bluuebunny/crossref_metadata_2025_split huggingface dataset:
How many people need expert symptom assessment but are not in the last year of life?
Authors: Maher J. , McConnel H. 
Published: May 2012

IntroductionEarlier palliative assessment and support for symptom self management may reduce distress and health resource use in incurable illness. The end of life tariff includes assessment of unstable symptoms, even if not in the last year of life. Current hospital recording systems do not allow timely identification of these individuals. Understanding how many people have palliative needs but are not in the last year of life will be increasingly important.Aims and MethodsTo identify people living with cancer at different phases across the care pathway including those at risk of developing complex symptoms, with progressive illness or at end of life. Using available data and clinically led assumptions we make indicative estimates of the number of people in different health states – particularly those with palliative care needs and not in the last year of life.ResultsWe estimate pathway phases for breast, prostate, colorectal and lung cancers. For example, we estimate that in one year 48,000 women develop breast cancer in the UK and 12,000 are in the last year of life 24,000 have progressive illness and are not in the last year of life.ConclusionWe provide ‘good enough’ estimates of the number of patients with different health needs and transition points in the cancer care pathway to stimulate debate and inform commissioners about areas of need. While cancer is seen to have the most predictable pattern of deterioration, as more incurable cancers become treatable, illness trajectories will become more comparable to other chronic illness. A similar approach might be taken with other illnesses.
Mortality and medical care after bereavement: a general practice cohort study
Authors: King M. , Varagunam M. , Petersen I. , Jones L. , Marston L. , Nareth I. 
Published: May 2012

IntroductionBereaved spouses or partners are thought to be at increased risk of morbidity and mortality. However, there are few large prospective studies and results are inconsistent. We estimated the relative mortality, prescription of psychotropic medication and use of primary medical care services in adults whose cohabitee died of cancer.Aims and MethodsCohort study using The Health Improvement Network (THIN) UK primary care database. Participants were (1) people aged over 40, who were registered with general practices and had been exposed to the death of a cohabitee from cancer; and (2) a comparison cohort frequency matched on five year age bands and sex who were cohabiting with a living partner. The baseline was chosen as six months before the date of the cancer death for the exposed group and a random date for the unexposed group. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using random effects Poisson regression to account for clustering within general practices and adjusting for other key variables.Results92,129 patients were studied for a median follow up of 4 years. Cohabitees of patients who died of cancer were less likely to die of any cause (IRR 0.71, 96% CI 0.68-0.74) after adjustment for age, gender, number of non-psychotropic prescriptions 6 months before the cancer death/index date, use of psychotropic medication 6 months before the cancer death/index date, smoking, alcohol and area deprivation score. Exposed patients were more likely to receive a prescription for antidepressant or hypnotic medication and to attend their GP both before and after the death of the cohabitee.ConclusionWe did not confirm increased mortality after bereavement of a cohabitee. Our finding may reflect the high quality of care that partners of people dying from cancer in the UK receive from palliative care and primary care services.
Patients' experiences and understandings of taking part in clinical trials for advanced cancer: a metasynthesis of findings
Authors: Nelson A. , Edwards M. , Byrne A. 
Published: May 2012

IntroductionAdvanced cancer patients have difficult decisions to make when offered further treatments in clinical trials. It is essential that such decisions are made with a full understanding of the potential impact of further treatment side effects and the trade off against this added symptom burden, and quality of life.Aims and MethodsTo present a metasynthesis of findings from three qualitative studies linked to clinical trials exploring patients' motivations, and understandings of the trials. Data from three qualitative studies were synthesised to explore themes associated with participants' motivations when joining a trial and their experiences and understandings of trial processes. The data set comprised interview transcripts from 60+ advanced cancer patients.ResultsIn retrospect, control arm patients were altruistic and accepting of their allocation, whereas intervention arm patients were more focussed on the potential treatment benefits. Some patients expressed a sense of pressure to do the right thing for family and clinicians. Joining a trial was sometimes seen as the only remaining treatment option. Both groups were pleased to be receiving enhanced care and attention as part of a clinical trial. Patients frequently misunderstood the potential effect of the treatment intervention; some wrongly thought that their treatment was anti cancer, some thought that they may be receiving a placebo when in fact they were on the treatment arm of the trial.ConclusionThe results raise concerns about equipoise in trials, truly informed consent, patients' expectations and experiences of participating trials and the potential impact on their symptom burden and quality of life.
Hypovitaminosis D in Hospice patients in a Caucasian West Midlands Population
Authors: McCarron N.M. , Meystre C. , Wells S. , Jones A.F. , Gittoes N. , Armour K. , Hodson J. , Webster C. 
Published: May 2012

