bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and cost-effectiveness of a virtual community of practice to improve the empowerment of patients with ischaemic heart disease: study protocol of a randomised controlled trial
Authors: González-González Ana Isabel , Perestelo-Pérez Lilisbeth , Koatz Débora , Ballester Marta , Pacheco-Huergo Valeria , Ramos-García Vanesa , Torres-Castaño Alezandra , Rivero-Santana Amado , Toledo-Chávarri Ana , Valcárcel-Nazco Cristina , Mateos-Rodilla Juana , Obaya-Rebollar Juan Carlos , García-García Javier , Díaz-Sánchez Santiago , Morales-Cobos Luis , Bosch-Fontcuberta Josep María , Vallejo-Camazón Nuria , Rodríguez-Almodovar Ana , del Castillo José Carlos , Muñoz-Balsa Marcos , del Rey-Granado Yolanda , Garrido-Elustondo Sofía , Tello-Bernabé María-Eugenia , Ramírez-Puerta Ana Belén , Orrego Carola 
Published: October 2020

IntroductionVirtual Communities of Practice (VCoP) or knowledge-sharing virtual communities offer ubiquitous access to information and exchange possibilities for people in similar situations, which might be especially valuable for the self-management of patients with chronic diseases. In view of the scarce evidence on the clinical and economic impact of these interventions on chronic conditions, we aim to evaluate the effectiveness and cost-effectiveness of a VCoP in the improvement of the activation and other patient empowerment measures in patients with ischaemic heart disease (IHD).Methods and analysisA pragmatic randomised controlled trial will be performed in Catalonia, Madrid and Canary Islands, Spain. Two hundred and fifty patients with a recent diagnosis of IHD attending the participating centres will be selected and randomised to the intervention or control group. The intervention group will be offered participation for 12 months in a VCoP based on a gamified web 2.0 platform where there is interaction with other patients and a multidisciplinary professional team. Intervention and control groups will receive usual care. The primary outcome will be measured with the Patient Activation Measure questionnaire at baseline, 6, 12 and 18 months. Secondary outcomes will include: clinical variables; knowledge (Questionnaire of Cardiovascular Risk Factors), attitudes (Self-efficacy Managing Chronic Disease Scale), adherence to the Mediterranean diet (Mediterranean Diet Questionnaire), level of physical activity (International Physical Activity Questionnaire), depression (Patient Health Questionnaire), anxiety (Hospital Anxiety Scale-A), medication adherence (Adherence to Refill Medication Scale), quality of life (EQ-5D-5L) and health resources use. Data will be collected from self-reported questionnaires and electronic medical records.Ethics and disseminationThe trial was approved by Clinical Research Ethics Committee of Gregorio Marañón University Hospital in Madrid, Nuestra Señora de Candelaria University Hospital in Santa Cruz de Tenerife and IDIAP Jordi Gol in Barcelona. The results will be disseminated through workshops, policy briefs, peer-reviewed publications, local/international conferences.Trial registration numberClinicalTrials.gov Registry (NCT03959631). Pre-results.
Long-term mortality in young and middle-aged adults hospitalised with chronic disease: a Danish cohort study
Authors: Skajaa Nils , Ording Anne Gulbech , Darvalics Bianka , Horvath-Puho Erzsebet , Sørensen Henrik Toft 
Published: October 2020

ObjectivesTo examine the long-term outcomes for patients hospitalised with chronic diseases at age 30, 40 or 50 years.DesignNationwide, population-based cohort study.SettingAll Danish hospitals, 1979–1989, with follow-up through 2014.ParticipantsPatients hospitalised during the study period with one, two or three or more chronic diseases and age-matched and sex-matched persons from the general population without chronic disease leading to hospitalisation: age-30 group: 13 857 patients and 69 285 comparators; age-40 group: 24 129 patients and 120 645 comparators; and age-50 group, 37 807 patients and 189 035 comparators.Main outcome measuresTwenty-five-year mortality risks based on Kaplan-Meier estimates, years-of-life-lost (YLLs) and mortality rate ratios based on Cox regression analysis. YLLs were computed for each morbidity level, as well as in strata of income, employment, education and psychiatric conditions.ResultsTwenty-five-year mortality risks and YLLs increased steadily with increasing number of morbidities leading to hospitalisation and age, but the risk difference with general population comparators remained approximately constant across age cohorts. In the age-30 cohort, the risk differences for patients compared with comparators were 35.0% (95% CI 32.5 to 37.5) with two diseases and 62.5% (54.3% to 70.3%) with three or more diseases. In the age-50 cohort, these differences were, respectively, 48.4% (47.4 to 49.3) and 61.7% (60.1% to 63.0%). Increasing morbidity burden augmented YLLs resulting from low income, unemployment, low education level and psychiatric conditions. In the age-30 cohort, YYLs attributable to low income were 2.4 for patients with one disease, 6.2 for patients with two diseases and 11.5 for patients with three or more diseases.ConclusionsAmong patients with multiple chronic diseases, the risk of death increases steadily with the number of chronic diseases and with age. Multimorbidity augments the already increased mortality among patients with low socioeconomic status.
Prognostic factors in metastatic breast cancer: a prospective single-centre cohort study in a Finnish University Hospital
Authors: Karihtala Peeter , Jääskeläinen Anniina , Roininen Nelli , Jukkola Arja 
Published: October 2020

