bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age and sex differences in hospitalisation of nursing home residents: a systematic review
Authors: Hoffmann Falk , Allers Katharina 
Published: October 2016

ObjectivesNursing home residents (NHRs) are frequently suffering from multimorbidity, functional and cognitive impairment, often leading to hospital admissions. Studies have found that male NHRs are more often hospitalised. The influence of age is inconclusive. We aimed to investigate the epidemiology of hospitalisations in NHRs, particularly focusing on age-specific and sex-specific differences.DesignA systematic review was performed in PubMed, CINAHL and Scopus. Quality of studies was assessed.SettingStudies conducted in nursing homes were included.ParticipantsNursing home residents.Primary and secondary outcomesOutcome measures were the prevalence, incidence or duration of all-cause hospitalisation by age or sex.ResultsWe identified 21 studies, 13 were conducted in the USA. The proportion of residents being hospitalised ranged across studies from 6.8% to 45.7% for various time periods of follow-up. A total of 20 studies assessed the influence of sex and found that hospitalisations are more often in male NHRs. A total of 16 studies conducted multivariate analyses and the OR of hospitalisation for males was between 1.22 and 1.67. Overall, 18 studies assessed the influence of age. Some studies showed an increasing proportion of admissions with increasing age, but several studies also found decreasing hospitalisations above the age of about 80–85 years. 8 of 13 studies conducting multivariate analyses included age as a continuous variable. Only 1 study reported stratified analyses by age and sex. 2 studies investigating primary causes of hospitalisation stratified by sex found some differences in main diagnoses.DiscussionMale NHRs are more often hospitalised than females, but reasons for that are not well investigated. The influence of age is less clear, but there seems to be no clear linear relationship between age and the proportion being hospitalised. Further studies should investigate age and sex differences in frequencies and reasons for hospitalisation in NHRs.
Increasing the uptake of long-acting reversible contraception in general practice: the Australian Contraceptive ChOice pRoject (ACCORd) cluster randomised controlled trial protocol
Authors: Mazza Danielle , Black Kirsten , Taft Angela , Lucke Jayne , McGeechan Kevin , Haas Marion , McKay Heather , Peipert Jeffery F 
Published: October 2016

IntroductionThe increased use of long-acting reversible contraceptives (LARCs), such as intrauterine devices and hormonal implants, has the potential to reduce unintended pregnancy and abortion rates. However, use of LARCs in Australia is very low, despite clinical practice guidance and statements by national and international peak bodies advocating their increased use. This protocol paper describes the Australian Contraceptive ChOice pRojet (ACCORd), a cluster randomised control trial that aims to test whether an educational intervention targeting general practitioners (GPs) and establishing a rapid referral service are a cost-effective means of increasing LARC uptake.Methods and analysisThe ACCORd intervention is adapted from the successful US Contraceptive CHOICE study and involves training GPs to provide ‘LARC First’ structured contraceptive counselling to women seeking contraception, and implementing rapid referral pathways for LARC insertion. Letters of invitation will be sent to 600 GPs in South-Eastern Melbourne. Using randomisation stratified by whether the GP inserts LARCs or not, a total of 54 groups will be allocated to the intervention (online ‘LARC First’ training and rapid referral pathways) or control arm (usual care). We aim to recruit 729 women from each arm. The primary outcome will be the number of LARCs inserted; secondary outcomes include the women's choice of contraceptive method and quality of life (Short Form Health Survey, SF-36). The costs and outcomes of the intervention and control will be compared in a cost-effectiveness analysis.Ethics and disseminationThe ACCORd study has been approved by the Monash University Human Research Ethics Committee: CF14/3990-2014002066 and CF16/188-2016000080. Any protocol modifications will be communicated to Ethics Committee and Trial Registration registry. The authors plan to disseminate trial outcomes through formal academic pathways comprising journal articles, nation and international conferences and reports, as well as using more ‘popular’ strategies including seminars, workshops and media engagements.Trial registration numberACTRN12615001346561.
Detection of HPV subtypes by mass spectrometry in FFPE tissue specimens: a reliable tool for routine diagnostics
Authors: Kriegsmann Mark , Wandernoth Petra , Lisenko Katharina , Casadonte Rita , Longuespée Rémi , Arens Norbert , Kriegsmann Jörg 
Published: October 2016

