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Clinical Interest (clinical + interest)
Selected AbstractsClinical interest: a study of the influence on general practitioners' prescribing,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2007Dorte Gilså Hansen MD Abstract Purpose To analyse the association between general practitioners' clinical interest and prescribing rates in four clinical areas: dyspepsia, depression, headache and diabetes. Methods Data concerning general practitioners' prescribing during 2004 were retrieved from a pharmacy database and linked with data from a physician questionnaire and the National Health Insurance Register. To counterbalance differences in practice populations all 1-year prevalences of prescribing were standardised according to age and gender. Participants were asked ,To what extent do you find the following areas interesting from a professional point-of- view?' Four rating categories were used. The association between clinical interest and standardised prescribing rates was investigated using logistic regression, the Kruskal-Wallis test and a trend test. Results A total of 68 (72%) single-handed general practitioners representative of the total group completed the questionnaire. We observed a two-fold ratio between the 90% and the 10% percentiles of the 1-year prevalences of antisecretory drugs, antidepressants, migraine drugs as well as anti-diabetics. The variation in prescribing of antidepressant and antisecretory drugs was far above chance level. No significant association with clinical interest could, however, be observed for any of the four clinical areas. Conclusion General practitioners' prescribing of the four classes of medical drugs varied considerably. However, only part of this variation was based on chance. This study did not confirm our hypothesis that general practitioners' level of clinical interest in one area corresponds with their prescribing of drugs used within that area. Copyright © 2007 John Wiley & Sons, Ltd. [source] A decreased positivity for CD90 on human mesenchymal stromal cells (MSCs) is associated with a loss of immunosuppressive activity by MSCs,CYTOMETRY, Issue 3 2009Diana Campioni Abstract Biologic and clinical interest in human mesenchymal stromal cells (hMSC) has risen over the last years, mainly due to their immunosuppressive properties. In this study, we investigated the basis of immunomodulant possible variability using hMSC from different sources (amniotic membrane, chorion, and bone marrow from either healthy subjects or patients with hematological malignancies, HM) and having discordant positivity for several immunological markers. The CD90+ hMSC reduced lymphoproliferative response in phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMC) via sHLA-G and IL-10 up-modulation. On the contrary, hMSC showing a significantly lower expression for CD90 antigen, elicited a lymphoproliferative allogeneic response in PHA/PBMCs without any increase in soluble HLA-G and IL-10 levels. These data seems to suggest that CD90 molecule may be considered a novel predictive marker for hMSC inhibitory ability, and might cooperate with HLA-G molecule in regulating suppressive versus stimulatory properties of hMSC. These results may have clinical implication in either transplantation or in regenerative medicine fields. © 2008 Clinical Cytometry Society [source] Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTP,S binding in the dorsal horn of the spinal cord of noninflamed and inflamed ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000L. J. Drew Abstract The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5,-[,-[35S]thio]triphosphate ([35S]GTP,S) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300,800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTP,S binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTP,S binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states. [source] In vitro Study of the Antibacterial Activity of Bioactive Glass-ceramic Scaffolds,ADVANCED ENGINEERING MATERIALS, Issue 7 2009Marta F. Gorriti Staphylococcus aureus is an opportunistic pathogen of major clinical interest for its high prevalence in biomaterial-related infections. This experimental study provides the first evidence in vitro that bioactive glass-ceramic scaffolds made from both 45S5 Bioglass® and from boron containing bioactive glass (45S5.2B) as well as their ionic dissolution products do no exhibit antibacterial effect against several strains of S. aureus. [source] Application of pharmacokinetic modelling to the routine therapeutic drug monitoring of anticancer drugsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2002Annick Rousseau Abstract Over the last 10 years, proofs of the clinical interest of therapeutic drug monitoring (TDM) of certain anticancer drugs have been established. Numerous studies have shown that TDM is an efficient tool for