ObjectivesAlthough novel early breast cancer prognostic factors are being continuously discovered, only rare factors predicting survival in metastatic breast cancer have been validated. The prognostic role of early breast cancer prognostic factors in metastatic disease also remains mostly unclear.Design and settingProspective cohort study in a Finnish University Hospital.Participants and outcomes594 women with early breast cancer were originally followed. Sixty-one of these patients developed distant metastases during the follow-up, and their primary breast cancer properties, such as tumour size, nodal status, oestrogen receptor (ER) and progesterone receptor expression, grade, proliferation rate, histopathological subtype and breast cancer subtype were analysed as potential prognostic factors for metastatic disease.ResultsIn multivariate analysis, the presence of lymph node metastases at the time of early breast cancer surgery (HR, 2.17; 95% CI, 1.09–4.31; p=0.027) and ER status (negative vs positive, HR, 2.16; 95% CI, 1.14–4.10; p=0.018) were significant predictors of survival in metastatic disease.ConclusionsThese results confirm ER status as a primary prognostic factor in metastatic breast cancer. Furthermore, it also suggests that the presence of initial lymph node metastases could serve as a prognostic factor in recurrent breast cancer.
Understanding pathways to inequalities in child mental health: a counterfactual mediation analysis in two national birth cohorts in the UK and Denmark
Authors: Lai Eric TC , Schlüter Daniela K , Lange Theis , Straatmann Viviane , Andersen Anne-Marie Nybo , Strandberg-Larsen Katrine , Taylor-Robinson David 
Published: October 2020

ObjectivesWe assessed social inequalities in child mental health problems (MHPs) and how they are mediated by perinatal factors, childhood illness and maternal mental health in two national birth cohorts.DesignLongitudinal cohort studySettingWe used data from the UK Millennium Cohort Study and the Danish National Birth Cohort.Primary and secondary outcome measuresWe applied causal mediation analysis to longitudinal cohort data. Socioeconomic conditions (SECs) at birth were measured by maternal education. Our outcome was child MHPs measured by the Strength and Difficulty Questionnaire at age 11. We estimated natural direct, indirect and total effects (TEs) of SECs on MHPs. We calculated the proportion mediated (PM) via three blocks of mediators—perinatal factors (smoking/alcohol use during pregnancy, birth weight and gestational age), childhood illness and maternal mental health.ResultsAt age 11 years, 9% of children in the UK and 3.8% in Denmark had MHPs. Compared with high SECs, children in low SECs had a higher risk of MHPs (relative risk (RR)=4.3, 95% CI 3.3 to 5.5 in the UK, n=13 112; and RR=6.2, 95% CI 4.9 to 7.8 in Denmark, n=35 764). In the UK, perinatal factors mediated 10.2% (95% CI 4.5 to 15.9) of the TE, and adding maternal mental health tripled the PM to 32.2% (95% CI 25.4 to 39.1). In Denmark, perinatal factors mediated 16.5% (95% CI 11.9 to 21.1) of the TE, and including maternal mental health increased the PM to 16.9% (95% CI 11.2 to 22.6). Adding childhood illness made little difference in either country.ConclusionSocial inequalities in child mental health are partially explained by perinatal factors in the UK and Denmark. Maternal mental health partially explained inequalities in the UK but not in Denmark.
Achieving universal health coverage for people with stroke in South Africa: protocol for a scoping review
Authors: van Niekerk Sjan-Mari , Inglis-Jassiem Gakeemah , Kamalakannan Sureshkumar , Fernandes Silke , Webster Jayne , English Rene , Smythe Tracey , Louw QA 
Published: October 2020

