bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Primary Care Physicians in Providing End-of-Life Care
Authors: Liu Jan Tse , Kovar-Gough Iris , Farabi Nabila , Animikwam Frank , Weers Sarah Beth , Phillips Julie 
Published: October 2018

Background: Primary care physicians (PCPs) frequently have long-term relationships with patients as well as their families. As such they are well positioned to care for their patients at the end of their lives. As the number of patients in need of end-of-life care continues to grow, it is critical to understand how PCPs can fulfill that need. The purpose of our study is to perform a narrative review of the literature and develop a theoretical model delineating the overarching roles played by PCPs in caring for patients at the end of life. Methods: For this narrative review, the authors searched Medline (PubMed), Embase, Cochrane Library, and Scopus up to March 22, 2017. Articles were not limited by geography. Results: Review of existing literature generally supports 4 broad categories as the primary roles for PCP involvement in end of life: pain and symptom management; information management, including transmitting and clarifying information, setting care priorities, and assisting patients with treatment decisions; coordinating care and collaborating with other providers; and addressing patients’ social, emotional, and spiritual needs. Conclusions: Based on the results of this review, PCPs provide a wide range of services to patients at the end of life. Promoting the provision of the full scope of services by PCPs will help ensure improved continuity of care while providing the highest quality of care for patients, both in the United States and around the world.
Agitated saline bubble–enhanced ultrasound for the positioning of cuffed, tunneled dialysis catheters in patients with end-stage renal disease
Authors: Passos Rogerio da Hora , Ribeiro Michel , da Conceição Luis Filipe Miranda Rebelo , Ramos Joao Gabriel Rosa , Ribeiro Juliana Caldas , Batista Paulo Benigno Pena , Dutra Margarida Maria Dantas , Rouby Jean Jacques 
Published: October 2018

Background: In patients with end-stage renal disease, the use of cuffed, tunneled dialysis catheters for hemodialysis has become integral to treatment plans. Fluoroscopy is a widely accepted method for the insertion and positioning of cuffed dialysis catheters, because it is easy to use, accurate and reliable, and has a relatively low incidence of complications. The purpose of our study was to evaluate the feasibility of tunneled hemodialysis catheter placement without the use of fluoroscopy but with a dynamic ultrasound-imaging-based guided technique. Methods: From January 2015 to December 2017, we performed an observational prospective cohort study of 56 patients with end-stage renal disease who required tunneled dialysis catheter placement. Results: The overall success rate for ultrasound-guided central access was 100%, with a mean number of 1.16 (±0.4) attempts per patient. There were no incidences of guide wire coiling/kinking, carotid puncture, pneumothorax, or catheter malfunction. Catheter flow during dialysis was 286 (±38) mL/min. The total number of catheter days was 7451, with a mean of 133 days and a range of 46–322 days. Life table analysis revealed primary patency rates of 100%, 96%, and 53% at 30, 60, and 120 days, respectively. Conclusion: Dynamic ultrasound-based visualization of microbubbles in the right atrium is a highly accurate method to detect percutaneous implantation of large-lumen, tunneled, central venous catheters without the need for fluoroscopic guidance technology. Future research should further develop and confirm these initial findings.
Healthy adjustment for new residents with dementia using SettleIN: A feasibility study in UK care homes
Authors: Hayward Janine K , Nunez Kayleigh Marie , Ballard Clive , Spector Aimee 
Published: October 2018

