bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between methodological characteristics and outcome in health technology assessments which included case series
Authors: Stein Ken , Dalziel Kim , Garside Ruth , Castelnuovo Emanuela , Round Ali 
Published: April 2008

Objectives:Case series constitute a weak form of evidence for effectiveness of health technologies. However, for a variety of reasons, such studies may be included in health technology assessments. There are no clear criteria for assessing the quality of case series. We carried out an empirical investigation of the association between outcome frequency and methodological characteristics in a sample of health technology assessments.Methods:Systematic reviews of functional endoscopic sinus surgery for nasal polyps, spinal cord stimulation for chronic back pain, and percutaneous transluminal coronary angioplasty and coronary artery bypass grafting for chronic stable angina were identified as containing more than forty case series. Data were extracted by one reviewer and checked by a second on population characteristics, outcomes, and the following methodological features: sample size, prospective/retrospective approach, consecutive recruitment, multi- or single-center organization, length of follow-up, independence of outcome measurement, and date of publication. Association between methodological features and outcome were explored in univariate and multivariate analyses using parametric and nonparametric tests and robust regression or analysis of variance/analysis of covariance, as appropriate.Results:Included reviews contained between forty-two and seventy-six case series studies, involving 5 to 172,283 participants. Reporting of methodological features was poor and limited the analyses. In general, we found little evidence of any association between methodological characteristics and outcome. Sample size is used as an inclusion criterion in many reviews of case series but was consistently shown to have no relationship to outcome in all analyses. A prospective approach was not associated with outcome. Insufficient data were available to explore consecutive recruitment. Mixed results were shown for length of follow-up, independence of outcome measurement, and publication date.Conclusion:We found little evidence to support the use of many of the factors included in tools used for quality assessment of case series. Importantly, we found no relationship between study size and outcome across the four examples studied. Isolated examples of a potentially important relationship between other methodological factors and outcome were shown, for example, blinding of outcome measurement, but these examples were not shown consistently across the small number of examples studied. Further research into the determinants of quality in case series studies is required to support health technology assessment.
Self-reports of health-care utilization: Diary or questionnaire?
Authors: van den Brink Mandy , van den Hout Wilbert B. , Stiggelbout Anne M. , Putter Hein , van de Velde Cornelis J. H. , Kievit Job 
Published: April 2008

Objectives:The feasibility and convergent validity of a cost diary and a cost questionnaire was investigated.Methods:Data were obtained as part of a cost-utility analysis alongside a multicenter clinical trial in patients with resectable rectal cancer. A sample of 107 patients from 30 hospitals was asked to keep a weekly diary during the first 3 months after surgery, and a monthly diary from 3 to 12 months after surgery. A second sample of seventy-two patients from twenty-eight hospitals in the trial received a questionnaire at 3, 6, and 12 months after surgery, referring to the previous 3 or 6 months. Format and items of the questions were similar and included a wide range of medical and nonmedical items and costs after hospitalization for surgery.Results:Small differences were found with respect to nonresponse (range, 79 to 86 percent) and missing questions (range, 1 to 6 percent between the diary and questionnaire). For most estimates of volumes of care and of costs, the diary and questionnaire did not differ significantly. Total 3-month nonhospital costs were €1,860, €1,280, and €1,050 in the diary sample and €1,860, €1,090, and €840 in the questionnaire sample at 3, 6, and 12 months after surgery, respectively (p=.50). However, with respect to open questions, the diary sample tended to report significantly more care.Conclusions:For the assessment of health-care utilization in economic evaluations alongside clinical trials, a cost questionnaire with structured closed questions may replace a cost diary for recall periods up to 6 months.
Toward a procedure for integrating moral issues in health technology assessment
Authors: Hofmann Bjørn 
Published: April 2008

