bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving opioid guideline adherence: evaluation of a multifaceted, theory-informed pilot intervention for family physicians
Authors: Leece Pamela , Shantharam Yalnee , Hassam Samah , Buchman Daniel Z , Hamilton Michael , Persaud Navindra , Kahan Meldon , Spithoff Sheryl , Srivastava Anita , Sproule Beth A , Carlin Leslie , Furlan Andrea D 
Published: January 2020

ObjectivesOpioid-related deaths continue to increase in North America, an epidemic that was initiated by high rates of opioid prescribing. We designed a multifaceted, theory-informed Opioid Self-Assessment (OSA) package, to increase adherence to the Canadian Opioid Guideline among family physicians. This study aimed to assess changes in Canadian family physicians’ knowledge and practices after completing the OSA package.DesignWe conducted a mixed-method evaluation using a pre-test and post-test design that involved the collection of both qualitative and quantitative data.SettingThis research was conducted in the primary care setting in Ontario, Canada.ParticipantsWe recruited a purposive sample of nine family physicians in Ontario who use long-term opioid therapy to treat patients with chronic pain.InterventionsThe OSA package included four components: an online knowledge test, an online learning programme, a safe medication practice self-assessment questionnaire and chart audit with feedback.Outcome measuresOur measures included changes in knowledge, opioid safety practices and physicians’ perspectives on the OSA package.ResultsWe found statistically significant improvements between pre-test and post-test knowledge scores at both baseline and 6-month follow-up. Physicians’ scores improved significantly on five of the seven core characteristics of the practice self-assessment questionnaire. On the chart audits, we observed an improvement in patient education between baseline and 6 months. Qualitative interviews showed that participants appreciated embedded resources in the OSA package. The completion of the package stimulated identification of gaps or deficits in practice and served as a useful reminder to discuss risk and safety with patients. Participants described the chart review as helpful in prompting discussions with their patients, identifying deficits and strengths and a ‘primary motivator’ for project participation.ConclusionsThe OSA package has the potential to improve medication safety practices in primary care related to opioid monitoring and adherence to current opioid guidelines.
Dynamic LED-light versus static LED-light for depressed inpatients: study protocol for a randomised clinical study
Authors: Volf Carlo , Aggestrup Anne Sofie , Petersen Paul Michael , Dam-Hansen Carsten , Knorr Ulla , Petersen Ema Erkocevic , Engstrøm Janus , Jakobsen Janus C , Hansen Torben Skov , Madsen Helle Østergaard , Hageman Ida , Martiny Klaus 
Published: January 2020

IntroductionRetrospective studies conducted in psychiatric inpatient wards have shown a relation between the intensity of daylight in patient rooms and the length of stay, pointing to an antidepressant effect of ambient lighting conditions. Light therapy has shown a promising antidepressant effect when administered from a light box. The emergence of light-emitting diode (LED) technology has made it possible to build luminaires into rooms and to dynamically mimic the spectral and temporal distribution of daylight. The objective of this study is to investigate the antidepressant efficacy of a newly developed dynamic LED-lighting system installed in an inpatient ward.Methods and analysisIn all, 150 inpatients with a major depressive episode, as part of either a major depressive disorder or as part of a bipolar disorder, will be included. The design is a two-arm 1:1 randomised study with a dynamic LED-lighting arm and a static LED-lighting arm, both as add-on to usual treatment in an inpatient psychiatric ward. The primary outcome is the baseline adjusted score on the 6-item Hamilton Depression Rating Scale at week 3. The secondary outcomes are the mean score on the Suicidal Ideation Attributes Scale at week 3, the mean score on the 17-item Hamilton Depression Rating Scale at week 3 and the mean score on the World Health Organisation Quality of Life-BREF (WHOQOL-BREF) at week 3. The spectral distribution of daylight and LED-light, with a specific focus on light mediated through the intrinsically photosensitive retinal ganglion cells, will be measured. Use of light luminaires will be logged. Assessors of Hamilton Depression Rating Scale scores and data analysts will be blinded for treatment allocation. The study was initiated in May 2019 and will end in December 2021.Ethics and disseminationNo ethical issues are expected. Results will be published in peer-reviewed journals, disseminated electronically and in print and presented at symposia.Trial registration numberNCT03821506; Pre-results.
Type 1 diabetes mellitus and educational attainment in childhood: a systematic review
Authors: Oakley Natalie Jayne , Kneale Dylan , Mann Mala , Hilliar Mariann , Dayan Colin , Gregory John W , French Robert 
Published: January 2020

