bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects ofMHRAdrug safety advice on time trends in prescribing volume and indices of clinical toxicity for quinine
Authors: Acheampong Paul , Cooper Gill , Khazaeli Behshad , Lupton David J. , White Sue , May Margaret T. , Thomas Simon H. L. 
Published: April 2013

AimsTo ascertain the effects of theMedicines andHealthcare productsRegulatoryAgency's (MHRA) safety update inJune 2010 on the volume of prescribing of quinine and on indices of quinine toxicity.MethodsWe analysed quarterly primary care total and quinine prescribing data forEngland and quinine prescribing volume for individualPrimaryCareTrusts in theNorthEast ofEngland from 2007/8 to 2011/12 obtained from theePACT.net database. We also analysed quinine toxicity enquiries to theNationalPoisonsInformationService (NPIS) viaToxbase® and by telephone between 2004/5 and 2011/12. Joinpoint regression andPearson's correlation tests were used to ascertain changes in trends in prescribing and indices of toxicity and associations between prescribing and indices of toxicity, respectively.ResultsTotal prescribing continued to increase, but annual growth in quinine prescribing inEngland declined from 6.0 to −0.6% following theMHRAupdate [difference −0.04 (95% confidence interval −0.07 to −0.01) quinine prescriptions per 100 patients per quarter,P= 0.0111]. Much larger reductions were observed inPrimaryCareTrusts that introduced comprehensive prescribing reviews. The previously increasing trend inToxbase® quinine searches was reversed [difference −19.76 (95% confidence interval −39.28 to −9.20) user sessions per quarter,P= 0.0575].Telephone enquiries toNPISfor quinine have declined, with stabilization of the proportion of moderate to severe cases of quinine poisoning since the update.ConclusionsTheMHRAadvice was followed by limited reductions in the growth in quinine prescribing and in indicators of quinine overdose and toxicity. Quinine prescribing, however, remains common, and further efforts are needed to reduce availability and use.
Population pharmacokinetics of recombinant human C1 inhibitor in patients with hereditary angioedema
Authors: Farrell Colm , Hayes Siobhan , Relan Anurag , van Amersfoort Edwin S. , Pijpstra Rienk , Hack C. Erik 
Published: April 2013

AimsTo characterize the pharmacokinetics (PK) of recombinant human C1 inhibitor (rhC1INH) in healthy volunteers and hereditary angioedema (HAE) patients.MethodsPlasma levels of C1INH following 294 administrations of rhC1INH in 133 subjects were fitted using nonlinear mixed‐effects modelling. The model was used to simulate maximal C1INH levels for the proposed dosing scheme.ResultsA one‐compartment model with Michaelis–Menten elimination kinetics described the data. Baseline C1INH levels were 0.901 [95% confidence interval (CI): 0.839–0.968] and 0.176 U ml−1 (95% CI: 0.154–0.200) in healthy volunteers and HAE patients, respectively. The volume of distribution of rhC1INH was 2.86 l (95% CI: 2.68–3.03). The maximal rate of elimination and the concentration corresponding to half this maximal rate were 1.63 U ml−1 h−1 (95% CI: 1.41–1.88) and 1.60 U ml−1 (95% CI: 1.14–2.24), respectively, for healthy volunteers and symptomatic HAE patients. The maximal elimination rate was 36% lower in asymptomatic HAE patients. Peak C1INH levels did not change upon repeated administration of rhC1INH. Bodyweight was found to be an important predictor of the volume of distribution. Simulations of the proposed dosing scheme predicted peak C1INH concentrations above the lower level of the normal range (0.7 U ml−1) for at least 94% of all patients.ConclusionsThe population PK model for C1INH supports a dosing scheme on a 50 U kg−1 basis up to 84 kg, with a fixed dose of 4200 U above 84 kg. The PK of rhC1INH following repeat administration are consistent with the PK following the first administration.
A systematic review and meta‐analysis of pharmacist‐led fee‐for‐services medication review
Authors: Hatah Ernieda , Braund Rhiannon , Tordoff June , Duffull Stephen B. 
Published: April 2013

