bluuebunny/crossref_metadata_2025_split huggingface dataset:
With blood in the joint – what happens next? Could activation of a pro‐inflammatory signalling axis leading to iRhom2/TNFα‐convertase‐dependent release of TNFα contribute to haemophilic arthropathy?
Authors: Haxaire C. , Blobel C. P. 
Published: April 2014

SummaryOne of the main complications of haemophilia A is haemophilic arthropathy (HA), a debilitating disease with a significant negative impact on motility and quality of life. Despite major advances in the treatment of haemophilia A, many patients still suffer from HA. We wish to develop new treatments for HA, but must first better understand its causes. Our laboratory studies molecular scissors that release the pro‐inflammatory cytokine tumour necrosis factor alpha (TNFα) from cells. TNFα is considered the ‘fire alarm’ of the body – it helps to fight infections, but can also cause diseases such as inflammatory arthritis. We know that the molecular scissors, called TNFα convertase (TACE), and its newly discovered regulator termed iRhom2 can be rapidly activated by small amounts of cytokines, growth factors, and pro‐inflammatory mediators present in the blood. We hypothesize that the rapid activation of TACE could help explain one of the unsolved mysteries regarding the development of HA, which is how even small amounts of blood can provoke a persistent inflammatory response. We propose that once blood enters the joint, iRhom2 and TACE are activated to release TNFα and that this could promote the development of HA in a similar manner to that in which it promotes rheumatoid arthritis (RA). We are currently using immune cells stimulated with blood degradation products, and mouse models of HA, to test this hypothesis. If successful, our study could provide the rationale for testing anti‐TNF antibodies, which are already used to treat RA, for the treatment of HA. In addition, they might uncover iRhom2 and TACE as attractive new candidate targets for the treatment of HA.
Monitoring of modified factor VIII and IX products
Authors: Kitchen S. , Gray E. , Mertens K. 
Published: April 2014

SummaryThe dawning era of novel recombinant factor VIII and factor IX concentrates, many of which have been bioengineered to achieve prolonged activity, brings with it the need to consider the most appropriate clinical laboratory approaches for potency assignment, as well as the measurement of postinfusion levels. This session will highlight the known limitations and inconsistencies between existing assay methodologies with respect to currently available products, and discuss some of the early data with respect to the novel agents.
Genomics of bleeding disorders
Authors: Goodeve A. C. , Pavlova A. , Oldenburg J. 
Published: April 2014

SummaryMolecular genetic tools are widely applied in inherited bleeding disorders. New genes involved in haemorrhagic disorders have been identified by genome wide linkage analysis on families with a specific phenotype. LMNA1 or MCFD in combined FV/FVIII‐deficiency and VKORC1 in vitamin K coagulation factor deficiency type 2 are two examples. Identification of the causative gene mutation has become standard for most bleeding disorders. Knowledge of the causative mutation allows genetic counselling in affected families and most importantly adds to the pathophysiological understanding of phenotypes. Haemophilia A represents a model as the F8 gene mutation predicts the risk of developing an inhibitor and more recently also the bleeding phenotype. In this review novel genetic diagnostic strategies for bleeding disorders are outlined and inhibitor formation is presented as an example for clinical relevant phenotype/genotype correlation studies.
Prophylaxis in real life scenarios
Authors: Fischer K. , Konkle B. , Broderick C. , Kessler C. M. 
Published: April 2014

