bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative study of patients’ feedback about Outpatient Parenteral Antimicrobial Therapy (OPAT) services in Northern England: implications for service improvement
Authors: Twiddy Maureen , Czoski Murray Carolyn J , Mason Samantha J , Meads David , Wright Judy M , Mitchell Elizabeth D , Minton Jane 
Published: January 2018

ObjectiveOutpatient parenteral antimicrobial therapy (OPAT) provides opportunities for improved cost savings, but in the UK, implementation is patchy and a variety of service models are in use. The slow uptake in the UK and Europe is due to a number of clinical, financial and logistical issues, including concern about patient safety. The measurement of patient experience data is commonly used to inform commissioning decisions, but these focus on functional aspects of services and fail to examine the relational aspects of care. This qualitative study examines patients’ experiences of OPAT.DesignIn-depth, semistructured interviews.SettingPurposive sample of OPAT patients recruited from four acute National Health Service (NHS) Trusts in Northern England. These NHS Trusts between them represented both well-established and recently set-up services running nurse at home, hospital outpatient and/or self-administration models.ParticipantsWe undertook 28 semistructured interviews and one focus group (n=4).ResultsDespite good patient outcomes, experiences were coloured by patients' personal situation and material circumstances. Many found looking after themselves at home more difficult than they expected, while others continued to work despite their infection. Expensive car parking, late running services and the inconvenience of waiting in for the nurse to arrive frustrated patients, while efficient services, staffed by nurses with the specialist skills needed to manage intravenous treatment had the opposite effect. Many patients felt a local, general practitioner or community health centre based service would resolve many of the practical difficulties that made OPAT inconvenient. Patients could find OPAT anxiety provoking but this could be ameliorated by staff taking the time to reassure patients and provide tailored information.ConclusionServices configurations must accommodate the diversity of the local population. Poor communication can leave patients lacking the confidence needed to be a competent collaborator in their own care and affect their perceptions of the service.
Establishing anchor-based minimally important differences (MID) with the EORTC quality-of-life measures: a meta-analysis protocol
Authors: Musoro Zebedee Jammbe , Hamel Jean-Francois , Ediebah Divine Ewane , Cocks Kim , King Madeleine T , Groenvold Mogens , Sprangers Mirjam A G , Brandberg Yvonne , Velikova Galina , Maringwa John , Flechtner Hans-Henning , Bottomley Andrew , Coens Corneel 
Published: January 2018

IntroductionAs patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated.Methods and analysisData will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for different cancer sites separately. Focus is on anchor-based methods. Anchors will be selected per disease site from available data. A disease-oriented and methodological panel will provide independent guidance on anchor selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and also to compare with several anchor-based methods. The effects of covariates, for example, gender, age, disease stage and so on, will also be investigated. We will examine how our estimated MIDs compare with previously published guidelines, hence further contributing to robust MID guidelines for the EORTC QLQ-C30.Ethics and disseminationAll patient data originate from completed clinical trials with mandatory written informed consent, approved by local ethical committees. Our findings will be presented at scientific conferences, disseminated via peer-reviewed publications and also compiled in a MID ‘blue book’ which will be made available online on the EORTC Quality of Life Group website as a free guideline document.
Association of erythrocyte parameters with metabolic syndrome in the Pearl River Delta region of China: a cross sectional study
Authors: Huang Ling Ling , Dou Dong-Mei , Liu Nan , Wang Xiao Xiao , Fu Li-Ying , Wu Xiao , Wang Peixi 
Published: January 2018

