bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of community-based chronic obstructive pulmonary disease service, a multidisciplinary intervention in an area of high deprivation: a longitudinal matched controlled study
Authors: Saini Pooja , Rose Tanith , Downing Jennifer , Matata Bashir , Pilsworth Samantha , Pemberton Allan , Comerford Terence , Wilson Keith , Shaw Matthew , Harper Lesley M , Daras Konstantinos , Barr Benjamin 
Published: May 2020

ObjectiveTo examine the effects of a consultant-led, community-based chronic obstructive pulmonary disease (COPD) service, based in a highly deprived area on emergency hospital admissions.DesignA longitudinal matched controlled study using difference-in-differences analysis to compare the change in outcomes in the intervention population to a matched comparison population, 5 years before and after implementation.SettingA deprived district in the North West of England between 2005 and 2016.InterventionA community-based, consultant-led COPD service providing diagnostics, treatment and rehabilitation from 2011 to 2016.Main outcome measuresEmergency hospital admissions, length of stay per emergency admission and emergency readmissions for COPD.ResultsThe intervention was associated with 24 fewer emergency COPD admissions per 100 000 population per year (95% CI −10.6 to 58.8, p=0.17) in the postintervention period, relative to the control group. There were significantly fewer emergency admissions in populations with medium levels of deprivation (64 per 100 000 per year; 95% CI 1.8 to 126.9) and among men (60 per 100 000 per year; 95% CI 12.3 to 107.3).ConclusionWe found limited evidence that the service reduced emergency hospital admissions, after an initial decline the effect was not sustained. The service, however, may have been more effective in some subgroups.
Perception of modern radiotherapy learning: study protocol for a mixed-methods analysis of trainees and trainers at a UK cancer centre
Authors: Walls Gerard , McAleer James J , Hanna Gerard G 
Published: May 2020

IntroductionRadiotherapy technology and postgraduate medical training have both evolved significantly over the last 20 years. Clinical Oncology is a recognised craft specialty where the apprenticeship model of clinical training is applicable. The challenges of learning radiotherapy in the modern radiotherapy department workplace have not been comprehensively described and no optimal method has been identified.Methods and analysisFive Clinical Oncology trainers and five Clinical Oncology trainees at a regional cancer centre will be invited to undertake a semistructured interview regarding their personal accounts of learning radiotherapy. Both trainees and consultants will be treated as equal co-investors in the process of radiotherapy learning, with the common shared aim of passing radiotherapy skills from trainers to trainees. Interviews will last up to 40 min. After transcription, an interpretative phenomenological analysis will be performed. All trainees and trainers at the same centre (n=34) will then be invited to complete the same purpose-built questionnaire. Four trainers and three trainees have piloted the questionnaire, and input was sought from the national leads of the biennial UK Clinical Oncology training survey. Significance testing will be performed on predefined questions and thematic analysis on white space questions.Ethics and disseminationMedical education research is evolving in Clinical Oncology and Radiation Oncology but there are few studies comprehensively assessing this from the viewpoint of trainees and trainers. Pending the success of the proposed study, the approach detailed represents a novel method that could be used to identify the strengths and weaknesses of radiotherapy training in other centres and settings. Ethical and governance approvals have been granted by the University Research Ethics Committee and the Integrated Research Application System, respectively. This study has been funded by Friends of the Cancer Centre.
Limiting surveillance imaging for patients with lymphoma in remission: a mixed methods study leading to a Choosing Wisely recommendation
Authors: Paltiel Ora , Raviv Sharabi Galor , Tzemach Reut , Rechavi Talya , Trachtenberg Estherina , Goldschmidt Neta , Dann Eldad J , Bar-Shalom Rachel 
Published: May 2020

