bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is cost-related non-collection of prescriptions associated with a reduction in health? Findings from a large-scale longitudinal study of New Zealand adults
Authors: Jatrana Santosh , Richardson Ken , Norris Pauline , Crampton Peter 
Published: November 2015

ObjectiveTo investigate whether cost-related non-collection of prescription medication is associated with a decline in health.SettingsNew Zealand Survey of Family, Income and Employment (SoFIE)-Health.ParticipantsData from 17 363 participants with at least two observations in three waves (2004–2005, 2006–2007, 2008–2009) of a panel study were analysed using fixed effects regression modelling.Primary outcome measuresSelf-rated health (SRH), physical health (PCS) and mental health scores (MCS) were the health measures used in this study.ResultsAfter adjusting for time-varying confounders, non-collection of prescription items was associated with a 0.11 (95% CI 0.07 to 0.15) unit worsening in SRH, a 1.00 (95% CI 0.61 to 1.40) unit decline in PCS and a 1.69 (95% CI 1.19 to 2.18) unit decline in MCS. The interaction of the main exposure with gender was significant for SRH and MCS. Non-collection of prescription items was associated with a decline in SRH of 0.18 (95% CI 0.11 to 0.25) units for males and 0.08 (95% CI 0.03 to 0.13) units for females, and a decrease in MCS of 2.55 (95% CI 1.67 to 3.42) and 1.29 (95% CI 0.70 to 1.89) units for males and females, respectively. The interaction of the main exposure with age was significant for SRH. For respondents aged 15–24 and 25–64 years, non-collection of prescription items was associated with a decline in SRH of 0.12 (95% CI 0.03 to 0.21) and 0.12 (95% CI 0.07 to 0.17) units, respectively, but for respondents aged 65 years and over, non-collection of prescription items had no significant effect on SRH.ConclusionOur results show that those who do not collect prescription medications because of cost have an increased risk of a subsequent decline in health.
Feedback on SMS reminders to encourage adherence among patients taking antipsychotic medication: a cross-sectional survey nested within a randomised trial
Authors: Kannisto Kati Anneli , Adams Clive E , Koivunen Marita , Katajisto Jouko , Välimäki Maritta 
Published: November 2015

ObjectivesTo explore feedback on tailored SMS reminders to encourage medication adherence and outpatient treatment among patients taking antipsychotic medication, and associations related to the feedback.DesignA cross-sectional survey nested within a nationwide randomised clinical trial (“Mobile.Net”ISRCTN27704027).SettingPsychiatric outpatient care in Finland.ParticipantsBetween September 2012 and December 2013, 403 of 558 adults with antipsychotic medication responded after 12 months of SMS intervention.Main outcome measureFeedback was gathered with a structured questionnaire based on Technology Acceptance Model theory. Data were analysed by Pearson's χ2test, binary logistic regression and stepwise multiple regression analyses.ResultsAlmost all participants (98%) found the SMS reminders easy to use and 87% felt that the SMS did not cause harm. About three-quarters (72%) were satisfied with the SMS received, and 61% found it useful. Divorced people were particularly prone to find SMS reminders useful (χ2=13.17, df=6, p=0.04), and people seeking employment were more often ‘fully satisfied’ with the SMS compared with other groups (χ2=10.82, df=4, p=0.029). People who were older at first contact with psychiatric services were more often ‘fully satisfied’ than younger groups (OR=1.02, 95% CI 1.01 to 1.04, p=0.007).ConclusionsThe feedback of patients taking antipsychotic medication on SMS services was generally positive. Overall, people were quite satisfied despite considerable variation in their sociodemographic background and illness history. Our results endorse that the use of simple easy-to-use existing technology, such as mobile phones and SMS, is acceptable in psychiatric outpatient services. Moreover, people using psychiatric outpatient services are able to use this technology. This acceptable and accessible technology can be easily tailored to each patient's needs and could be customised to the needs of the isolated or jobless. This is an area in which much careful evaluation is needed.
A nationwide study of patients hospitalised for poisoning in Korea based on Korea National Hospital Discharge In-Depth Injury Survey data from 2005 to 2009
Authors: Kim Kyunghee , Choi Jae Wook , Park Miso , Kim Min Soo , Lee Eun Sun 
Published: November 2015