Objectives This study aimed to develop and explore feasibility of SettleIN, a staff-led programme about healthy adjustment for people with dementia following care home placement. The main foci were intervention feasibility and the impact of the programme on resident quality of life and mood. Method A manualised intervention developed through consultation with 47 experts was trialled using a mixed-method design. Thirteen new residents with dementia and 24 staff were recruited from six UK care homes. Outcomes were measured at baseline, intervention completion and four-week follow-up. Analysis of staff interviews and field notes is reported. Results Most experts deemed SettleIN to be well structured, comprehensive and appropriate. However, uptake of SettleIN was low. When implemented, staff emphasised integration ease and staff benefits, but that SettleIN may not be universally suitable. High attrition, most commonly due to death and hospitalisation, and partial results from only four participants meant that there was a lack of support for the positive outcomes. Feasibility problems included a lack of staff time and dependency on families for some components. Conclusion SettleIN is acceptable to a wide range of stakeholders though does not appear to be feasible in its current form and improvements are recommended. A second pilot phase is required, which will address the reasons for the high attrition rate in this study and amend the methodology accordingly. This is an important work, as a manualised and standardised approach to healthy adjustment in care is unique and could have huge clinical significance if effective.
Association of TRPV1 and TLR4 through the TIR domain potentiates TRPV1 activity by blocking activation-induced desensitization
Authors: Min Hyunjung , Cho Woo-Hyun , Lee Hyunkyoung , Choi Boomin , Kim Yoon-Jung , Lee Han Kyu , Joo Yeonhee , Jung Sung Jun , Choi Se-Young , Lee Soojin , Lee Sung Joong 
Published: October 2018

Background We have previously reported that histamine-induced pruritus was attenuated in toll-like receptor 4 (TLR4) knockout mice due to decreased transient receptor potential V1 (TRPV1) sensitivity. Our results implied that TLR4 potentiated TRPV1 activation in sensory neurons; however, the molecular mechanism has yet to be elucidated. In this study, we investigated the molecular mechanisms of TLR4-mediated TRPV1 potentiation using TLR4-deficient sensory neurons and a heterologous expression system. Methods Primary sensory neurons were obtained from wild-type or TLR4 knockout mice, and HEK293T cells expressing TRPV1 and TLR4 were prepared by transient transfection. TRPV1 activity was analyzed by calcium imaging, fluorophotometry, and patch-clamp recording. Subcellular protein distribution was tested by immunocytochemistry and cell surface biotinylation assay. Protein interaction was assessed by western blot and immunoprecipitation assay. Results Direct association between TRPV1 and TLR4 was detected in HEK293T cells upon heterologous TRPV1 and TLR4 expression. In an immunoprecipitation assay using TLR4-deletion mutants and soluble toll/interleukin-1 receptor (TIR) protein, the cytoplasmic TIR domain of TLR4 was required for TLR4-TRPV1 association and TRPV1 potentiation. In TLR4-deficient sensory neurons, the activation-induced desensitization of TRPV1 increased, accompanied by enhanced TRPV1 clearance from the cell membrane upon activation compared to wild-type neurons. In addition, heterologous TLR4 expression inhibited activation-induced TRPV1 endocytosis and lysosomal degradation in HEK293T cells. Conclusion Our data show that direct association between TRPV1 and TLR4 through the TIR domain enhances TRPV1 activity by blocking activation-induced TRPV1 desensitization.
The Duke treadmill score with bicycle ergometer: Exercise capacity is the most important predictor of cardiovascular mortality
Authors: Salokari Esko , Laukkanen Jari A , Lehtimaki Terho , Kurl Sudhir , Kunutsor Setor , Zaccardi Francesco , Viik Jari , Lehtinen Rami , Nikus Kjell , Kööbi Tiit , Turjanmaa Väinö , Kähönen Mika , Nieminen Tuomo 
Published: October 2018