SummaryProphylaxis has become the standard mantra of care for those individuals with severe haemophilia A and B. Primary prophylaxis is advocated to prevent the occurrence of symptomatic acute spontaneous haemarthroses and to preserve joint structure and function. Typically, twice or thrice weekly infusions of factor VIII or IX concentrates are integral to this treatment approach. Secondary prophylaxis is initiated after the relentless cycle of progressive joint damage has been triggered by prior haemarthroses and is intended to preserve existing joint health by preventing additional spontaneous bleeding events. Event‐driven prophylaxis involves the administration of clotting factor concentrates to prevent acute traumatic bleeds, which are anticipated to occur in association with surgical or physical trauma. This regimen enhances the effectiveness of primary or secondary prophylaxis protocols or on‐demand approaches to replacement therapy. Besides the marked reduction in the so‐called annual bleed rate, prophylaxis regimens frequently increase personal self‐confidence to embark on a more active and physical lifestyle; however, in reality, prophylaxis must be individualized in accordance with bleeding phenotypes, with the unique pharmacokinetic profile of administered replacement clotting factor concentrates, with the specific clinical scenario, and with the degree of intensity anticipated for any physical activity. The introduction of extended half‐life replacement products will also influence how these prophylaxis regimens will be accomplished. The following scenarios will discuss how prophylaxis regimens can be implemented to protect the individual from developing spontaneous and activity‐induced acute bleeding complications and to maintain an improved quality of life.
Assessment of outcomes
Authors: Blanchette V. S. , O’Mahony B. , McJames L. , Mahlangu J. N. 
Published: April 2014

SummaryEffective healthcare delivery necessitates evaluation of the effect of interventions in the form of outcome assessment. Treatment effect includes measurement of how the patient feels, functions and survives following healthcare interventions. In haemophilia, which is a rare bleeding disorder, outcome assessment was characterized by a lack of validated outcome measurement tools and the challenges of hemophilia study design to collect outcome data. The aim of this communication is to share current thinking and, through practical examples, provide a state of the art practice in the assessment of hemophilia outcomes from a healthcare provider, patient/family and funder perspective. This discussion is timely and particularly relevant to the care of people with hemophilia on the eve of a number of novel hemophilia treatment products which are about to be licensed for use, specifically the long‐acting factor VIII and factor IX concentrates. The first section by Dr Blanchet gives an overview of the tools currently available for assessment of structure/function, patient activities and patient participation in hemophilia healthcare delivery, pointing out the challenge of developing new tools and appropriate validation of currently available tools. The second section by Mr Brian O'Mahony emphasizes the essential collaboration and partnership between healthcare providers and people with hemophilia in collating the outcome data. In the third and final section, Mr Leigh McJames, gives a funder's perspective of the desirable outcomes of hemophilia care.
Primary haemostasis: newer insights
Authors: Berndt M. C. , Metharom P. , Andrews R. K. 
Published: April 2014

SummaryAt the same time as biophysical and omics approaches are drilling deeper into the molecular details of platelets and other blood cells, as well as their receptors and mechanisms of regulation, there is also an increasing awareness of the functional overlap between human vascular systems. Together, these studies are redefining the intricate networks linking haemostasis and thrombosis with inflammation, infectious disease, cancer/metastasis and other vascular pathophysiology. The focus of this state‐of‐the‐art review is some of the newer advances relevant to primary haemostasis. Of particular interest, platelet‐specific primary adhesion‐signalling receptors and associated activation pathways control platelet function in flowing blood and provide molecular links to other systems. Platelet glycoprotein (GP)Ibα of the GPIb‐IX‐V complex and GPVI not only initiate platelet aggregation and thrombus formation by primary interactions with von Willebrand factor and collagen, respectively, but are also involved in coagulation, leucocyte engagement, bacterial or viral interactions, and are relevant as potential risk markers in a range of human diseases. Understanding these systems in unprecedented detail promises significant advances in evaluation of individual risk, in new diagnostic or therapeutic possibilities and in monitoring the response to drugs or other treatment.
Haemophilia care – beyond the treatment guidelines
Authors: Srivastava A. 
Published: April 2014