BackgroundUnder the ‘Choosing Wisely’ (CW) framework, professional organisations internationally have advocated limiting imaging for asymptomatic patients following curative cancer therapy, based on limited value and high cost. F18-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) was widely adopted locally for surveillance lymphoma imaging after 2004.ObjectivesPrior to ratification of a local CW recommendation to limit surveillance imaging in lymphoma, we aimed to assess: (A) performance characteristics of surveillance FDG-PET/CT; (B) rates, clinical consequences and costs of false positives (FP); and (C) patients and professionals’ attitudes towards overuse.MethodsMixed methods (quantitative and qualitative) study. We analysed surveillance FDG-PET/CT results of two patient cohorts (n1=215 Hodgkin lymphoma and non-Hodgkin lymphoma; n2=203 Hodgkin lymphoma only). FPs were defined by negative biopsy or clinical follow-up. We held focus group discussions and in-depth interviews eliciting attitudes of 26 patients and 11 clinicians, respectively.ResultsFPs were observed in 25.1% (95% CI 20.5 to 30.5) per scan—cohort 1, and 41.7% (95% CI 37.9 to 45.6) per patient—cohort 2, engendering frequent additional testing. Specific characteristics and location of findings altered the FP rate. The estimated cost per relapse detected was $50 000 (cohort 2). Patients sought reassurance via surveillance imaging, which they considered highly accurate, yet stressful. Aware of radiation risks, they were largely unconcerned about consequences of FPs. Confidence in the treating physicians was an important factor in patients’ acceptance of forgoing imaging. Clinicians, frequently under patient pressure to order imaging, generally believed that it did not affect prognosis (with important exceptions), welcomed professional guidelines, but rejected regulatory restrictions on its use.ConclusionAcceptance of CW recommendations to limit overuse may be enhanced by quantitative data on consequences and costs of surveillance imaging, supplemented by qualitative data on patient and physician attitudes.
Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary
Authors: Keeley Paul , Buchanan Deans , Carolan Clare , Pivodic Lara , Tavabie Simon , Noble Simon 
Published: May 2020

The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients.MethodsWe undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19.Results12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure.ConclusionsThere remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.
High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus
Authors: Koelmeyer Rachel , Nim Hieu Tri , Nikpour Mandana , Sun Ying B , Kao Amy , Guenther Oliver , Morand Eric , Hoi Alberta 
Published: May 2020

ObjectiveDisease severity in SLE is an important concept related to disease activity, treatment burden and prognosis. We set out to evaluate if high disease activity status (HDAS), based on ever attainment of a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) disease activity score of ≥10, is an indicator for disease severity in SLE.MethodsUsing prospectively collected data, we assessed the association of HDAS with sociodemographic and disease characteristics and adverse clinical outcomes using logistic regression or generalised estimating equations.ResultsOf 286 patients with SLE, who were observed for a median (range) of 5.1 years (1–10.8 years), 43.7% experienced HDAS at least once during the observational period. Autoantibody positivity, particularly anti-dsDNA and anti-Sm positivity, were associated with increased likelihood of HDAS. Age ≥45 years at diagnosis was associated with reduced likelihood of HDAS (p=0.002). Patients with HDAS had higher Physician Global Assessment score (>1: OR 8.1, p<0.001) and were more likely to meet criteria for flare (mild/moderate flare: OR 4.4, p<0.001; severe flare: OR 17.2, p<0.001) at the time of experiencing HDAS. They were also more likely to have overall higher disease activity, as defined by time-adjusted mean SLEDAI-2K score in the highest quartile (OR 11.7, 95% CI 5.1 to 26.6; p>0.001), higher corticosteroid exposure (corticosteroid dose in highest quartile: OR 7.7, 95% CI 3.9 to 15.3; p<0.001) and damage accrual (OR 2.3, 95% CI 1.3 to 3.9; p=0.003) when compared with non-HDAS patients.ConclusionsHDAS is associated with more severe disease, as measured by higher disease activity across time, corticosteroid exposure and damage accrual. The occurrence of HDAS may be a useful prognostic marker in the management of SLE.
Posterior reversible encephalopathy syndrome (PRES): presentation, diagnosis and treatment
Authors: Parasher Anant , Jhamb Rajat 
Published: May 2020