AimThe aim was to examine the impact of fee‐for‐service pharmacist‐led medication review on patient outcomes and quantify this according to the type of review undertaken, e.g. adherence support and clinical medication review.MethodsRelevant published studies were identified from Medline, Embase and International Pharmaceutical Abstract databases (from inception to February 2011). Study inclusion criteria were fee‐for‐service medication review, presence of a control group and pre‐specified patient outcomes. Outcomes were grouped into primary (changes in biomarkers, hospitalization, and mortality) and secondary outcomes (medication adherence, economic implications and quality of life). Meta‐analyses for primary outcomes were conducted using random effects models and secondary outcomes were summarized using descriptive statistics.ResultsOf the 135 relevant articles located, 21 studies met the inclusion criteria for primary outcomes and 32 for secondary outcomes. Significant results favouring pharmacists' intervention were found for blood pressure (OR 3.50, 95% CI 1.58, 7.75, P = 0.002) and low density lipoprotein (OR 2.35, 95% CI 1.17, 4.72, P = 0.02). Outcomes on hospitalization (OR 0.69, 95% CI 0.39, 1.21, P = 0.19) and mortality (OR 1.50, 95% CI 0.65 to 3.46, P = 0.34) indicated no differences between the groups. On subgroup analysis, clinical medication review (OR 0.46, 95% CI 0.26, 0.83, P = 0.01) but not adherence support review (OR 0.88, 95% CI 0.59, 1.32, P = 0.54) reduced hospitalization.ConclusionsThe majority of the studies (57.9%) showed improvement in medication adherence. Fee‐for‐service pharmacist‐led medication reviews showed positive benefits on patient outcomes. Interventions that include a clinical review had a significant impact on patient outcomes by attainment of target clinical biomarkers and reduced hospitalization.
Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside
Authors: Deutsch Varda R. , Tomer Aaron 
Published: April 2013

SummaryMegakaryocytopoiesis involves the commitment of haematopoietic stem cells, proliferation and terminal differentiation of megakaryocytic progenitors (MK‐p) and maturation of megakaryocytes (MKs) to produce functional platelets. This complex process occurs in specialized niches in the bone marrow where MKs align adjacent to vascular endothelial cells, form proplatelet projections and release platelets into the circulation. Thrombopoietin (THPO, TPO) is the primary growth factor for the MK lineage and necessary at all stages of development. THPO is constitutively produced in the liver, and binds to MPL (c‐Mpl) receptor on platelets and MKs. This activates a cascade of signalling molecules, which induce transcription factors to drive MK development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free THPO, which induces a concentration‐dependant compensatory response of marrow‐MKs to enhance platelet production. Newly developed thrombopoietic agents operating via MPL receptor facilitate platelet production in thrombocytopenic states, primarily immune thrombocytopenia. Other drugs are available for attenuating malignant thrombocytosis. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease states, and the innovative drugs and therapeutic modalities to stimulate or decrease thrombopoiesis.
Outcomes of treatment for relapsed acute lymphoblastic leukaemia in children with Down syndrome
Authors: Meyr Franziska , Escherich Gabriele , Mann Georg , Klingebiel Thomas , Kulozik Andreas , Rossig Claudia , Schrappe Martin , Henze Günter , von Stackelberg Arend , Hitzler Johann 
Published: April 2013

SummaryChildren with Down syndrome (DS) have a greater risk for developing both acute lymphoblastic leukaemia (ALL) and significant adverse effects of chemotherapy. We investigated their outcome with, and tolerance of, treatment protocols for relapsed ALL optimized in the paediatric population without DS. Probability of survival and causes of treatment failure were determined for 49 children with DS and a matched cohort of 98 children without DS among 2160 children treated for relapsed ALL in clinical trials conducted by the Berlin‐Frankfurt‐Münster ALL Relapse Study Group between 1983 and 2012. Despite more favourable ALL relapse characteristics, children with DS experienced lower event‐free (EFS) and overall survival (OS) than the control group without DS (EFS 17 ± 08% vs. non‐DS 41 ± 06%, P = 0·006; OS 17 ± 09% vs. non‐DS 51 ± 06%, P < 0·001). Children with DS developed more frequently fatal complications of treatment (34 ± 07% vs. non‐DS 10 ± 04%, P < 0·001). During the last decade, EFS and OS were no longer significantly different in children with and without DS (EFS 31 ± 09% vs. 36 ± 09%, P = 0·399; OS 31 ± 12% vs. 53 ± 09%, P = 0·151). DS proved an independent prognostic factor of outcome after ALL relapse. Induction deaths and treatment‐related mortality but not subsequent relapse were the main barrier to successful outcomes of relapse therapy in children with DS.
Children's strategies to handle cancer: a video ethnography of imaginal coping
Authors: Rindstedt C. 
Published: April 2013