IntroductionOur hospice multi-disciplinary team was challenged by failing to deliver adequate pain relief to an elderly anicteric woman with locally advanced cholangiocarcinoma but with no known bone metastases. She was immobilised by severe knee pain resistant to optimal pain pathway prescribing and Allied Health Professional support. The patient was placed in a nursing home due to her immobility. Subsequently her serum vitamin D (VitD) was reported undetectable, and symptoms were explained by osteomalacia.Aims and MethodsTo test patients with clinical symptoms and susceptible disease profiles for VitD deficiency. Serum VitD levels of 16 caucasian hospice patients (6 female; 10 male) with symptoms suggestive deficiency were compared to 10,474 caucasian hospital patients (7,140 female; 3,334 male) in the same 10 month period.ResultsHospice median VitD was 11.65 µg/L (Interquartile Range = 6.66 - 15.25) (sufficient >20 µg/l; insufficient 6-20 µg/L; severe deficiency <6µg/L) This differed significantly from the hospital median VitD of 16.50 µg/L (Interquartile Range = 9.70 - 33.40;) Mann-Whitney p=0.016. Age and gender distribution differed between the two groups but controlling for this with a general linear model the difference in VitD remained significant (p value=0.011).ConclusionHospice patients had lower VitD levels than hospital patients, despite the differences in age and gender. Resistant pain is a common problem in hospice patients and may lead to unnecessary morbidity and institutionalisation. As part of holistic care VitD deficiency requires exclusion as a cause of morbidity in patients with pain and susceptible disease profiles. Its incidence in hospice patients warrants further investigation.
Developing Patient Controlled Analgesia (PCA) in the home for children and young people (CYP)
Authors: Boggs T. , Rajapske D. , Kelly P. , R. Hollowell D. , Howard R. , Craig F. , Bluebond-Langner M. 
Published: May 2012

IntroductionPain management for CYP in advanced disease is sub-optimal and, of concern to parents and palliative care professionals. PCA provides the patient, with a mechanism to rapidly and safely self-administer a bolus dose of analgesia in response to their experiences of pain. There is limited evidence on its use for CYP receiving palliative care.Aims and MethodsTo identify the salient issues and challenges in developing a home PCA service for CYP patients of a tertiary palliative care (PC) service. A mixed methods processual evaluation including: (a) longitudinal systematic participant observations of multidisciplinary project team planning meetings, PC team rounds and PCA training sessions, (b) interviews with community and tertiary based staff providing palliative care, (c) prospective pain data from CYP and carers (d) retrospective case review of parenteral analgesia utilisation, (e) survey of affiliated community services.ResultsWe identified the following issues to consider when developing this service: (1) only small numbers of CYP require PCA, limiting the potential for developing and sustaining clinical expertise, (2) introduction of PCA is time sensitive requiring rapid and flexible responses from a range of services, (3) normalisation of PCA as a symptom management technique reduced safety concerns and increased professional, parent and CYP confidence.ConclusionPreliminary analysis suggests provision of PCA in the home is feasible although resource intensive. Further research is now required to address the efficacy of this symptom management technique, in this patient population.
Nurses' decisions to use anticipatory prescriptions in end of life care: study overview
Authors: Wilson E. , Brown J. , Seymour J. 
Published: May 2012

