bluuebunny/crossref_metadata_2025_split huggingface dataset:
RELATE—a randomised controlled feasibility trial of a Relating Therapy module for distressing auditory verbal hallucinations: a study protocol
Authors: Lincoln Tania M , Pillny Matthias , Schlier Björn , Hayward Mark 
Published: June 2021

IntroductionAuditory verbal hallucinations (AVHs) are associated with distress and reduced functioning. Research suggests that distress is associated with the voice hearer’s responding to AVH in a passive and subordinate manner. A novel approach focuses on relating to AVH and teaches assertive responses to AVH using experiential role-plays. A small pilot study found a large effect of this approach on AVH distress but an independent multicentre study is required to ascertain effectiveness across different settings. We aim to estimate the expected effect for a subsequent trial to demonstrate that adding a module of Relating Therapy (RT) to treatment as usual (TAU) is superior to TAU alone in reducing AVH distress. We also test the feasibility of patient recruitment, therapist training, and therapy monitoring in different psychological and psychiatric outpatient facilities in Germany.Methods and analysisWe will recruit 75 patients diagnosed with a schizophrenia spectrum disorder and persistent distressing AVH across four sites. Patients will be randomised to receive either 16 sessions of RT plus TAU or TAU alone within a 5-month period. Randomisation will be stratified by sites. Single-blind assessments will take place at baseline, at 5 months (T1) and at 9 months (T2). The primary outcome is the distress factor score of the AVH subscale of the Psychotic Symptoms Rating Scale at T2 adjusted for the baseline value. Secondary outcomes are change in depressive symptoms, quality of life, time spent in structured activities as well as negative relating to voices and to other people.Ethics and disseminationThe trial has received ethical approval from the German Psychological Society Ethics Committee. The trial results will be disseminated through conference presentations, peer-reviewed publications and social media.Trial registration numberClinicalTrials.gov Registry (NCT04578314).
Provision of critical care for the elderly in Europe: a retrospective comparison of national healthcare frameworks in intensive care units
Authors: Wernly Bernhard , Beil Michael , Bruno Raphael Romano , Binnebössel Stephan , Kelm Malte , Sigal Sviri , van Heerden Peter Vernon , Boumendil Ariane , Artigas Antonio , Cecconi Maurizio , Marsh Brian , Moreno Rui , Oeyen Sandra , Bollen Pinto Bernardo , Szczeklik Wojciech , Leaver Susannah , Walther Sten Mikael , Schefold Joerg C , Joannidis Michael , Fjølner Jesper , Zafeiridis Tilemachos , de Lange Dylan , Guidet Bertrand , Flaatten Hans , Jung Christian 
Published: June 2021

ObjectivesIn Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI.SettingICUs in 16 European countries.ParticipantsIn total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems.Primary and secondary outcomes measuresWe chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies.ResultsIn SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p<0.001), longer length of ICU stays (90±162 vs 72±134 hours; p<0.001) and increased levels of organ support. The ICU mortality (aOR 1.50, 95% CI 1.09 to 2.06; p=0.01) was consistently higher in the SHI; however, the 30-day mortality (aOR 0.89, 95% CI 0.66 to 1.21; p=0.47) was similar between THS and SHI. In a sensitivity analysis stratifying for the health economic data, the 30-day mortality was higher in SHI, in low GDP per capita (aOR 2.17, 95% CI 1.42 to 3.58) and low HDI (aOR 1.22, 95% CI 1.64 to 2.20) settings.ConclusionsThe 30-day mortality was similar in both systems. Patients in SHI were older, sicker and frailer at baseline, which could be interpreted as a sign for a more liberal admission policy in SHI. We believe that the observed trend towards ICU excess mortality in SHI results mainly from a more liberal admission policy and an increase in treatment limitations.Trial registration numbersNCT03134807 and NCT03370692.
Muscle stimulation in advanced idiopathic pulmonary fibrosis: a randomised placebo-controlled feasibility study
Authors: Nolan Claire M , Patel Suhani , Barker Ruth E , Walsh Jessica A , Polgar Oliver , Maddocks Matthew , George Peter M , Renzoni Elisabetta A , Wells Athol U , Molyneaux Philip L , Kouranos Vasilis , Chua Felix , Maher Toby M , Man William D-C 
Published: June 2021