SummaryCare for people with haemophilia (PWH) has improved much over the last two decades leading to near normal lives for those receiving early regular prophylaxis with clotting factor concentrates (CFC). Yet, there are significant limitations of those practices. In the absence of a well‐defined optimal prophylaxis protocol, there are wide variations in practices with a two to threefold difference in doses. In those parts of the world where there are constraints on the availability of CFC, episodic replacement remains the norm for most patients even though it is evident that this does not change the natural history of the disease over a wide range of doses. Suitable prophylactic protocols therefore need to be developed wherever possible at these doses. Finally, there are only limited data on long‐term outcomes in haemophilia from anywhere in the world. The practice of documenting specific outcomes as part of the regular evaluation of PWH needs to be established and the appropriate instruments used to assess them. Definitions of clinical events and endpoints of interventions in clinical studies are being developed to help such data collection. The correlations between different replacement therapy protocols and specific outcomes will help define what is best at different dose levels. Such data will allow better health planning and treatment choices throughout the world.
Headache in Children With Chiari I Malformation
Authors: Toldo Irene , Tangari Marta , Mardari Rodica , Perissinotto Egle , Sartori Stefano , Gatta Michela , Calderone Milena , Battistella Pier Antonio 
Published: April 2014

BackgroundHeadache is the most common symptom of Chiari 1 malformation, a condition characterized by the herniation of cerebellar tonsils through the foramen magnum. However, the headache pattern of cases with Chiari 1 malformations is not well defined in the literature, especially in children.ObjectiveThe aim of this retrospective chart review was to evaluate the frequency and the characteristics of headache in children with Chiari 1 malformation at initial evaluation and during follow up.MethodsForty‐five cases with tonsillar ectopia were selected among 9947 cases under 18 years of age who underwent neuroimaging between 2002 and 2010. A semistructured clinical interview (mean follow‐up: 5.2 years) was conducted. Headache was classified according to the second edition of the International Classification of Headache Disorders.ResultsPossible associations between clinical picture, in particular headache pattern, but also other signs and symptoms attributable to Chiari 1 malformation, and the extent of tonsillar ectopia were found for 3 different groups: those with borderline (<5 mm, N = 12), mild (5‐9 mm, N = 27), and severe tonsillar ectopia (≥10 mm, N = 6), respectively. Twenty‐four out of 33 (73%) cases with Chiari 1 malformation complained of headache, and 9/33 (27%) of those patients (5 with mild and 4 with severe tonsillar ectopia) reported headache attributed to Chiari 1 malformation.ConclusionsIn our studied pediatric population, the most common symptom for cases diagnosed with Chiari 1 malformation was headache, and headache attributed to Chiari 1 malformation was the most common headache pattern in patients with Chiari 1 malformation. The presence of headache attributed to Chiari 1 malformation along with 3 other signs or symptoms of Chiari 1 malformation were highly predictive of severe tonsillar ectopia.
How General Practitioners Treat Migraine in Children – Evaluation of a Headache Guideline
Authors: de Coo Ilse F. , de Jong Gosse , Zielman Ronald , van den Berg Jan S.P. 
Published: April 2014

BackgroundMigraine is a common illness in children associated with a negative impact on the quality of life. In the Netherlands, treatment of migraine is commonly performed by general practitioners (GPs). The migraine guideline of the Dutch College of General Practitioners recommends inactivity and acetaminophen in patients with migraine who are younger than 18 years of age.ObjectiveThe aim of our study was to evaluate the pharmacological treatment of migraine in children by GPs before referral to the hospital. Our objective was to answer the following questions. First, are GPs inclined to prescribe medication not listed in the Dutch College of General Practitioners Guideline? Second, which clinical characteristics are associated with the use of medication not listed in this guideline?MethodsIn this retrospective cross‐sectional study, prescribed medication and migraine characteristics were investigated in Dutch migraine patients (age <18 years), using hospital records and a paper‐and‐pencil questionnaire.ResultsA total of 223 children were included. Medications not listed in the guideline were used in 41.3% of the patients before referral. In children younger than 12 years, the use of medication not listed in the guideline was associated with an older age, when compared with children who were treated according to the guideline. In the group of patients older than 11 years, the use of medication not listed in the guideline was associated with a longer history of migraine and a longer duration of the migraine attacks.ConclusionsMedications not listed in the GPs guideline were used in a large portion of the patients younger than 18 years with migraine who were referred to secondary care.
Medication Overuse Headache: Self‐Perceived and Actual Knowledge Among Pharmacy Staff
Authors: Hedenrud Tove , Babic Naida , Jonsson Pernilla 
Published: April 2014