Background The Duke treadmill score, a widely used treadmill testing tool, is a weighted index combining exercise time or capacity, maximum ST-segment deviation and exercise-induced angina. No previous studies have investigated whether the Duke treadmill score and its individual components based on bicycle exercise testing predict cardiovascular death. Design Two populations with a standard bicycle testing were used: 3936 patients referred for exercise testing (2371 men, age 56 ± 13 years) from the Finnish Cardiovascular Study (FINCAVAS) and a population-based sample of 2683 men (age 53 ± 5.1 years) from the Kuopio Ischaemic Heart Disease study (KIHD). Methods Cox regression was applied for risk prediction with cardiovascular mortality as the primary endpoint. Results In FINCAVAS, during a median 6.3-year (interquartile range (IQR) 4.5–8.2) follow-up period, 180 patients (4.6%) experienced cardiovascular mortality. In KIHD, 562 patients (21.0%) died from cardiovascular causes during the median follow-up of 24.1 (IQR 18.0–26.2) years. The Duke treadmill score was associated with cardiovascular mortality in both populations (FINCAVAS, adjusted hazard ratio (HR) 3.15 for highest vs. lowest Duke treadmill score tertile, 95% confidence interval (CI) 1.83–5.42, P < 0.001; KIHD, adjusted HR 1.71, 95% CI 1.34–2.18, P < 0.001). However, after progressive adjustment for the Duke treadmill score components, the score was not associated with cardiovascular mortality in either study population, as exercise capacity in metabolic equivalents of task was the dominant harbinger of poor prognosis. Conclusions The Duke treadmill score is associated with cardiovascular mortality among patients who have undergone bicycle exercise testing, but metabolic equivalents of task, a component of the Duke treadmill score, proved to be a superior predictor.
Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review
Authors: DePhillipo Nicholas N. , Aman Zachary S. , Kennedy Mitchell I. , Begley J.P. , Moatshe Gilbert , LaPrade Robert F. 
Published: October 2018

Background: Recent investigations on the biochemical pathways after a musculoskeletal injury have suggested that vitamin C (ascorbic acid) may be a viable supplement to enhance collagen synthesis and soft tissue healing. Purpose: To (1) summarize vitamin C treatment protocols; (2) report on the efficacy of vitamin C in accelerating healing after bone, tendon, and ligament injuries in vivo and in vitro; and (3) report on the efficacy of vitamin C as an antioxidant protecting against fibrosis and promoting collagen synthesis. Study Design: Systematic review; Level of evidence, 2. Methods: A systematic review was performed, with the inclusion criteria of animal and human studies on vitamin C supplementation after a musculoskeletal injury specific to collagen cross-linking, collagen synthesis, and biologic healing of the bone, ligament, and tendon. Results: The initial search yielded 286 articles. After applying the inclusion and exclusion criteria, 10 articles were included in the final analysis. Of the preclinical studies evaluating fracture healing, 2 studies reported significantly accelerated bone healing in the vitamin C supplementation group compared with control groups. The 2 preclinical studies evaluating tendon healing reported significant increases in type I collagen fibers and scar tissue formation with vitamin C compared with control groups. The 1 preclinical study after anterior cruciate ligament (ACL) reconstruction reported significant short-term (1-6 weeks) improvements in ACL graft incorporation in the vitamin C group compared with control groups; however, there was no long-term (42 weeks) difference. Of the clinical studies evaluating fracture healing, 1 study reported no significant differences in the rate of fracture healing at 50 days or functional outcomes at 1 year. Vitamin C supplementation was shown to decrease oxidative stress parameters by neutralizing reactive oxygen species through redox modulation in animal models. No animal or human studies reported any adverse effects of vitamin C supplementation. Conclusion: Preclinical studies demonstrated that vitamin C has the potential to accelerate bone healing after a fracture, increase type I collagen synthesis, and reduce oxidative stress parameters. No adverse effects were reported with vitamin C supplementation in either animal models or human participants; thus, oral vitamin C appears to be a safe supplement but lacks clinical evidence compared with controls. Because of the limited number of human studies, further clinical investigations are needed before the implementation of vitamin C as a postinjury supplement.
ERS statement on harmonised standards for lung cancer registration and lung cancer services in Europe
Authors: Rich Anna L. , Baldwin David R. , Beckett Paul , Berghmans Thierry , Boyd Jeanette , Faivre-Finn Corinne , Galateau-Salle Françoise , Gamarra Fernando , Grigoriu Bogdan , Hansen Niels-Christian G. , Hardavella Georgia , Jakobsen Erik , Jovanovic Dragana , Konsoulova Assia , Massard Gilbert , McPhelim John , Meert Anne-Pascale , Milroy Robert , Mutti Luciano , Paesmans Marianne , Peake Michael D. , Putora Paul Martin , de Ruysscher Dirk K.M. , Sculier Jean-Paul , Schepereel Arnaud , Subotic Dragan R. , Van Schil Paul , Blum Torsten Gerriet 
Published: October 2018