ObjectivesThe primary objective of this systematic review was to evaluate available literature on whether type 1 diabetes mellitus (T1DM) has an impact on educational attainment in individuals undertaking high stakes standardised testing at the end of compulsory schooling.DesignA systematic review was undertaken comparing educational attainment for individuals with and without T1DM who have undertaken high stakes testing at the end of compulsory schooling.Data sourcesA comprehensive search of MEDLINE, MEDLINE (epub ahead of print, in-process and other non-indexed citations), EMBASE, Web of Science, British Education Index, Education Resources Information Center and Cumulative Index to Nursing and Allied Health Literature was undertaken on 15 January 2018 and updated on 17 January 2019.Eligibility criteriaIncluded studies fulfilled the following criteria: observational study or randomised controlled trial; included individuals who have undertaken high stakes testing at the end of compulsory schooling; compared the grades obtained by individuals with T1DM with a representative population control.Data extraction and synthesisTwo reviewers performed study selection and data extraction independently. Quality and risk of bias in the observational studies included were assessed using the Newcastle-Ottawa Scale. A detailed narrative synthesis of the included studies was completed.Results3103 articles were identified from the database search, with two Swedish cohort studies (using the same linked administrative data) meeting final inclusion criteria. A small but statistically significant difference was reported in mean final grades, with children with T1DM found to have lower mean grades than their non-diabetic counterparts (adjusted mean difference 0.07–0.08).ConclusionsMore contemporary research is required to evaluate the impact of T1DM in childhood on educational attainment in individuals undertaking high stakes standardised testing at the end of compulsory schooling, taking into consideration the substantial advances in management of T1DM in the last decade.PROSPERO registration numberCRD42017084078.
Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017
Authors: Lou Lixia , Wang Linyan , Zhang Yaoyi , Chen Guofeng , Lin Lele , Jin Xiaoli , Huang Yi , Chen Jian 
Published: January 2020

ObjectivesTo investigate sex difference in global gastric cancer incidence by year, age and socioeconomical status.DesignAn international comparative study.SettingWe obtained the global and national sex-specific incidence of gastric caner by year and age from the Global Burden of Disease Study 2017. The human development index (HDI) in 2017 as an indicator of national socioeconomical status was extracted from the Human Development Report.Main outcome measuresSex-specific incidence of gastric cancer was compared by year and age at the global level. Linear regression analyses were performed to explore socioeconomic-associated sex difference in gastric cancer incidence.ResultsDespite declining incidence of global gastric cancer in both sexes between 1990 and 2017, relative sex difference showed an increasing trend, with male to female ratios of age-standardised incidence rates (ASRs) rising from 1.86 to 2.20. Sex difference was almost negligible under 45 years of age and relative difference maximised in the age range of 65–69 years with male to female ratios of ASRs being 2.74. Both absolute sex difference (standardised β=0.256, p<0.001) and relative difference (standardised β=0.387, p<0.001) in ASRs were positively associated with HDI.ConclusionsThis study revealed that decreasing incidence of global gastric cancer was accompanied by widening sex difference in the past few decades. Men always had higher incidence than women. Greater sex difference was found in older age and in more developed countries. These findings highlight the importance of making sex-sensitive health policy to cope with the global gastric cancer burden.
‘Immunising’ physicians against availability bias in diagnostic reasoning: a randomised controlled experiment
Authors: Mamede Sílvia , de Carvalho-Filho Marco Antonio , de Faria Rosa Malena Delbone , Franci Daniel , Nunes Maria do Patrocinio Tenorio , Ribeiro Ligia Maria Cayres , Biegelmeyer Julia , Zwaan Laura , Schmidt Henk G 
Published: January 2020

