bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic monitoring device event modelling on an individual‐subject basis using adaptive Poisson regression
Authors: Knafl George J. , Fennie Kristopher P. , Bova Carol , Dieckhaus Kevin , Williams Ann B. 
Published: February 2004

AbstractAn adaptive approach to Poisson regression modelling is presented for analysing event data from electronic devices monitoring medication‐taking. The emphasis is on applying this approach to data for individual subjects although it also applies to data for multiple subjects. This approach provides for visualization of adherence patterns as well as for objective comparison of actual device use with prescribed medication‐taking. Example analyses are presented using data on openings of electronic pill bottle caps monitoring adherence of subjects with HIV undergoing highly active antiretroviral therapies. The modelling approach consists of partitioning the observation period, computing grouped event counts/rates for intervals in this partition, and modelling these event counts/rates in terms of elapsed time after entry into the study using Poisson regression. These models are based on adaptively selected sets of power transforms of elapsed time determined by rule‐based heuristic search through arbitrary sets of parametric models, thereby effectively generating a smooth non‐parametric regression fit to the data. Models are compared using k‐fold likelihood cross‐validation. Copyright © 2004 John Wiley & Sons, Ltd.
Comparison of Bayesian, classical, and heuristic approaches in identifying acute disease events in lung transplant recipients
Authors: Troiani John S. , Carlin Bradley P. 
Published: February 2004

AbstractThis study compares a typical heuristic algorithm with classical and Bayesian regression models in ascertaining the presence of acute bronchopulmonary disease events in lung transplant recipients. These models attempt to predict whether an epoch will end in an event, based on the preceding two weeks of data. The data consist of 150 two‐week epochs of daily to biweekly spirometry and symptom covariates for 30 subjects over 60 subject‐years. Seventy‐five ‘event’ epochs end on a day when an acute bronchopulmonary disease event is documented in the medical record; 75 randomly selected ‘non‐event’ epochs end on a day when no event is documented. The data are partitioned by randomly assigning 15 subjects for training and the remaining 15 subjects for testing. For cross‐validation, a second random partition is generated from the same data set. The statistical models are trained and tested on both partitions. For the heuristic algorithm, its historical event classifications on the same test cases are used. Classification performance on both partitions of all models is compared using receiver operating characteristic curves, sensitivity and specificity, and a Shannon information score. Data partition did not appreciably affect statistical model performance. All statistical models, unlike the heuristic algorithm, performed significantly different than chance (family significance <0.05, Pearson independence chi‐square, Bonferroni multiple correction), and better than the heuristic algorithm. The best models were Bayesian changepoint models. Through a clinically oriented discussion, a case classified by all of these algorithms is presented, suggesting the clinical usefulness of the Bayesian approach compared with the classical and heuristic approaches. Copyright © 2004 John Wiley & Sons, Ltd.
Non‐linear survival analysis using neural networks
Authors: Ripley Ruth M. , Harris Adrian L. , Tarassenko Lionel 
Published: February 2004

AbstractWe describe models for survival analysis which are based on a multi‐layer perceptron, a type of neural network. These relax the assumptions of the traditional regression models, while including them as particular cases. They allow non‐linear predictors to be fitted implicitly and the effect of the covariates to vary over time. The flexibility is included in the model only when it is beneficial, as judged by cross‐validation.Such models can be used to guide a search for extra regressors, by comparing their predictive accuracy with that of linear models. Most also allow the estimation of the hazard function, of which a great variety can be modelled.In this paper we describe seven different neural network survival models and illustrate their use by comparing their performance in predicting the time to relapse for breast cancer patients. Copyright © 2004 John Wiley & Sons, Ltd.
Sensitivity analyses for unmeasured confounding assuming a marginal structural model for repeated measures
Authors: Brumback Babette A. , Hernán Miguel A. , Haneuse Sebastien J. P. A. , Robins James M. 
Published: February 2004

