P‐Pharm software. The final structural model comprised a biexponential function with first‐order input and allowance for time‐dependent change in both clearance (CL) and initial volume of distribution (V  ). Values of these parameters were allowed to increase or decrease exponentially to an asymptotic value.Results Increase in individual values of CL and increase or decrease in individual values of V with time was observed in applying the model to the experimental data.Conclusions A time‐dependent increase in the clearance of methadone is consistent with auto‐induction of CYP3A4, the enzyme responsible for much of the metabolism of the drug. The changes in V  with time might reflect both up‐ and down‐regulation of α1‐acid glycoprotein, the major plasma binding site for methadone. By accounting for adaptive kinetic changes, the POP‐PK model provides an improved basis for forecasting plasma methadone concentrations to predict and adjust dosage of the drug and to monitor compliance in opiate‐users on maintenance treatment.
Birth outcome following maternal use of metoclopramide
Authors: Sørensen Henrik Toft , Nielsen Gunnar Lauge , Christensen Kaare , Tage‐jensen Ulrik , Ekbom Ers , Baron John , Group The Euromap study 
Published: March 2003

Aims
Metoclopramide is an antiemetic drug used widely during pregnancy for nausea and vomiting. Because of its frequent use any adverse effects on infant health would have major public health implications. We therefore examined the safety of metoclopramide during pregnancy.
Methods
Using the Pharmaco‐Epidemiological Prescription Database of North Jutland County, we identified 309 women with singleton pregnancies who had prescriptions for metoclopramide fom 1 January 1991 to 31 December 1996. Information on malformations, birth weight, preterm deliveries and stillbirth were compared with 13 327 references who did not receive prescriptions of any kind during pregnancy.
Results
Mean birth weight among exposed women was 3480 g compared with 3470 g among nonexposed. Based on logistic regression models no major differences in the risk were found concerning malformations (OR= 1.11; 95% confidence interval (CI): 0.6–2.1); low birth weight (OR= 1.79; 95% CI: 0.8–3.9) or preterm delivery (OR= 1.02; 95 CI: 0.6–1.7).
Conclusions
We could not document any association between the use of metoclopramide during pregnancy and adverse pregnancy outcome. Because of the limited power of our study further research is required.
Single dose methodology to assess the influence of an α1‐adrenoceptor antagonist on uroflowmetric parameters in patients with benign prostatic hyperplasia
Authors: Curtis S. P. , Eardley I. , Boyce M. , Larson P. , Haesen R. , Gottesdiener K. , Gertz B. J. 
Published: March 2003

Aims
To establish methodology which rapidly and reliably assesses the effect of an α1‐adrenoceptor antagonist on peak urine flow rates in men with benign prostatic hyperplasia (BPH). This methodology could then be applied to screening new drugs to treat BPH.
Methods
Twenty‐five patients with BPH enrolled in a double‐blind, placebo‐controlled, two‐period crossover study. Patients were either withdrawn from their current α1‐adrenoceptor antagonist therapy (n = 22) or were untreated prestudy (n = 3) and all met prespecified uroflowmetric criteria including: (1) a peak urine flow rate (Qmax) < 12 ml s−1 off therapy (or  < 10 ml s−1 if untreated prestudy) and (2) a decrease in peak urine flow rate (Qmax) of > 2 ml s−1 after withdrawal from therapy. Study treatment consisted of tamsulosin 0.4 mg (or matching placebo) once daily for 8 days in a two‐period crossover. Uroflowmetry was performed predose and once postdose (4.5–5.5 h postdose) on day 1, and once postdose (4.5–5.5 h postdose) on day 8 of each treatment period.
Results
After a single dose of tamsulosin, the least‐square mean difference between tamsulosin and placebo in the change from baseline Qmax was 2.8 ml s−1 (P = 0.017 vs placebo). After 8 days dosing of tamsulosin, the least‐square mean difference between tamsulosin and placebo in the change from baseline Qmax was also 2.8 ml s−1 (P = 0.044 vs placebo). Additionally, there was no significant difference observed between the single and multiple dose results (P > 0.200 for between group difference).
Conclusions
Both single and multiple doses of tamsulosin 0.4 mg increased Qmax in men with BPH. A single dose produced a comparable response to multiple dose administration. The magnitude of the effect was greater than the effect generally seen in longer term clinical trials, but this difference may be explained by the patient population in this study which was preselected for ‘responsiveness’ to an α1‐adrenoceptor antagonist. These results support the utility of single dose uroflowmetric measurements in rapidly providing preliminary data on new investigational agents, specifically agents which act to increase urine flow in men with BPH. However, clinical efficacy would still need to be confirmed with longer term clinical trials.