bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamics and dimensions of intra-party conflict: Introduction to the special issue
Authors: Gherghina Sergiu , Close Caroline , Kopecký Petr
Published: March 2019

Existing research on intra-party unity and conflict has mostly focused on (dis)unity within the legislative branch of the party at the national level, while neglecting conflict between the different faces or at different levels of the party. Intra-party unity and conflict have also been routinely defined and operationalized through ideological homogeneity or distance, although intra-party conflicts are multidimensional and dynamic phenomena. The articles included in this special issue seek to address these shortcomings in the literature. Their contributions are threefold: (1) they theorize intra-party conflict as a dynamic and multifaceted concept; (2) they explore conflicts across and between several party faces, and among different intra-party actors; (3) they investigate the determinants and management of conflict at several party levels.
Conflicting Logics of Public Relations in the English NHS: A Qualitative Study of Communications and Engagement
Authors: Carter Pam , Dent Mike , Martin Graham
Published: March 2019

Since the formation of the National Health Service (NHS), all UK citizens have been entitled to access a universal health service, but radical changes to the NHS are now occurring. Although recent NHS policy claims that ‘the NHS belongs to us all’ and ‘the NHS is a social movement’, these collectivist rhetorical claims appear when such communitarian discourse is under threat, as NHS’s Five Year Forward View tries to square the circle of efficiency, quality, and equity. Historically, patients and user-groups have formed support networks and social movements, and collectively campaigned for their voices to be heard by policymakers, clinicians, and managers. In contrast to the discourse of user movements, the field of marketing and public relations generally relies on the idea of the public as consumers rather than citizens. As complex governance arrangements blur the lines between public and private, concerns have been raised about how ‘spin’ associated with public relations might contravene accountability, communicative rationality, and deliberative or participatory democracy. Using qualitative methods, we conducted empirical research in two localities to explore the role of communications and engagement staff as they worked to ‘transform’ the NHS in line with the vision of the Five Year Forward View. We gathered documentary data and interview data from people whose roles required them to ‘do engagement’. These staff came from a range of backgrounds, including professional marketing backgrounds, and many were unaware of emancipatory goals or user-led involvement and activism. Our analysis examines the competing logics of marketing and patient empowerment within a key stakeholder matrix document and that surfaced in participants’ accounts of their engagement practices.
‘He that toucheth pitch shall be defiled therewith’:1 Challenges for Contaminated Land Remediation after Brexit
Authors: Brown Lloyd A.
Published: March 2019

Eight years have passed since the Contaminated Land Capital Projects (CLCP) funding was abolished in Wales; this was the main source of public sector funding for contaminated land identification and remediation. Yet, despite the CLCP’s abolition in 2010, the Welsh Government announced in October 2018 that it would assist in funding a significant proportion (some 60%) of the remediation of a residential site in Anglesey. Research into the site’s remediation has showed that this public sector engagement has been made possible by EU funding. However, the replenishment of the Welsh Government’s funds is not wholly uplifting. In fact, the situation gives rise to a deep sense of foreboding. It ultimately leads to questions as to what will happen to land remediation following Brexit, when European funding is no longer available to supplement the public sector’s purse.
Constructivist theories of political incorporation
Authors: Fittante Daniel
Published: March 2019

Drawing upon ethnographic data collected in Glendale, California, this study applies constructivist theories of ethnic politics to political incorporation research. The analysis demonstrates how the evolving loci of political incorporation—from marginalized racial minorities in urban centers to multi-ethnic migrants in prosperous suburbs—have given rise to new agents (ethnopolitical entrepreneurs) in new spaces (ethnoburbs). In these evolving spaces, community leaders emphasize, consciously and unconsciously, specific attributes, which determine, in part, whether co-ethnics support selected candidates. Specific emphases lead to both the nomination of prospective politicians as well as the political incorporation of newcomers. By applying constructivist theories of ethnic politics to the study of political incorporation, this article expands and refines discourses in both fields of study. Based upon a case study of the intra-ethnically diverse yet highly mobilized Armenian community in Glendale, California, the paper’s findings synthesize the strengths of both analytical perspectives.
‘I was not able to go there’: Introducing a skills perspective about how tourists navigate in Los Angeles
Authors: Lucas Leopold
Published: March 2019