ObjectivesTo assess the acceptability of neuromuscular electrical stimulation (NMES) of the quadriceps muscles in people with idiopathic pulmonary fibrosis (IPF) and to identify whether a future definitive trial is feasible.DesignA randomised, parallel, two-group, participant and assessor-blinded, placebo-controlled feasibility trial with embedded qualitative interviews.SettingOutpatient department, Royal Brompton and Harefield Hospitals.ParticipantsTwenty-two people with IPF: median (25th, 75th centiles) age 76 (74, 82) years, forced vital capacity 62 (50, 75) % predicted, 6 min walk test distance 289 (149, 360) m.InterventionsUsual care (home-based exercise, weekly telephone support, breathlessness management leaflet) with either placebo or active NMES for 6 weeks, with follow-up at 6 and 12 weeks.Primary outcome measuresFeasibility of recruitment and retention, treatment uptake and adherence, outcome assessments, participant and outcome assessor blinding and adverse events related to interventions.Secondary outcome measuresOutcome measures with potential to be primary or secondary outcomes in a definitive clinical trial. In addition, purposively sampled participants were interviewed to capture their experiences and acceptability of the trial.ResultsOut of 364 people screened, 23 were recruited: 11 were allocated to each group and one was withdrawn prior to randomisation. Compared with the control group, a greater proportion of the intervention group completed the intervention, remained in the trial blinded to group allocation and experienced intervention-related adverse events. Assessor blinding was maintained. The secondary outcome measures were feasible with most missing data associated with the accelerometer. Small participant numbers precluded identification of an outcome measure suitable for a definitive trial. Qualitative findings demonstrated that trial process and active NMES were acceptable but there were concerns about the credibility of placebo NMES.ConclusionsPrimarily owing to recruitment difficulties, a definitive trial using the current protocol to evaluate NMES in people with IPF is not feasible.Trial registration numberNCT03499275.
Patient and stakeholder involvement in resilient healthcare: an interactive research study protocol
Authors: Guise Veslemøy , Aase Karina , Chambers Mary , Canfield Carolyn , Wiig Siri 
Published: June 2021

IntroductionResilience in healthcare (RiH) is understood as the capacity of the healthcare system to adapt to challenges and changes at different system levels, to maintain high-quality care. Adaptive capacity is founded in the knowledge, skills and experiences of the people in the system, including patients, family or next of kin, healthcare providers, managers and regulators. In order to learn from and support useful adaptations, research is needed to better understand adaptive capacity and the nature and context of adaptations. This includes research on the actors involved in creating resilient healthcare, and how and in what circumstances different groups of patients and other key healthcare stakeholders enact adaptations that contribute to resilience across all levels of the healthcare system.Methods and analysisThis 5-year study applies an interactive design in a two-phased approach to explore and conceptualise patient and stakeholder involvement in resilient healthcare. Study phase 1 is exploratory and will use such data collection methods as literature review, document analysis, interviews and focus groups. Study phase 2 will use a participatory design approach to develop, test and evaluate a conceptual model for patient and stakeholder involvement in RiH. The study will involve patients and other key stakeholders as active participants throughout the research process.Ethics and disseminationThe RiH research programme of which this study is a part is approved by the Norwegian Centre for Research Data (No. 864334). Findings will be disseminated through scientific articles, presentations at national and international conferences, through social media and popular press, and by direct engagement with the public, including patient and stakeholder representatives.
ABC of prescribing exercise as medicine: a narrative review of the experiences of general practitioners and patients
Authors: O'Regan Andrew , Pollock Michael , D'Sa Saskia , Niranjan Vikram 
Published: June 2021

