bluuebunny/crossref_metadata_2025_split huggingface dataset:
Searching for and use of conference abstracts in health technology assessments: Policy and practice
Authors: Dundar Yenal , Dodd Susanna , Williamson Paula , Walley Tom , Dickson Rumona 
Published: February 2008

Objectives:Current policy and practice regarding identification of and extent of use of data from conference abstracts in health technology assessment reviews (TARs) are examined.Methods:The methods used were (i) survey of TAR groups to identify general policy and experience related to use of abstract data, and (ii) audit of TARs commissioned by the National Institute for Health and Clinical Excellence (NICE) and published between January 2000 and October 2004.Results:Five of seven TAR groups reported a general policy that included searching for and including studies available as conference abstracts and presentations. A total of sixty-three published HTA reports for NICE were identified. Of these reports, thirty-eight identified at least one randomized controlled trial available as an abstract/presentation. Twenty-six (68 percent) of these thirty-eight TARs included studies available as abstracts.Conclusions:There are variations in policy and practice across TAR groups regarding the searching for and inclusion of studies available as conference abstracts. There is a need for clarity and transparency for review teams regarding how abstract data are managed. If conference abstracts are to be included, reviewers need to allocate additional time for searching and managing data from these sources. Review teams should also be encouraged to state explicitly their search strategies for identifying conference abstracts, their methods for assessing these abstracts for inclusion and, where appropriate, how the data were used and their effect on the results.
Technology assessment and knowledge brokering: The case of assisted reproduction in The Netherlands
Authors: van Kammen Jessika , Jansen Carin W. , Bonsel Gouke J. , Kremer Jan A. M. , Evers Johannes L. H. , Wladimiroff Juriy W. 
Published: February 2008

Objectives:Even when policy makers show interest and evidence-informed and convincing HTA studies are available, use of assessment products is not guaranteed. In this article, we report our experience with knowledge brokering to foster evidence-informed policy making on cost-effective treatment and reimbursement of assisted reproduction in The Netherlands.Methods:From earlier work in the field of knowledge brokering, we foresaw the need for a deliberative strategy to manage the inherent tension between scientific rigor demanded by researchers and responsiveness to real-time needs demanded by policy makers. Therefore, we structured the process in three distinct steps: (i) agreement about the main messages from the research, (ii) analysis of the policy context and of the meaning of the main messages for the actors involved, and (iii) an invitational meeting to make recommendations for action.Results:One of the recommendations that would require changes in ministerial policy was followed up instantly, whereas the other recommendation is still under debate. The Dutch Society of Obstetrics and Gynecology activated the revision of two guidelines. The patient organization uses the new scientific insights in informing members and the public. Closing the loop, The Netherlands Organisation for Health Research and Development (ZonMw) funded research to close knowledge gaps that became apparent in the process.Conclusions:Knowledge brokering is a promising approach to bring HTA into practice. We conclude that the methodologies to feed research results into the policy process are still in an incipient stage and need further development.
Economics of tandem mass spectrometry screening of neonatal inherited disorders
Authors: Pandor Abdullah , Eastham Joe , Chilcott James , Paisley Suzy , Beverley Catherine 
Published: February 2008

Objectives:The aim of this study was to evaluate the cost-effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS).Methods:A systematic review of clinical efficacy evidence and cost-effectiveness modeling of screening in newborn infants within a UK National Health Service perspective was performed. Marginal costs, life-years gained, and cost-effectiveness acceptability curves are presented.Results:Substituting the use of tandem MS for existing technologies for the screening of PKU increases costs with no increase in health outcomes. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS, with an operational range of 50,000 to 60,000 specimens per system per year, would result in a mean incremental cost of −£17,298 (−£129,174, £66,434) for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 57.3 (28.0, 91.4) life-years.Conclusions:Cost-effectiveness analysis using economic modeling indicates that substituting the use of tandem MS for existing technologies for the screening of PKU alone is not economically justified. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS would be economically attractive.
Genetic screening by DNA technology: A systematic review of health economic evidence
Authors: Rogowski Wolf 
Published: February 2008