controlling the toxicity of therapeutic drugs, and a few trials have even demonstrated that it can improve their efficacy. This article critically reviews TDM tools based on pharmacokinetic modelling of anticancer drugs. The administered dose of anticancer drugs is sometimes adjusted individually using either a priori or a posteriori methods. The most frequent clinical application of a priori formulae concerns carboplatin and allows the computation of the first dose based on biometrical and biological data such as weight, age, gender, creatinine clearance and glomerular filtration rate. A posteriori methods use drug plasma concentrations to adjust the subsequent dose(s). Thus, nomograms allowing dose adjustment on the basis of blood concentration are routinely used for 5-fluorouracil given as long continuous infusions. Multilinear regression models have been developed, for example for etoposide, doxorubicin, carboplatin, cyclophosphamide and irinotecan, to predict a single exposure variable [such as area under concentration,time curve (AUC)] from a small number of plasma concentrations obtained at predetermined times after a standard dose. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided, is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Unlike the other a posteriori methods, Bayesian estimation is based on population pharmacokinetic studies and can take into account the effects of different individual factors on the pharmacokinetics of the drug. Bayesian estimators have been used to determine maximum tolerated systemic exposure thresholds (e.g. for topotecan or teniposide) as well as for the routine monitoring of drugs characterized by a very high interindividual pharmacokinetic variability such as methotrexate or carboplatin. The development of these methods has contributed to improving cancer chemotherapy in terms of patient outcome and survival and should be pursued. [source] Peripheral T-cell lymphoma gene expression profilesHEMATOLOGICAL ONCOLOGY, Issue 3 2006B. Martinez-Delgado Abstract Expression profiling using DNA microarrays has been very helpful to improve our knowledge of the pathobiology of many tumour types, including lymphomas. Peripheral T-cell lymphomas (PTCL) constitute an heterogeneous group of tumours with different morphologic, immunophenotypic, and clinical characteristics. Their complexity and their low frequency in the western countries have made difficult the identification of molecular events responsible of the development of these tumours. The first studies on expression profiling of PTCL have also revealed heterogeneity at this level, mainly regarding the PTCL NOS subgroup. Different molecular subgroups within PTCL unspecified have been identified associated to different expression profiles. However, the clinical significance of this molecular sub-classification remains to be probed in studies involving larger number of samples. In addition, the expression level of NF-kB pathway genes allowed to differentiate two PTCL subgroups, and this difference could have clinical interest. In general, PTCL expression profiles are difficult to interpret due to the significant proportion of other infiltrating cells accompanying the tumour. However, microarrays are being a helpful tool in the initial task of dissecting the PTCL expression profile. Copyright © 2006 John Wiley & Sons, Ltd. [source] The human hippocampus at 7 T,In vivo MRIHIPPOCAMPUS, Issue 1 2009Jens M. Theysohn Abstract The human hippocampus plays a central role in various neuropsychiatric disorders, such as temporal lobe epilepsy (TLE), Alzheimer's dementia, mild cognitive impairment, and schizophrenia. Its volume, morphology, inner structure, and function are of scientific and clinical interest. Magnetic resonance (MR) imaging is a widely employed tool in neuroradiological workup regarding changes in brain anatomy, (sub-) volumes, and cerebral function including the hippocampus. Gain in intrinsic MR signal provided by higher field strength scanners and concomitant improvements in spatial resolution seem highly valuable. An examination protocol permitting complete, high-resolution imaging of the human hippocampus at 7 T was implemented. Coronal proton density, T2, T2*, and fluid-attenuated inversion recovery contrasts were acquired as well as an isotropic 3D magnetization-prepared rapid acquisition gradient-echo (500 ,m isotropic voxel dimension, noninterpolated). Observance of energy deposition restrictions within acceptable scan times remained challenging in the acquisition of thin, spin-echo-based sections. At the higher resolution enabled by 7 T, demarcation of the hippocampus and some internal features including gray/white matter differentiation and depiction of the hippocampal mantle becomes much more viable when compared with 1.5 T; thus, in the future, this imaging technology might help in the diagnosis of subtle hippocampal changes. © 2008 