IntroductionCommunity nurses working in primary care and in care homes registered to provide nursing care for older people have a key role in activating prescriptions written in advance of symptoms and distress that patients may have at the end of life (anticipatory prescribing). However, little is known about the decision-making processes employed by nurses or their experiences in this area of practice.Aims and MethodsTo determine the roles and experiences of community nurses in end of life medication decisions, using sedation in end of life care as an exemplar. A mixed method case study design involving four community nursing teams and four nursing homes in three Cancer Networks. The study takes place in two phases. Phase one is an ethnography using participant observation of nurses involved in decision making about the use of anticipatory prescriptions for sedation in end of life care. In addition, up to 15 interviews will be conducted at each study site (n=120) with healthcare professionals who have played a part in prescribing, dispensing or administration of sedation medication. In phase two a questionnaire survey, informed by existing literature and findings from the ethnography, will be used to access views from district nurses, specialist palliative care nurses, and nursing home nurses across the three Cancer Networks.ResultsPhase one of this study is due to commence in October 2011 and results are expected in May 2013.
Takotsubo cardiomyopathy: pathophysiology and treatment
Authors: Milinis Kristijonas , Fisher Michael 
Published: May 2012

Abstract
Since it was first described 20 years ago in Japan, takotsubo cardiomyopathy has received considerable interest from the medical community around the world, particularly in recent years. Although takotsubo cardiomyopathy was originally described as a transient, stress-induced dysfunction of the left ventricular apex, other morphological subtypes have now been described. The pathogenesis of this disorder is likely to be catecholamine mediated myocyte damage and microvascular dysfunction; however, a number of possible alternative theories have been suggested. These include oxidative stress, transient coronary obstruction and oestrogen deficiency, the last explaining the high prevalence of takotsubo cardiomyopathy in women. The treatment remains largely supportive; however, a number of agents have been implicated in the acute stage and long term. Although most of the patients show complete recovery, there is a high risk of complications at the initial presentation requiring intense support.
Transferring chromosome DNA fragments from multiple donor cells into a host strain for yeast strain improvement
Authors: Shi Xian’ai , Wang Hang , Wang Hao , Wang Zhiming , Meng Chun 
Published: May 2012

Based on a common biological phenomenon — homologous recombination — a novel method was developed by transferring chromosome DNA fragments extracted from multiple donor cells into a host strain. Through this method of transferring DNA fragments, foreign DNA fragments are introduced into one host cell and multiple positive traits from multiple strains may be integrated into the host strain. We first confirmed its feasibility in both prokaryotic and eukaryotic cells by selecting reverse mutants to prototrophy from auxotrophic strains through receiving chromosomal DNA fragments of wild-type parental strains. We then applied this method to Saccharomyces cerevisiae to improve its ethanol and temperature tolerance. We introduced donor chromosome DNA fragments from different S. cerevisiae strains with improvements in ethanol or temperature tolerance into a common strain S. cerevisiae and obtained a strain with much superior ethanol and temperature tolerance. The results showed that the Transferring DNA Fragments method provides a new way for strain breeding.
PYOGENIC FLEXOR TENOSYNOVITIS: ONE YEAR'S EXPERIENCE AT A UK HAND UNIT AND A REVIEW OF THE CURRENT LITERATURE
Authors: Nikkhah Dariush , Rodrigues Jeremy , Osman Khabab , DeJager Lodewikus 
Published: May 2012

We report outcomes and learning points from flexor sheath infection (FSI) cases presenting over one year to a United Kingdom (UK) hand unit.Between August 2009 and August 2010, 16 FSIs were confirmed from operation note findings. Patient age ranged from 12 to 82 years. All patients were posted a quickDASH questionnaire. In all cases, surgery was performed within 24 hours, via distal and palmar incisions, with 0.9% saline irrigation. Seven patients (44%) responded to questionnaires. Of these, most achieved a good functional outcome, with a mean quickDASH of 7.14. Four cases (25%) had no triggering event. Beta-haemolytic streptococcus was cultured in three cases (18%). Its presence was significantly associated with a requirement for multiple operations (p < 0.032), and with prolonged admission of up to nine days (p < 0.009). We suggest that close liaison with microbiology services and early identification of beta-haemolytic streptococcus may predict the need for multiple washouts in FSI.
Antitumor Activity of Targeted and Cytotoxic Agents in Murine Subcutaneous Tumor Models Correlates with Clinical Response
Authors: Wong Harvey , Choo Edna F. , Alicke Bruno , Ding Xiao , La Hank , McNamara Erin , Theil Frank-Peter , Tibbitts Jay , Friedman Lori S. , Hop Cornelis E.C.A. , Gould Stephen E. 
Published: May 2012