This article argues that considering individuals’ skills is fundamental in explaining tourists’ practices. Navigation here is conceptualized as one of the spatial stakes that individuals must address when they inhabit a city. From this question, this article emphasizes the fact that coping with space should not be taken for granted but requires skills that relate to individuals’ own levels of experience in terms of the practices of places. To this end, this article first engages in a theoretical discussion of Goffman, Ingold and Wittgenstein’s ideas. Then, at the empirical level, importance is given to tourists’ experiences, as they describe their ways of coping with space. Through an original mapping of their itineraries in Los Angeles, we examine tourists’ justification process concerning their ‘régimes d’action’.
Mapping the political economy of education technology: A networks perspective
Authors: Regan Priscilla M , Khwaja Elsa Talat
Published: March 2019

The field of education technology (edtech) has emerged as a complex, multimillion-dollar industry, with various hubs in the USA leading the boom. This exploratory article uses a networks perspective to reveal the power dynamics of investor firms in edtech. The analysis examines the current top venture capitalists and their edtech companies, based on primary funding relationships. The article begins with an explanation of how edtech emerged, an overview of the K-12 environment, and an analysis as to why edtech companies have become vital players in the education sector in the USA. This study highlights the most influential actors in the edtech political economy and their structures and interactions, and concludes with recommendations for future research. The investigation has involved examining the top investors and companies closely, alongside the political and economic motivations behind their investments.
Communication With Friends and the Academic Adjustment of First- and Non-First-Generation Students in the First Year of College
Authors: Cheong Yeram , Gauvain Mary , Palbusa Julienne A.
Published: March 2019

This study examines the role of communication with on-campus friends on first-year students’ college adjustment, measured by academic self-efficacy, among first- and non-first-generation students. It also tests whether school connectedness, students’ perceived sense of being part of the institution, mediates the relation between communication and academic self-efficacy. Participants were 246 students (55% first generation) from diverse ethnic backgrounds attending a large public university in southwestern United States. Participants completed an online survey that included the Academic Self-Efficacy Scale and School Connectedness Scale and responded to questions about frequency and mode of communication about academic, social, and personal concerns with on-campus friends. Regardless of college-generation status, students’ frequency of communication with on-campus friends was positively related to academic self-efficacy and school connectedness mediated this relation. Implications for student affairs professionals and future research are discussed.
Are There Missed Opportunities to Maximize Organ Donation Registrations? An Examination of Driver’s License Applications Across the United States
Authors: Stevens Jack , Tumin Dmitry , Shaffer Kelly L. , Bickman Leonard , Hoagwood Kimberly E. , Hayes Don
Published: March 2019

Introduction:

With 116 000 people waiting for transplants and 8000 patients dying annually on waiting lists, the United States has a considerable organ shortage. An insufficient number of Americans have registered to become organ donors when obtaining driver’s licenses or ID cards. Across states, there is considerable variability in organ donor registration rates as well as driver’s license applications.

Methods:

The purpose of this project was to describe the variability in the phrasing of the organ donor registration question by state bureaus of motor vehicles as well as other application questions that might influence this decision. In particular, the frequency of states employing empirically supported messages to increase donor registrations was ascertained. The content and phrasing of 46 different driver’s license applications was coded in regard to seeking organ donor registrations.

Findings:

No states used the empirically supported strategies of reciprocity, descriptive norms, or loss/gain framing from the interdisciplinary field of behavioral economics. Twelve states used injunctive norms to signify social approval for organ donation. Many state applications had lengthy organ donation sections and health questions that could discourage donor registrations.

Discussion:

There is an extremely low use of empirically supported messages to increase organ donation registrations in driver’s license applications in the United States. Opportunities exist for thoughtful consideration of the wording of driver’s license applications. States interested in exploring ways to increase donations could undertake controlled variation of applications to test the effects of message framing on registration rates.
Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients
Authors: Liu Michelle , Husain Shahid , Famure Olusegun , Li Yanhong , Kim S. Joseph
Published: March 2019

Background:

Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients.

Design:

This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes.