Wiley-Liss, Inc. [source] Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database,,HUMAN MUTATION, Issue 6 2007Audrey Petitjean Abstract The tumor suppressor gene TP53 is frequently mutated in human cancers. More than 75% of all mutations are missense substitutions that have been extensively analyzed in various yeast and human cell assays. The International Agency for Research on Cancer (IARC) TP53 database (www-p53.iarc.fr) compiles all genetic variations that have been reported in TP53. Here, we present recent database developments that include new annotations on the functional properties of mutant proteins, and we perform a systematic analysis of the database to determine the functional properties that contribute to the occurrence of mutational "hotspots" in different cancer types and to the phenotype of tumors. This analysis showed that loss of transactivation capacity is a key factor for the selection of missense mutations, and that difference in mutation frequencies is closely related to nucleotide substitution rates along TP53 coding sequence. An interesting new finding is that in patients with an inherited missense mutation, the age at onset of tumors was related to the functional severity of the mutation, mutations with total loss of transactivation activity being associated with earlier cancer onset compared to mutations that retain partial transactivation capacity. Furthermore, 80% of the most common mutants show a capacity to exert dominant-negative effect (DNE) over wild-type p53, compared to only 45% of the less frequent mutants studied, suggesting that DNE may play a role in shaping mutation patterns. These results provide new insights into the factors that shape mutation patterns and influence mutation phenotype, which may have clinical interest. Hum Mutat 28(6), 622,629, 2007. Published 2007 Wiley-Liss, Inc. [source] Synthesis of (R)- and (S)-[O-methyl - 11C]N -[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]- N,-(4-methoxy-phenyl)-urea as candidate high affinity ,1 -adrenoceptor PET radioligandsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2005Stefan Wagner Abstract Molecular imaging and quantification of myocardial ,1 -adrenoceptor (AR) rather than total , -AR density is of great clinical interest since cardiac biopsy studies suggest that myocardial ,1 -AR density is reduced in patients with chronic heart failure whereas cardiac ,2 -AR density may vary. Positron emission tomography (PET), with appropriate radioligands, offers the possibility to assess , -AR density non-invasively in humans. However, no PET radioligand for the selective imaging of cardiac ,1 -ARs is clinically available. Here some derivatives of the well characterized ,1 -AR selective antagonist, ICI 89,406, namely the enantiomers of N -[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]- N,-(4-hydroxy-phenyl)-urea (5a and 5b) were synthesized and evaluated in vitro. The (R)-isomer 5a was more ,1 -selective but has lower affinity than its (S)-enantiomer 5b (,1 -AR selectivity: 6100 vs 1240; ,1 -affinity: K1 = 0.288 nM vs K1 = 0.067 nM). Etherification of the analogous desmethyl precursors, 5e and 5f, respectively, with [11C]iodomethane gave 11C-labelled versions of 5a and 5b, namely 5g and 5h, in 44 ± 5% radiochemical yield (decay-corrected) and 97.4 ± 1.3% radiochemical purity with specific radioactivities of 26.4 ± 9.4 GBq/µmol within 41.2 ± 3.4 min from the end of bombardment (n = 14). 5g and 5h are now being evaluated as candidate radioligands for myocardial ,1 -ARs. Copyright © 2005 John Wiley & Sons, Ltd. [source] Surface protein patterns govern morphology, proliferation, and expression of cellular markers but have no effect on physiological properties of cortical precursor cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2008Anna K. Magnusson Abstract The ability to differentiate and give rise to neurons, astrocytes, and oligodendrocytes is an inherent feature of neural stem cells, which raises hopes for cell-based therapies of neurodegenerative diseases. However, there are many hurdles to cross before such regimens can be applied clinically. A considerable challenge is to elucidate the factors that contribute to neural differentiation. In this study, we evaluated the possibility of steering neuronal maturation by growing cortical precursor cells on microscale surface patterns of extracellular matrix (ECM) proteins. When the cells were encouraged to extend processes along lines of ECM proteins, they displayed a much more mature morphology, less proliferation capacity, and greater expression of a neuronal marker in comparison with cells grown in clusters on ECM dots. This implied that the growth pattern alone could play a crucial role for neural differentiation. However, in spite of the strikingly different morphology, when performing whole-cell patch-clamp experiments, we never observed any differences in the functional properties