BackgroundExercise prescribing can help patients to overcome physical inactivity, but its use in general practice is limited. The purpose of this narrative review was to investigate contemporaneous experiences of general practitioners and patients with exercise prescribing.MethodPubMed, Scopus, Science Direct and Cochrane reviews were reviewed using the terms ‘exercise prescription’, ‘exercise prescribing’, ‘family practice’, ‘general practice’, ‘adults’ and ‘physical activity prescribing’.ResultsAfter screening by title, abstract and full paper, 23 studies were selected for inclusion. Qualitative, quantitative and mixed-methods studies revealed key experiences of general practitioners and patients. Barriers identified included: physician characteristics, patients’ physical and psychosocial factors, systems and cultural failures, as well as ambiguity around exercise prescribing. We present a synthesis of the key strategies to overcome these using an ABC approach: A: assessment of physical activity: involves asking about physical activity, barriers and risks to undertaking an exercise prescription; B: brief intervention: advice, written prescription detailing frequency, intensity, timing and type of exercise; and C: continued support: providing ongoing monitoring, accountability and progression of the prescription. Multiple supports were identified: user-friendly resources, workshops for doctors, guidelines for specific illnesses and multimorbidity, electronic devices, health system support and collaboration with other healthcare and exercise professionals.DiscussionThis review has identified levers for facilitating exercise prescribing and adherence to it. The findings have been presented in an ABC format as a guide and support for general practitioners to prescribe exercise.
Prevalence and mechanisms of injuries in water polo: a systematic review
Authors: Croteau Felix , Brown Harry , Pearsall David , Robbins Shawn M 
Published: June 2021

ObjectiveTo summarise the information available in the literature on the prevalence of injuries in water polo and injury risk factors.MethodsProtocol was registered on Open Science Framework. MEDLINE, CINAHL, Embase and SPORTDiscus databases were searched for keywords relating to water polo and injuries on 3 February 2021. References were searched for additional studies. Only original research papers in English or French were included, and studies without an injured group were excluded. A data extraction file was made based on the Cochrane Collaboration recommendations. Study quality was evaluated with the Newcastle-Ottawa scales for cohorts and a modified version for cross-sectional studies.ResultsThe initial search yielded 581 articles, with 5 more added from reference lists, but only 41 remained after removing duplicates and applying inclusion/exclusion criteria. Thirty-one articles identified the head, fingers and shoulders as the most common sites of injury. Ten articles on mechanism of injury focused mainly on the shoulder, with degenerative changes, posture, scapular alignment, strength, flexibility and overhead shooting kinematics as the main injury risk factors. Publication types included cohort studies, cross-sectional studies, and one case series.ConclusionsMost traumatic injuries affect the hands and the head from unexpected contact with the ball or opponents. Conversely, training injuries seem to affect mainly the shoulder area. Low level evidence suggests a correlation between shoulder injuries and lack of strength or flexibility as well as large volumes of overhead throwing. Further prospective research is needed to investigate risk factors for other body areas.
Smoking cessation, weight gain and risk of cardiovascular disease
Authors: Wang Xiaowen , Dong Jia-Yi , Cui Renzhe , Muraki Isao , Shirai Kokoro , Yamagishi Kazumasa , Kokubo Yoshihiro , Saito Isao , Yatsuya Hiroshi , Sawada Norie , Iso Hiroyasu , Tsugane Shoichiro 
Published: June 2021

ObjectiveTo examine whether the relationship between smoking cessation and risk of cardiovascular disease (CVD) was modified by weight gain.MethodsA total of 69 910 participants (29 650 men and 46 260 women) aged 45–74 years were grouped into six groups by smoking status in the first and 5-year surveys: sustained smokers, recent quitters according to postcessation weight gain (no weight gain, 0.1–5.0 kg, >5.0 kg), long-term quitters and never smokers. Quitting smoking within and longer than 5 years were defined as recent and long-term quitters, respectively. We used Cox proportional hazard models to estimate the HR for incident CVD, coronary heart disease (CHD) and stroke.ResultsWe identified 4023 CVDs (889 CHDs and 3217 strokes) during a median of 14.8 years of follow-up. Compared with sustained smokers, the multivariable HR (95% CI) for CVD was 0.66 (0.52 to 0.83) for recent quitters without weight gain, 0.71 (0.55 to 0.90) for recent quitters with weight gain of 0.1–5.0 kg, 0.70 (0.44 to 1.10) for recent quitters with weight gain of >5.0 kg, 0.56 (0.49 to 0.64) for long-term quitters, and 0.60 (0.55 to 0.66) for never smokers. The analysis restricted to men showed a similar association. Prespecified analysis by age suggested that recent quitters overall had a lower HR for CVD among those aged <60 years vs ≥60 years. Similar patterns of association were observed in CHD and stroke.ConclusionsPostcessation weight gain did not attenuate the protective association between smoking cessation and risk of CVD.
Evaluation of tumor immune contexture among intrinsic molecular subtypes helps to predict outcome in early breast cancer
Authors: Klopfenstein Quentin , Derangère Valentin , Arnould Laurent , Thibaudin Marion , Limagne Emeric , Ghiringhelli Francois , Truntzer Caroline , Ladoire Sylvain 
Published: June 2021