Objectives:Although ethics has been on the agenda in health technology assessment (HTA) since its inception, the integration of moral issues is still not standard and is performed in a vast variety of ways. Therefore, there is a need for a procedure for integrating moral issues in HTA.Methods:Literature review of existing approaches together with application of various theories in moral philosophy and axiology.Results:The article develops a set of questions that addresses a wide range of moral issues related to the assessment and implementation of health technology. The issues include general moral issues and moral issues related to stakeholders, methodology, characteristics of technology, and to the HTA process itself. The questions form a kind of checklist for use in HTAs.Conclusions:The presented approach for integrating moral issues in HTA has a broad theoretical foundation and has shown to be useful in practice. Integrating ethical issues in HTAs can be of great importance with respect to the dissemination of HTA results and in efficient health policy making.
Technology assessment in dentistry: A comparison of the longevity and cost-effectiveness of inlays
Authors: Gandjour Afschin , Kerschbaum Thomas , Reis Andreas , Lauterbach Karl Wilhelm 
Published: April 2008

Objectives:An example of technology assessment in dental care by evaluating the (cost-)effectiveness of types of three-surface inlays (gold, laboratory-fabricated ceramic, and chairside CAD/CAM ceramic) is provided.Methods:MEDLINE, EMBASE, and the Cochrane Library were searched for studies published between 1966 and June 2003 that reported annual survival probabilities and annual observations. The longevity of different types of inlays was measured by the number of failure-free years. Annual survival rates from different studies were pooled by weighing the rates of each study by the inverse of the variance of the effect estimate. A cost-effectiveness analysis from the perspective of German private health insurers was performed using billing charges.Results:Three, five, and two case series on laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays, respectively, were included. Over a 9-year observation period, the number of undiscounted failure-free years was 8.62 (95 percent confidence interval, 8.40–8.85), 8.65 (8.58–8.73), and 8.76 (8.72–8.80) for laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays, respectively. Laboratory-fabricated ceramic inlays were the most expensive.Conclusions:While laboratory-fabricated ceramic, chairside CAD/CAM ceramic, and gold inlays had a strikingly similar failure-free survival rate, laboratory-fabricated ceramic inlays had the highest costs and, thus, were less cost-effective than chairside CAD/CAM ceramic and gold inlays.
Spinal cord stimulation for failed back surgery syndrome: A decision-analytic model and cost-effectiveness analysis
Authors: Taylor Rebecca J. , Taylor Rod S. 
Published: April 2008

Objectives:The aim of this study was to develop a decision-analytic model to assess the cost-effectiveness of spinal cord stimulation (SCS), relative to nonsurgical conventional medical management (CMM), for patients with failed back surgery syndrome (FBSS).Methods:A decision tree and Markov model were developed to synthesize evidence on both health-care costs and outcomes for patients with FBSS. Outcome data of SCS and CMM were sourced from 2-year follow-up data of two randomized controlled trials (RCTs). Treatment effects were measured as levels of pain relief. Short- and long-term health-care costs were obtained from a detailed Canadian costing study in FBSS patients. Results are presented as incremental cost per quality adjusted life year (QALY) and expressed in 2003 Euros. Costs were discounted at 6 percent and outcomes at 1.5 percent.Results:Over the lifetime of the patient, SCS was dominant (i.e., SCS is cost-saving and gives more health gain relative to CMM); a finding that was robust across sensitivity analyses. At a 2-year time horizon, SCS gave more health gain but at an increased cost relative to CMM. Given the uncertainty in effectiveness and cost parameters, the 2-year cost-effectiveness of SCS ranged from €30,370 in the base case to €63,511 in the worst-case scenario.Conclusions:SCS was found to be both more effective and less costly than CMM, over the lifetime of a patient. In the short-term, although SCS is potentially cost-effective, the model results are highly sensitive to the choice of input parameters. Further empirical data are required to improve the precision in the estimation of short-term cost-effectiveness.
Diffusion of published cost-utility analyses in the field of health policy and practice
Authors: Sonnad Seema S. , Greenberg Dan , Rosen Allison B. , Neumann Peter J. 
Published: April 2008

