bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemophilia B: impact on patients and economic burden of disease
Authors: Thomson Thomas , Strandberg-Larsen Martin , Gater Adam 
Published: August 2011

SummaryWorldwide, haemophilia is the most common hereditary bleeding disorder. The incidence of haemophilia B, however, is considerably less than haemophilia A and consequently appears to have received less attention in the research literature. This article aims to summarise the available evidence documenting the patient and economic burden associated with haemophilia B and current methods of disease management. Both the immediate and long-term clinical consequences of haemophilia B can have significant implications for patients in terms of functional limitations and diminished health-related quality of life (HRQOL). Evidence demonstrates that primary prophylaxis is the optimal strategy for replacing missing clotting factor IX (FIX) and managing haemophilia B. Use of recombinant FIX (rFIX) over plasma-derived FIX (pd-FIX) is also generally preferred for safety reasons. Prophylaxis using currently available rFIX products, however, requires a demanding regimen of intravenous infusions 2–3 times a week which may have significant implications for adherence and ultimately the long-term efficacy of such regimens. Only limited assessments of the cost-effectiveness of prophylactic versus on-demand FIX treatment regimens have been conducted to date. Prophylaxis, however, is generally more costly as greater quantities of FIX are consumed. Any reduction in FIX replacement dosing frequency is expected to improve patient adherence and contribute to improved clinical outcomes, further supporting the costeffectiveness of such interventions. Although a rare disease, as economic constraints for healthcare increase, generating further information regarding the key clinical, patient and economic outcomes associated with haemophilia B will be essential for supporting improvements in care for people with haemophilia B.
Suboptimal anticoagulation with pre-hospital heparin in ST-elevation myocardial infarction
Authors: Hermanides Renicus , Dambrink Jan-Henk , Boer Menko-Jan , Hoorntje Jan , Gosselink A. T. , Suryapranata Harry , Zijlstra Felix , van ’t Hof Arnoud , Ottervanger Jan ,   the Zwolle Myocardial Infarction Study Group
Published: August 2011

SummaryThis is a prospective, observational study performed in all consecutive ST-elevation myocardial infarction (STEMI) patients who had activated clotting time (ACT) measurement on arrival in the cathlab before coronary angiography. We studied the therapeutic effects of a pre-hospital fixed heparin bolus dose in consecutive patients with STEMI. A total of 1,533 patients received pre-hospital administration of aspirin, high dose clopidogrel (600 mg) and a fixed bolus dose of 5,000 IU unfractionated heparin (UFH), according to the national ambulance protocols. Some patients were also treated with glycoprotein IIb/IIIa inhibitors (GPI) in the ambulance. A therapeutic ACT range was defined according to the ESC guidelines as 200–250 seconds when patients had GPI pretreatment and 250–350 seconds when no GPI pretreatment. Of the 1,533 patients, 216 patients (14.1%) had an ACT within the therapeutic range, 82.3% of the patients had a too low ACT, whereas 3.5% of the patients had a too high ACT. After multivariable analysis, the only independent predictor of a too low ACT was increasing weight (odds ratio 1.02/kg, 95% confidence interval 1.01–1.03, p=0.001). Patients with a too low ACT had less often an open infarct related vessel (initial TIMI flow 2,3) as compared to patients with an ACT in range (36.5% vs. 45.9%, p=0.013). In only a minority of patients with STEMI, pre-hospital treatment with a fixed bolus dose UFH is within the therapeutic ACT range. Increased weight is an independent determinant of a too low ACT. We strongly recommend weight adjusted administration of UFH in the ambulance.
Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia
Authors: Jankowitz Rachel , Jaworski Kristen , Merricks Elizabeth , Kloos Mark , Nichols Timothy , Ragni Margaret 
Published: August 2011

SummaryLack of effective treatment for menorrhagia is the greatest unmet healthcare need in women with von Willebrand disease (VWD). We conducted a single-centre phase II clinical trial to determine efficacy and safety of recombinant IL-11 (rhIL-11, Neumega®) given subcutaneously for up to seven days during six consecutive menstrual cycles each in seven women with mild VWD and menorrhagia refractory to haemostatic or hormonal agents. rhIL-11 reduced menstrual bleeding severity as measured by pictorial blood assessment chart (PBAC) ≥50% (to <100) in 71% of subjects, cycle severity ≥50% in 71%, and bleeding duration ≥2 days in 85%, all p≤0.01. After rhIL-11, plasma VWF:RCo increased 1.1-fold, but did not correlate with PBAC, r=0.116, bleeding duration, r=0.318, or cycle severity, r=-0.295, or hsCRP, r=-0.003, all p>0.05. Platelet VWF mRNA expression by quantitative PCR increased mean four-fold (1.0–13.5). rhIL-11 was well tolerated with grade 1 or less fluid retention, flushing, conjunctival erythema, and local bruising. In summary, rhIL-11 reduces menorrhagia safely and warrants further study.
Identification of thrombin-like activity in ovarian cancer associated ascites and modulation of multiple cytokine networks
Authors: Morena Emilia , Belotti Dorina , Carraro Fabio , Allavena Paola , Giavazzi Raffaella , Naldini Antonella 
Published: August 2011