AbstractBackgroundThis article explores how children use fantasy, play, and coping (imaginal coping) in order to handle chronic illness. Imaginal coping, as a theoretical construct, is defined as the use of imagination to deal with the hardships of illness. The overarching aim has been to investigate the various ways in which categories of staff members (doctors, nurses, play therapists, and hospital clowns) and parents support children in their coping. Focus has thus been on collaborative or interactive aspects of playful coping.MethodA large proportion of the data collected consists of 93 h of video‐recorded interactions between children, parents and staff. The collection of data involved fieldwork carried out with the use of a video ethnographic method, making it possible thereby to analyse and work with data in greater detail. For more than one year, five children with leukaemia were followed as each made their regular visits to a children's cancer clinic in a children's hospital in Sweden.ResultsCollaborative storytelling, humorous treatment practices, playful rituals, as well as role‐reversal play, were all types of events involving staff–child collaboration and creative improvisation.ConclusionsStaff, along with parents, played a significant role in the coping process. In various ways, the staff members helped the parents to respond to their children in ways adaptive for coping. It can be seen that imaginal coping is a highly interactional business. In this study it is shown that parents socialize coping; this is sometimes undertaken explicitly, for example, through coaching (in the form of instructions or suggestions) and teaching. But often it is achieved through modelling or intent participation, with the child observing staff members' treatment practices.
Reliability and validity of the Parent Efficacy for Child Healthy Weight Behaviour (PECHWB) scale
Authors: Palmer F. , Davis M. C. 
Published: April 2013

AbstractBackgroundInterventions for childhood overweight and obesity that target parents as the agents of change by increasing parent self‐efficacy for facilitating their child's healthy weight behaviours require a reliable and valid tool to measure parent self‐efficacy before and after interventions. Nelson and Davis developed the Parent Efficacy for Child Healthy Weight Behaviour (PECHWB) scale with good preliminary evidence of reliability and validity. The aim of this research was to provide further psychometric evidence from an independent Australian sample.MethodsData were provided by a convenience sample of 261 primary caregivers of children aged 4–17 years via an online survey. PECHWB scores were correlated with scores on other self‐report measures of parenting efficacy and 2‐ to 4‐week test–retest reliability of the PECHWB was assessed.ResultsThe results of the study confirmed the four‐factor structure of the PECHWB (Fat and Sugar, Sedentary Behaviours, Physical Activity, and Fruit and Vegetables) and provided strong evidence of internal consistency and test–retest reliability, as well as good evidence of convergent validity.ConclusionFuture research should investigate the properties of the PECHWB in a sample of parents of overweight or obese children, including measures of child weight and actual child healthy weight behaviours to provide evidence of the concurrent and predictive validity of PECHWB scores.
Tumour diameter is a predictor of mesorectal and mesenteric lymph node metastases in anorectal melanoma
Authors: Wang M. , Zhang Z. , Zhu J. , Sheng W. , Lian P. , Liu F. , Cai S. , Xu Y. 
Published: April 2013