Abstract
Purpose: Immunodeficient mice transplanted with subcutaneous tumors (xenograft or allograft) are widely used as a model of preclinical activity for the discovery and development of anticancer drug candidates. Despite their widespread use, there is a widely held view that these models provide minimal predictive value for discerning clinically active versus inactive agents. To improve the predictive nature of these models, we have carried out a retrospective population pharmacokinetic–pharmacodynamic (PK–PD) analysis of relevant xenograft/allograft efficacy data for eight agents (molecularly targeted and cytotoxic) with known clinical outcome.
Experimental Design: PK–PD modeling was carried out to first characterize the relationship between drug concentration and antitumor activity for each agent in dose-ranging xenograft or allograft experiments. Next, simulations of tumor growth inhibition (TGI) in xenografts/allografts at clinically relevant doses and schedules were carried out by replacing the murine pharmacokinetics, which were used to build the PK–PD model with human pharmacokinetics obtained from literature to account for species differences in pharmacokinetics.
Results: A significant correlation (r = 0.91, P = 0.0008) was observed between simulated xenograft/allograft TGI driven by human pharmacokinetics and clinical response but not when TGI observed at maximum tolerated doses in mice was correlated with clinical response (r = 0.36, P = 0.34).
Conclusions: On the basis of these analyses, agents that led to greater than 60% TGI in preclinical models, at clinically relevant exposures, are more likely to lead to responses in the clinic. A proposed strategy for the use of murine subcutaneous models for compound selection in anticancer drug discovery is discussed. Clin Cancer Res; 18(14); 3846–55. ©2012 AACR.
A Case Study of Processes Impacting Precipitation Phase and Intensity during the Vancouver 2010 Winter Olympics
Authors: Thériault Julie M. , Rasmussen Roy , Smith Trevor , Mo Ruping , Milbrandt Jason A. , Brugman Melinda M. , Joe Paul , Isaac George A. , Mailhot Jocelyn , Denis Bertrand 
Published: May 2012

Abstract
Accurate forecasting of precipitation phase and intensity was critical information for many of the Olympic venue managers during the Vancouver 2010 Olympic and Paralympic Winter Games. Precipitation forecasting was complicated because of the complex terrain and warm coastal weather conditions in the Whistler area of British Columbia, Canada. The goal of this study is to analyze the processes impacting precipitation phase and intensity during a winter weather storm associated with rain and snow over complex terrain. The storm occurred during the second day of the Olympics when the downhill ski event was scheduled. At 0000 UTC 14 February, 2 h after the onset of precipitation, a rapid cooling was observed at the surface instrumentation sites. Precipitation was reported for 8 h, which coincided with the creation of a nearly 0°C isothermal layer, as well as a shift of the valley flow from up valley to down valley. Widespread snow was reported on Whistler Mountain with periods of rain at the mountain base despite the expectation derived from synoptic-scale models (15-km grid spacing) that the strong warm advection would maintain temperatures above freezing. Various model predictions are compared with observations, and the processes influencing the temperature, wind, and precipitation types are discussed. Overall, this case study provided a well-observed scenario of winter storms associated with rain and snow over complex terrain.
GATA2 zinc finger 1 mutations associated with biallelic CEBPA mutations define a unique genetic entity of acute myeloid leukemia
Authors: Greif Philipp A. , Dufour Annika , Konstandin Nikola P. , Ksienzyk Bianka , Zellmeier Evelyn , Tizazu Belay , Sturm Jutta , Benthaus Tobias , Herold Tobias , Yaghmaie Marjan , Dörge Petra , Hopfner Karl-Peter , Hauser Andreas , Graf Alexander , Krebs Stefan , Blum Helmut , Kakadia Purvi M. , Schneider Stephanie , Hoster Eva , Schneider Friederike , Stanulla Martin , Braess Jan , Sauerland Maria Cristina , Berdel Wolfgang E. , Büchner Thomas , Woermann Bernhard J. , Hiddemann Wolfgang , Spiekermann Karsten , Bohlander Stefan K. 
Published: May 2012