AbstractRobins introduced marginal structural models (MSMs) and inverse probability of treatment weighted (IPTW) estimators for the causal effect of a time‐varying treatment on the mean of repeated measures. We investigate the sensitivity of IPTW estimators to unmeasured confounding. We examine a new framework for sensitivity analyses based on a nonidentifiable model that quantifies unmeasured confounding in terms of a sensitivity parameter and a user‐specified function. We present augmented IPTW estimators of MSM parameters and prove their consistency for the causal effect of an MSM, assuming a correct confounding bias function for unmeasured confounding. We apply the methods to assess sensitivity of the analysis of Hernánet al., who used an MSM to estimate the causal effect of zidovudine therapy on repeated CD4 counts among HIV‐infected men in the Multicenter AIDS Cohort Study. Under the assumption of no unmeasured confounders, a 95 per cent confidence interval for the treatment effect includes zero. We show that under the assumption of a moderate amount of unmeasured confounding, a 95 per cent confidence interval for the treatment effect no longer includes zero. Thus, the analysis of Hernánet al.is somewhat sensitive to unmeasured confounding. We hope that our research will encourage and facilitate analyses of sensitivity to unmeasured confounding in other applications. Copyright © 2004 John Wiley & Sons, Ltd.
Test for qualitative interaction in equivalence trials when the number of centres is large
Authors: Yan Xin 
Published: February 2004

AbstractWe propose a generalized testing procedure to test for qualitative interaction in equivalence trails when the number of centres is large. The proposed testing procedure allows for an adaptable definition of qualitative interaction that can take into account the total number of centres. A tuning parameter k (k 0) is introduced to quantify qualitative interaction. The testing procedure is proposed for equivalence trials with symmetric or asymmetric margins. In addition to the test procedure, we also provide explicit formulae for the power calculation. The proposed test is relatively easy to implement using any statistical software. Examples for detecting qualitative interaction are given to illustrate the method. Copyright © 2004 John Wiley & Sons, Ltd.
FGF‐2 enhances TGF‐β1‐induced periosteal chondrogenesis
Authors: Stevens Molly M. , Marini Robert P. , Martin Ivan , Langer Robert , Shastri V. Prasad 
Published: February 2004

AbstractThe use of periosteum as a cell source for the in vitro engineering of grafts for articular cartilage repair requires the development of methods to obtain high viable cell numbers in the early stages of culture. In this study, we demonstrate that the addition of a mitogen, fibroblast growth factor‐2 (FGF‐2), during the early stage of the in vitro culture of periosteum in the presence of transforming growth factor‐β1 (TGF‐β1), significantly enhances cell proliferation, which results in increased neo‐cartilage formation at later stages. Periosteal explants were cultured in vitro within alginate or agarose based gels in the presence of either FGF‐2 for the first week, TGF‐β1 for the first 2 weeks, FGF‐2 and TGF‐β1 for the first week and first 2 weeks respectively, or no added factors. Consistent with previous studies, periosteum derived neo‐chondrogenesis occurred only in the presence of TGF‐β1. The neo‐cartilage was found to contain cartilage specific proteoglycans and Type‐II collagen as determined by safranin‐O and immunohistochemical staining respectively. Further medium supplementation with FGF‐2 stimulated early cell proliferation (>3 fold higher total DNA content per explant at day 10). This resulted in a marked increase in the size of the cultured explants and in the total area of the explant staining positive for safranin‐O (from around 50% to 85%, (p < 0.05)) after 6 weeks culture. The ability to generate significant quantities of neo‐cartilage within a biocompatible and biodegradable matrix such as alginate, which lacks the immunogenicity of agarose, could open new pathways to utilizing such constructs in articular cartilage tissue engineering applications. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Referred pain is dependent on sensory input from the periphery: A psychophysical study
Authors: Laursen R.J. , Graven‐Nielsen T. , Jensen T.S. , Arendt‐Nielsen L. 
Published: February 2004