ObjectiveThe aim of this study was to investigate knowledge about medication overuse headache (MOH) among pharmacy staff.BackgroundMOH is a public health problem both in Sweden and in many other countries. Persons with MOH have limited contact with health care, and medications used are to large extent over‐the‐counter (OTC) medications. Therefore, pharmacists have an important role in, eg, advising these individuals about their medication use. Little is, however, known about the actual level of knowledge about MOH among pharmacy staff, which determines the quality of their advice to MOH sufferers.MethodsA total of 326 questionnaires were distributed to 44 pharmacies in Gothenburg, Sweden. The questionnaire included background questions, questions about advice on headache treatment, source of knowledge about MOH, and questions on self‐perceived and actual knowledge on MOH.ResultsThe response rate was 70%. A majority of the pharmacy staff (90.6%) considered themselves to have knowledge about MOH to some or a greater extent. Almost half had learned about MOH through their university/vocational education. Only 8.6% knew that all 5 headache medications listed in the questionnaire can cause development of MOH, but 40% responded correctly on which treatment advice one can give a person with MOH. Actual knowledge on treatment advice differed significantly between groups of self‐perceived knowledge.ConclusionThe knowledge on MOH is insufficient among pharmacy staff, but with the proper knowledge, pharmacy staff is well positioned to effect both primary and secondary prevention of MOH. We suggest not only increasing educational efforts about MOH within pharmacy programs but also continuing education at the pharmacies for all staff. Further, it is also important to increase knowledge among pharmacy customers.
CAM in the Real World: You May Practice Evidence‐Based Medicine, But Your Patients Don't
Authors: Cowan Robert P. 
Published: April 2014

BackgroundComplementary and Alternative Medicine (CAM) approaches are widely used among individuals suffering from headache. The medical literature has focused on the evidence base for such use and has largely ignored the fact that these approaches are in wide use despite that evidence base.DiscussionThis article focuses on the uses of CAM by patients and suggests strategies for understanding and addressing this use without referring back to the evidence base. The rationale for this discussion pivots on the observation that patients are already using these approaches, and for many there are anecdotal and historical bases for use which patients find persuasive in the absence of scientific evidence.ConclusionUntil such time as the body of scientific literature adequately addresses non‐conventional approaches, physicians must acknowledge and understand, as best as possible, CAM approaches which are in common use by patients. This is illustrated with a case study and examples from practice. This article does not review the evidence base for various CAM practices as this has been done well elsewhere.
‘Today and more than ever, I FEEL LIKE A RESEARCHER’: successful online learning collaborations between librarians and a Graduate School
Authors: Newall Elizabeth , Gratton Christine , Maltby Jane 
Published: April 2014

AbstractThis article describes the development and delivery of an online module at the University of Nottingham on the literature review process. In particular, it discusses how academic librarians collaborated with researcher developers at the Graduate School at the University to deliver a highly successful online learning experience for students. The article provides an overview of the course, a discussion on the experiences of both the tutors and participants involved, concentrating specifically on those in Medicine and Health Sciences. Details about future international collaborations and development of the course are also provided.
Duration of injury correlates with necrosis in caerulein‐induced experimental acute pancreatitis: implications for pathophysiology
Authors: Jacob Tony G. , Raghav Rahul , Kumar Ajay , Garg Pramod K. , Roy Tara S. 
Published: April 2014