ObjectiveIncreasing studies have reported that erythrocyte parameters, including red blood cells (RBCs), haematocrit (HCT), haemoglobin (Hb) and red blood cell distribution width (RDW), are associated with metabolic syndrome (MetS) in adults worldwide. However, the association, stratified by sex, remains to be elucidated, particularly in the Pearl River Delta region of China. Therefore, our aim was to explore the association of erythrocyte parameters with MetS, stratified by sex, in the Pearl River Delta region of China.MethodsIn this cross sectional study, 2161 men and 2511 women were enrolled. MetS was diagnosed using a modified version of the Adult Treatment Panel III criteria. Logistic regression analyses were performed to calculate adjusted ORs of erythrocyte parameters associated with MetS stratified by sex.ResultsThe prevalence of MetS was higher in women than in men (35.2%vs26.7%). RBC, HCT, Hb and RDW values increased linearly with the number of MetS components from 0 to 5 identified in both men and women. Among men, the ORs of MetS risk increased across the tertiles of Hb (Q2: OR=1.921, 95% CI=1.170 to 3.151; Q3: OR=1.992, 95%CI=1.198 to 3.312). Men in the highest tertiles of RDW had a 2.752-fold increased risk of suffering from MetS compared with those in the reference group. Among women, the ORs of MetS risk also increased across the tertiles of Hb (Q2: OR=1.538, 95%CI=1.008 to 2.348; Q3: OR=1.665, 95%CI=1.075 to 2.578). Women in the highest tertiles of RBC had a 1.718-fold increased risk of experiencing MetS compared with those in the reference group.ConclusionsMetS was more prevalent in women than in men. The association between erythrocyte parameters and MetS differed between the sexes. RBC and Hb were identified as risk factors for MetS in women and Hb and RDW as risk factors in men.
Epidemiology of new-onset atrial fibrillation following coronary artery bypass graft surgery
Authors: Filardo Giovanni , Damiano Ralph J , Ailawadi Gorav , Thourani Vinod H , Pollock Benjamin D , Sass Danielle M , Phan Teresa K , Nguyen Hoa , da Graca Briget 
Published: January 2018

ObjectivesPostoperative atrial fibrillation (AF) following coronary artery bypass graft surgery (CABG) is significantly associated with reduced survival, but poor characterisation and inconsistent definitions present barriers to developing effective prophylaxis and management. We sought to address this knowledge gap.MethodsFrom 2002 to 2010, 11 239 consecutive patients without AF underwent isolated CABG at five sites. Clinical data collected for the Society of Thoracic Surgeons (STS) Database were augmented with details on AF detected via continuous in-hospital ECG/telemetry monitoring to assess new-onset post-CABG AF (adjusted for STS risk of mortality); time to first AF; durations of first and longest AF episodes; total in-hospital time in AF; number of in-hospital AF episodes; operative mortality; stroke; discharge in AF; and length of stay (LOS).ResultsUnadjusted incidence of new-onset post-CABG AF was 29.5%. Risk-adjusted incidence was 33.1% and varied little over time (P=0.139). Among 3312 patients with post-CABG AF, adjusted median time to first AF was 52 (IQR: 48–55) hours; mean (SD) duration of first and longest events were 7.2 (5.3,9.1) and 13.1 (10.4,15.9) hours, respectively, and adjusted median total time in AF was 22 (IQR: 18–26) hours. Adjusted rates of operative mortality, stroke and discharge in AF did not vary significantly over time (P=0.156, P=0.965 and P=0.347, respectively). LOS varied (P=0.035), but in no discernible pattern.ConclusionsEach year, ~800 000 people undergo CABG worldwide; >264 000 will develop post-CABG AF. Onset is typically 2–3 days post-CABG and episodes last, on average, several hours. Effective prophylaxis and management is urgently needed to reduce associated risks of adverse outcomes.
Low prevalence of ideal cardiovascular health in Peru
Authors: Benziger Catherine P , Zavala-Loayza José Alfredo , Bernabe-Ortiz Antonio , Gilman Robert H , Checkley William , Smeeth Liam , Malaga German , Miranda Juan Jaime 
Published: January 2018