AbstractAimAnorectal melanoma is a rare neoplasm with poor prognosis. The aim of this study was to investigate what clinicopathological factors predict lymph node metastases and to investigate their association with survival.MethodPatients undergoing surgery with curative intent for primary anorectal melanoma in Fudan University Shanghai Cancer Center between 1989 and 2011 were studied retrospectively. The associations between clinicopathological factors and lymph node metastases and prognosis were determined.ResultsForty‐three patients underwent a potentially curative resection with a median follow‐up of 20 months; the 5‐year overall survival rate was 29.6% with median overall survival of 28 months. Tumour diameter > 3 cm was associated with mesorectal and mesenteric lymph node metastases (P = 0.013). Perineural invasion (hazard ratio 5.683; 95% CI 1.978–16.328; P = 0.001) was the only factor that independently predicted survival.ConclusionTumour diameter was associated with mesorectal and mesenteric lymph node metastases; therefore, wide local excision may not be appropriate for surgery with curative intent for patients with a tumour diameter ≥ 3 cm. Perineural invasion was an important prognostic factor for anorectal melanoma.
Using AI to Understand Key Success Features in Evolving CTSAs
Authors: Kusch Jennifer D. , Nelson David A. , Simpson Deborah , Gerrits Ronald , Glass Laurie 
Published: April 2013

AbstractA vital role for Clinical and Translational Science Award (CTSA) evaluators is to first identify and then articulate the necessary change processes that support the research infrastructures and achieve synergies needed to improve health through research. The use of qualitative evaluation strategies to compliment quantitative tracking measures (e.g., number of grants/publications) is an essential but under‐utilized approach in CTSA evaluations. The Clinical and Translational Science Institute of Southeast Wisconsin implemented a qualitative evaluation approach using appreciative inquiry (AI) that has revealed three critical features associated with CTSA infrastructure transformation success: developing open communication, creating opportunities for proactive collaboration, and ongoing attainment of milestones at the key function group level. These findings are consistent with Bolman & Deal's four interacting hallmarks of successful organizations: structural (infrastructure), political (power distribution; organizational politics), human resource (facilitating change among humans necessary for continued success), and symbolic (visions and aspirations). Data gathered through this longitudinal AI approach illuminates how these change features progress over time as CTSA funded organizations successfully create the multiinstitutional infrastructures to connect laboratory discoveries with the diagnosis and treatment of human disease.
How to Build an Integrated Biobank: The Washington University Translational Cardiovascular Biobank & Repository Experience
Authors: Yamada Kathryn A. , Patel Akshar Y. , Ewald Gregory A. , Whitehead Donna S. , Pasque Michael K. , Silvestry Scott C. , Janks Deborah L. , Mann Douglas L. , Nerbonne Jeanne M. 
Published: April 2013

AbstractTranslational studies that assess and extend observations made in animal models of human pathology to elucidate relevant and important determinants of human diseases require the availability of viable human tissue samples. However, there are a number of technical and practical obstacles that must be overcome in order to perform cellular and electrophysiological studies of the human heart. In addition, changing paradigms of how diseases are diagnosed, studied and treated require increasingly complex integration of rigorous disease phenotyping, tissue characterization and detailed delineation of a multitude of “_omics”. Realizing the need for quality‐controlled human cardiovascular tissue acquisition, annotation, biobanking and distribution, we established the Translational Cardiovascular Biobank & Repository at Washington University School of Medicine. Several critical details are essential for the success of cardiovascular biobanking including coordinated, trained and dedicated staff members; adequate, nonrestrictive informed consent protocols; and fully integrated clinical data management applications for annotating, tracking and sharing of tissue and data resources. Labor and capital investments into growing biobanking resources will facilitate collaborative efforts aimed at limiting morbidity and mortality due to heart disease and improving overall cardiovascular health.
An Evaluation Tool for Collaborative Clinical Research Centers
Authors: Tragus Robin , Cody Jannine D. 
Published: April 2013

AbstractThere is a need for metrics that describe the full range of services provided by a clinical research unit; given that services have expanded to include such things as investigator training, regulatory compliance monitoring, and budget negotiations. We developed a tool and methodology that allows tracking of these expanded services. This not only allowed us to more accurately describe the work of the research unit staff, but to monitor the status of a study across the entire study lifespan from the idea to the publication. In addition to measuring work, it allows us to anticipate future needs in clinical staff and expertise because we are involved very early in study planning. We also expect that by analyzing these data from many studies over time, we will identify process barriers that will direct future program improvement.
Developing Future Clinician Scientists while Supporting a Research Infrastructure
Authors: Holsti Maija , Adelgais Kathleen M. , Willis Leah , Jacobsen Kammy , Clark Edward B. , Byington Carrie L. 
Published: April 2013