BackgroundDiagnostic errors have often been attributed to biases in physicians’ reasoning. Interventions to ‘immunise’ physicians against bias have focused on improving reasoning processes and have largely failed.ObjectiveTo investigate the effect of increasing physicians’ relevant knowledge on their susceptibility to availability bias.Design, settings and participantsThree-phase multicentre randomised experiment with second-year internal medicine residents from eight teaching hospitals in Brazil.InterventionsImmunisation: Physicians diagnosed one of two sets of vignettes (either diseases associated with chronic diarrhoea or with jaundice) and compared/contrasted alternative diagnoses with feedback. Biasing phase (1 week later): Physicians were biased towards either inflammatory bowel disease or viral hepatitis. Diagnostic performance test: All physicians diagnosed three vignettes resembling inflammatory bowel disease, three resembling hepatitis (however, all with different diagnoses). Physicians who increased their knowledge of either chronic diarrhoea or jaundice 1 week earlier were expected to resist the bias attempt.Main outcome measurementsDiagnostic accuracy, measured by test score (range 0–1), computed for subjected-to-bias and not-subjected-to-bias vignettes diagnosed by immunised and not-immunised physicians.ResultsNinety-one residents participated in the experiment. Diagnostic accuracy differed on subjected-to-bias vignettes, with immunised physicians performing better than non-immunised physicians (0.40 vs 0.24; difference in accuracy 0.16 (95% CI 0.05 to 0.27); p=0.004), but not on not-subjected-to-bias vignettes (0.36 vs 0.41; difference −0.05 (95% CI −0.17 to 0.08); p=0.45). Bias only hampered non-immunised physicians, who performed worse on subjected-to-bias than not-subjected-to-bias vignettes (difference −0.17 (95% CI −0.28 to −0.05); p=0.005); immunised physicians’ accuracy did not differ (p=0.56).ConclusionsAn intervention directed at increasing knowledge of clinical findings that discriminate between similar-looking diseases decreased physicians’ susceptibility to availability bias, reducing diagnostic errors, in a simulated setting. Future research needs to examine the degree to which the intervention benefits other disease clusters and performance in clinical practice.Trial registration number68745917.1.1001.0068.
Current status of pain medicine training in anesthesiology and pain medicine residency programs in university hospitals of Korea: a survey of residents’ opinions
Authors: Lee Jin Young , Kim Shin Hyung , Yoo Yongjae , Choi Seong Soo , Kim Sang Hun , Park Yoo Jung , Byeon Gyeong Jo , Kim Yeon Dong , Kim Jung Eun , Kang Se Hee , Kim Jia , Kim Min Ju , Park Hue Jung 
Published: January 2020

BackgroundIn Korea, anesthesiologists are expected to be mainstream pain medicine (PM) practitioners. However, anesthesiology and pain medicine (APM) residency programs mostly emphasize anesthesia learning, leading to insufficient PM learning. Therefore, this study evaluated the current status of PM training in APM residency programs in 10 Korean university hospitals.MethodsOverall, 156 residents undergoing APM training participated anonymously in our survey, focusing on PM training. We assessed the aim, satisfaction status, duration, opinion on duration, desired duration, weaknesses of the training programs and plans of residents after graduating. We divided the residents into junior (first and second year) and senior (third and fourth year). Survey data were compared between groups.ResultsSenior showed significantly different level of satisfaction grade than did junior (p=0.026). Fifty-seven (81.4%) residents in junior and forty (46.5%) residents in senior underwent PM training for ≤2 months. Most (108; 69.2%) residents felt that the training period was too short for PM learning and 95 (60.9%) residents desired a training period of ≥6 months. The most commonly expressed weakness of the training was low interventional opportunity (29.7%), followed by short duration (26.6%). After residency, 80 (49.1%) residents planned to pursue a fellowship.ConclusionsDissatisfaction with PM training was probably due to a structural tendency of the current program towards anesthesia training and insufficient clinical experience, which needs to be rectified, with a change in PM curriculum.
Group II p21-activated kinase, PAK4, is needed for activation of focal adhesion kinases, MAPK, GSK3, and β-catenin in rat pancreatic acinar cells
Authors: Ramos-Álvarez Irene , Lee Lingaku , Jensen Robert T. 
Published: January 2020