ObjectivesIn light of the need to develop an integrated database on poisoning incidents in Korea, this study seeks to determine the characteristics of poisoning incidents in Korea by age, gender, location of incident, causative substance and patient prognosis.Data sourcesThe Korea National Hospital Discharge In-Depth Injury Survey results (2005–2009) from the Korea Centers for Disease Control and Prevention were used.Participants3826 participants in the survey who had been hospitalised for poisoning incidents.ResultsThe poisoning hospitalisation rate per 100 000 population was higher in women (1.735) than in men (1.372) and increased with age: the rate was 0.458 among individuals aged ≤9 years, 0.481 among those aged 10–19 years, 1.584 among those aged 20–64 years and 4.053 among those aged ≥65 years. The intentional poisoning hospitalisation rate differed by gender and age group. Women aged ≤19 years and 20–64 years showed a higher hospitalisation rate than men, while men aged ≥65 years showed a higher hospitalisation rate than women in the same age group. The most common poisoning substance was pesticides (33.6%), while antiepileptic, sedative-hypnotic and antiparkinsonism drugs and psychotropic drugs, not elsewhere classified were also very common. Poisoning in those aged ≤9 years usually involved other drugs, while pesticides were the most common substances in those aged 20–64 years and ≥65 years.ConclusionsThis study analysed poisoning incidents in Korea from 2005 to 2009, by age and gender, causative substance, and characteristics. The results of this study may serve as evidence for new strategies in Korea to prevent poisoning.
Amiloride Clinical Trial In Optic Neuritis (ACTION) protocol: a randomised, double blind, placebo controlled trial
Authors: McKee Justin B , Elston John , Evangelou Nikos , Gerry Stephen , Fugger Lars , Kennard Christopher , Kong Yazhuo , Palace Jacqueline , Craner Matthew 
Published: November 2015

IntroductionNeurodegeneration is a widely accepted contributor to the development of long-term disability in multiple sclerosis (MS). While current therapies in MS predominantly target inflammation and reduce relapse rate they have been less effective at preventing long-term disability. The identification and evaluation of effective neuroprotective therapies within a trial paradigm are key unmet needs. Emerging evidence supports amiloride, a licenced diuretic, as a neuroprotective agent in MS through acid sensing ion channel blockade. Optic neuritis (ON) is a common manifestation of MS with correlates of inflammation and neurodegeneration measurable within the visual pathways. Amiloride Clinical Trial In Optic Neuritis (ACTION) will utilise a multimodal approach to assess the neuroprotective efficacy of amiloride in acute ON.Methods and analysis46 patients will be recruited within 28 days from onset of ON visual symptoms and randomised on a 1:1 basis to placebo or amiloride 10 mg daily. Double-blinded treatment groups will be balanced for age, sex and visual loss severity by a random-deterministic minimisation algorithm. The primary objective is to demonstrate that amiloride is neuroprotective in ON as assessed by scanning laser polarimetry of the peripapillary retinal nerve fibre layer (RNFL) thickness at 6 months in the affected eye compared to the unaffected eye at baseline. RNFL in combination with further retinal measures will also be assessed by optical coherence tomography. Secondary outcome measures on brain MRI will include cortical volume, diffusion-weighted imaging, resting state functional MRI, MR spectroscopy and magnetisation transfer ratio. In addition, high and low contrast visual acuity, visual fields, colour vision and electrophysiology will be assessed alongside quality of life measures.Ethics and disseminationEthical approval was given by the south central Oxford B research ethics committee (REC reference: 13/SC/0022). The findings from ACTION will be disseminated through peer-reviewed publications and at scientific conferences.Trial registration numberEudraCT2012-004980-39, ClinicalTrials.gov Identifier:NCT01802489.
‘Big needles, small bodies’—the absence of acupuncture treatment for infants in contemporary Shanghai: a qualitative study
Authors: Skjeie Holgeir , Brekke Mette 
Published: November 2015