AbstractBackgroundSupporting clinical research is a national priority. Clinician scientists are rare and clinical trials in academic medical centers (AMC) often fail to meet enrollment goals. Undergraduate students interested in biomedical careers often lack opportunities to perform clinical research.ObjectiveDescribe an innovative undergraduate course that supports clinical research in an AMC.MethodsThe course, Clinical Research Methods and Practice, offers undergraduate students the opportunity to learn clinical research through didactic and practical experiences. The students in turn support clinician scientists’ conduct of clinical studies in an AMC. Clinician scientists receive research support and participate in mentoring sessions for students.ResultsOver seven semesters, 128 students have assisted in 21 clinical studies located in outpatient and inpatient units of two hospitals. Students identified and screened eligible patients, collected clinical data, assisted in obtaining informed consent, and transported specimens. Many of the clinician scientists have met their enrollment goals and several have been top‐enrollers in multicenter clinical trials as a result of student support.ConclusionsThe Clinical Research Methods and Practice class addresses barriers to clinical research in AMC. This may be a model for institutions committed to mentoring students early in their career and to developing infrastructures for clinical research. Clin Trans Sci 2013; Volume 6: 94–97
Cytomorphological features of metastatic squamous cell carcinoma in serous effusions
Authors: Huang C. C. , Michael C. W. 
Published: April 2013

ObjectiveTo study the cytomorphological features of squamous cell carcinoma (SCC) in serous effusions.MethodsConventional smears from 23 SCC were reviewed for the following features: cellularity, single cells, cell clusters, long cords, squamous pearls, cell‐in‐cell, ‘windows’, polygonal cells, anucleated cells, tadpole cells, fibre cells, third‐type cells, refractile cytoplasmic ring, two‐tone cytoplasm, cytoplasmic density, cytoplasmic vacuoles, signet ring cells, nuclear/cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleolus, anaplastic cells and mitosis. Subsequently, we also reviewed 15 reactive mesothelium, 18 mesotheliomas and 24 adenocarcinomas for comparison.ResultsMost SCC smears comprised mixed populations of single cells and cell clusters. Keratinized squamous cells and squamous pearls were diagnostic for well‐differentiated SCC. Squamous eddies, appreciated on the cell block sections appearing as two‐dimensional cell clusters with a swirling pattern, were characteristic for SCC. Poorly differentiated/third‐type cells with atypical cytoplasmic keratinization, manifest as two‐tone cytoplasm with a well‐defined border and occasionally a refractile central ring, were an important clue for the squamous origin of the cells. Features including cell‐in‐cell, cytoplasmic vacuolation, double or multinucleated cells, anaplastic cells and mitotic figures were present in various degrees, and were not of diagnostic value.ConclusionsCertain cytological features are diagnostic for SCC, whereas other features of poorly differentiated SCC often overlap with those of reactive mesothelial cells, mesothelioma, metastatic adenocarcinoma or urothelial carcinoma in serous effusions. The combination of clinical history, appropriate immunohistochemical panel and cytomorphological features are important to ensure a correct diagnosis.
Community Members' Engagement with and Involvement in Genomic Research: Lessons to Learn from the Field
Authors: Folayan Morenike O. , Oyedeji Kolawole S. , Fatusi Olawunmi A. 
Published: April 2013

AbstractIn this paper, we describe the potential role laypersons on ethics committees can play in ensuring community concerns are addressed in the design and implementation of genomic research. We draw inferences from the outcome of an empirical study of the impact of training of laypersons to address community engagement issues in ethics review of research protocol. While this paper does not advocate a particular solution, it describes the importance of community engagement in genomic research, the current limitations there are in engaging communities in the design of these research projects and how communities can be indirectly engaged in the design and implementation of genomic research through the engagement of laypersons on ethics committees. However, to ensure that these laypersons can play this role, their capacity needs to be built to play this role appropriately. There is evidence to show that where resources are invested in building the capacity of laypersons to play their role as community ‘watchdogs’ in research, they play this role aptly. Community engagement is important in genomic research as genomic researchers will increasingly require community perspectives in critical ethics decision making.