between cells grown on the two patterns. These results clearly demonstrate that morphological appearances are not representative measures of the functional phenotype or grade of neuronal maturation, stressing the importance of complementary electrophysiological evidence. To develop successful transplantation therapies, increased cell survival is critical. Because process-bearing neurons are sensitive and break easily, it would be of clinical interest to explore further the differentiating capacity of the cells cultured on the ECM dot pattern, described in this article, which are devoid of processes but display the same functional properties as neurons with mature morphology. © 2008 Wiley-Liss, Inc. [source] Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: Effects of brain-derived neurotrophic factor and fibroblast growth factorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2007Josef M. Miller Abstract The extent to which neurotrophic factors are able to not only rescue the auditory nerve from deafferentation-induced degeneration but also promote process regrowth is of basic and clinical interest, as regrowth may enhance the therapeutic efficacy of cochlear prostheses. The use of neurotrophic factors is also relevant to interventions to promote regrowth and repair at other sites of nerve trauma. Therefore, auditory nerve survival and peripheral process regrowth were assessed in the guinea pig cochlea following chronic infusion of BDNF + FGF1 into scala tympani, with treatment initiated 4 days, 3 weeks, or 6 weeks after deafferentation from deafening. Survival of auditory nerve somata (spiral ganglion neurons) was assessed from midmodiolar sections. Peripheral process regrowth was assessed using pan-Trk immunostaining to selectively label afferent fibers. Significantly enhanced survival was seen in each of the treatment groups compared to controls receiving artificial perilymph. A large increase in peripheral processes was found with BDNF + FGF1 treatment after a 3-week delay compared to the artificial perilymph controls and a smaller enhancement after a 6-week delay. Neurotrophic factor treatment therefore has the potential to improve the benefits of cochlear implants by maintaining a larger excitable population of neurons and inducing neural regrowth. © 2007 Wiley-Liss, Inc. [source] Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1cJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2003Shigeki Ohmachi Abstract Degeneration of dopaminergic neurons of the substantia nigra causes Parkinson's disease. Therefore, neurotrophic factors for dopaminergic neurons are of substantial clinical interest. Fibroblast growth factor (FGF)-20 preferentially expressed in the substantia nigra pars compacta (SNPC) of the rat brain significantly enhanced the survival of midbrain dopaminergic neurons. Here we examined the mechanism of action of FGF-20 on dopaminergic neurons. FGF-20 slightly enhanced the survival of total neurons of the midbrain, indicating that it preferentially enhanced the survival of dopaminergic neurons. FGF receptor (FGFR)-1c was found to be expressed abundantly in dopaminergic neurons in the SNPC but at much lower levels in neurons of other midbrain regions by in situ hybridization. FGF-20 was also found to bind FGFR-1c with high affinity with the BIAcore system. Furthermore, FGF-20 activated the mitogen-activated protein kinase (MAPK) pathway, which is the major intracellular signaling pathway of FGFs. Both the FGFR-1 inhibitor SU5402 and the MAPK pathway inhibitor PD98059 also significantly inhibited the activation of the MAPK pathway by FGF-20 and the neurotrophic activity of FGF-20. The present findings indicate that the activation of the MAPK pathway by FGF-20 signaling through FGFR-1c plays important roles in the survival of dopaminergic neurons in the SNPC. © 2003 Wiley-Liss, Inc. [source] Initial biofilm formation of Streptococcus sobrinus on various orthodontics appliancesJOURNAL OF ORAL REHABILITATION, Issue 11 2004D. Steinberg summary, Biofilms accumulate on hard and soft surface in the oral cavity. Accumulation of biofilms on orthodontic appliance bear scientific and clinical interest. The objection of this study was to examine the formation of dental biofilm by Streptococcus sobrinus on different types of orthodontics appliances, using a model consisting of host and bacterial constituents. The adsorption pattern of saliva to the orthodontics appliances was determined by means of gel electrophoresis coupled with computerized densitometry techniques. The amount of salivary proteins adsorbed onto the surfaces was measured using the Bradford method. Sucrose-dependent bacterial adhesion to the saliva-coated orthodontics appliances was tested by radioactive-labelled S. sobrinus. Our results show different adsorption patterns of salivary proteins to the various orthodontic appliances as modules, brackets, springs and intra