PAK4 is the only member of the Group II p21-activated kinases (PAKs) present in rat pancreatic acinar cells and is activated by gastrointestinal hormones/neurotransmitters stimulating PLC/cAMP and by various pancreatic growth factors. However, little is known of the role of PAK4 activation in cellular signaling cascades in pancreatic acinar cells. In the present study, we examined the role of PAK4’s participation in five different cholecystokinin-8 (CCK-8)-stimulated signaling pathways (PI3K/Akt, MAPK, focal adhesion kinase, GSK3, and β-catenin), which mediate many of its physiological acinar-cell effects, as well as effects in pathophysiological conditions. To define PAK4’s role, the effect of two different PAK4 inhibitors, PF-3758309 and LCH-7749944, was examined under experimental conditions that only inhibited PAK4 activation and not activation of the other pancreatic PAK, Group I PAK2. The inhibitors’ effects on activation of these five signaling cascades by both physiological and pathophysiological concentrations of CCK, as well as by 12- O-tetradecanoylphobol-13-acetate (TPA), a PKC-activator, were examined. CCK/TPA activation of focal adhesion kinases(PYK2/p125FAK) and the accompanying adapter proteins (paxillin/p130CAS), Mek1/2, and p44/42, but not c-Raf or other MAPKs (JNK/p38), were mediated by PAK4. Activation of PI3K/Akt/p70s6K was independent of PAK4, whereas GSK3 and β-catenin stimulation was PAK4-dependent. These results, coupled with recent studies showing PAK4 is important in pancreatic fluid/electrolyte/enzyme secretion and acinar cell growth, show that PAK4 plays an important role in different cellular signaling cascades, which have been shown to mediate numerous physiological and pathophysiological processes in pancreatic acinar cells.NEW & NOTEWORTHY In pancreatic acinar cells, cholecystokinin (CCK) or 12- O-tetradecanoylphobol-13-acetate (TPA) activation of focal adhesion kinases (p125FAK,PYK2) and its accompanying adapter proteins, p130CAS/paxillin; Mek1/2, p44/42, GSK3, and β-catenin are mediated by PAK4. PI3K/Akt/p70s6K, c-Raf, JNK, or p38 pathways are independent of PAK4 activation.
Facilitating Cancer Epidemiologic Efforts in Cleveland via Creation of Longitudinal De-Duplicated Patient Data Sets
Authors: Tian Ye D. , Menegay Harry , Waite Kristin A. , Saroufim Paola G. , Beno Mark F. , Barnholtz-Sloan Jill S. 
Published: January 2020

Abstract

Background:
Cleveland, Ohio, is home to three major hospital systems serving approximately 80% of the Northeast Ohio population. The Cleveland Clinic, University Hospitals Health System, and MetroHealth are direct competitors for primary and specialty care, and patient overlap between these systems is high. Fragmentation of health data that exist in silos at these health systems produces an overestimation of disease burden due to double and sometimes triple counting of patients. As a result, longitudinal population-based studies across the Cleveland patient population are impeded unless accurate and actionable clinically derived health data sets can be created.

Methods:
The Cleveland Institute for Computational Biology has developed the De-Duplicate and De-Identify Research Engine (DeDeRE) that, without any exchange of personal health identifiers (PHI) between health systems, will effectively de-duplicate the patients between one or more health entities.

Results:
The immediate utility of this software for cancer epidemiology is the increased accuracy in measuring cancer burden and the potential to perform longitudinal studies with de-duplicated, de-identified data sets.

Conclusions:
The DeDeRE software developed and tested here accomplishes its goals without exposing PHIs using a state-of-the-art, trusted privacy preservation network enabled by a hash-based matching algorithm.

Impact:
This paper will guide the reader through the functions currently developed in DeDeRE and how a healthcare organization (HCO) employing the release version of this technology can begin sharing data with one or more additional HCOs in a collaborative and noncompetitive manner to create a regional population health resource for cancer researchers.
See all articles in this CEBP Focus section, “Modernizing Population Science.”
Association of Anti-TNF with Decreased Survival in Steroid Refractory Ipilimumab and Anti-PD1–Treated Patients in the Dutch Melanoma Treatment Registry
Authors: Verheijden Rik J. , May Anne M. , Blank Christian U. , Aarts Maureen J.B. , van den Berkmortel Franchette W.P.J. , van den Eertwegh Alfonsus J.M. , de Groot Jan Willem B. , Boers-Sonderen Marye J. , van der Hoeven Jacobus J.M. , Hospers Geke A. , Piersma Djura , van Rijn Rozemarijn S. , ten Tije Albert J. , van der Veldt Astrid A.M. , Vreugdenhil Gerard , van Zeijl Michiel C.T. , Wouters Michel W.J.M. , Haanen John B.A.G. , Kapiteijn Ellen , Suijkerbuijk Karijn P.M. 
Published: January 2020

Abstract

Purpose:
Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown.