ObjectiveTo explore contemporary practices and clinical recommendations regarding the use of acupuncture for infants by Traditional Chinese Medicine (TCM) practitioners in Shanghai.DesignA qualitative study consisting of four field visits between February 2014 and March 2015. Data was collected using participant observation, focus group interview, in-depth interview, textbook page analysis and informant validation.Participants14 Shanghainese professionals, including interpreters and TCM practitioners, of which seven were acupuncturists.SettingThe Longhua Hospital (paediatric, acupuncture and Tui na departments) in southern Shanghai and the campus of the Shanghai University of Traditional Chinese Medicine.ResultsThe Longhua Hospital outpatient acupuncture clinic receives 400 consultations on average per day. Children, including patients from the paediatric department, are referred to this clinic. During 3 days of participant observations at this department, we saw two children. No infants. During 3 days at the paediatric department and 1 day at the Tui na department we saw no referrals. Formal interviews and informal conversations with acupuncturists and other TCM professionals revealed that acupuncture was neither routinely practiced nor recommended for infants and small children. Acupuncture was considered potentially painful for this young patient population. Alternative treatment options such as herbal treatments or medical massage were widely available and preferred. Western medical diagnostics and treatment were also used, recommended, and trusted.ConclusionsAcupuncture for infants is not a preferred therapeutic method among TCM practitioners working in contemporary Shanghai. Acupuncture on broad indications in infants appears to be a Western practice with little basis in TCM modern-day practice.
The prevalence of medical error related to end-of-life communication in Canadian hospitals: results of a multicentre observational study
Authors: Heyland Daren K , Ilan Roy , Jiang Xuran , You John J , Dodek Peter 
Published: November 2015

BackgroundIn the hospital setting, inadequate engagement between healthcare professionals and seriously ill patients and their families regarding end-of-life decisions is common. This problem may lead to medical orders for life-sustaining treatments that are inconsistent with patient preferences. The prevalence of this patient safety problem has not been previously described.MethodsUsing data from a multi-institutional audit, we quantified the mismatch between patients’ and family members’ expressed preferences for care and orders for life-sustaining treatments. We recruited seriously ill, elderly medical patients and/or their family members to participate in this audit. We considered it a medical error if a patient preferred not to be resuscitated and there were orders to undergo resuscitation (overtreatment), or if a patient preferred resuscitation (cardiopulmonary resuscitation, CPR) and there were orders not to be resuscitated (undertreatment).ResultsFrom 16 hospitals in Canada, 808 patients and 631 family members were included in this study. When comparing expressed preferences and documented orders for use of CPR, 37% of patients experienced a medical error. Very few patients (8, 2%) expressed a preference for CPR and had CPR withheld in their documented medical orders (Undertreatment). Of patients who preferred not to have CPR, 174 (35%) had orders to receive it (Overtreatment). There was considerable variability in overtreatment rates across sites (range: 14–82%). Patients who were frail were less likely to be overtreated; patients who did not have a participating family member were more likely to be overtreated.ConclusionsMedical errors related to the use of life-sustaining treatments are very common in internal medicine wards. Many patients are at risk of receiving inappropriate end-of-life care.
Dabigatran etexilate and reduction in serum apolipoprotein B
Authors: Joseph Philip , Pare Guillaume , Wallentin Lars , Connolly Stuart , Yusuf Salim , Wang Jia , Ezekowitz Michael , Eikelboom John , Siegbahn Agneta , Reilly Paul , Themeles Ellison , Oldgren Jonas 
Published: November 2015