AbstractPosterior reversible encephalopathy syndrome (PRES) is a neurological disorder which is characterised by variable symptoms, which include visual disturbances, headache, vomiting, seizures and altered consciousness. The exact pathophysiology of PRES has not been completely explained, but hypertension and endothelial injury seem to be almost always present. Vasoconstriction resulting in vasogenic and cytotoxic edema is suspected to be responsible for the clinical symptoms as well as the neuro-radiological presentation. On imaging studies, Symmetrical white matter abnormalities suggestive of edema are seen in the computer tomography (CT) and magnetic resonance imaging (MRI) scans, commonly but not exclusively in the posterior parieto-occipital regions of the cerebral hemispheres. The management is chiefly concerned with stabilization of the patient, adequate and prompt control of blood pressure, prevention of seizures and timely caesarean section in obstetric cases with pre-eclampsia/eclampsia. In conclusion, persistently elevated blood pressures remain the chief culprit for the clinical symptoms as well as the neurological deficits. Early diagnosis by diffusion weighted MRI scans, and differentiation from other causes of altered sensorium i.e. seizures, meningitis and psychosis, is extremely important to initiate treatment and prevent further complications. Although most cases resolve successfully and carry a favorable prognosis, patients with inadequate therapeutic support or delay in treatment may not project a positive outcome.
Overcoming Genetically Based Resistance Mechanisms to PD-1 Blockade
Authors: Torrejon Davis Y. , Abril-Rodriguez Gabriel , Champhekar Ameya S. , Tsoi Jennifer , Campbell Katie M. , Kalbasi Anusha , Parisi Giulia , Zaretsky Jesse M. , Garcia-Diaz Angel , Puig-Saus Cristina , Cheung-Lau Gardenia , Wohlwender Thomas , Krystofinski Paige , Vega-Crespo Agustin , Lee Christopher M. , Mascaro Pau , Grasso Catherine S. , Berent-Maoz Beata , Comin-Anduix Begoña , Hu-Lieskovan Siwen , Ribas Antoni 
Published: May 2020

Abstract

Mechanism-based strategies to overcome resistance to PD-1 blockade therapy are urgently needed. We developed genetic acquired resistant models of JAK1, JAK2, and B2M loss-of-function mutations by gene knockout in human and murine cell lines. Human melanoma cell lines with JAK1/2 knockout became insensitive to IFN-induced antitumor effects, while B2M knockout was no longer recognized by antigen-specific T cells and hence was resistant to cytotoxicity. All of these mutations led to resistance to anti–PD-1 therapy in vivo. JAK1/2-knockout resistance could be overcome with the activation of innate and adaptive immunity by intratumoral Toll-like receptor 9 agonist administration together with anti–PD-1, mediated by natural killer (NK) and CD8 T cells. B2M-knockout resistance could be overcome by NK-cell and CD4 T-cell activation using the CD122 preferential IL2 agonist bempegaldesleukin. Therefore, mechanistically designed combination therapies can overcome genetic resistance to PD-1 blockade therapy.

Significance:
The activation of IFN signaling through pattern recognition receptors and the stimulation of NK cells overcome genetic mechanisms of resistance to PD-1 blockade therapy mediated through deficient IFN receptor and antigen presentation pathways. These approaches are being tested in the clinic to improve the antitumor activity of PD-1 blockade therapy.
This article is highlighted in the In This Issue feature, p. 1079
TGFβ (Transforming Growth Factor-Beta)–Activated Kinase 1 Regulates Arteriovenous Fistula Maturation
Authors: Hu Haidi , Lee Shin-Rong , Bai Hualong , Guo Jianming , Hashimoto Takuya , Isaji Toshihiko , Guo Xiangjiang , Wang Tun , Wolf Katharine , Liu Shirley , Ono Shun , Yatsula Bogdan , Dardik Alan 
Published: May 2020

Objective:
Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access but have high rates of primary maturation failure. Successful AVF maturation requires wall thickening with deposition of ECM (extracellular matrix) including collagen and fibronectin, as well as lumen dilation. TAK1 (TGFβ [transforming growth factor-beta]–activated kinase 1) is a mediator of noncanonical TGFβ signaling and plays crucial roles in regulation of ECM production and deposition; therefore, we hypothesized that TAK1 regulates wall thickening and lumen dilation during AVF maturation.