AbstractCytogenetically normal acute myeloid leukemia (CN-AML) with biallelic CEBPA gene mutations (biCEPBA) represents a distinct disease entity with a favorable clinical outcome. So far, it is not known whether other genetic alterations cooperate with biCEBPA mutations during leukemogenesis. To identify additional mutations, we performed whole exome sequencing of 5 biCEBPA patients and detected somatic GATA2 zinc finger 1 (ZF1) mutations in 2 of 5 cases. Both GATA2 and CEBPA are transcription factors crucial for hematopoietic development. Inherited or acquired mutations in both genes have been associated with leukemogenesis. Further mutational screening detected novel GATA2 ZF1 mutations in 13 of 33 biCEBPA-positive CN-AML patients (13/33, 39.4%). No GATA2 mutations were found in 38 CN-AML patients with a monoallelic CEBPA mutation and in 89 CN-AML patients with wild-type CEBPA status. The presence of additional GATA2 mutations (n=10) did not significantly influence the clinical outcome of 26 biCEBPA-positive patients. In reporter gene assays, all tested GATA2 ZF1 mutants showed reduced capacity to enhance CEBPA-mediated activation of transcription, suggesting that the GATA2 ZF1 mutations may collaborate with biCEPBA mutations to deregulate target genes during malignant transformation. We thus provide evidence for a genetically distinct subgroup of CN-AML. The German AML cooperative group trials 1999 and 2008 are registered with the identifiers NCT00266136 and NCT01382147 at www.clinicaltrials.gov.
Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection
Authors: Okagawa Tomohiro , Konnai Satoru , Ikebuchi Ryoyo , Suzuki Saori , Shirai Tatsuya , Sunden Yuji , Onuma Misao , Murata Shiro , Ohashi Kazuhiko 
Published: May 2012

Abstract
The immunoinhibitory receptor T cell immunoglobulin domain and mucin domain-3 (Tim-3) and its ligand, galectin-9 (Gal-9), are involved in the immune evasion mechanisms for several pathogens causing chronic infections. However, there is no report concerning the role of Tim-3 in diseases of domestic animals. In this study, cDNA encoding for bovine Tim-3 and Gal-9 were cloned and sequenced, and their expression and role in immune reactivation were analyzed in bovine leukemia virus (BLV)-infected cattle. Predicted amino acid sequences of Tim-3 and Gal-9 shared high homologies with human and mouse homologues. Functional domains, including tyrosine kinase phosphorylation motif in the intracellular domain of Tim-3 were highly conserved among cattle and other species. Quantitative real-time PCR analysis showed that bovine Tim-3 mRNA is mainly expressed in T cells such as CD4+ and CD8+ cells, while Gal-9 mRNA is mainly expressed in monocyte and T cells. Tim-3 mRNA expression in CD4+ and CD8+ cells was upregulated during disease progression of BLV infection. Interestingly, expression levels for Tim-3 and Gal-9 correlated positively with viral load in infected cattle. Furthermore, Tim-3 expression level closely correlated with up-regulation of IL-10 in infected cattle. The expression of IFN-γ and IL-2 mRNA was upregulated when PBMC from BLV-infected cattle were cultured with Cos-7 cells expressing Tim-3 to inhibit the Tim-3/Gal-9 pathway. Moreover, combined blockade of the Tim-3/Gal-9 and PD-1/PD-L1 pathways significantly promoted IFN-γ mRNA expression compared with blockade of the PD-1/PD-L1 pathway alone. These results suggest that Tim-3 is involved in the suppression of T cell function during BLV infection.