SummaryBlood coagulation cascades can be activated by different mechanisms and to different levels in cancer patients. In a study conducted on the transcriptional profile of epithelial ovarian cancer patients a number of possible links between coagulation and inflammation have been suggested and we and others have reported that, in addition to its central role in blood coagulation and haemostasis, thrombin is a powerful regulator of inflammatory responses. Here, we report that thrombin-like activities were present in the malignant ascites of patients with ovarian carcinoma. Malignant ascites significantly enhanced the release of cytokines/chemokines, which have been previously shown to support tumour progression, such as interleukin (IL)-6, IL-1β, CCL2 and CXCL8, in human peripheral blood mononuclear cells of healthy volunteers. Interestingly, ascites enhanced the release of the anti-inflammatory cytokine IL-10 and inhibited the production of interferon-γ and IL-12. The presence of the anticoagulant antithrombin reversed IL-12 inhibition induced by ascites in human monocytes. Finally, the use of thrombin and of the specific thrombin receptor (PAR) agonist peptides, TFLLRN and AYGPK, suggests that IL-12 inhibition is thrombin-specific and related to PAR-1, but not to PAR-4. These findings underline the tight relationship between the coagulation pathway, where thrombin is the key enzyme, and cytokine modulation, including IL-12 inhibition, which is a critical feature of the tumour microenvironment, and may represent a powerful strategy used by tumours to escape immune surveillance.
Heterozygosity for R1141X in
ABCC6
and Risk of Ischemic Vascular Disease
Authors: Hornstrup Louise S. , Tybjærg-Hansen Anne , Haase Christiane L. , Nordestgaard Børge G. , Sillesen Henrik , Grande Peer , Frikke-Schmidt Ruth 
Published: August 2011

Background—
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by loss-of-function mutations in ABCC6 and characterized by elastic calcification leading to dermal, ocular, and ischemic vascular disease. We tested the hypothesis that heterozygosity for R1141X, the most frequent PXE-causing mutation in Caucasians, associated with risk of ischemic vascular disease, as previous studies suggested 4- to 11-fold risk of ischemic heart disease (IHD) in heterozygotes.

Methods and Results—
We studied 10 276 persons from the general population, including 1985 with IHD and 989 with ischemic cerebrovascular disease (ICVD). We examined 45 603 individuals from a cross-sectional general population study, of whom 3738 had IHD and 2335 had ICVD. Finally, we compared 4851 patients with IHD and 625 patients with ICVD with, respectively, 4851 and 625 matched control subjects. We genotyped participants in all studies for ABCC6 R1141X. The frequency of R1141X was 0.6% in all populations studied. ABCC6 R1141X genotype was not associated with an increased risk of IHD, myocardial infarction, ICVD, or ischemic stroke. Furthermore, R1141X genotype did not interact with age on risk of the largest end point, IHD. Finally, R1141X genotype did not associate with variation in plasma levels of high-sensitivity C-reactive protein, fibrinogen, blood pressure, or lipid and lipoproteins in the general population.

Conclusions—
In 4 studies including 66 831 participants and 13 642 cases with ischemic vascular events, heterozygosity for ABCC6 R1141X did not associate with risk of IHD, myocardial infarction, ICVD, or ischemic stroke.
A Shift in Western Tropical Pacific Sea Level Trends during the 1990s
Authors: Merrifield Mark A. 
Published: August 2011

Abstract
Pacific Ocean sea surface height trends from satellite altimeter observations for 1993–2009 are examined in the context of longer tide gauge records and wind stress patterns. The dominant regional trends are high rates in the western tropical Pacific and minimal to negative rates in the eastern Pacific, particularly off North America. Interannual sea level variations associated with El Niño–Southern Oscillation events do not account for these trends. In the western tropical Pacific, tide gauge records indicate that the recent high rates represent a significant trend increase in the early 1990s relative to the preceding 40 years. This sea level trend shift in the western Pacific corresponds to an intensification of the easterly trade winds across the tropical Pacific. The wind change appears to be distinct from climate variations centered in the North Pacific, such as the Pacific decadal oscillation. In the eastern Pacific, tide gauge records exhibit higher-amplitude decadal fluctuations than in the western tropical Pacific, and the recent negative sea level trends are indistinguishable from these fluctuations. The shifts in trade wind strength and western Pacific sea level rate resemble changes in dominant global modes of outgoing longwave radiation and sea surface temperature. It is speculated that the western Pacific sea level response indicates a general strengthening of the atmospheric circulation over the tropical Pacific since the early 1990s that has developed in concert with recent warming trends.
Quantitative Flood Forecasting on Small- and Medium-Sized Basins: A Probabilistic Approach for Operational Purposes
Authors: Silvestro Francesco , Rebora Nicola , Ferraris Luca 
Published: August 2011