The European Respiratory Society (ERS) task force for harmonised standards for lung cancer registration and lung cancer services in Europe recognised the need to create a single dataset for use in pan-European data collection and a manual of standards for European lung cancer services.The multidisciplinary task force considered evidence from two different sources, reviewing existing national and international datasets alongside the results of a survey of clinical data collection on lung cancer in 35 European countries. A similar process was followed for the manual of lung cancer services, with the task force using existing guidelines and national or international recommendations for lung cancer services to develop a manual of standards for services in Europe.The task force developed essential and minimum datasets for lung cancer registration to enable all countries to collect the same essential data and some to collect data with greater detail. The task force also developed a manual specifying standards for lung cancer services in Europe.Despite the wide variation in the sociopolitical landscape across Europe, the ERS is determined to encourage the delivery of high-quality lung cancer care. Both the manual of lung cancer services and the minimum dataset for lung cancer registration will support this aspiration.
Patterns of regional lung physiology in cystic fibrosis using ventilation magnetic resonance imaging and multiple-breath washout
Authors: Smith Laurie J. , Collier Guilhem J. , Marshall Helen , Hughes Paul J.C. , Biancardi Alberto M. , Wildman Martin , Aldag Ina , West Noreen , Horsley Alex , Wild Jim M. 
Published: October 2018

Hyperpolarised helium-3 (3He) ventilation magnetic resonance imaging (MRI) and multiple-breath washout (MBW) are sensitive methods for detecting lung disease in cystic fibrosis (CF). We aimed to explore their relationship across a broad range of CF disease severity and patient age, as well as assess the effect of inhaled lung volume on ventilation distribution.32 children and adults with CF underwent MBW and3He-MRI at a lung volume of end-inspiratory tidal volume (EIVT). In addition, 28 patients performed3He-MRI at total lung capacity.3He-MRI scans were quantitatively analysed for ventilation defect percentage (VDP), ventilation heterogeneity index (VHI) and the number and size of individual contiguous ventilation defects. From MBW, the lung clearance index, convection-dependent ventilation heterogeneity (Scond) and convection–diffusion-dependent ventilation heterogeneity (Sacin) were calculated.VDP and VHI at EIVTstrongly correlated with lung clearance index (r=0.89 and r=0.88, respectively), Sacin (r=0.84 and r=0.82, respectively) and forced expiratory volume in 1 s (FEV1) (r=−0.79 and r=−0.78, respectively). Two distinct3He-MRI patterns were highlighted: patients with abnormal FEV1had significantly (p<0.001) larger, but fewer, contiguous defects than those with normal FEV1, who tended to have numerous small volume defects. These two MRI patterns were delineated by a VDP of ∼10%. At total lung capacity, when compared to EIVT, VDP and VHI reduced in all subjects (p<0.001), demonstrating improved ventilation distribution and regions of volume-reversible and nonreversible ventilation abnormalities.
Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH
Authors: Hill David B. , Long Robert F. , Kissner William J. , Atieh Eyad , Garbarine Ian C. , Markovetz Matthew R. , Fontana Nicholas C. , Christy Matthew , Habibpour Mehdi , Tarran Robert , Forest M. Gregory , Boucher Richard C. , Button Brian 
Published: October 2018