Approach and Results:

In both human and mouse AVF, immunoreactivity of TAK1, JNK (c-Jun N-terminal kinase), p38, collagen 1, and fibronectin was significantly increased compared with control veins. Manipulation of TAK1 in vivo altered AVF wall thickening and luminal diameter; reduced TAK1 function was associated with reduced thickness and smaller diameter, whereas activation of TAK1 function was associated with increased thickness and larger diameter. Arterial magnitudes of laminar shear stress (20 dyne/cm
2
) activated noncanonical TGFβ signaling including TAK1 phosphorylation in mouse endothelial cells.

Conclusions:
TAK1 is increased in AVF, and TAK1 manipulation in a mouse AVF model regulates AVF thickness and diameter. Targeting noncanonical TGFβ signaling such as TAK1 might be a novel therapeutic approach to improve AVF maturation.
Association of TIM-1 (T-Cell Immunoglobulin and Mucin Domain 1) With Incidence of Stroke
Authors: Song Lu , Sun Jiangming , Söderholm Martin , Melander Olle , Orho-Melander Marju , Nilsson Jan , Borné Yan , Engström Gunnar 
Published: May 2020

Objective:
The aim of this study was to investigate if there is a causal relationship between circulating levels of TIM-1 (T-cell immunoglobulin and mucin domain 1) and incidence of stroke.

Approach and Results:

Plasma TIM-1 was analyzed in 4591 subjects (40% men; mean age, 57.5 years) attending the Malmö Diet and Cancer Study. Incidence of stroke was studied in relation to TIM-1 levels during a mean of 19.5 years follow-up. Genetic variants associated with TIM-1 (pQTLs [protein quantitative trait loci]) were examined, and a 2-sample Mendelian randomization analysis was performed to explore the role of TIM-1 in stroke using summary statistics from our pQTLs and the MEGASTROKE consortium. A total of 416 stroke events occurred during follow-up, of which 338 were ischemic strokes. After risk factor adjustment, TIM-1 was associated with increased incidence of all-cause stroke (hazards ratio for third versus first tertile, 1.44 [95% CI, 1.10–1.87];
P
for trend, 0.004), and ischemic stroke (hazards ratio, 1.42 [95% CI, 1.06–1.90];
P
for trend, 0.011). Nineteen independent lead SNPs, located in three genomic risk loci showed significant associations with TIM-1 (
P
<5×10
−8
). A 2-sample Mendelian Randomization analysis suggested a causal effect of TIM-1 on stroke (β=0.083,
P
=0.0004) and ischemic stroke (β=0.102,
P
=7.7×10
−5
).

Conclusions:
Plasma level of TIM-1 is associated with incidence of stroke. The genetic analyses suggest that this could be a causal relationship.
Global cardiovascular care: an overview of high-level political commitment
Authors: Vervoort Dominique , Parikh Umang M , Raj Ankit , Swain JaBaris D 
Published: May 2020