BackgroundThe prognosis of early breast cancer is linked to clinic-pathological stage and the molecular characteristics of intrinsic tumor cells. In some patients, the amount and quality of tumor-infiltrating immune cells appear to affect long term outcome. We aimed to propose a new tool to estimate immune infiltrate, and link these factors to patient prognosis according to breast cancer molecular subtypes.MethodsWe performed in silico analyses in more than 2800 early breast cancer transcriptomes with corresponding clinical annotations. We first developed a new gene expression deconvolution algorithm that accurately estimates the quantity of immune cell populations (tumor immune contexture, TIC) in tumors. Then, we studied associations between these immune profiles and relapse-free and overall survival among the different intrinsic molecular subtypes of breast cancer defined by PAM50 classification.ResultsTIC estimates the abundance of 15 immune cell subsets. Both myeloid and lymphoid subpopulations show different spread among intrinsic molecular breast cancer subtypes. A high abundance of myeloid cells was associated with poor outcome, while lymphoid cells were associated with favorable prognosis. Unsupervised clustering describing the 15 immune cell subsets revealed four subgroups of breast tumors associated with distinct patient survival, but independent from PAM50. Adding this information to clinical stage and PAM50 strongly improves the prediction of relapse or death.ConclusionsOur findings make it possible to refine the survival stratification of early patients with breast cancer by incorporating TIC in addition to PAM50 and clinical tumor burden in a prognostic model validated in training and validation cohorts.
Direct and indirect immune effects of CMP-001, a virus-like particle containing a TLR9 agonist
Authors: Sabree Shakoora A , Voigt Andrew P , Blackwell Sue E , Vishwakarma Ajaykumar , Chimenti Michael S , Salem Aliasger K , Weiner George J 
Published: June 2021

BackgroundCMP-001, also known as vidutolimod, is a virus-like particle containing a TLR9 agonist that is showing promise in early clinical trials. Our group previously demonstrated that the immunostimulatory effects of CMP-001 are dependent on an anti-Qβ antibody response which results in opsonization of CMP-001 and uptake by plasmacytoid dendritic cells (pDCs) that then produce interferon (IFN)-α. IFN-α then leads to an antitumor T-cell response that is responsible for the in vivo efficacy of CMP-001. Here, we explore mechanisms by which the initial effects of CMP-001 on pDCs activate other cells that can contribute to development of an antitumor T-cell response.MethodsUptake of CMP-001 by various peripheral blood mononuclear cell (PBMC) populations and response to anti-Qβ-coated CMP-001 were evaluated by flow cytometry and single-cell RNA sequencing. Purified monocytes were treated with anti-Qβ-coated CMP-001 or recombinant IFN-α to evaluate direct and secondary effects of anti-Qβ-coated CMP-001 on monocytes.ResultsMonocytes had the highest per cell uptake of anti-Qβ-coated CMP-001 with lower levels of uptake by pDCs and other cell types. Treatment of PBMCs with anti-Qβ-coated CMP-001 induced upregulation of IFN-responsive genes including CXCL10, PDL1, and indoleamine-2,3-dioxygenase (IDO) expression by monocytes. Most of the impact of anti-Qβ-coated CMP-001 on monocytes was indirect and mediated by IFN-α, but uptake of anti-Qβ-coated CMP-001 altered the monocytic response to IFN-α and resulted in enhanced expression of PDL1, IDO, and CD80 and suppressed expression of CXCL10. These changes included an enhanced ability to induce autologous CD4 T-cell proliferation.ConclusionsAnti-Qβ-coated CMP-001 induces IFN-α production by pDCs which has secondary effects on a variety of cells including monocytes. Uptake of anti-Qβ-coated CMP-001 by monocytes alters their response to IFN-α, resulting in enhanced expression of PDL1, IDO and CD80 and suppressed expression of CXCL10. Despite aspects of an immunosuppressive phenotype, these monocytes demonstrated increased ability to augment autologous CD4 T-cell proliferation. These findings shed light on the complexity of the mechanism of action of anti-Qβ-coated CMP-001 and provide insight into pathways that may be targeted to further enhance the efficacy of this novel approach to immunotherapy.
Design, synthesis and immunological evaluation of self-assembled antigenic peptides from dual-antigen targets: a broad-spectrum candidate for an effective antibreast cancer therapy
Authors: Shi Wei , Qiu Qianqian , Feng Ziying , Tong Zhenzhen , Guo Weiwei , Zou Feng , Yue Na , Huang Wenlong , Qian Hai 
Published: June 2021