Objectives:The Human Genome Project has led to a multitude of new potential screening targets on the level of human DNA. The aim of this systematic review is to critically summarize the evidence from health economic evaluations of genetic screening in the literature.Methods:Based on an extensive explorative search, an appropriate algorithm for a systematic database search was developed. Twenty-one health economic evaluations were identified and appraised using published quality criteria.Results:Genetic screening for eight conditions has been found to be investigated by health economic evaluation: hereditary breast and ovarian cancer, familial adenomatous polyposis (FAP) colorectal cancer, hereditary nonpolyposis colorectal carcinoma (HNPCC), retinoblastoma, familial hypercholesterolemia, hereditary hemochromatosis, insulin-dependent diabetes mellitus, and cystic fibrosis. Results range from dominated to cost-saving. Population-wide genetic screening may be considered cost-effective with limited quality of evidence only for three conditions. The methodology of the studies was of varying quality. Cost-effectiveness was primarily influenced by mutation prevalence, genetic test costs, mortality risk, effectiveness of treatment, age at screening, and discount rate.Conclusions:Health economic evidence on genetic screening is limited: Only few conditions have properly been evaluated. Based on the existing evidence, healthcare decision makers should consider the introduction of selective genetic screening for FAP and HNPCC. As genetic test costs are declining, the existing evaluations may warrant updating. Especially in the case of hereditary hemochromatosis, genetic population screening may be about to turn from a dominated to a cost-effective or even cost-saving intervention.
Economic evaluation of empirical antisecretory therapy versusHelicobacter pylorifor management of dyspepsia: A randomized trial in primary care
Authors: Jarbol Dorte Ejg , Bech Mickael , Kragstrup Jakob , Havelund Troels , de Muckadell Ove B. Schaffalitzky 
Published: February 2008

Objectives:An economic evaluation was performed of empirical antisecretory therapy versus test forHelicobacter pyloriin the management of dyspepsia patients presenting in primary care.Methods:A randomized trial in 106 general practices in the County of Funen, Denmark, was designed to include prospective collection of clinical outcome measures and resource utilization data. Dyspepsia patients (n=722) presenting in general practice with more than 2 weeks of epigastric pain or discomfort were managed according to one of three initial management strategies: (i) empirical antisecretory therapy, (ii) testing forHelicobacter pylori, or (iii) empirical antisecretory therapy, followed byHelicobacter pyloritesting if symptoms improved. Cost-effectiveness and incremental cost-effectiveness ratios of the strategies were determined.Results:The mean proportion of days without dyspeptic symptoms during the 1-year follow-up was 0.59 in the group treated with empirical antisecretory therapy, 0.57 in theH. pyloritest-and-eradicate group, and 0.53 in the combination group. After 1 year, 23 percent, 26 percent, and 22 percent, respectively, were symptom-free. Applying the proportion of days without dyspeptic symptoms, the cost-effectiveness for empirical treatment,H. pyloritest and the combination were 12,131 Danish kroner (DKK), 9,576 DKK, and 7,301 DKK, respectively. The incremental cost-effectiveness going from the combination strategy to empirical antisecretory treatment orH. pyloritest alone was 54,783 DKK and 39,700 DKK per additional proportion of days without dyspeptic symptoms.Conclusions:Empirical antisecretory therapy confers a small insignificant benefit but costs more than strategies based on test forH. pyloriand is probably not a cost-effective strategy for the management of dyspepsia in primary care.
Health economic evaluation in Greece
Authors: Rovithis Dimitrios 
Published: February 2008