SummaryPancreatic acinar cell necrosis is indicative of severe pancreatitis and the degree of necrosis is an index of its outcome. We studied whether the dose and duration of injury correlates with severity, particularly in terms of necrosis, in caerulein‐induced acute pancreatitis (AP) in Swiss albino mice. In addition to control group 1 (G1), groups 2 and 3 received four injections of caerulein every hour but were sacrificed at five hours (G2) and nine hours (G3) respectively, and group 4 received eight injections and was sacrificed at nine hours (G4). The severity of pancreatitis was assessed histopathologically and biochemically. The histopathological scores of pancreatitis in groups 3 and 4 were significantly higher than in groups 1 and 2 (4 vs. 1, 4 vs. 2, 3 vs. 1, 3 vs. 2; P < 0.05). TUNEL‐positive apoptotic cells were significantly higher in groups 2 and 3 compared with groups 1 and 4 (P < 0.05). Necrosis was significantly more in group 4 than other groups (37.49% (4.68) vs. 19.97% (1.60) in G2; 20.36% (1.56) in G3; P = 0.006 for G 2 vs. 4 and P = 0.019 for G 3 vs. 4). Electron microscopy revealed numerous autophagosomes in groups 2 and 3 and mitochondrial damage and necrosis in group 4. The pancreatic and pulmonary myeloperoxidase activity in group 4 was significantly higher than that in the other groups (P < 0.01). Hence, severity of pancreatitis is a function of the dose of injurious agent, while inflammation is both dose and duration dependent, which may also explain the wide spectrum of severity of AP seen in clinical practice.
HLA‐A, HLA‐B and HLA‐DRB1 allele and haplotype diversity among volunteer bone marrow donors from Croatia
Authors: Grubic Z. , Burek Kamenaric M. , Mikulic M. , Stingl Jankovic K. , Maskalan M. , Zunec R. 
Published: April 2014

SummaryThe determination of human leucocyte antigen (HLA)‐A, HLA‐B and HLA‐DRB1 alleles in the routine procedure of a volunteer hematopoietic stem cell (HSC) donor's registration in the Croatian Bone Marrow Donor Registry (CBMDR) is performed to enhance the odds of finding a suitable HLA compatible donor for patients in need of a HSC transplantation worldwide. However, besides its original purpose, it also provides valuable information about the HLA polymorphism among Croats. The aim of the present study was to analyse the HLA allele and haplotype frequencies in a sample of 4000 donors from CBMDR. The distribution of HLA‐A, HLA‐B and HLA‐DRB1 alleles did not demonstrate significant differences from the data reported for other European populations. The higher frequency of B*40:02 allele in comparison with B*40:01 and DRB1*11:04 in comparison with DRB1*11:01 is interesting because it represents a difference in comparison with the Western and Northern European populations which are a main source of donors for Croatian patients. The haplotype frequencies show a greater variation and difference in comparison with data from other registries and populations; however, due to a lack of high‐resolution haplotype data, comparison was possible only with a very limited number of other populations.
A promoter polymorphism (rs3806798) of interleukin‐15 gene is associated with chronic hepatitis B virus infection in the Chinese Han population
Authors: Zhang X. , Sun X. H. , Li M. , Zhou Z. H. , Gao Y. Q. 
Published: April 2014

SummaryThis study aimed to investigate the association between the polymorphisms of IL‐15 gene and susceptibility to chronic hepatitis B virus (HBV) infection in the Chinese Han population. A total of 234 patients with chronic HBV infection and 150 age‐ and sex‐matched healthy controls in the Chinese population were enrolled in this case–control study. Genotyping of ten single nucleotide polymorphisms (SNPs) in the IL‐15 gene was carried out via Sequenom MassARRAY system. The association analysis demonstrated that SNP rs3806798 (A/T) had a significant difference in the distribution between patients and healthy controls (P = 0.033). Moreover, a significantly increased risk of HBV infection was found to be associated with IL‐15 rs3806798 A allele among male patients and HBeAg‐negative patients, compared with IL‐15 rs3806798 T allele (P = 0.003; P = 0.046, respectively). Furthermore, haplotype analysis revealed that haplotype ATAGG (rs3806798, rs12508866, rs1519551, rs6819823 and rs2857261, respectively) in block 1 was significantly associated with HBV infection (P = 0.022). In conclusion, we found an association between IL‐15 rs3806798 and the risk of chronic HBV infection in a sample of Chinese Han population.