BackgroundThe prevalence of and factors associated with ideal cardiovascular health (ICH) by sociodemographic characteristics in Peru is not well known.MethodsThe American Heart Association’s ICH score comprised 3 ideal health factors (blood pressure, untreated total cholesterol and glucose) and 4 ideal health behaviours (smoking, body mass index, high physical activity and fruit and vegetable consumption). ICH was having 5 to 7 of the ideal health metrics. Baseline data from the Center of Excellence in Chronic Diseases, a prospective cohort study in adults aged ≥35 years in 4 Peruvian settings, was used (n=3058).ResultsNo one met all 7 of ICH metrics while 322 (10.5%) had ≤1 metric. Fasting plasma glucose was the most prevalent health factor (72%). Overall, compared with ages 35–44 years, the 55–64 years age group was associated with a lower prevalence of ICH (prevalence ratio 0.54, 95% CI 0.40 to 0.74, P<0.001). Compared with those in the lowest tertile of socioeconomic status, those in the middle and highest tertiles were less likely to have ICH after adjusting for sex, age and education (P<0.001).ConclusionThere is a low prevalence of ICH. This is a benchmark for the prevalence of ICH factors and behaviours in a resource-poor setting.
Against proportional shortfall as a priority-setting principle
Authors: Altmann Samuel 
Published: January 2018

As the demand for healthcare rises, so does the need for priority setting in healthcare. In this paper, I consider a prominent priority-setting principle: proportional shortfall. My purpose is to argue that proportional shortfall, as a principle, should not be adopted. My key criticism is that proportional shortfall fails to consider past health.Proportional shortfall is justified as it supposedly balances concern for prospective health while still accounting for lifetime health, even though past health is deemed irrelevant. Accounting for this lifetime perspective means that the principle may indirectly consider past health by accounting for how far an individual is from achieving a complete, healthy life. I argue that proportional shortfall does not account for this lifetime perspective as it fails to incorporate the fair innings argument as originally claimed, undermining its purported justification.I go on to demonstrate that the case for ignoring past health is weak, and argue that past health is at least sometimes relevant for priority-setting decisions. Specifically, when an individual’s past health has a direct impact on current or future health, and when one individual has enjoyed significantly more healthy life years than another.Finally, I demonstrate that by ignoring past illnesses, even those entirely unrelated to their current illness, proportional shortfall can lead to instances of double jeopardy, a highly problematic implication. These arguments give us reason to reject proportional shortfall.
Major adverse cardiac and cerebrovascular event and patients’ quality of life after endoscopic vein harvesting as compared with open vein harvest (MAQEH): a pilot study
Authors: Luckraz Heyman , Cartwright Carly , Nagarajan Kumaresan , Kaur Prabhjeet , Nevill Alan 
Published: January 2018

BackgroundThis is a prospective, comparative, pilot and follow-up (2-year postoperatively) study in patients undergoing coronary artery bypass graft surgery where the long saphenous vein was harvested either by the endoscopic vein harvest (EVH) technique or open vein harvest (OVH) technique. Quality of life (QOL) and major adverse cardiac and cerebrovascular events (MACCE) were assessed.MethodsAlive patients who were initially part of a pilot study when EVH was introduced in our institution were included (n=48 EVH, n=49 OVH). Patients were sent a QOL questionnaire (SF12v2; 12-item medical outcomes study short form health survey version 2.0), and their cardiologist and general practitioner were contacted to assess MACCE.ResultsMedian follow-up was 32 and 33 months, respectively. Three patients died (2 EVH, 1 OVH). Of the remaining 97 patients who were sent a questionnaire, 76% patients returned the form. More patients from the EVH group returned the QOL questionnaire (82% vs 71%). Time taken to return to normal daily activities was much shorter in EVH (median 6 (2–30) weeks) compared with OVH (median 9 (2–50) weeks) (P<0.05). QOL questionnaire revealed significant difference in physical score at follow-up: 45.3 (10.2) for EVH group and 40.7 (11.0) for OVH group (P<0.05). There was no difference in mental scores (46.9 (10.5) vs 49.2 (9.1), P=0.4). There were no significant differences in MACCEs including death between the two groups (12.2% vs 13.9%, P=0.5).ConclusionEVH patients returned to normal daily activities faster than OVH patients and experienced better physical QOL even after 2 years postoperatively with no increase in MACCE during follow-up.
Motoneuron excitability of the quadriceps decreases during a fatiguing submaximal isometric contraction
Authors: Finn Harrison T. , Rouffet David M. , Kennedy David S. , Green Simon , Taylor Janet L. 
Published: January 2018