Objectives: There is a growing volume of literature on health economic evaluation, with this form of analysis becoming increasingly influential at the decision-making level worldwide. The purpose of this study was to review the current state of health economic evaluation in Greece, with a view to uncovering reasons why its use in this country is limited.Methods: A search of the NHS Economic Evaluation Database was undertaken. The search included cost, cost-of-illness, cost-minimization, cost-effectiveness, cost-consequences, cost-utility, and cost-benefit analyses and was narrowed only to Greek authors undertaking solo or joint health economic evaluation in Greece.Results: The search revealed that, in Greece, very little health economic evaluation has been undertaken. The main reason for the lack of interest is that the current chaotic healthcare system structure and financing does not provide the appropriate incentives to stimulate a powerful interest in this type of research. This condition is a result of the lack of a long-term national health policy and the hesitation of the present and past Greek governments to date to proceed to large-scale reforms because of political considerations. The Greek governments have also been content with the good health indicators being achieved.Conclusions: Even if it is accepted that good health prevails in Greece, slower economic growth rates, an ageing population, and the continuous immigration will place increasing pressure on healthcare resources and will necessitate a more rational use of these resources. Health economic evaluation, by weighing benefits against costs, therefore, has an important role to play.
Cost-effectiveness analysis of strategies for HER2 testing of breast cancer patients in France
Authors: Morelle Magali , Haslé Elodie , Treilleux Isabelle , Michot Jean-Philippe , Bachelot Thomas , Penault-Llorca Frédérique , Carrère Marie-Odile 
Published: February 2008

Objectives: A cost-effectiveness analysis was conducted comparing diagnostic strategies for determining the HER2 status of invasive breast carcinomas, as an indication for trastuzumab at metastatic relapse.Methods: A decision tree compared five strategies distinguished by (i) the use of immunohistochemical (IHC) and/or fluorescent in situ hybridization (FISH) techniques, and (ii) the test schedule (at initial diagnosis or metastatic relapse). Most cost and effectiveness data came from a French multicentric study of 2,045 patients from eight hospitals. We were not able to select final criteria for trastuzumab effectiveness, because published data rely on IHC techniques not used in France (i.e., HercepTest). We, therefore, selected two intermediate criteria for inappropriate treatment at relapse, that is, patients with HER2-amplified tumors not receiving trastuzumab (Criterion 1) and HER2-nonamplified tumors improperly treated with trastuzumab (Criterion 2). Sensitivity analyses were then performed to assess the robustness of the results to (i) discount rate, (ii) cost of FISH, and (iii) tissue fixation technique.Results: The strategy using IHC at diagnosis was dominated by the four other strategies. Among these approaches, the only efficient strategy for both criteria was IHC used alone at metastatic relapse; strategies using FISH, or IHC followed by FISH on IHC2+ cases were efficient for Criterion 1, whereas IHC followed by FISH on IHC2+ and 3+ cases was efficient for Criterion 2.Conclusions: Determining HER2 status at diagnosis, as an indication for trastuzumab at metastatic relapse, incurs substantial incremental costs, which do not appear to be justified. No other strategy can be excluded at first.
Growth form and population genetic structure ofAzorella selagoon sub-Antarctic Marion Island
Authors: Mortimer Elizabeth , McGeoch Melodie A. , Daniels Savel R. , Vuuren Bettine Jansen van 
Published: February 2008

AbstractSeven community complexes have been described across sub-Antarctic Marion Island, amongst these fellfield that comprise low plant cover dominated byAzorella selagoHook. f.Azorellais considered a keystone species since it forms nutrient rich environments for microarthropod communities and epiphytic plants. Two distinct growth forms typifyAzorella, namely discrete cushions and continuous mats. Whether these continuous mats normally consist of a single large cushion individual, or whether several individual plants merge, interdigitating to form a continuous area, remains unclear. As such, it is important to obtain some measure ofAzorellagrowth dynamics before embarking on phylogeographic studies. Previous genetic studies indicated that several microarthropod species are significantly substructured across Marion Island, but it remains unclear whether similar subdivisions characterizeAzorella. We used chloroplast sequence data (trnH-psbA) and amplified fragment length polymorphism (AFLP) to investigate these questions. No sequence variation characterized thetrnH-psbA region inAzorellaacross Marion Island. In contrast, the AFLP results indicated that anA. selagomat comprises multiple individuals. We argue that mats can be formed through at least two processes namely fragmentation, where parts of the cushion plant die off creating open areas for the establishment of different individuals and/or high density of interdigitating individuals merging to form the mat. Fragment data further indicated significant substructure forAzorellaacross Marion Island (FST = 0.101,P = 0.01) and we attribute this to past vicariance.
Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas
Authors: Drakos Elias , Rassidakis George Z. , Medeiros L. Jeffrey 
Published: February 2008