Objectives:The diffusion of cost-utility analyses (CUAs) through the medical literature was examined, documenting visible patterns and determining how they correspond with expectations about the diffusion of process innovations.Methods:This study used 539 CUAs from a registry. It includes data elements comprising year of publication, the research center in which the study was performed, the clinical area covered by the CUA, and the specific journal. Finally, each paper was assigned to a journal type that could be one of the three categories: health services research, general medicine, or clinical specialty.Results:When the average number of publications is plotted against time, the plot reveals an S-shaped curve. It appears that, whereas CUAs initially were published more frequently in general medical or health services research journals, there was a clear increase in the diffusion of CUA into subspecialty journals over time. The concentration ratio for research centers as measured by the Herfindhal–Hirschman Index decreased over time.Conclusions:The spread of CUA through the medical literature follows patterns identified for the diffusion of other new technologies and processes. Future research should focus on what impact this spread has had on the practice of medicine and formulation of health policy.
Insulin exocytosis in Goto-Kakizaki rat β-cells subjected to long-term glinide or sulfonylurea treatment
Authors: Kawai Junko , Ohara-Imaizumi Mica , Nakamichi Yoko , Okamura Tadashi , Akimoto Yoshihiro , Matsushima Satsuki , Aoyagi Kyota , Kawakami Hayato , Watanabe Takashi , Watada Hirotaka , Kawamori Ryuzo , Nagamatsu Shinya 
Published: April 2008

Sulfonylurea and glinide drugs display different effects on insulin granule motion in single β-cells in vitro. We therefore investigated the different effects that these drugs manifest towards insulin release in an in vivo long-term treatment model. Diabetic GK (Goto-Kakizaki) rats were treated with nateglinide, glibenclamide or insulin for 6 weeks. Insulin granule motion in single β-cells and the expression of SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) proteins were then analysed. Perifusion studies showed that decreased first-phase insulin release was partially recovered when GK rats were treated with nateglinide or insulin for 6 weeks, whereas no first-phase release occurred with glibenclamide treatment. In accord with the perifusion results, TIRF (total internal reflection fluorescence) imaging of insulin exocytosis showed restoration of the decreased number of docked insulin granules and the fusion events from them during first-phase release for nateglinide or insulin, but not glibenclamide, treatment; electron microscopy results confirmed the TIRF microscopy data. Relative to vehicle-treated GK β-cells, an increased number of SNARE clusters were evident in nateglinide- or insulin-treated cells; a lesser increase was observed in glibenclamide-treated cells. Immunostaining for insulin showed that nateglinide treatment better preserved pancreatic islet morphology than did glibenclamide treatment. However, direct exposure of GK β-cells to these drugs could not restore the decreased first-phase insulin release nor the reduced numbers of docked insulin granules. We conclude that treatment of GK rats with nateglinide and glibenclamide varies in long-term effects on β-cell functions; nateglinide treatment appears overall to be more beneficial.
Endoplasmic reticulum Ca2+ measurements reveal that the cardiac ryanodine receptor mutations linked to cardiac arrhythmia and sudden death alter the threshold for store-overload-induced Ca2+ release
Authors: Jones Peter P. , Jiang Dawei , Bolstad Jeff , Hunt Donald J. , Zhang Lin , Demaurex Nicolas , Chen S. R. Wayne 
Published: April 2008

A number of RyR2 (cardiac ryanodine receptor) mutations linked to ventricular arrhythmia and sudden death are located within the last C-terminal ∼500 amino acid residues, which is believed to constitute the ion-conducting pore and gating domain of the channel. We have previously shown that mutations located near the C-terminal end of the predicted TM (transmembrane) segment 10, the inner pore helix, can either increase or decrease the propensity for SOICR (store-overload-induced Ca2+ release), also known as spontaneous Ca2+ release. In the present study, we have characterized an RyR2 mutation, V4653F, located in the loop between the predicted TM 6 and TM 7a, using an ER (endoplasmic reticulum)-targeted Ca2+-indicator protein (D1ER). We directly demonstrated that SOICR occurs at a reduced luminal Ca2+ threshold in HEK-293 cells (human embryonic kidney cells) expressing the V4653F mutant as compared with cells expressing the RyR2 wild-type. Single-channel analyses revealed that the V4653F mutation increased the sensitivity of RyR2 to activation by luminal Ca2+. In contrast with previous reports, the V4653 mutation did not alter FKBP12.6 (FK506-binding protein 12.6 kDa; F506 is an immunosuppressant macrolide)–RyR2 interaction. Luminal Ca2+ measurements also showed that the mutations R176Q/T2504M, S2246L and Q4201R, located in different regions of the channel, reduced the threshold for SOICR, whereas the A4860G mutation, located within the inner pore helix, increased the SOICR threshold. We conclude that the cytosolic loop between TM 6 and TM 7a plays an important role in determining the SOICR threshold and that the alteration of the threshold for SOICR is a common mechanism for RyR2-associated ventricular arrhythmia.
Generation of an agonistic binding site for blockers of the M3 muscarinic acetylcholine receptor
Authors: Thor Doreen , Schulz Angela , Hermsdorf Thomas , Schöneberg Torsten 
Published: April 2008