IntroductionStroke is the second most common cause of death after HIV/AIDS and a significant health burden in South Africa. The extent to which universal health coverage (UHC) is achieved for people with stroke in South Africa is unknown. Therefore, a scoping review to explore the opportunities and challenges within the South African health system to facilitate the achievement of UHC for people with stroke is warranted.Methods and analysisThe scoping review will follow the approach recommended by Levac, Colquhoun and O’Brien, which includes five steps: (1) identifying the research question, (2) identifying relevant studies, (3) selecting the studies, (4) charting the data, and (5) collating, summarising and reporting the results. Health Systems Dynamics Framework and WHO Framework on integrated people-centred health services will be used to map, synthesise and analyse data thematically.Ethics and disseminationEthical approval is not required for this scoping review, as it will only include published and publicly available data. The findings of this review will be published in an open-access, peer-reviewed journal and we will develop an accessible summary of the results for website posting and stakeholder meetings.
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors
Authors: Razak Albiruni RA , Cleary James M , Moreno Victor , Boyer Michael , Calvo Aller Emiliano , Edenfield William , Tie Jeanne , Harvey R Donald , Rutten Annemie , Shah Manish A , Olszanski Anthony J , Jäger Dirk , Lakhani Nehal , Ryan David P , Rasmussen Erik , Juan Gloria , Wong Hansen , Soman Neelesh , Smit Marie-Anne Damiette , Nagorsen Dirk , Papadopoulos Kyriakos P 
Published: October 2020

BackgroundTo determine the safety and efficacy of the anti-colony-stimulating factor 1 receptor (anti-CSF1R) monoclonal antibody AMG 820 in combination with pembrolizumab in patients with select solid tumors.Patients and methodsPatients had advanced, refractory mismatch repair-proficient colorectal cancer, pancreatic cancer, or non-small cell lung cancer (NSCLC) with low (<50%) programmed cell death-ligand 1 (PD-L1) expression and were naïve to anti-programmed cell death-1 (PD-1)/PD-L1 or had relapsed/refractory NSCLC after anti-PD-1/PD-L1 treatment with low or high (≥50%) PD-L1 expression; all were anti-CSF1/CSF1R naïve. Patients received 1100 mg or 1400 mg AMG 820 plus 200 mg pembrolizumab intravenously every 3 weeks. The primary endpoints were incidence of dose-limiting toxicities (DLTs) and adverse events (AEs) and objective response rate per immune-related Response Evaluation Criteria in Solid Tumours at the recommended combination dose.ResultsOverall, 116 patients received ≥1 dose of AMG 820 plus pembrolizumab (18 at 1400 mg AMG 820; 98 at 1100 mg AMG 820). Most patients (64%) were male; the median age was 64 (range 30–86) years. Seven patients had DLTs (1 at 1400 mg AMG 820; 6 at 1100 mg AMG 820). Almost all patients (99.1%) had AEs, 87.9% with grade ≥3 AEs. The most common AEs were increased aspartate aminotransferase (59.5%), fatigue (48.3%), periorbital/face edema (48.3%), and rash/maculopapular rash (37.1%). The best response was immune-related partial response in 3 patients (3%; duration of response 9.2, 10.0, 12.5 months) and immune-related stable disease in 39 patients (34%). None of the completed phase II cohorts met the predefined threshold for efficacy. Post-treatment there was accumulation of serum colony-stimulating factor 1 (CSF1) and interleukin-34, reduction in CSF1-dependent CD16-expressing monocytes, and increased PD-L1 expression and CD4 and CD8 cell numbers in tumor biopsies.ConclusionsThe recommended combination dose of 1100 mg AMG 820 plus 200 mg pembrolizumab had an acceptable safety profile. Although pharmacodynamic effects were observed, antitumor activity was insufficient for further evaluation of this combination in selected patient populations.Trial registration numberNCT02713529
Translating Cancer Risk Prediction Models into Personalized Cancer Risk Assessment Tools: Stumbling Blocks and Strategies for Success
Authors: Waters Erika A. , Taber Jennifer M. , McQueen Amy , Housten Ashley J. , Studts Jamie L. , Scherer Laura D. 
Published: October 2020