AbstractThe mammalian target of rapamycin mTOR is a central element in an evolutionary conserved signalling pathway that regulates cell growth, survival and proliferation, orchestrating signals originating from growth factors, nutrients or particular stress stimuli. Two important modulators of mTOR activity are the AKT and ERK/MAPK signalling pathways. Many studies have shown that mTOR plays an important role in the biology of malignant cells, including deregulation of the cell cycle, inactivation of apoptotic machinery and resistance to chemotherapeutic agents. The development of several mTOR inhibitors, in addition to rapamycin, has facilitated studies of the role of mTOR in cancer, and verified the antitumour effect of mTOR inhibition in many types of neoplasms, including lymphomas. Clinical trials of rapamycin derivatives in lymphoma patients are already in development and there are encouraging preliminary results, such as the substantial response of a subset of mantle cell lymphoma patients to the rapamycin analogue temsirolimus. Based on results obtained from in vitro and in vivo studies of the mTOR pathway in lymphomas, it seems that better understanding of mTOR regulation will reveal aspects of lymphomagenesis and contribute to the development of more powerful, targeted therapies for lymphoma patients.
Indications for the sentinel node: multicentric, size of tumor, prior surgery
Authors: Hanker L. C. , Rody A. , Ruckhaeberle E. , Kaufmann M. 
Published: February 2008

AbstractSentinel lymph node biopsy (SLNB) has been adopted as an applicable alternative to the standard axillary lymph node dissection (ALND) level I and II. It makes possible a less extensive axillary surgery in patients with early breast cancer with negative lymph node, who would not benefit from further dissection, in order to prevent unnecessary morbidity. On the other hand, SLNB is not appropriate in every clinical circumstance. In some clinical situations like tumor size T1 and T2, SLNB is, meanwhile, regarded as a standard procedure. In other settings like increased age and body mass index, pregnancy, ductal carcinoma in situ (DCIS), neoadjuvant chemotherapy, advanced disease (T3 and T4), prior surgery and multifocal/multicentric disease, there is a controversial debate about the importance of SLNB. This article reviews the absolute and relative contraindications of this procedure in respect to the latter three clinical situations.For the advanced breast cancers T3 and T4, there seems to be an increasing evidence of an acceptable accuracy, although it should be further evaluated in randomized clinical trials (RCT). The indication of SLNB in previously operated patients depends on the type of prior surgery. A diagnostic biopsy does not represent a contraindication, whereas the sentinel node biopsy should not be used after an extensive breast surgery neither in the context of oncologic nor non-oncologic purposes. In the context of multicentric disease, there is growing evidence that SLNB is suitable, but actually it should be restricted to RCT. However, the multifocal disease is only a relative contraindication, that is it could be applied in well-selected patients.
Role of gp130‐mediated signalling pathways in the heart and its impact on potential therapeutic aspects
Authors: Fischer P , Hilfiker‐Kleiner D 
Published: February 2008