Muscle pain can be characterized by local pain and pain referred to distant somatic structures with concomitant cutaneous and deep somatosensory changes. The mechanisms responsible for referred muscle pain are poorly understood. The aim of this study was to study the origin of experimentally‐induced referred muscle pain by anaesthetizing the skin overlying the referred pain area and to quantify deep somatosensory changes in the area.Fourteen healthy subjects (mean age = 25.1 years, range 22–34 years) were included in a placebo controlled study consisting of two sessions separated by 1 week. Two stimulation needles were inserted into the right anterior tibial muscle. Electrical stimuli (1Q Hz) were delivered by a computer‐controlled constant current stimulator. The intensity required to generate referred pain was determined and the circumference of the referred pain area was marked. At the centre of the area, pressure pain threshold and pinprick perception threshold were determined. Either an anaesthetic cream (EMLA®, Astra AB, Sweden) or a placebo cream (Astra AB, Sweden) covered by an occlusive dressing was applied to the marked referred pain area for 90 min. Afterwards, a 600‐s stimulation at 150% of the referred pain threshold was induced while the VAS score of referred pain was recorded continuously. Pressure pain threshold and pinprick perception threshold were determined before, during and 5 min after the prolonged stimulation.A significantly lower referred pain visual analogue scale (VAS) score was recorded during the interval from 50 to 150s (p=0.04). The area under the referred pain VAS score vs time curve tended to be lower (22.7%) with the application of skin anaesthetic (p=0.07). The mean referred pain threshold and the mean referred pain area did not differ significantly between the two sessions (p>0.6). No difference was found in pressure pain threshold between the two treatments or between the four recordings during each session (p>0.8). Pinprick perception threshold increased significantly after EML® application (p<0.04).Decreased referred pain intensity with application of anaesthetic cream at the referred pain site indicates that referred muscle pain depends on input from the periphery (skin) in humans.
Multidisciplinary rehabilitation for chronic back pain in an outpatient setting: A controlled randomized trial
Authors: Keller S. , Ehrhardt‐Schmelzer S. , Herda C. , Schmid S. , Basler H.‐D. 
Published: February 2004

Based on existing models for pain chronicity and effective treatment strategies for patients with chronic low back pain, a multidisciplinary rehabilitation programme for an outpatient group setting was developed. The main treatment components address the patient's physical functional capacity (functional restoring), cognitive and affective processes (pain management strategies), and behavioural and ergonomical aspects (back school elements).Short‐term (immediately after intervention) and long‐term effects (at 6‐months follow‐up) of the intervention were assessed in a randomized controlled study. Dependent variables were pain measures, functional capacity, disability, muscular strength and endurance, pain and posture‐related self‐efficacy, attitudes, depression, well‐being, beiavioural habits and posture assessed by a standardized behavioural observation method.Immediately after the intervention, patients in the treatment group (n= 36) showed significant improvement over patients in the control group (n= 29) in all variables except depression and muscular strength and endurance. At 6‐months follow‐up, compared to pretreatment scores, patients continued to show beneficial effects in pain intensity and frequency, posture, posture‐related self‐efficacy and well‐being. In contrast to post‐treatment results, there were also significant improvements in strength and endurance.Overall results testify to the effectiveness of the intervention programme. Future studies (with larger sample sizes) should aim at a further improvement of functional capacity and disability perception, an analysis of differential treatment effects, and strategies for an improved long‐term maintenance of the changes induced by the programme.
Pain management of arteriovenous fistula cannulation in haemodialysis children: Efficacy of EMLA anaesthetic cream
Authors: Benini F. , Gobber D. , Lago P. , Agosto C. , Carli G. , Zacchello F. 
Published: February 2004