BackgroundConsidering the narrow immune response spectrum of a single epitope, and the nanoparticles (NPs) as a novel adjuvant can achieve efficient delivery of antigenic peptides safely, a nano-system (denoted as DSPE-PEG-Man@EM-NPs) based on cathepsin B-responsive antigenic peptides was designed and synthesized.MethodsHighly affinitive antigenic peptides were delivered by self-assembled NPs, and targeted erythrocyte membranes acted as a peptide carrier to improve antigenic peptides presentation and to strengthen cytotoxic T-cells reaction. Cathepsin B coupling could release antigenic peptides rapidly in dendritic cells.ResultsEvaluations showed that DSPE-PEG-Man@EM-NPs had obvious inhibitory effects towards both MCF-7 and MDA-MB-231 human breast cancer cell lines.ConclusionOverall, this strategy provides a novel strategy for boosting cytotoxic T lymphocytes response, thereby expanding the adaptation range of tumor antigenic peptides and improving the therapeutic effect of tumor immunotherapy with nanomedicine.
Embolization strategies for intracranial dural arteriovenous fistulas with an isolated sinus: a single-center experience in 20 patients
Authors: Hendriks Eef J , Lynch Jeremy , Swaminathan Saravana Kumar , Nicholson Patrick , Agid Ronit , Radovanovic Ivan , Pereira Vitor M , terBrugge Karel , Krings Timo 
Published: June 2021

BackgroundIntracranial dural arteriovenous fistulas (DAVFs) draining into an isolated sinus segment constitute a specific entity within the spectrum of cranial dural AV shunts, with under-reporting of their optimal treatment.ObjectiveTo describe the multimodal treatment approach to isolated sinus DAVFs in a large single-center cohort.MethodsRetrospective analysis of adult patients with an isolated sinus DAVF treated at our institution between 2004 and 2020 was performed. Cases were analyzed for demographics, clinical presentation, angiographic findings, treatment techniques, angiographic and clinical outcomes, and complications.ResultsOf 317 patients with DAVFs, 20 (6.3%) with an isolated sinus DAVF underwent treatment. Transarterial embolization was performed through the middle meningeal artery in 9 of 12 procedures, with a success rate of 66.7%. Transarterial glue embolization proved successful in two of five procedures (40%) and Onyx in six of seven procedures (85.7%). Transvenous embolization (TVE) with navigation via the occlusion into the isolated sinus was successful in seven out of nine procedures (77.8%). All three open TVE and one pure open surgical procedure gained complete closure of the fistula. There were two major complications. Complete occlusion of the fistula was eventually obtained in all cases (100%).ConclusionsIsolated sinus DAVFs are always aggressive and require a multimodal approach to guarantee closure of the shunt. Transarterial treatment with Onyx achieves good results. Transvenous treatment appears equally successful, navigating into the occluded segment across the occlusion or via burr hole as backup.