ObjectiveCarboxylesterases, which convert dabigatran etexilate to its active form, dabigatran, have also been shown to influence lipoprotein metabolism, although any pleotropic effects of the drug based on this possible mechanism has not been evaluated. We examined the effects of dabigatran etexilate on serum lipoprotein markers in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study.Methods2513 participants from the RE-LY randomised control trial with baseline and 3-month apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) measurements were included. We prospectively compared the effects of dabigatran 110 mg twice daily, dabigatran 150 mg twice daily and warfarin on changes in ApoB and ApoA1 concentrations using a mixed model analysis.ResultsFrom baseline to 3 months, a significant reduction in ApoB concentration was observed with low-dose dabigatran (−0.057 (95% CI −0.069 to −0.044) g/L, p<0.001) and high-dose dabigatran (−0.065 (95% CI −0.078 to −0.053) g/L, p<0.001) but not warfarin (−0.006 g/L (95% CI −0.018 to 0.007) g/L, p=0.40). Compared with warfarin, ApoB reduction was significantly greater with both doses of dabigatran (p<0.001 for both groups). Reductions in ApoA1 concentrations did not statistically differ with either dose of dabigatran when compared with warfarin.ConclusionsDabigatran is associated with a significant (∼7%) reduction in ApoB concentration, suggesting a novel effect of this drug on lipoprotein metabolism. Further studies are needed to determine the mechanism of this observed effect, and its impact on clinical outcomes.
Isometry generators in momentum representation of the Dirac theory on the de Sitter spacetime
Authors: Cotăescu Ion I. , Băltăţeanu Doru-Marcel 
Published: November 2015

In this paper, it is shown that the covariant representation (CR) transforming the Dirac field under de Sitter isometries is equivalent to a direct sum of two unitary irreducible representations (UIRs) of the Sp(2, 2) group transforming alike the particle and antiparticle field operators in momentum representation. Their basis generators and Casimir operators are written down for the first time finding that these representations are equivalent to an UIR from the principal series whose canonical labels are determined by the fermion mass and spin. The properties of the conserved observables (i.e. one-particle operators) associated to the de Sitter isometries via Noether theorem and of the corresponding Pauli–Lubanski type operator are also pointed out.
Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers
Authors: Kaczkowski Bogumil , Tanaka Yuji , Kawaji Hideya , Sandelin Albin , Andersson Robin , Itoh Masayoshi , Lassmann Timo , Hayashizaki Yoshihide , Carninci Piero , Forrest Alistair R.R. 
Published: November 2015

Abstract
Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genome-wide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression. Cancer Res; 76(2); 216–26. ©2015 AACR.
Dysregulation of miR-212 Promotes Castration Resistance through hnRNPH1-Mediated Regulation of AR and AR-V7: Implications for Racial Disparity of Prostate Cancer
Authors: Yang Yijun , Jia Dingwu , Kim Hogyoung , Abd Elmageed Zakaria Y. , Datta Amrita , Davis Rodney , Srivastav Sudesh , Moroz Krzysztof , Crawford Byron E. , Moparty Krishnarao , Thomas Raju , Hudson Robert S. , Ambs Stefan , Abdel-Mageed Asim B. 
Published: November 2015

Abstract
Purpose: The causes of disproportionate incidence and mortality of prostate cancer among African Americans (AA) remain elusive. The purpose of this study was to investigate the mechanistic role and assess clinical utility of the splicing factor heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) in prostate cancer progression among AA men.
Experimental Design: We employed an unbiased functional genomics approach coupled with suppressive subtractive hybridization (SSH) and custom cDNA microarrays to identify differentially expressed genes in microdissected tumors procured from age- and tumor grade–matched AA and Caucasian American (CA) men. Validation analysis was performed in independent cohorts and tissue microarrays. The underlying mechanisms of hnRNPH1 regulation and its impact on androgen receptor (AR) expression and tumor progression were explored.
Results: Aberrant coexpression of AR and hnRNPH1 and downregulation of miR-212 were detected in prostate tumors and correlate with disease progression in AA men compared with CA men. Ectopic expression of miR-212 mimics downregulated hnRNPH1 transcripts, which in turn reduced expression of AR and its splice variant AR-V7 (or AR3) in prostate cancer cells. hnRNPH1 physically interacts with AR and steroid receptor coactivator-3 (SRC-3) and primes activation of androgen-regulated genes in a ligand-dependent and independent manner. siRNA silencing of hnRNPH1 sensitized prostate cancer cells to bicalutamide and inhibited prostate tumorigenesis in vivo.
Conclusions: Our findings define novel roles for hnRNPH1 as a putative oncogene, splicing factor, and an auxiliary AR coregulator. Targeted disruption of the hnRNPH1-AR axis may have therapeutic implications to improve clinical outcomes in patients with advanced prostate cancer, especially among AA men. Clin Cancer Res; 22(7); 1744–56. ©2015 AACR.
Folate Receptor–Targeted Polymeric Micellar Nanocarriers for Delivery of Orlistat as a Repurposed Drug against Triple-Negative Breast Cancer
Authors: Paulmurugan Ramasamy , Bhethanabotla Rohith , Mishra Kaushik , Devulapally Rammohan , Foygel Kira , Sekar Thillai V. , Ananta Jeyarama S. , Massoud Tarik F. , Joy Abraham 
Published: November 2015