Cystic fibrosis (CF) is a recessive genetic disease that is characterised by airway mucus plugging and reduced mucus clearance. There are currently alternative hypotheses that attempt to describe the abnormally viscous and elastic mucus that is a hallmark of CF airways disease, including: 1) loss of CF transmembrane regulator (CFTR)-dependent airway surface volume (water) secretion, producing mucus hyperconcentration-dependent increased viscosity, and 2) impaired bicarbonate secretion by CFTR, producing acidification of airway surfaces and increased mucus viscosity.A series of experiments was conducted to determine the contributions of mucus concentrationversuspH to the rheological properties of airway mucus across length scales from the nanoscopic to macroscopic.For length scales greater than the nanoscopic,i.e.those relevant to mucociliary clearance, the effect of mucus concentration dominated over the effect of airway acidification.Mucus hydration and chemical reduction of disulfide bonds that connect mucin monomers are more promising therapeutic approaches than alkalisation.
Probiotic supplements containing Lactobacillus reuteri does not affect the levels of matrix metalloproteinases and interferons in oral wound healing
Authors: Twetman Svante , Pedersen Anne Marie Lynge , Yucel-Lindberg Tulay 
Published: October 2018

AbstractObjectiveThe use of beneficial bacteria may stimulate wound healing. We performed a randomized, placebo-controlled double-blind cross-over study comprising ten healthy volunteers. The aim was to investigate the impact of topical and systemic applications of probiotic lactobacilli (Lactobacillus reuteri) on the healing of standardized wounds (punch biopsies) in the oral mucosa. The expression of selected matrix metalloproteinases (MMP’S) and interferons (IFN’s) was analyzed with multiplex immunoassays in the wound exudate during the first healing week (day 2, 5 and 8).ResultsAll participants completed the study and in all cases, the healing after the punch biopsies was uneventful. The concentrations of MMP-1, MMP-2, MMP-3 decreased with time in both the test- and control group. The MMP levels were consistently lower during the probiotic intervention when compared with placebo but the differences were not statistically significant. Likewise, the concentrations if IFN-alpha2, IFN-beta and IFN-gamma decreased with time with no significant differences between the test and placebo interventions. Within the limitations of this pilot study, we were unable to demonstrate an influence of probiotic supplements containingL. reuterion the concentrations of selected matrix metalloproteinases and interferons from mucosal wounds within 1 week after a standardized punch biopsy.Trial registrationClinicalTrials.gov Identifier NCT03210779. Date of registration: July 7, 2017
Blood mRNA Measurement (NETest) for Neuroendocrine Tumor Diagnosis of Image-Negative Liver Metastatic Disease
Authors: Malczewska Anna , Bodei Lisa , Kidd Mark , Modlin Irvin M 
Published: October 2018

Abstract

Context
Early cancer detection is critical to optimize treatment. This is particularly problematic in neuroendocrine tumors (NETs), which exhibit an ∼5-year diagnostic delay due to covert symptoms, limitations in imaging, and circulating biomarkers. Despite development of continuous monitoring strategies utilizing advanced modalities [CT/MRI or 68Gallium positron emission tomography (PET)/CT] or a repertoire of monoanalyte biomarkers [e.g., chromogranin A (CgA), pancreastatin, serotonin], detection of minimal residual disease or microrecurrence remains elusive. Emerging molecular liquid biopsies (e.g., NETest) provide a substantially improved threshold for disease detection.

Case Description
We describe the utility of a blood-based multigene PCR neuroendocrine measurement (NETest), which is representative of core molecular drivers of neuroendocrine tumorigenesis, to detect hepatic micrometastases in a patient with negative blood biomarkers and negative anatomical/functional imaging. The 52-year-old woman, who had undergone margin-negative resection for a NET of the ileocecal valve, developed persistently elevated NETest levels 8 months later. CT/MRI/68Gallium PET and biomarkers remained negative. Blood multigene analysis identified disease, and peptide receptor radionuclide therapy (PRRT) was undertaken. Over 9 months, NETest levels increased (conventional biomarkers/imaging remained normal). Liver biopsy was undertaken, and foci of a 3-mm NET in segment VI were histologically documented. At 3.3 years after PRRT, the disease remained as a microscopic burden and stable biomarker/68Gallium PET/MRI occult despite elevated blood levels of NET genes.

Conclusions
Blood measurement of NET transcripts can identify image- and CgA-negative disease. A NET liquid biopsy strategy has clinical utility in the early identification of residual or metastatic disease and optimizes consideration of adjuvant therapeutic intervention.