AimsHuman papilloma virus (HPV) infection is a causative agent for approximately 5% of all new cancer cases in humans. The virus is detected in cervical, anal, vaginal, penile, vulvar and head and neck cancers and has prognostic implications. Thus, test systems are required to detect high-risk but also low-risk HPV subtypes with high specificity and sensitivity in a time-effective and cost-effective manner. In the present study we developed a new mass spectrometry (MS)-based test system for the detection of HPV infections in formalin-fixed paraffin-embedded (FFPE) tissue samples.MethodsA high-throughput matrix-assisted laser desorption ionisation time of flight MS-based assay was applied to genotype 19 HPV types in FFPE tissue specimens (n=46). The results from the MS assay were compared with the results obtained from two hybridisation-based test systems: the HPV 3.5 LCD-array kit and the EuroArrayHPV system.ResultsIn 36 out of 46 (78%) tissue samples, a HPV infection could be detected by the MS-based HPV assay. In 16 samples (44%) only one and in 20 samples (56%) two to six HPV subtypes were identified. The overall agreement of all three assays was almost perfect (Cohen's k value: 0.83).ConclusionsThe MS-based assay is highly sensitive, reliable as well as cost-effective and represents a suitable technology for the detection of HPV infections in FFPE tissue material.
Unintentional injury in England: an analysis of the emergency care data set pilot in Oxfordshire from 2012 to 2014
Authors: Kirkwood Graham , Hughes Thomas C , Pollock Allyson M 
Published: October 2016

BackgroundA pilot injury data collection exercise at the emergency departments (EDs) of Oxford University Hospitals National Health Service (NHS) Foundation Trust (OUH) ran from 2012 to 2014 to inform the current development of the new NHS England emergency care data set.MethodsData collected at the EDs of OUH 1 January 2012 to 30 March 2014 analysed for Oxford City and Cherwell District Council areas. Data completeness and quality checked against Hospital Episode Statistic (HES) returns.ResultsOf the 63 877 injury attendances recorded at the 2 sites, 26 536 were unintentional with a home postcode within Oxford City or Cherwell District Council areas. The most frequent location, mechanism, activity and diagnosis were home (39.1% of all unintentional injuries (UIs)), low-level falls (47.1%), leisure (31.1%) and ‘injuries to unspecified part of trunk, limb or body region’ (20.5%), respectively. The most deprived quintile of the population (Index of Multiple Deprivation (IMD) 1) had the highest European Age Standardised Rate (EASR) for all UIs and IMD 5 had the lowest, 54.4 (95% CI 52.3 to 56.5) and 32.2 (31.4 to 33.0) per 1000 person-years, respectively. There was a significant association between increasing levels of deprivation and an increasing incidence rate ratio (IRR) for all UIs, for those in the home, for low-level fall UIs and for non-sport leisure UIs with a particularly sharp increase in the IRR for IMD 1 compared with IMD 5. Sport-related injuries were inversely related to deprivation apart from football.ConclusionsThis pilot has demonstrated both the feasibility and importance of prioritising the collection of a national injury data set.
Common toxidromes in movement disorder neurology
Authors: Malek N , Baker M R 
Published: October 2016

ABSTRACTBackgroundPhysicians can come across patients who are exposed to certain prescription drugs or toxins that can result in adverse effects and complications which have high rates of morbidity and mortality.ObjectiveTo summarise the key clinical features and management of the common movement disorder toxidromes relevant to physicians (with an interest in neurology).MethodsWe searched PUBMED from 1946 to 2016 for papers relating to movement toxidromes and their treatment. The findings from those studies were then summarised and are presented here.ResultsThe key features of 6 of the common movement disorder toxidromes and their treatment are tabulated and highlighted. The management of toxidromes with the highest mortality like neuroleptic malignant syndrome and serotonin syndrome are discussed in detail.ConclusionThere are several toxidromes that have the potential to become a serious life-threatening emergency if there is a delay in recognition of key clinical features and instituting the appropriate treatment at the earliest is crucial.
Taking care of volunteers in a stroke trial: a new assisted-management strategy
Authors: Stuart Amber C , Sico Jason J , Viscoli Catherine M , Tayal Ashis H , Inzucchi Silvio E , Ford Gary A , Furie Karen L , Cote Robert , Spence J David , Tanne David , Kernan Walter N 
Published: October 2016