AbstractThe forecast of rainfall-driven floods is one of the main themes of analysis in hydrometeorology and a critical issue for civil protection systems. This work describes a complete hydrometeorological forecast system for small- and medium-sized basins and has been designed for operational applications. In this case, because of the size of the target catchments and to properly account for uncertainty sources in the prediction chain, the authors apply a probabilistic framework. This approach allows for delivering a prediction of streamflow that is valuable for decision makers and that uses as input quantitative precipitation forecasts (QPF) issued by a regional center that is in charge of hydrometeorological predictions in the Liguria region of Italy. This kind of forecast is derived from different meteorological models and from the experience of meteorologists. Single-catchment and multicatchment approaches have been operationally implemented and studied. The hydrometeorological forecasting chain has been applied to a series of case studies with encouraging results. The implemented system makes effective use of the quantitative information content of rainfall forecasts issued by expert meteorologists for flood-alert purposes.
Comparison of Minimally Invasive Techniques in Tongue Base Surgery in Patients with Obstructive Sleep Apnea
Authors: Babademez Mehmet Ali , Yorubulut Mehmet , Yurekli Muge Fethiye , Gunbey Emre , Baysal Selcan , Acar Baran , Karaşen Rıza Murat 
Published: August 2011

ObjectiveTo compare the effectiveness and morbidity of 3 microinvasive tongue base surgical procedures combined with uvulopalatopharyngoplasty (UPPP) in supine‐dependent obstructive sleep apnea (OSA) patients.Study DesignA prospective, randomized clinical study.SettingA tertiary referral center.MethodsFifty OSA patients were randomly advised to undergo UPPP combined with low‐temperature bipolar radiofrequency (group 1), submucosal minimally invasive lingual excision with radiofrequency (SMILE‐R; group 2), or submucosal minimally invasive lingual excision with a harmonic scalpel (SMILE‐H; group 3). The Epworth Sleepiness Scale, the visual analog scale (VAS) for snoring, the pre‐ and postoperative 3‐month polysomnography (PSG) findings, and the decrease in tongue volume using magnetic resonance imaging (MRI) were compared. The operation times, the postoperative pain VAS score, the analgesic requirement, and the time in commencing a normal diet were compared in the 3 groups.ResultsThe decrease in apnea‐hypopnea index (AHI) and supine AHI values at the postoperative 3‐month time point was significant in group 2 (P <. 05). The decrease in tongue volume at the 3‐month postoperative time point according to the MRI evaluations was higher in groups 1 and 2 (P <. 05). In the subjective comparison of effectiveness, there was no significant difference. The operation time was significantly lower in group 3. In the assessment of postoperative pain, no significant difference was found between the groups.ConclusionWhen the PSG findings and MRI were evaluated, UPPP + SMILE‐R were found to be more effective. No significant difference was found between the 3 techniques when morbidity and complications were compared.
A randomized controlled trial of the effects of muscle stretching, manual therapy and steroid injections in addition to ‘stay active’ care on health-related quality of life in acute or subacute low back pain
Authors: Grunnesjö Marie I , Bogefeldt Johan P , Blomberg Stefan IE , Strender Lars-Erik , Svärdsudd Kurt F 
Published: August 2011

Objective: To evaluate the health-related quality of life effects of muscle stretching, manual therapy and steroid injections in addition to ‘stay active’ care in acute or subacute low back pain patients. Study design: A randomized, controlled trial during 10 weeks with four treatment groups. Setting: Nine primary health care and one outpatient orthopaedic hospital department. Subjects: One hundred and sixty patients with acute or subacute low back pain. Interventions: Ten weeks of ‘stay active’ care only (group 1), or ‘stay active’ and muscle stretching (group 2), or ‘stay active’, muscle stretching and manual therapy (group 3), or ‘stay active’, muscle stretching, manual therapy and steroid injections (group 4). Main measures: The Gothenburg Quality of Life instrument subscales Well-being score and Complaint score. Results: In a multivariate analysis adjusted for possible outcome affecting variables other than the treatment given Well-being score was 68.4 (12.5), 72.1 (12.4), 72,3 (12.4) and 72.7 (12.5) in groups 1–4, respectively ( P for trend <0.05). There were significant trends for the well-being components patience ( P < 0.005), energy ( P < 0.05), mood ( P < 0.05) and family situation ( P < 0.05). The remaining two components and Complaint score showed a non-significant trend towards improvement. Conclusion: The effects on health-related quality of life were greater the larger the number of treatment modalities available. The ‘stay active’ treatment group, with the most restricted number of modalities, had the most modest health-related quality of life improvement, while group 4 with the most generous choice of treatment modalities, had the greatest improvement.
Effective home programme intervention for adults: a systematic review
Authors: Novak Iona 
Published: August 2011