During fatiguing voluntary contractions, the excitability of motoneurons innervating arm muscles decreases. However, the behavior of motoneurons innervating quadriceps muscles is unclear. Findings may be inconsistent because descending cortical input influences motoneuron excitability and confounds measures during exercise. To overcome this limitation, we examined effects of fatigue on quadriceps motoneuron excitability tested during brief pauses in descending cortical drive after transcranial magnetic stimulation (TMS). Participants ( n = 14) performed brief (~5-s) isometric knee extension contractions before and after a 10-min sustained contraction at ~25% maximal electromyogram (EMG) of vastus medialis (VM) on one ( n = 5) or two ( n = 9) days. Electrical stimulation over thoracic spine elicited thoracic motor evoked potentials (TMEP) in quadriceps muscles during ongoing voluntary drive and 100 ms into the silent period following TMS (TMS-TMEP). Femoral nerve stimulation elicited maximal M-waves (Mmax). On the 2 days, either large (~50% Mmax) or small (~15% Mmax) TMS-TMEPs were elicited. During the 10-min contraction, VM EMG was maintained ( P = 0.39), whereas force decreased by 52% (SD 13%) ( P < 0.001). TMEP area remained unchanged ( P = 0.9), whereas large TMS-TMEPs decreased by 49% (SD 28%) ( P = 0.001) and small TMS-TMEPs by 71% (SD 22%) ( P < 0.001). This decline was greater for small TMS-TMEPs ( P = 0.019; n = 9). Therefore, without the influence of descending drive, quadriceps TMS-TMEPs decreased during fatigue. The greater reduction for smaller responses, which tested motoneurons that were most active during the contraction, suggests a mechanism related to repetitive activity contributes to reduced quadriceps motoneuron excitability during fatigue. By contrast, the unchanged TMEP suggests that ongoing drive compensates for altered motoneuron excitability. NEW & NOTEWORTHY We provide evidence that the excitability of quadriceps motoneurons decreases with fatigue. Our results suggest that altered intrinsic properties brought about by repetitive activation of the motoneurons underlie their decreased excitability. Furthermore, we note that testing during voluntary contraction may not reflect the underlying depression of motoneuron excitability because of compensatory changes in ongoing voluntary drive. Thus, this study provides evidence that processes intrinsic to the motoneuron contribute to muscle fatigue of the knee extensors.
Repeated testing for the assessment of individual response to exercise training
Authors: Hecksteden Anne , Pitsch Werner , Rosenberger Friederike , Meyer Tim 
Published: January 2018

Observed response to regular exercise training differs widely between individuals even in tightly controlled research settings. However, the respective contributions of random error and true interindividual differences as well as the relative frequency of nonresponders are disputed. Specific challenges of analyses on the individual level as well as a striking heterogeneity in definitions may partly explain these inconsistent results. Repeated testing during the training phase specifically addresses the requirements of analyses on the individual level. Here we report a first implementation of this innovative design amendment in a head-to-head comparison of existing analytical approaches. To allow for comparative implementation of approaches we conducted a controlled endurance training trial (1 yr walking/jogging, 3 days/wk for 45 min with 60% heart rate reserve) in healthy, untrained subjects ( n = 36, age = 46 ± 8 yr; body mass index 24.7 ± 2.7 kg/m2; V̇o2max36.6 ± 5.4). In the training group additional V̇o2maxtests were conducted after 3, 6, and 9 mo. Duration of the control condition was 6 mo due to ethical constraints. General efficacy of the training intervention could be verified by a significant increase in V̇o2maxin the training group ( P < 0.001 vs. control). Individual training response of relevant magnitude (>0.2 × baseline variability in V̇o2max) could be demonstrated by several approaches. Regarding the classification of individuals, only 11 of 20 subjects were consistently classified, demonstrating remarkable disagreement between approaches. These results are in support of relevant interindividual variability in training efficacy and stress the limitations of a responder classification. Moreover, this proof-of-concept underlines the need for tailored methodological approaches for well-defined problems.NEW & NOTEWORTHY This work reports a first implementation of a repeated testing training trial for the investigation of individual response. This design amendment was recently proposed to address specifically the statistical requirements of analyses on the individual level. Moreover, a comprehensive comparison of previously published methods exemplifies the striking heterogeneity of existing approaches.
RNF126 as a Biomarker of a Poor Prognosis in Invasive Breast Cancer and CHEK1 Inhibitor Efficacy in Breast Cancer Cells
Authors: Yang Xiaosong , Pan You , Qiu Zhaojun , Du Zhanwen , Zhang Yao , Fa Pengyan , Gorityala Shashank , Ma Shanhuai , Li Shunqiang , Chen Ceshi , Wang Hongbing , Xu Yan , Yan Chunhong , Ruth Keri , Ma Zhefu , Zhang Junran 
Published: January 2018