Background and purposeProviding participants with evidence-based care for secondary prevention is an ethical and scientific priority for trials in stroke therapy. The optimal strategy, however, is uncertain. We report the performance of a new approach for delivering preventive care to trial participants.MethodsParticipants were enrolled in the Insulin Resistance Intervention after Stroke trial, which examined the insulin sensitiser, pioglitazone versus placebo for prevention of stroke and myocardial infarction after ischaemic stroke or transient ischaemic attack. Preventive care was the responsibility of the participants’ personal healthcare providers, but investigators monitored care and provided feedback annually. We studied achievement of 8 prevention goals at baseline and 3 annual visits, with a focus on 3 priority goals: blood pressure <140/90 mm Hg, low-density lipoprotein (LDL) cholesterol <2.59 mmol/L and antithrombotic therapy.ResultsThe proportion of participants achieving the priority goals was highest for antithrombotic use (96–99% in each year) and similar for blood pressure (66–72% in each year) and LDL (68–70% in each year). All 3 priority goals were achieved by 47–52% of participants in any given year. However, only 22% of participants achieved all 3 goals in each year.ConclusionsA strategy of monitoring care and providing feedback was associated with high average yearly achievement of 3 priority secondary prevention goals, but the majority of trial participants did not persist in being at goal over time.Trial registration numberNCT00091949.
A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma
Authors: Deniger Drew C. , Kwong Mei Li M. , Pasetto Anna , Dudley Mark E. , Wunderlich John R. , Langhan Michelle M. , Lee Chyi-Chia Richard , Rosenberg Steven A. 
Published: October 2016

Abstract
Purpose: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAFV600 mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma.
Experimental Design: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Metastases resected prior to and after 2 weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation, and recognition of autologous tumor.
Results: The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response, and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TILs and peripheral blood T cells were inhibited in vitro by research-grade vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality, and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TILs grown from pre- and post-vemurafenib metastases.
Conclusions: Coadministration of vemurafenib and TILs was safe and feasible and generated objective clinical responses in this small pilot clinical trial. Clin Cancer Res; 23(2); 351–62. ©2016 AACR.
See related commentary by Cogdill et al., p. 327
Molecular Profiling to Determine Clonality of Serial Magnetic Resonance Imaging/Ultrasound Fusion Biopsies from Men on Active Surveillance for Low-Risk Prostate Cancer
Authors: Palapattu Ganesh S. , Salami Simpa S. , Cani Andi K. , Hovelson Daniel H. , Lazo de la Vega Lorena , Vandenberg Kelly R. , Bratley Jarred V. , Liu Chia-Jen , Kunju Lakshmi P. , Montgomery Jeffery S. , Morgan Todd M. , Natarajan Shyam , Huang Jiaoti , Tomlins Scott A. , Marks Leonard S. 
Published: October 2016

Abstract
Purpose: To determine whether MRI/ultrasound (MRI/US) fusion biopsy facilitates longitudinal resampling of the same clonal focus of prostate cancer and to determine whether high-grade cancers can evolve from low-grade clones.
Experimental Design: All men on active surveillance who underwent tracking MRI/US fusion biopsy of Gleason 6 prostate cancer, on at least two distinct occasions, between 2012 and 2014 were enrolled. MRI/US fusion was used to track and resample specific cancer foci. IHC for ERG and targeted RNA/DNA next-generation sequencing (NGS) were performed on formalin-fixed paraffin-embedded prostate biopsy specimens to assess clonality.
Results: Thirty-one men with median age and PSA of 65 years and 4.6 ng/mL, respectively, were analyzed. The median sampling interval was 12 months (range, 5–35). Of the 26 evaluable men, ERG IHC concordance was found between initial and repeat biopsies in 25 (96%), indicating resampling of the same clonal focus over time. Targeted NGS supported ERG IHC results and identified unique and shared driving mutations, such as IDH1 and SPOP, in paired specimens. Of the nine men (34.6%) who were found to have Gleason ≥7 on repeat biopsy, all displayed temporal ERG concordance. Prioritized genetic alterations were detected in 50% (13/26) of paired samples. Oncogenic mutations were detected in 22% (2/9) of Gleason 6 cancers prior to progression and 44% (4/9) of Gleason ≥7 cancers when progression occurred.
Conclusions: Precise tracking of prostate cancer foci via MRI/US fusion biopsy allowed subsequent resampling of the same clonal focus of cancer over time. Further research is needed to clarify the grade progression potential of Gleason 6 prostate cancer. Clin Cancer Res; 23(4); 985–91. ©2016 AACR.
Mutant BRAF Upregulates MCL-1 to Confer Apoptosis Resistance that Is Reversed by MCL-1 Antagonism and Cobimetinib in Colorectal Cancer
Authors: Kawakami Hisato , Huang Shengbing , Pal Krishnendu , Dutta Shamit K. , Mukhopadhyay Debabrata , Sinicrope Frank A. 
Published: October 2016