The aim of the present study was to evaluate the efficacy of EMLA cream (containing a eutectic mixture of local anaesthetics) in controlling pain due to arteriovenous fistula cannulation in teenagers undergoing chronic haemodialysis. The study was conducted in two phases, one prospective, the other a blind randomized trial, at the Paediatric Haemodialysis service of the Paediatrics Department of Padua University, Italy. It involved six teenagers, aged 12–18 years. Pain was measured using the visual analogue scale, indirect evaluation by nurses and a four‐category verbal rating scale.Results showed that: (1) the visual analogue scale calls for an adequate training period; and (2) the EMLA cream might be effective in controlling cannulation‐related pain but emotional factors, such as uncontrolled fear and stress, can interfere with the global efficacy of the analgesic approach.
Morphine use and pharmacokinetics in patients with chest pain due to suspected or definite acute myocardial infarction
Authors: Everts B. , Karlson B.W. , Herlitz J. , Hedner T. 
Published: February 2004

The characteristics of chest pain due to suspected acute myocardial infarction and morphine use during the first 3 hospital days are described in a population of 2988 consecutive patients admitted to hospital.The duration of pain was usually less than 24h (mean 20.9±0.55h), and only 24.8% of patients experienced chest pain of longer duration. The majority of patients had only one attack of pain, but 34.4% experienced four or more attacks during hospitalization. A mean morphine dose of 6.7±0.2mg was administered over the 3 hospitalization days, but surprisingly 52.4% of all patients required no morphine analgesia at all. Independent predictors of an increased morphine consumption were initial degree of suspicion of acute myocardial infarction, ST changes on admission ECG, male sex, a history of angina pectoris and a history of congestive heart failure. In a separate pharmacokinetic/pharmacodynamic study in 10 patients, plasma concentrations of morphine and its major metabolites, morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G), were measured after intravenous administration of morphine. In this patient group, terminal half‐life of unchanged morphine ranged from 0.77 to 3.22h. M3G and M6G plasma concentrations increased gradually up to 60–90 min after the intravenous morphine injection.Initial pain intensity by numerical rating scale was 6.6±0.6 (arbitrary units), and after morphine administration, there was a rapid and significant decrease in pain intensity. After 20 min, pain relief was 69±11% and remained at this level during the following 8 h observation period.It is concluded that the need for morphine administration in patients with suspected or definite acute myocardial infarction, differs among subgroups of patients and, in particular, higher doses are needed in those with a strong suspicion of myocardial infarction at arrival. When intravenous morphine is given, it attains full effect 20 min after injection. Furthermore, the active morphine metabolites M3G and M6G appear rapidly in thecirculation, which could influence the analgesic response to morphine treatment.
Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome
Authors: Andersson M. , Bagby J.R. , Dyrehag L.‐E. , Gottfries C.‐G. 
Published: February 2004

Positive results of pilot studies of the effect of staphylococcus toxoid vaccine in patients with fibromyalgia and chronic fatigue syndrome were the incitement to the present, placebo‐controlled study. It included 28 patients who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome. The effect of vaccination with a staphylococcus toxoid was compared with the effect of injections of sterile water. Psychometric assessment was made using 15 items from the comprehensive psychopathological rating scale (CPRS), Zung's self‐rating depression scale and clinical global impressions (CGI). The visual analogue scale (VAS) was used to measure pain levels, and a hand‐held electronic pressure algometer was used to measure pressure pain thresholds.Significant improvement was seen in seven of the 15 CPRS items in the vaccine group when pretreatment values were compared to post‐treatment values. In CPRS ‘fatiguability';, there were significant intergroup differences, and in CPRS ‘pain'; intergroup differences bordered on significance. There was no significant improvement in CPRS items in the placebo group. Clinical global impressions showed significant improvement in the vaccine‐treated group, and VAS did so in both groups.In a follow‐up study of 23 patients, the vaccine treatment was continued for 2–6 years. Fifty percent were rehabilitated successfully and resumed half‐time or full‐time work.The results of this study support the authors' hypothesis that treatment with staphylococcus toxoid may be a fruitful strategy in patients with fibromyalgia and chronic fatigue syndrome.
Upside assay sensitivity in a dental pain model
Authors: Breivik E.K. , Haanaes H.R. , Barkvoll P. 
Published: February 2004