oral elastics. Modules and brackets demonstrated the most affinity to salivary proteins. A surface dependent adhesion profile was recorded, showing a high affinity of albumin and amylase to modules. Bacterial accumulation was the highest on modules compared with springs which demonstrated the least bacterial adhesion. Our study demonstrates the specificity of biofilm formation on the different orthodontic appliances. Formation of a variety of dental biofilms has a significant impact on the progression of dental diseases associated with orthodontic treatment. [source] Oral mucosal versus cutaneous sensory testing: a review of the literatureJOURNAL OF ORAL REHABILITATION, Issue 10 2002R. Jacobs summary, The innervation of skin and oral mucosa plays a major physiological role in exteroception. It also has a clinical interest as illustrated by sensory changes after neurosurgical procedures. These sensory changes often rely only on the patients' subjective reports, although objective assessments are possible. This review compares the neurophysiological features of the trigeminal sensory pathways with those of cutaneous sensory innervation. In this review, three receptor groups will be discussed: mechanoreceptors, thermoreceptors and nociceptors. Differences between receptors in the glabrous skin, the hairy skin and the oral mucosa will be highlighted. Sensory testing devices have been developed to quantify psychophysiological parameters such as the threshold level for receptor activation upon mechanical stimulation, but such devices have been merely developed to determine the threshold of skin receptors (tactile, thermal). Later on, some have been adapted to suit the particularities of the oral environment. This review attempts to compare the available literature on test devices for oral versus cutaneous tactile function. It summarizes what is common or rather particular to the devices used to study either cutaneous or oral receptors. [source] Is growth hormone a radioprotective agent?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2006SB Tekin Abstract There is currently substantial clinical interest in growth hormone (GH) as a protective agent against radiation-related normal tissue injury. To further assess the potential radiation injury-preventive effects of GH, these effects were studied in rats by using a radiation-induced skin injury model. Group 1 received neither GH nor irradiation (control group). Group 2 received 30 Gy of gamma irradiation as a single dose to the right hind legs of the rats (radiation group). Group 3 and 4 received the same irradiation plus either 0.01 U/kg/day GH (RT + 0.01 GH group) or 0.02 U/kg/day GH (RT + 0.02 GH group) subcutaneously. Clinically and histopathologically, acute skin reactions were assessed by two independent experts in radiation oncology and pathology, respectively. Irradiation increased dermatitis in rats when compared with the control group. The severity of radiodermatitis in the rats in the RT + 0.01 GH and RT + 0.02 GH groups was significantly lower than that in the RT group; radiodermatitis developed earlier in the RT group than in the other groups. GH was efficacious in preventing epidermal atrophy, dermal degeneration such as oedema and collagen fibre loss, and hair follicle atrophy, but not better than in the control group. These results are preliminary to studies that will be performed with higher doses of GH in radiation-treated cancer patients, with the aim of reducing radiation-induced toxicity. [source] Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized studyLIVER TRANSPLANTATION, Issue 6 2006Luca Aldrighetti Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response. Liver Transpl 12:941,949, 2006. © 2006 AASLD. [source] Expression of CD68+ tumor-associated macrophages in patients with diffuse large B-cell lymphoma and its relation to prognosisPATHOLOGY INTERNATIONAL, Issue 8 2008Sverker Hasselblom Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies have shown that the presence of a high number of TAM is related to poor prognosis, suggesting that TAM predominantly exert pro-tumoral activity. The prognostic role of TAM in patients with diffuse large B-cell lymphoma (DLBCL), however, is so far unknown. Therefore, TAM were immunohistochemically stained with a CD68 antibody in a retrospective, population-based study including 176 DLBCL patients treated with curative intent. With the exception that patients >60 years of age had a larger number of CD68+ cells (1143 vs 1018 cells/mm2; P = 0.05), no significant differences were found between the number of CD68+ cells and other clinical factors. Similarly, germinal center B-cell (GCB)/non-GCB immunophenotype or low/high Ki-67 percentage were not associated with CD68 expression. Finally, no significant correlation was found between the number of CD68+ cells and progression-free survival (P = 0.34) or overall survival (P = 0.94). These