Abstract
Cancer risk prediction models such as those published in Cancer Epidemiology, Biomarkers, and Prevention are a cornerstone of precision medicine and public health efforts to improve population health outcomes by tailoring preventive strategies and therapeutic treatments to the people who are most likely to benefit. However, there are several barriers to the effective translation, dissemination, and implementation of cancer risk prediction models into clinical and public health practice. In this commentary, we discuss two broad categories of barriers. Specifically, we assert that the successful use of risk-stratified cancer prevention and treatment strategies is particularly unlikely if risk prediction models are translated into risk assessment tools that (i) are difficult for the public to understand or (ii) are not structured in a way to engender the public's confidence that the results are accurate. We explain what aspects of a risk assessment tool's design and content may impede understanding and acceptance by the public. We also describe strategies for translating a cancer risk prediction model into a cancer risk assessment tool that is accessible, meaningful, and useful for the public and in clinical practice.
Exploring the Legality of the Constitutional and Independence Referendums in Nagorno-Karabakh under International Law
Authors: Bagheri Saeed 
Published: October 2020

Abstract
As a result of the constitutional referendum held on 20 February 2017 in the unrecognised Nagorno-Karabakh Republic, both the name and administration of the autonomous region of Nagorno-Karabakh changed. According to the new Constitution, adopted with an 87 per cent majority, Nagorno-Karabakh’s name is now the Republic of Artsakh, its Armenian name, and the system is changing from semi-presidential to presidential. This study discusses the legality of the referendum, the third since Nagorno-Karabakh was established in 1991; it evaluates the referendum in the context of the secession and the right to self-determination in international law. Having looked at similar cases, the article challenges the compatibility of all referenda held in the region with the uti possidetis juris principle and principle of territorial integrity under international law.
Rotated Spectral Principal Component Analysis (rsPCA) for Identifying Dynamical Modes of Variability in Climate Systems
Authors: Guilloteau Clément , Mamalakis Antonios , Vulis Lawrence , Le Phong V. V. , Georgiou Tryphon T. , Foufoula-Georgiou Efi 
Published: October 2020

AbstractSpectral PCA (sPCA), in contrast to classical PCA, offers the advantage of identifying organized spatiotemporal patterns within specific frequency bands and extracting dynamical modes. However, the unavoidable trade-off between frequency resolution and robustness of the PCs leads to high sensitivity to noise and overfitting, which limits the interpretation of the sPCA results. We propose herein a simple nonparametric implementation of sPCA using the continuous analytic Morlet wavelet as a robust estimator of the cross-spectral matrices with good frequency resolution. To improve the interpretability of the results, especially when several modes of similar amplitude exist within the same frequency band, we propose a rotation of the complex-valued eigenvectors to optimize their spatial regularity (smoothness). The developed method, called rotated spectral PCA (rsPCA), is tested on synthetic data simulating propagating waves and shows impressive performance even with high levels of noise in the data. Applied to global historical geopotential height (GPH) and sea surface temperature (SST) daily time series, the method accurately captures patterns of atmospheric Rossby waves at high frequencies (3–60-day periods) in both GPH and SST and El Niño–Southern Oscillation (ENSO) at low frequencies (2–7-yr periodicity) in SST. At high frequencies the rsPCA successfully unmixes the identified waves, revealing spatially coherent patterns with robust propagation dynamics.
Classical versus non-classical EGFR mutations: Erlotinib response and impact of renal insufficiency
Authors: Celik Emir , Samanci Nilay Sengul , Karadag Mehmet , Demirci Nebi Serkan , Cikman Duygu Ilke , Derin Sumeyra , Bedir Sahin , Degerli Ezgi , Oruc Kerem , Oztas Nihan Senturk , Demirelli Fuat Hulusi 
Published: October 2020