Objective: To summarize evidence on effective home programme intervention for adults and describe characteristics of successful home programmes. Data sources: A search was conducted of MEDLINE, CINAHL, PsycINFO, EMBASE, DARE, The Physiotherapy Evidence Database, Cochrane Database of Systematic Reviews, OTSeeker and Google Scholar and references in manuscripts retrieved. Review methods: Two independent reviewers determined whether retrieved study abstracts met inclusion criteria: human subjects; adults; home programme intervention; systematic reviews, randomized controlled trials or controlled trials. Included papers were appraised for study design, participants, type and intensity of intervention, and outcomes. Methodological quality of trials was rated using the PEDro scale (1–10 highest). Results: Thirty-two papers were retrieved (6 systematic reviews, 26 trials). The 23 randomized controlled trials and 3 controlled trials were appraised. All the retrieved papers were level 1a, 1b or 2b evidence. Major findings were: (a) home programme intervention was more effective than no intervention at all; (b) home programme intervention was equally effective to expert-provided therapy, except when therapeutic modalities were used; and (c) different instruction formats produced similar outcomes. Home programmes with favourable outcomes were more likely to: involve the patients in establishing the programme; intervene on the person, task and environment; and provide feedback about progress. Dose did not appear to be related to outcome. Conclusion: There is grade 1A evidence supporting the effectiveness of home programmes for adults. Home programmes are as effective as expert-provided therapy.
Junior doctors’ learning and development in foundation year 1 posts in palliative medicine
Authors: Morrison Catherine , Forbes Karen 
Published: August 2011

Background: The ability to provide good palliative care to patients is increasingly recognised as a core clinical skill that all doctors should possess. Few junior doctors, however, feel competent in breaking bad news, pain relief and the care of dying patients by the time they are fully registered to practice. Aim: The aim of this study was to explore doctors’ experiences in foundation year 1 (F1) palliative medicine posts. Design: Participants underwent semi-structured interviews and interview transcripts were analysed using Interpretative Phenomenological Analysis. Setting/participants: The study involved a purposive sample of six F1 doctors matched in 2005-2006 to rotations incorporating palliative medicine posts at two acute hospital National Health Service (NHS) Trusts and one NHS hospice in the UK. Results: F1 doctors were satisfied with the learning opportunities provided by the posts, which achieved the right balance between supported and autonomous working. They described learning through their day-to-day interactions with staff, including specialist nurses, and by practising their skills on the job. Some struggled, however, to make the transition to a more independent learning style in the clinical environment. Trainees felt the post helped them to develop generic skills, such as symptom control, diagnosing dying and breaking bad news. Whilst they found split posts and on-call rotas disrupted their palliative care learning, these offered important opportunities to learn additional F1 skills. Conclusions: F1 posts in palliative medicine in the UK have positive influences on perceived generic skills development and practice. These findings might encourage the development of more rotations incorporating palliative medicine in the future.
A tale of three labels: translating the JUPITER trial data into regulatory claims
Authors: Ridker Paul M 
Published: August 2011

Background Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Purpose Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. Methods The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C <130 mg/dL and hsCRP ≥2 mg/L, provides the only available data on rosuvastatin for primary prevention of cardiovascular disease. Thus, the JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. Results JUPITER demonstrated a 44% reduction ( p < 0.000001) in the trial pre-specified primary endpoint (nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, coronary revascularization, or cardiovascular death) with no evidence of heterogeneity across geographic regions. In response to these data, the US Food and Drug Administration label for rosuvastatin in primary prevention came closest to the actual JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with ‘at least two conventional risk factors for cardiovascular disease,’ a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to ‘high risk individuals' ignoring hsCRP and using instead a post hoc definition of ‘high risk’ that comprised a subgroup of less than 10% of the study population who contributed but 67 events to the study total and did not show statistical significance when compared to placebo. None of the regulatory labels included the trial primary endpoint; instead, each focused on separate and different components of the primary endpoint. Similar discrepancies were found between European and North American regulatory agencies with regard to earlier pivotal trials of statins for primary prevention, but not for secondary prevention. Limitations The JUPITER experience represents a case study and is not a systematic review of the regulatory decision process. Conclusions Labeling indications can vary widely in different regulatory environments even when based on the same trial data.