data indicate that the pro-tumor effect of TAM has limited clinical relevance in DLBCL patients, which could imply that therapeutic strategies aimed at enhancing their anti-tumor activity are of continuous clinical interest. [source] Clinical interest: a study of the influence on general practitioners' prescribing,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2007Dorte Gilså Hansen MD Abstract Purpose To analyse the association between general practitioners' clinical interest and prescribing rates in four clinical areas: dyspepsia, depression, headache and diabetes. Methods Data concerning general practitioners' prescribing during 2004 were retrieved from a pharmacy database and linked with data from a physician questionnaire and the National Health Insurance Register. To counterbalance differences in practice populations all 1-year prevalences of prescribing were standardised according to age and gender. Participants were asked ,To what extent do you find the following areas interesting from a professional point-of- view?' Four rating categories were used. The association between clinical interest and standardised prescribing rates was investigated using logistic regression, the Kruskal-Wallis test and a trend test. Results A total of 68 (72%) single-handed general practitioners representative of the total group completed the questionnaire. We observed a two-fold ratio between the 90% and the 10% percentiles of the 1-year prevalences of antisecretory drugs, antidepressants, migraine drugs as well as anti-diabetics. The variation in prescribing of antidepressant and antisecretory drugs was far above chance level. No significant association with clinical interest could, however, be observed for any of the four clinical areas. Conclusion General practitioners' prescribing of the four classes of medical drugs varied considerably. However, only part of this variation was based on chance. This study did not confirm our hypothesis that general practitioners' level of clinical interest in one area corresponds with their prescribing of drugs used within that area. Copyright © 2007 John Wiley & Sons, Ltd. [source] Reporting of minimum clinically important differences in surgical trialsANZ JOURNAL OF SURGERY, Issue 4 2009Irwin Kashani Background:, The minimum clinically important difference (MCID) is the smallest difference in outcome between the groups that would be of clinical interest. It influences the estimates that are made to determine the required sample side. The aim of this study was to explore the reporting of the MCID in surgical trials. Method:, Surgical trials that were published between January 1981 and December 2006 in five prestigious surgical journals were evaluated. Selected for study were trials that studied two groups and reported the main outcome event as a proportion. Results:, Only 21% (100/486) of the admissible surgical trials mentioned a value for the MCID when estimating the sample size. There was a trend, however, for compliance with these factors to increase during the study period. The present post-hoc calculations of the required sample size, which were based on the observed differences between the groups at the end of the study, suggested that one-third of the trials should have accrued at least fivefold the number of patients. Although reporting an estimate of the sample size was associated with the study of more patients (median sample size 145 vs 100), it was not associated with the reporting of more positive results, that is, 61% (95/155) versus 65% (214/331). Conclusion:, There has been an improvement in the proportion of surgical trials reporting formal estimates of sample size during the last three decades. But the construct of these estimates is often suspect because of a failure to provide realistic values for the MCID. [source] A Semiparametric Joint Model for Longitudinal and Survival Data with Application to Hemodialysis StudyBIOMETRICS, Issue 3 2009Liang Li Summary In many longitudinal clinical studies, the level and progression rate of repeatedly measured biomarkers on each subject quantify the severity of the disease and that subject's susceptibility to progression of the disease. It is of scientific and clinical interest to relate such quantities to a later time-to-event clinical endpoint such as patient survival. This is usually done with a shared parameter model. In such models, the longitudinal biomarker data and the survival outcome of each subject are assumed to be conditionally independent given subject-level severity or susceptibility (also called frailty in statistical terms). In this article, we study the case where the conditional distribution of longitudinal data is modeled by a linear mixed-effect model, and the conditional distribution of the survival data is given by a Cox proportional hazard model. We allow unknown regression coefficients and time-dependent covariates in both