Abstract
Oncogenic BRAFV600E mutations activate MAPK signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer. In BRAFV600E-mutant colorectal cancers, treatment failure may be related to BRAFV600E-mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAFV600E can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using colorectal cancer cell lines isogenic for BRAF. BRAFV600E-induced MCL-1 upregulation was confirmed by ectopic BRAFV600E expression that activated MEK/ERK signaling to phosphorylate (MCL-1Thr163) and stabilize MCL-1. Upregulation of MCL-1 was mediated by MEK/ERK shown by the ability of ERK siRNA to suppress MCL-1. Stabilization of MCL-1 by phosphorylation was shown by a phosphorylation-mimicking mutant and an unphosphorylated MCL-1 mutant that decreased or increased MCL-1 protein turnover, respectively. MEK/ERK inhibition by cobimetinib suppressed MCL-1 expression/phosphorylation and induced proapoptotic BIM to a greater extent than did vemurafenib in BRAFV600E cell lines. MCL-1 knockdown versus control shRNA significantly enhanced cobimetinib-induced apoptosis in vitro and in HT29 colon cancer xenografts. The small-molecule MCL-1 inhibitor, A-1210477, also enhanced cobimetinib-induced apoptosis in vitro that was due to disruption of the interaction of MCL-1 with proapoptotic BAK and BIM. Knockdown of BIM attenuated BAX, but not BAK, activation by cobimetinib plus A-1210477. In summary, BRAFV600E-mediated MEK/ERK activation can upregulate MCL-1 by phosphorylation/stabilization to confer apoptosis resistance that can be reversed by MCL-1 antagonism combined with cobimetinib, suggesting a novel therapeutic strategy against BRAFV600E-mutant CRCs. Mol Cancer Ther; 15(12); 3015–27. ©2016 AACR.
Ascochlorin Enhances the Sensitivity of Doxorubicin Leading to the Reversal of Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma
Authors: Dai Xiaoyun , Ahn Kwang Seok , Wang Ling Zhi , Kim Chulwon , Deivasigamni Amudha , Arfuso Frank , Um Jae-Young , Kumar Alan Prem , Chang Young-Chae , Kumar Dhiraj , Kundu Gopal C. , Magae Junji , Goh Boon Cher , Hui Kam Man , Sethi Gautam 
Published: October 2016

AbstractIncreasing evidence has indicated that epithelial-to-mesenchymal transition (EMT) at the advanced stage of liver cancer not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radiotherapies. Here, we report that ascochlorin (ASC), an isoprenoid antibiotic, could potentiate the cytotoxic effect of doxorubicin on HCCLM3, SNU387, SNU49, and SK-Hep-1 hepatocellular carcinoma cells, which had a predominantly mesenchymal signature with low expression of E-cadherin but high expression of N-cadherin. Co-administration of ASC reduced doxorubicin-induced invasion/migration and modulated EMT characteristics in mesenchymal cells. This process was probably mediated by the E-cadherin repressors Snail and Slug. In addition, ASC increased sensitivity to doxorubicin treatment by directly inhibiting STAT3 binding to the Snail promoter. We also observed that ASC significantly enhanced the effect of doxorubicin against tumor growth and inhibited metastasis in an HCCLM3_Luc orthotopic mouse model. Collectively, our data demonstrate that ASC can increase sensitivity to doxorubicin therapy and reverse the EMT phenotype via the downregulation of STAT3-Snail expression, which could form the basis of a novel therapeutic approach against hepatocellular carcinoma. Mol Cancer Ther; 15(12); 2966–76. ©2016 AACR.
Impact of Socioeconomic Status on Patients Supported With a Left Ventricular Assist Device
Authors: Clerkin Kevin J. , Garan Arthur Reshad , Wayda Brian , Givens Raymond C. , Yuzefpolskaya Melana , Nakagawa Shunichi , Takeda Koji , Takayama Hiroo , Naka Yoshifumi , Mancini Donna M. , Colombo Paolo C. , Topkara Veli K. 
Published: October 2016