The extent of surgical trauma was related to postoperative pain intensity in a previous study. However, more extensive surgical procedures with higher baseline pain intensity did not appear to influence the ability to document the additive analgesic effect of codeine when given with paracetamol, partly due to large interindividual variation in baseline pain intensity. The aim of the present study was to attempt to improve upside assay sensitivity in this dental pain model by: (1) selecting patients with high baseline pain intensity; and (2) closer supervision of outpatients' drug intake and compliance with protocol. Only patients with baseline pain ≥ 50 on a 100 mm visual analogue scale after wisdom tooth surgery were included. Twenty patients were given paracetamol 1000 mg with or without codeine 60 mg in repeated doses in a randomized and double‐blind manner. Intake of the first dose of test medication and its effects were closely supervised, while the two following doses were taken at 3‐h intervals after the patient had left the clinic. Pain intensity was measured with the visual analogue scale for 8 h. More pain relief was revealed when codeine 60 mg was added to paracetamol 1000 mg on the following measures of effect: change of pain intensity with time (p<0.05, MannWhitney), sum of pain intensities (p=0.019), pain intensity difference (p≤0.05), sum of pain intensity differences (p<0.05), pain reduction index (p<0.05) and global‐evaluation score (p=0.006).The study confirms that this dental pain model, when controlled for sufficient and homogeneous baseline pain and patient compliance, does have sufficient upside assay sensitivity to discriminate between paracetamol with and without codeine.
Role of oxidative stress and nitric oxide in regulation of spontaneous tone in aorta of DOCA‐salt hypertensive rats
Authors: Ghosh Mahua , Wang Hui Di , McNeill J Robert 
Published: February 2004

The roles of nitric oxide (NO), superoxide anion (O2−), and hydrogen peroxide (H2O2) in the modulation of spontaneous tone were investigated in isolated aorta from deoxycorticosterone acetate (DOCA)‐salt hypertensive rats.
Increases in preload from 1 to 5 g were accompanied by increases in spontaneous tone in aortic rings from DOCA‐salt hypertensive rats but not from SHAM‐normotensive rats.
Tone was higher in endothelium‐denuded aortic rings than in endothelium‐intact vessels. Inhibition of nitric oxide synthase (NOS) with 300 μM NG‐nitro‐L‐arginine methyl ester (L‐NAME) increased spontaneous tone.
Basal O2− generation was higher in aortic rings from DOCA‐salt hypertensive rats than in those from SHAM‐normotensive rats. Stretch increased O2− levels even further in the DOCA‐salt group. In rings isolated from DOCA‐salt hypertensive rats, administration of the O2− scavenger, superoxide dismutase (SOD, 150 U ml−1), or the nicotinamide adenine dinucleotide phosphate (NADPH)‐oxidase inhibitor, apocynin (100 μM), completely abolished the development of spontaneous tone in endothelium‐intact aortic rings but not in endothelium‐denuded or in L‐NAME‐treated rings. SOD and apocynin decreased the generation of O2− in endothelium‐intact, endothelium‐denuded, and L‐NAME‐treated aortic rings.
Oral treatment of DOCA‐salt hypertensive rats with the O2− scavengers, tempol or tiron, or with apocynin for 3 weeks prevented the development of hypertension and abolished the increases in O2− generation and spontaneous tone.
Administration of catalase (1000 U ml−1) to aortic rings increased spontaneous tone in vessels from DOCA‐salt hypertensive rats.
Administration of the cyclooxygenase (COX) inhibitor, valeroyl salicylate, or the thromboxane/prostaglandin antagonist, SQ 29548, to aortic rings abolished tone.
The results suggest that NO plays a major role in preventing the generation of spontaneous tone in isolated aortic rings from DOCA‐salt hypertensive rats. NADPH‐oxidase‐derived O2− enhanced spontaneous tone by inactivating NO. Endogenous H2O2 appears to mitigate the increase in tone. In addition, a COX component may also contribute to spontaneous tone.

British Journal of Pharmacology (2004) 141, 562–573. doi:10.1038/sj.bjp.0705557