Introduction Erlotinib is an effective treatment option for EGFR-mutant non-small cell lung cancer. It is important to predict patients who will respond better to erlotinib. We designed this study to investigate the effect of renal insufficiency (RI) on erlotinib treatment outcomes. Methods All patients receiving erlotinib were stratified into 3 groups. Group 1 consisted of non-RI subjects with classical epidermal growth factor receptor (EGFR) mutations, Group 2 consisted of those with RI (Estimated glomerular filtration rate <60 mL/min) and classical EGFR mutations, and Group 3 consisted of those with non-classical EGFR mutations. Results 82 patients were included in the study. Median progression-free survival (PFS) in patients with classical mutation was approximately 6 months shorter in those with RI, although not statistically significant. Median overall survival (OS) in Group 1, 2 and 3 was 34.1 months, 35.2 months, and 15 months, respectively and although not statistically significant, median OS was 20 months shorter in Group 3. Univariate and multivariate cox-regression analysis revealed shorter PFS and OS in males and those with ECOG ≥2 while PFS and OS were longer in those with recurrent lung tumors and generating rash during erlotinib treatment. There was no difference between RI and non-RI patients in terms of adverse events except for fatigue and appetite loss. Conclusions This research showed OS in patients with and without RI was comparable. Although not statistically significant, PFS in patients with classical mutation was approximately 6 months shorter in those with RI patients.
Mental Practice Combined With Physical Practice to Enhance Upper Extremity Functional Ability Poststroke: A Systematic Review
Authors: Alashram Anas R. , Annino Giuseppe , Al-qtaishat Mohammed , Padua Elvira 
Published: October 2020

Background: Upper extremity deficits are one of the most common impairments in individuals with stroke. Mental practice is exercised cognitively in the absence of the physical trials. The effects of the combination of mental and physical practice remain unclear. Objectives: This study aimed to examine the effects of combined physical practice and mental practice on the upper extremity functional ability poststroke, to identify which stroke population is most likely to benefit from the intervention, and to determine the effective treatment dosage. Methods: We searched in the PubMed, SCOPUS, National Rehabilitation Information REHABDATA, PEDro, and Web of Science until February 2020. Randomized clinical trials examined the effects of combined physical practice and mental practice on the upper extremity functional ability in people with a stroke. The risk of bias was evaluated and the effect sizes were calculated. Results: Nine studies met our inclusion criteria. In total, 230 stroke survivors were included in this analysis (mean age: 60.84 years). This review found that combining physical practice and mental practice has beneficial effects in improving the upper extremity functional ability poststroke. Conclusion: Combining physical practice and mental practice improves the upper extremity functional ability poststroke, this improvement can extend for 3 months after the treatment intervention. We propose that using 30 to 60 min of physical practice followed by 30 min of mental practice, 2 to 3 times weekly for 6 to 10 weeks, may give meaningful effects in individuals with stroke.
Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease
Authors: Haji Gulam , Wiegman Coen H. , Michaeloudes Charalambos , Patel Mehul S. , Curtis Katrina , Bhavsar Pankaj , Polkey Michael I. , Adcock Ian M. , Chung Kian Fan ,   on behalf of the COPDMAP consortium
Published: October 2020

Abstract
Background
Mitochondrial damage and dysfunction have been reported in airway and quadriceps muscle cells of patients with chronic obstructive pulmonary disease (COPD). We determined the concomitance of mitochondrial dysfunction in these cells in COPD.

Methods
Bronchial biopsies were obtained from never- and ex-smoker volunteers and COPD patients (GOLD Grade 2) and quadriceps muscle biopsies from the same volunteers in addition to COPD patients at GOLD Grade 3/4 for measurement of mitochondrial function.

Results
Decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mtROS) and decreased superoxide dismutase 2 (SOD2) levels were observed in mitochondria isolated from bronchial biopsies from Grade 2 patients compared to healthy never- and ex-smokers. There was a significant correlation between ΔΨm and FEV1 (% predicted), transfer factor of the lung for carbon monoxide (TLCOC % predicted), 6-min walk test and maximum oxygen consumption. In addition, ΔΨm was also associated with decreased expression levels of electron transport chain (ETC) complex proteins I and II. In quadriceps muscle of Grade 2 COPD patients, a significant increase in total ROS and mtROS was observed without changes in ΔΨm, SOD2 or ETC complex protein expression. However, quadriceps muscle of GOLD Grade 3/4 COPD patients showed an increased mtROS and decreased SOD2 and ETC complex proteins I, II, III and V expression.

Conclusions
Mitochondrial dysfunction in the airways, but not in quadriceps muscle, is associated with airflow obstruction and exercise capacity in Grade 2 COPD. Oxidative stress-induced mitochondrial dysfunction in the quadriceps may result from similar disease processes occurring in the lungs.