GPCRs (G-protein-coupled receptors) exist in a spontaneous equilibrium between active and inactive conformations that are stabilized by agonists and inverse agonists respectively. Because ligand binding of agonists and inverse agonists often occurs in a competitive manner, one can assume an overlap between both binding sites. Only a few studies report mutations in GPCRs that convert receptor blockers into agonists by unknown mechanisms. Taking advantage of a genetically modified yeast strain, we screened libraries of mutant M3Rs {M3 mAChRs [muscarinic ACh (acetylcholine) receptors)]} and identified 13 mutants which could be activated by atropine (EC50 0.3–10 μM), an inverse agonist on wild-type M3R. Many of the mutations sensitizing M3R to atropine activation were located at the junction of intracellular loop 3 and helix 6, a region known to be involved in G-protein coupling. In addition to atropine, the pharmacological switch was found for other M3R blockers such as scopolamine, pirenzepine and oxybutynine. However, atropine functions as an agonist on the mutant M3R only when expressed in yeast, but not in mammalian COS-7 cells, although high-affinity ligand binding was comparable in both expression systems. Interestingly, we found that atropine still blocks carbachol-induced activation of the M3R mutants in the yeast expression system by binding at the high-affinity-binding site (Ki ∼10 nM). Our results indicate that blocker-to-agonist converting mutations enable atropine to function as both agonist and antagonist by interaction with two functionally distinct binding sites.
Lysophosphatidic acid-induced transactivation of epidermal growth factor receptor regulates cyclo-oxygenase-2 expression and prostaglandin E2 release via C/EBPβ in human bronchial epithelial cells
Authors: He Donghong , Natarajan Viswanathan , Stern Randi , Gorshkova Irina A. , Solway Julian , Spannhake Ernst Wm. , Zhao Yutong 
Published: April 2008

We have demonstrated that LPA (lysophosphatidic acid)-induced IL (interleukin)-8 secretion was partly mediated via transactivation of EGFR [EGF (epidermal growth factor) receptor] in HBEpCs (human bronchial epithelial primary cells). The present study provides evidence that LPA-induced transactivation of EGFR regulates COX (cyclo-oxygenase)-2 expression and PGE2 [PG (prostaglandin) E2] release through the transcriptional factor, C/EBPβ (CCAAT/enhancer-binding protein β), in HBEpCs. Treatment with LPA (1 μM) stimulated COX-2 mRNA and protein expression and PGE2 release via Gαi-coupled LPARs (LPA receptors). Pretreatment with inhibitors of NF-κB (nuclear factor-κB), JNK (Jun N-terminal kinase), or down-regulation of c-Jun or C/EBPβ with specific siRNA (small interference RNA) attenuated LPA-induced COX-2 expression. Downregulation of EGFR by siRNA or pretreatment with the EGFR tyrosine kinase inhibitor, AG1478, partly attenuated LPA-induced COX-2 expression and phosphorylation of C/EBPβ; however, neither of these factors had an effect on the NF-κB and JNK pathways. Furthermore, LPA-induced EGFR transactivation, phosphorylation of C/EBPβ and COX-2 expression were attenuated by overexpression of a catalytically inactive mutant of PLD2 [PLD (phospholipase D) 2], PLD2-K758R, or by addition of myristoylated PKCζ [PKC (protein kinase C) ζ] peptide pseudosubstrate. Overexpression of the PLD2-K758R mutant also attenuated LPA-induced phosphorylation and activation of PKCζ. These results demonstrate that LPA induces COX-2 expression and PGE2 production through EGFR transactivation-independent activation of transcriptional factors NF-κB and c-Jun, and EGFR transactivation-dependent activation of C/EBPβ in HBEpCs. Since COX-2 and PGE2 have been shown to be anti-inflammatory in airway inflammation, the present data suggest a modulating and protective role of LPA in regulating innate immunity and remodelling of the airways.
Effects of hook size and barbless hooks on hooking injury, catch per unit effort, and fish size in a mixed-species recreational fishery in the western Mediterranean Sea
Authors: Alós Josep , Palmer Miquel , Grau Antoni Maria , Deudero Salud 
Published: April 2008