Abstract
Purpose: (i) To investigate the expression of the E3 ligase, RNF126, in human invasive breast cancer and its links with breast cancer outcomes; and (ii) to test the hypothesis that RNF126 determines the efficacy of inhibitors targeting the cell-cycle checkpoint kinase, CHEK1.
Experimental Design: A retrospective analysis by immunohistochemistry (IHC) compared RNF126 staining in 110 invasive breast cancer and 78 paired adjacent normal tissues with clinicopathologic data. Whether RNF126 controls CHEK1 expression was determined by chromatin immunoprecipitation and a CHEK1 promoter driven luciferase reporter. Staining for these two proteins by IHC using tissue microarrays was also conducted. Cell killing/replication stress induced by CHEK1 inhibition was evaluated in cells, with or without RNF126 knockdown, by MTT/colony formation, replication stress biomarker immunostaining and DNA fiber assays.
Results: RNF126 protein expression was elevated in breast cancer tissue samples. RNF126 was associated with a poor clinical outcome after multivariate analysis and was an independent predictor. RNF126 promotes CHEK1 transcript expression. Critically, a strong correlation between RNF126 and CHEK1 proteins was identified in breast cancer tissue and cell lines. The inhibition of CHEK1 induced a greater cell killing and a higher level of replication stress in breast cancer cells expressing RNF126 compared to RNF126 depleted cells.
Conclusions: RNF126 protein is highly expressed in invasive breast cancer tissue. The high expression of RNF126 is an independent predictor of a poor prognosis in invasive breast cancer and is considered a potential biomarker of a cancer's responsiveness to CHEK1 inhibitors. CHEK1 inhibition targets breast cancer cells expressing higher levels of RNF126 by enhancing replication stress. Clin Cancer Res; 24(7); 1629–43. ©2018 AACR.
The Immune Checkpoint Modulator OX40 and Its Ligand OX40L in NK-Cell Immunosurveillance and Acute Myeloid Leukemia
Authors: Nuebling Tina , Schumacher Carla Emilia , Hofmann Martin , Hagelstein Ilona , Schmiedel Benjamin Joachim , Maurer Stefanie , Federmann Birgit , Rothfelder Kathrin , Roerden Malte , Dörfel Daniela , Schneider Pascal , Jung Gundram , Salih Helmut Rainer 
Published: January 2018

AbstractThe TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint to reinforce antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte subset that contributes to antitumor immunity, particularly in leukemia. Accordingly, these cells are being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer of ex vivo expanded polyclonal NK cells (pNKC). Here, we analyzed whether and how OX40 and its ligand (OX40L) influence NK-cell function and antileukemia reactivity. We report that OX40 is expressed on leukemic blasts in a substantial percentage of patients with acute myeloid leukemia (AML) and that OX40 can, after stimulation with agonistic OX40 antibodies, mediate proliferation and release of cytokines that act as growth and survival factors for the leukemic cells. We also demonstrate that pNKC differentially express OX40L, depending on the protocol used for their generation. OX40L signaling promoted NK-cell activation, cytokine production, and cytotoxicity, and disruption of OX40–OX40L interaction impaired pNKC reactivity against primary AML cells. Together, our data implicate OX40/OX40L in disease pathophysiology of AML and in NK-cell immunosurveillance. Our findings indicate that effects of the OX40–OX40L receptor–ligand system in other immune cell subsets and also malignant cells should be taken into account when developing OX40-targeted approaches for cancer immunotherapy. Cancer Immunol Res; 6(2); 209–21. ©2018 AACR.