IL‐6‐type cytokines bind to plasma membrane receptor complexes containing the common signal transducing receptor chain gp130 that is ubiquitously expressed in most tissues including the heart. The two major signalling cascades activated by the gp130 receptor, SHP2/ERK and STAT pathways, have been demonstrated to play important roles in cardiac development, hypertrophy, protection and remodelling in response to physiological and pathophysiological stimuli. Experimental data, both in vivo and in vitro, imply beneficial effects of gp130 signalling on cardiomyocytes in terms of growth and survival. In contrast, it has been reported that elevated serum levels of IL‐6 cytokines and gp130 proteins are strong prognostic markers for morbidity and mortality in patients with heart failure or after myocardial infarction. Moreover, it has been shown that the local gp130 receptor system is altered in failing human hearts. In the present review, we summarize the basic principles of gp130 signalling, which requires simultaneous activation of STAT and ERK pathways under the tight control of positive and negative intracellular signalling modulators to provide a balanced biological outcome. Furthermore, we highlight the key role of the gp130 receptor and its major downstream effectors in the heart in terms of development and regeneration and in response to various physiological and pathophysiological stress situations. Finally, we comment on tissue‐specific diversity and challenges in targeted pharmacological interference with components of the gp130 receptor system.British Journal of Pharmacology (2008) 153, S414–S427; doi:10.1038/bjp.2008.1; published online 4 February 2008
Gates and filters: unveiling the physiological roles of nicotinic acetylcholine receptors in dopaminergic transmission
Authors: Wonnacott S 
Published: February 2008

Neuronal nicotinic acetylcholine receptors (nAChRs) in the brain have been enigmatic players on the cerebral stage. As ligand‐gated ion channels they were expected to mediate fast cholinergic transmission, yet their influence appears to be modulatory. Two reviews in this issue of the BJP consider the relationship between nAChRs and endogenous ACh, with respect to the modulation of dopaminergic signalling. In his review, Maskos posits that in midbrain dopamine neurons, somatodendritic nAChRs activated by cholinergic inputs from the pedunculopontine tegmental nucleus (PPTg) and laterodorsal tegmental nucleus (LDTg) serve as a ‘gate’ that facilitates the switch to burst firing. In the terminal field, Exley and Cragg argue that nAChRs function as a ‘presynaptic filter’ to enhance the contrast between single and repetitive spike firing. Thus somatodendritic and presynaptic nAChRs exert subtle and complementary influences in responding to cholinergic inputs.British Journal of Pharmacology (2008) 153, S2–S4; doi:10.1038/sj.bjp.0707583; published online 4 February 2008
Analysis of the effects of oestrogen receptor α (ERα)‐ and ERβ‐selective ligands given in combination to ovariectomized rats
Authors: Hertrampf T , Seibel J , Laudenbach U , Fritzemeier K H , Diel P 
Published: February 2008

Background and purpose:Studies with oestrogen receptorα (ERα)‐ and ERβ‐selective compounds have already shown that the effects of 17β‐estradiol (E2) on body weight, movement drive and bone‐protection are mediated via ERα. This study was based on the hypothesis that activation of ERβ may antagonize ERα‐mediated effects and designed to investigate potential effects of ERα/ERβ heterodimers.Experimental approach:Ovariectomized (OVX) female Wistar rats were treated with combinations of the ERα‐specific agonist 16α‐LE2 (ALPHA; 1 and 10 μg kg−1 d−1), the ERβ‐specific agonist 8β‐VE2 (BETA; 100 μg kg−1 d−1), the phytoestrogen, genistein (10 mg kg−1 d−1) and with the anti‐oestrogen compound, ICI 182,780 (3 mg kg−1 d−1) for three weeks. The combined effects of the substances on body weight increase, tibial bone mineral density (BMD) and the influence on running wheel activity (RWA) were investigated.Key results:OVX‐induced body weight increase was reduced by co‐administration of genistein and BETA. Co‐application of BETA or genistein with ALPHA had no effect on ALPHA‐mediated bone‐protection. The RWA of OVX animals was significantly reduced by treatment with genistein but stimulated by application of ALPHA. The stimulatory effect of ALPHA on RWA could be antagonized by co‐treatment with the pure antioestrogen ICI 182,780 but also by co‐administration of genistein or BETA.Conclusions and implications:Our results indicate that activation of ERβ may modulate ERα‐mediated physiological effectsin vivo. The observation that substances with selective affinity for ERβ are able to antagonize distinct physiological functions, like RWA, may be of great relevance to the pharmaceutical use of such drugs.British Journal of Pharmacology(2008)153, 1432–1437; doi:10.1038/sj.bjp.0707664; published online 4 February 2008