Background Six billion people worldwide lack access to safe, timely, and affordable cardiac surgical and interventional care when needed. Cardiovascular diseases are the leading cause of mortality and morbidity around the world, and include a significant surgical backlog of rheumatic and congenital heart diseases. Here, we review the political commitment by the WHO, the UN, and the World Bank to build and strengthen healthcare services for cardiovascular diseases, with a particular focus on cardiac surgical and interventional cardiology services around the world. Methods A literature search was performed in the WHO, UN, and World Bank Governing Body databases to identify policy documents mentioning curative cardiovascular disease care. The Governing Body documentation, the Institutional Repository for Information Sharing database of the WHO, and the Official Document System of the UN were used. Documents only discussing prevention of cardiovascular diseases were excluded. Results Fifty-nine unique documents were identified, including 56 from the WHO, 3 from the World Bank, and none from the UN; 12 (20.4%) documents mentioned cardiac surgery, and 6 (10.2%) contained some actionable language to incorporate cardiac surgical services, but none was explicitly dedicated to cardiac surgical services. Conclusion Although growing, high-level political commitment for curative cardiovascular health services remains minimal. Increased awareness is needed to develop comprehensive cardiovascular care that is necessary to mitigate the increasing burden of premature morbidity and mortality from cardiac disease, and to work towards the Sustainable Development Goals and Universal Health Coverage.
Long-term objective and subjective outcomes following bilateral implantation of diffractive bifocal or trifocal intraocular lenses
Authors: Vargas Veronica , Alio Jorge L , Oliveira Renan F. , Renna Antonio , Yebana Pilar 
Published: May 2020

Objective To evaluate and compare the objective and subjective outcomes after the bilateral implantation of a diffractive bifocal and trifocal intraocular lens. Methods This is a case–control, single-center observational study which included 27 patients; 16 patients were implanted bilaterally with the bifocal AcrySof IQ ReSTOR+3.0D and 11 patients with the trifocal AT LISA tri 839MP. Uncorrected visual acuity at distance, intermediate, and near under mesopic and photopic conditions using ETDRS charts with 10% and 100% contrast, corrected distance visual acuity, and binocular defocus curve in photopic conditions; binocular contrast sensitivity under mesopic and photopic conditions for far and near distances were assessed. The Visual Function Questionnaire-25 questionnaire was used to assess patients' satisfaction. All the measurements were performed 6–24 months after cataract surgery. Results The ReSTOR group had better binocular uncorrected near visual acuity in photopic conditions with low and high contrast charts ( p = 0.040 and p = 0.033, respectively), as well as in far contrast sensitivity measurement under mesopic conditions with a spatial frequency of 3 cycles per degree ( p = 0.034). There was not a significant difference between the two study groups in uncorrected near, intermediate or distance vision under mesopic conditions. The AT LISA tri study group had better subjective outcomes. Conclusion Both intraocular lenses restore visual acuity after cataract surgery. The ReSTOR intraocular lens provides better objective outcomes than the AT LISA tri, although the latter provides better subjective outcomes. The relevance of this study is the evaluation of both objective and subjective outcomes.
Cultural Adaptation and Preliminary Validation of the Proxy-Rated Sinhala Version of the Stroke and Aphasia Quality of Life Generic Scale–39
Authors: Kariyawasam PN , Pathirana KD , Hewage DC , Dissanayake RDA 
Published: May 2020

Background:Health-related quality of life (HRQOL) is an important measure that enables evaluation of rehabilitation outcomes. Stroke and Aphasia Quality of Life Generic Scale–39 (SAQOL-39g) is a disease-specific questionnaire that measures HRQOL of patients with stroke. This study was conducted to adapt the preliminary version of proxy-rated Sinhala version of the SAQOL-39g.Methods:The study was conducted with the participation of 115 proxies of the patients with stroke. The SAQOL-39g was translated and back translated, and culturally adapted by evaluating the items of the questionnaire. The culturally adapted scale was evaluated for its internal consistency, test-retest reliability, and validity.Results:The mean age of the patients with stroke was 67.07 (standard deviation [SD] = 11.2) years; males comprising two-thirds of the study sample (67% [n = 77]). The proxy-rated Sinhala version of the SAQOL-39g showed excellent internal consistency (α = 0.98 [overall score]), 0.97, 0.96, and 0.95 for physical, communication, and psychosocial domains, respectively. The intraclass correlation coefficient (ICC) was 0.92 for overall, and 0.93, 0.92, and 0.91 for physical, communication, and psychosocial domains, respectively. Factor analysis extracted 3 factors with 72.4% of the variance.Conclusions:Proxy-rated Sinhala version of the SAQOL-39g is a psychometrically sound, reliable, and valid tool to assess the post-stroke quality of life of Sinhala-speaking patients with stroke and aphasia.