Experimental Design:
Using data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients.

Results:
A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade ≥3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity [hazard ratio (HRadj) = 0.77; 95% confidence interval (CI), 0.63–0.93]. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF ± steroids for steroid-refractory toxicity compared with patients who were managed with steroids only (HRadj = 1.61; 95% CI, 1.03–2.51), with a median OS of 17 and 27 months, respectively.

Conclusions:
Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti-TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.
See related commentary by Weber and Postow, p. 2085
TGFβ and Hippo Pathways Cooperate to Enhance Sarcomagenesis and Metastasis through the Hyaluronan-Mediated Motility Receptor (HMMR)
Authors: Ye Shuai , Liu Ying , Fuller Ashley M. , Katti Rohan , Ciotti Gabrielle E. , Chor Susan , Alam Md. Zahidul , Devalaraja Samir , Lorent Kristin , Weber Kristy , Haldar Malay , Pack Michael A. , Eisinger-Mathason T.S. Karin 
Published: January 2020

Abstract

High-grade sarcomas are metastatic and pose a serious threat to patient survival. Undifferentiated pleomorphic sarcoma (UPS) is a particularly dangerous and relatively common sarcoma subtype diagnosed in adults. UPS contains large quantities of extracellular matrix (ECM) including hyaluronic acid (HA), which is linked to metastatic potential. Consistent with these observations, expression of the HA receptor, hyaluronan-mediated motility receptor (HMMR/RHAMM), is tightly controlled in normal tissues and upregulated in UPS. Moreover, HMMR expression correlates with poor clinical outcome in these patients. Deregulation of the tumor-suppressive Hippo pathway is also linked to poor outcome in these patients. YAP1, the transcriptional regulator and central effector of Hippo pathway, is aberrantly stabilized in UPS and was recently shown to control RHAMM expression in breast cancer cells. Interestingly, both YAP1 and RHAMM are linked to TGFβ signaling. Therefore, we investigated crosstalk between YAP1 and TGFβ resulting in enhanced RHAMM-mediated cell migration and invasion. We observed that HMMR expression is under the control of both YAP1 and TGFβ and can be effectively targeted with small-molecule approaches that inhibit these pathways. Furthermore, we found that RHAMM expression promotes tumor cell proliferation and migration/invasion. To test these observations in a robust and quantifiable in vivo system, we developed a zebrafish xenograft assay of metastasis, which is complimentary to our murine studies. Importantly, pharmacologic inhibition of the TGFβ–YAP1–RHAMM axis prevents vascular migration of tumor cells to distant sites.

Implications:
These studies reveal key metastatic signaling mechanisms and highlight potential approaches to prevent metastatic dissemination in UPS.YAP1 and TGFβ cooperatively enhance proliferation and migration/invasion of UPS and fibrosarcomas.
L-glutamine for sickle cell disease: Knight or pawn?
Authors: Sadaf Alina , Quinn Charles T 
Published: January 2020

Oxidative stress is an important contributor to the pathophysiology of sickle cell disease. The pathways involved are complex and interlinked. L-glutamine is an amino acid with myriad roles in the body, including the synthesis of antioxidants, such as reduced glutathione and the cofactors NAD(H) and NADP(H), as well as nitric oxide—so it has therapeutic potential as an antioxidant. However, the relative impact of L-glutamine on the redox environment in red blood cells in sickle cell disease is not fully understood, and there are few therapeutic trials in sickle cell disease. Following the FDA approval of L-glutamine for sickle cell disease, more research is still needed to understand its clinical effects and role in therapy.Impact statementL-glutamine has been recently approved by the FDA for the prevention of acute complications in sickle cell disease (SCD). However, there are many gaps in our understanding of the biologic role of glutamine and its therapeutic implications in SCD. This review summarizes the pre-clinical and clinical evidence that can inform clinical decision-making and future research on glutamine therapy in SCD patients.