models. The proposed estimators are maximizers of an exact correction to the joint log likelihood with the frailties eliminated as nuisance parameters, an idea that originated from correction of covariate measurement error in measurement error models. The corrected joint log likelihood is shown to be asymptotically concave and leads to consistent and asymptotically normal estimators. Unlike most published methods for joint modeling, the proposed estimation procedure does not rely on distributional assumptions of the frailties. The proposed method was studied in simulations and applied to a data set from the Hemodialysis Study. [source] Ultrafiltration characteristics of pegylated proteinsBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2006Jessica R. Molek Abstract There is growing clinical interest in the use of pegylated recombinant proteins with enhanced stability, half-life, and bioavailability. The objective of this study was to develop a quantitative understanding of the ultrafiltration characteristics of a series of pegylated proteins with different degrees of pegylation. Sieving data were compared with available theoretical models and with corresponding results for the partition coefficient in size exclusion chromatography (SEC). The sieving coefficients of the pegylated proteins depended not only on the protein size and the total molecular weight of the polyethylene glycol (PEG) but also on the number of PEG chains. This is in sharp contrast to the partition coefficient in SEC, which was uniquely determined by the total molecular weight of the PEG and protein. This difference is due to the deformation and/or elongation of the PEG chains caused by the convective flow into the membrane pores, an effect that is not present in SEC. These results provide important insights into the transport and separation characteristics of pegylated proteins. © 2006 Wiley Periodicals, Inc. [source] Usefulness of multidetector CT imaging to assess vascular stents in children with congenital heart disease: An in vivo and in vitro study,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 4 2008Joachim G. Eichhorn MD Abstract Objective: To evaluate varying CT settings to visualize pediatric vascular stents in comparison to digital angiography (DA). Background: There is a great clinical interest in substituting noninvasive methods to follow up children with congenital heart disease after interventional treatment. Materials and Methods: CT studies in small children with transcatheter placed stents were reviewed, retrospectively. Furthermore, eight stents were implanted in tubes and partially obstructed. CT exams were performed on varying scanners (4 up to 64 slices) with corresponding tube settings. The effects of dose on image quality were evaluated regarding stent size, strut thickness, and in-stent stenoses in comparison to DA. Results: Fourteen children with 28 implanted stents were identified. Significant differences between higher and lower radiation settings were not found, corresponding with the phantom, where moderate tube setting showed the best results. In vitro, there was an improvement with increasing number of detector rows, which resulted in a decrease of stent strut overestimation (295% down to 201%; P < 0.0001) and a better agreement with DA measurements for mild (78% up to 91%; P = 0.003) and moderate in-stent stenoses (80% up to 99%; P = 0.0001). Conclusion: Higher radiation exposure settings did not improve image quality, suggesting that the exams could be performed at a lower radiation dose. © 2008 Wiley-Liss, Inc. [source] 11 Dawn Patrol Patient Follow-up ProtocolACADEMIC EMERGENCY MEDICINE, Issue 2008Justin Williams Follow-up of patients after their emergency department course provides a rich educational experience for residents, but due to time and logistical constraints, is infrequently performed in a scheduled and rigorous manner. The Dawn Patrol initiative was added to our residency curriculum to facilitate and protocolize patient follow-up for education and feedback on patient care. It also strives to improve communication with inpatient services, and provides a means of collection for morbidity / mortality and risk management cases. Our process functions by charging the clinical senior resident who is going off-shift, with reviewing the admission record for the past 24 hours. Interesting, clinically important, or cryptic case presentations are selected via our electronic medical record for review at the end of Morning Report. Generally, 1-3 new cases are selected for review each weekday morning. These cases are then recorded on a dry erase board in the Morning Report room, and the cases are followed until inpatient discharge, or are no longer of clinical interest. Visits to the inpatient wards are encouraged. Patient callbacks of outpatients are also eligible for inclusion. The cases are updated daily, and generally 5-10 cases