Abstract
Alós, J., Palmer, M., Grau, A. M., and Deudero, S. 2008. Effects of hook size and barbless hooks on hooking injury, catch per unit effort, and fish size in a mixed-species recreational fishery in the western Mediterranean Sea. – ICES Journal of Marine Science, 65: 899–905. The effects of hook size (small vs. large) and type (conventional vs. barbless) on hooking injury, catch per unit effort (cpue), and fish size in a mixed-species recreational fishery in the Balearic Islands (western Mediterranean) are evaluated. Hook size was the most important predictor of deep-hooking, which is reduced by the use of large hooks. The size of fish captured was another predictor of deep-hooking incidence, because large fish tended to be caught in deep-hooking locations. Deep-hooking was highly correlated with the presence of bleeding, and unhooking time was reduced by the use of large hooks and barbless hooks, although differences were small. To determine the effects of different hook treatments on cpue and species composition, a mixed-effect linear model was used as a univariate procedure, and redundancy analysis was used as a multivariate analysis. Results showed a drastic decrease in cpue with barbless hooks. In contrast, large hooks reduced the incidence of hooking injuries, with a small reduction in catch rate. Moreover, large hooks were associated with a larger mean size of fish caught than small hooks. Hence, control of hook size, along with other traditional management measures that involve the release of fish, is presented as a management option for sustainable development of recreational fisheries in the western Mediterranean Sea.
Adherence to statin or aspirin or both in patients with established cardiovascular disease: exploring healthy behaviour vs. drug effects and 10‐year follow‐up of outcome
Authors: Wei Li , Fahey Tom , MacDonald Thomas M. 
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Aspirin and statins are widely‐used drugs in patients with cardiovascular disease.• There is less information on healthy behaviour vs. drug effects. WHAT THIS STUDY ADDS • Long‐term adherence to aspirin and statin treatments in patients with established cardiovascular disease has been investigated.• Poor health behaviour is not a sufficient explanation of adverse outcome in poorly adherent patients.AimsTo characterize adherence in patients with established cardiovascular disease taking statins and aspirin and to estimate the effects of adherence due to health behaviour, a lack of beneficial drug effect, or both on recurrence of cardiovascular disease or all‐cause mortality over 10 years.MethodsA population‐based cohort study using a record‐linkage database in Tayside, Scotland. Subjects with cardiovascular disease (n = 7657; 4185 aspirin‐alone cohort, 671 statin‐alone cohort and 2801 combination use cohort) were studied between 1993 and 2003. The effects of adherence on recurrence of cardiovascular disease or mortality were assessed using Poisson regression model.ResultsIn subjects taking both aspirin and statins, those adherent to statins but not aspirin had a lower risk of recurrence [adjusted risk ratio (RR) 0.64; 95% confidence interval 0.49, 0.82], but those adherent to aspirin but not statins has no such effect (adjusted RR 0.91; 0.72, 1.15), suggesting that adherence behaviour alone was not responsible for the beneficial effect. Within the group adherent to aspirin, ≥80% adherence to statins was associated with reduced recurrence compared with those poorly adherent (adjusted RR 0.76; 0.62, 0.94), but no such effect of aspirin was seen in those adherent to statins. Similar results were found for all‐cause mortality.ConclusionsPoor health behaviour is not a sufficient explanation of adverse outcome in poorly adherent patients. Adverse outcome is more likely to be driven by foregone drug benefits.