Abstract
Triple-negative breast cancer (TNBC) is a recalcitrant malignancy with no available targeted therapy. Off-target effects and poor bioavailability of the FDA-approved antiobesity drug orlistat hinder its clinical translation as a repurposed new drug against TNBC. Here, we demonstrate a newly engineered drug formulation for packaging orlistat tailored to TNBC treatment. We synthesized TNBC-specific folate receptor–targeted micellar nanoparticles (NP) carrying orlistat, which improved the solubility (70–80 μg/mL) of this water-insoluble drug. The targeted NPs also improved the delivery and bioavailability of orlistat to MDA-MB-231 cells in culture and to tumor xenografts in a nude mouse model. We prepared HEA–EHA copolymer micellar NPs by copolymerization of 2-hydroxyethylacrylate (HEA) and 2-ethylhexylacrylate (EHA), and functionalized them with folic acid and an imaging dye. Fluorescence-activated cell sorting (FACS) analysis of TNBC cells indicated a dose-dependent increase in apoptotic populations in cells treated with free orlistat, orlistat NPs, and folate-receptor–targeted Fol-HEA-EHA-orlistat NPs in which Fol-HEA-EHA-orlistat NPs showed significantly higher cytotoxicity than free orlistat. In vitro analysis data demonstrated significant apoptosis at nanomolar concentrations in cells activated through caspase-3 and PARP inhibition. In vivo analysis demonstrated significant antitumor effects in living mice after targeted treatment of tumors, and confirmed by fluorescence imaging. Moreover, folate receptor–targeted Fol-DyLight747-orlistat NP–treated mice exhibited significantly higher reduction in tumor volume compared to control group. Taken together, these results indicate that orlistat packaged in HEA-b-EHA micellar NPs is a highly promising new drug formulation for TNBC therapy. Mol Cancer Ther; 15(2); 221–31. ©2015 AACR.
Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer
Authors: Lund Amanda W. , Medler Terry R. , Leachman Sancy A. , Coussens Lisa M. 
Published: November 2015

AbstractSkin is a highly ordered immune organ that coordinates rapid responses to external insult while maintaining self-tolerance. In healthy tissue, lymphatic vessels drain fluid and coordinate local immune responses; however, environmental factors induce lymphatic vessel dysfunction, leading to lymph stasis and perturbed regional immunity. These same environmental factors drive the formation of local malignancies, which are also influenced by local inflammation. Herein, we discuss clinical and experimental evidence supporting the tenet that lymphatic vessels participate in regulation of cutaneous inflammation and immunity, and are important contributors to malignancy and potential biomarkers and targets for immunotherapy.Significance: The tumor microenvironment and tumor-associated inflammation are now appreciated not only for their role in cancer progression but also for their response to therapy. The lymphatic vasculature is a less-appreciated component of this microenvironment that coordinates local inflammation and immunity and thereby critically shapes local responses. A mechanistic understanding of the complexities of lymphatic vessel function in the unique context of skin provides a model to understand how regional immune dysfunction drives cutaneous malignancies, and as such lymphatic vessels represent a biomarker of cutaneous immunity that may provide insight into cancer prognosis and effective therapy. Cancer Discov; 6(1); 22–35. ©2015 AACR.