are reviewed per day in approximately 10 minutes. The staff member attending Morning Report is responsible for providing bulleted teaching points on each case. The Dawn Patrol patient follow-up initiative seeks to improve emergency medicine resident education by facilitating and protocolizing patient follow-up, and provides real-time feedback on patient care performed in the emergency department. [source] Scanning beyond the limits of standard OCT: OCT scans of the peripheral retina and the anterior chamber angle with a slitlamp integtrated FD-OCT systemACTA OPHTHALMOLOGICA, Issue 2009M STEHOUWER Purpose Exploring the quality of OCT images of the peripheral retina and anterior chamber angle made through a 3-mirror contactlens and a new FD-OCT device integrated into a slit lamp. Methods Patients with peripheral lesions (n=10) and glaucoma (n=10), seen in the outpatient clinic of the Academic Medical Center, were scanned with a Fourier Domain OCT integrated into a common Topcon slitlamp (SLD light source, central wavelength 830 nm, bandwidth 30 nm, 1024 pixel CCD camera, scan speed 5k A-scans per second, up to 1024 A-scans per b-scan). For posterior segment scans a fast Z-tracking system in the reference arm compensates for the dynamic character (movements of patient, handheld lens, slitlamp) of the examination. Scans of peripheral lesions, and the anterior chamber angle were made with a 3-mirror lens, while simultaneously the lesions were observed with the slitlamp. Results Scans of the peripheral retina obtained with a 3-mirror lens with the FD-OCT integrated into the slitlamp were of reasonably good quality and lesions, like peripheral laser scars, could be clearly identified. Compared to stand alone OCT systems, the integrated OCT system reached more peripheral lesions. The anterior chamber angle scanned through a 3-mirror lens enabled scans of the angle structures. Conclusion It is possible to scan the peripheral retina and anterior chamber angle through a 3-mirror contact lens with the slitlamp with integrated OCT. These scans could be of clinical interest in patients with pathology in the peripheral retina pathology or the anterior chamber angle. [source] Lactate dehydrogenase predicts hypoxic ischaemic encephalopathy in newborn infants: a preliminary studyACTA PAEDIATRICA, Issue 8 2010Mathias Karlsson Abstract Background:, Enzyme leakage as a result of hypoxia-ischaemia induced cell damage in affected organs is seen together with hypoxic ischaemic encephalopathy (HIE) after perinatal asphyxia. Aim:, To investigate whether plasma lactate dehydrogenase [LDH], alanine aminotransferase [ALT] and aspartate aminotransferase [AST] during the first 12 h after birth predict HIE and adverse neurodevelopment outcome in newborn term infants with intra-partum signs of foetal distress. Methods:, Enzymes were measured within 12 h post partum in newborn infants with differing degree of HIE (n = 41) and in infants with signs of foetal distress during birth (n = 205) without HIE (non-HIE group). All infants were randomized into two groups. One group (n = 123) was used for calculation of cut off limits for the enzymes studied and the other group (n = 123) was used for calculation of the predictive value of the enzymes for detection of HIE. Results:, Using ROC curves, a cut off level of 1049 U/L for [LDH] was the best predictor of HIE (sensitivity 100% and specificity 97%) but also for long term outcome after HIE. Conclusion: [LDH] is a good predictor of HIE during the first 12 h after birth. This result is of clinical interest offering a potential inexpensive and safe prognostic marker in newborn infants with perinatal asphyxia. [source] Reviewing the vascular supply of the anterior abdominal wall: Redefining anatomy for increasingly refined surgeryCLINICAL ANATOMY, Issue 2 2008W.M. Rozen Abstract The abdominal wall integument is becoming the standard donor tissue for postmastectomy breast reconstruction, with its vascular supply of key importance to the reconstructive surgeon. Refinements in tissue transfer, from pedicled to free flaps and musculocutaneous to perforator flaps, have required increasing understanding of finer levels of this vascular anatomy. The widespread utilization of the deep inferior epigastric artery (DIEA) perforator flap, particularly for breast reconstruction, has rekindled clinical interest in further levels of anatomical detail, in particular the location and course of the musculocutaneous perforators of the DIEA. Advances in operative techniques, and anatomical and imaging technologies, have facilitated an increase in this understanding. The current review comprises an appraisal of both the anatomical and clinical literature, with a view to highlighting the key anatomical features of the abdominal wall vasculature as related to reconstructive flaps. Clin. Anat. 21:89,98, 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||||||||