Background—
Low socioeconomic status (SES) is a known risk factor for heart failure, mortality among those with heart failure, and poor post heart transplant (HT) outcomes. This study sought to determine whether SES is associated with decreased waitlist survival while on left ventricular assist device (LVADs) support and after HT.

Methods and Results—

A total of 3361 adult patients bridged to primary HT with an LVAD between May 2004 and April 2014 were identified in the UNOS database (United Network for Organ Sharing). SES was measured using the Agency for Healthcare Research and Quality SES index using data from the 2014 American Community Survey. In the study cohort, SES did not have an association with the combined end point of death or delisting on LVAD support (
P
=0.30). In a cause-specific unadjusted model, those in the top (hazard ratio, 1.55; 95% confidence interval, 1.14–2.11;
P
=0.005) and second greatest SES quartile (hazard ratio 1.50; 95% confidence interval, 1.10–2.04;
P
=0.01) had an increased risk of death on device support compared with the lowest SES quartile. Adjusting for clinical risk factors mitigated the increased risk. There was no association between SES and complications. Post-HT survival, both crude and adjusted, was decreased for patients in the lowest quartile of SES index compared with all other SES quartiles.

Conclusions—
Freedom from waitlist death or delisting was not affected by SES. Patients with a higher SES had an increased unadjusted risk of waitlist mortality during LVAD support, which was mitigated by adjusting for increased comorbid conditions. Low SES was associated with worse post-HT outcomes. Further study is needed to confirm and understand a differential effect of SES on post-transplant outcomes that was not seen during LVAD support before HT.
Procedural and Long-Term Outcomes of Bioresorbable Scaffolds Versus Drug-Eluting Stents in Chronic Total Occlusions
Authors: Azzalini Lorenzo , Giustino Gennaro , Ojeda Soledad , Serra Antonio , La Manna Alessio , Ly Hung Q. , Bellini Barbara , Benincasa Susanna , Chavarría Jorge , Gheorghe Livia L. , Longo Giovanni , Miccichè Eligio , D’Agosta Guido , Picard Fabien , Pan Manuel , Tamburino Corrado , Latib Azeem , Carlino Mauro , Chieffo Alaide , Colombo Antonio 
Published: October 2016

Background—
There is little evidence regarding the efficacy and safety of bioresorbable scaffolds (BRS) for the percutaneous treatment of chronic total occlusions.

Methods and Results—

We performed a multicenter registry of consecutive chronic total occlusion patients treated with BRS (Absorb; Abbott Vascular) and second-generation drug-eluting stents (DES) at 5 institutions. Long-term target-vessel failure (a composite of cardiac death, target-vessel myocardial infarction, and ischemia-driven target-lesion revascularization) was the primary end point. Inverse probability of treatment weight–adjusted Cox regression was used to account for pretreatment differences between the 2 groups. A total of 537 patients (n=153 BRS; n=384 DES) were included. BRS patients were younger and had lower prevalence of comorbidities. Overall mean Japan-Chronic Total Occlusion (J-CTO) score was 1.43±1.16, with no differences between groups. Procedural success was achieved in 99.3% and 96.6% of BRS- and DES-treated patients, respectively (
P
=0.07). At a median follow-up of 703 days, there were no differences in target-vessel failure between BRS and DES (4.6% versus 7.7%;
P
=0.21). By adjusted Cox regression analysis, there were still no significant differences between BRS and DES (hazard ratio, 1.54; 95% confidence interval, 0.69–3.72;
P
=0.34). However, secondary analyses suggested a signal toward higher ischemia-driven target-lesion revascularization with BRS.

Conclusions—
Implantation of BRS versus second-generation DES in chronic total occlusion was associated with similar risk of target-vessel failure at long-term follow-up. However, a signal toward increased ischemia-driven target-lesion revascularization with BRS was observed. Large randomized studies should confirm these findings.