Results:

Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein–Barr virus (EBV) mismatched (D+/R−) transplants and 12 from EBV-positive recipients (R+). Recipients with D+/R− matches were at a significantly higher risk of developing PTLD than R+ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78).

Discussion:

Epstein–Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.
Evaluation theory and its application to military assessments
Authors: Keith Andrew , Ahner Darryl , Curtis Nicole
Published: March 2019

Evaluation theory provides a rigorous foundation for the practice of military operation assessment. Government and industry assessors have used evaluation theory to improve the effectiveness of assessment across a wide range of fields. This article focuses on the relationship between evaluation theory and military assessment. We briefly survey the major evaluation approaches with a focus on connecting the theoretical models to practical security-related applications. These evaluation approaches include expertise-oriented, program-oriented, decision-oriented, and participant-oriented models. Within the overarching framework of these approaches, we consider alternative monitoring and evaluation designs in detail, including descriptive designs (case study, cross-sectional, time-series), quasi-experimental designs (interrupted time-series, comparison group, case study), and experimental designs (posttest-only, pre-post). Then, we discuss quantitative and qualitative methods for analyzing and reporting uncertainty with respect to each design alternative, with an emphasis on mixed-method approaches. Throughout the review, we make the relationship between evaluation theory and operation assessment practice explicit through examples, and we suggest more detailed references where appropriate.
Impact of rural versus urban geographic location on length of stay after carotid endarterectomy
Authors: Minc Samantha D , Misra Ranjita , Holmes Sari D , Ren Yue , Marone Luke
Published: March 2019

Background

Reducing the incidence of extended length of stay (ELOS) after carotid endarterectomy (CEA), defined as LOS > 1 day, is an important quality improvement focus of the Vascular Quality Initiative (VQI). Rural patients with geographic barriers pose a particular challenge for discharge and may have higher incidences of ELOS as a result. The purpose of this study was to examine the impact of patients’ home geographic location on ELOS after CEA.

Methods

The VQI national database for CEA comprised the sample for analyses ( N = 66,900). Rural-Urban Commuting Area (RUCA) codes, a validated system used to classify the nation’s census tracts according to rural and urban status, was applied to the VQI database and used to indicate patients’ home geographic location. LOS was categorized into two groups: LOS ≤ 1 day (66%) and LOS > 1 day (ELOS) (34%). Multivariable logistic regression was conducted to examine the effect of geographic location on ELOS after adjustment for age, gender, race, and comorbid conditions.

Results

A total of 66,900 patients were analyzed and the mean age of the sample was 70.5 ± 9.3 years (40% female). After adjustment for covariates, the urban group had increased risk for ELOS (OR = 1.20, p < 0.001). Other factors that significantly increased risk for ELOS were non-White race/Latinx/Hispanic ethnicity (OR = 1.44, p < 0.001) and nonelective status (OR = 3.31, p < 0.001). In addition, patients treated at centers with a greater percentage of urban patients had greater risk for ELOS (OR = 1.008, p < 0.001).

Conclusions

These analyses found that geographic location did impact LOS, but not in the hypothesized direction. Even with adjustment for comorbidities and other factors, patients from urban areas and centers with more urban patients were more likely to have ELOS after CEA. These findings suggest that other mechanisms, such as racial disparities, barriers in access to care, and disparities in support after discharge for urban patients may have a significant impact on LOS.
Are ultrasound foetal circumference measurement methods interchangeable?
Authors: John Dudley Nicholas
Published: March 2019

A variety of methods is available for the ultrasound measurement of foetal circumferences; ellipse fitting and derived measurements are often used interchangeably based on an assumption of equivalence, despite evidence that results may differ. The aim of this study was to investigate the differences between ellipse fitting and derived circumferences in clinical practice. Head and abdominal circumferences originally measured using ellipse fitting were retrospectively derived from anterior–posterior and transverse diameters using a widely used formula. Where the necessary measurements were available, foetal weight was estimated. Differences between ellipse fitted and derived measurements were compared using Bland–Altman plots. Images from 65 patients (gestational age 20 to 40 weeks) were collected; four head circumference and five abdominal circumference images were excluded due to poor image quality. Data were available for estimated foetal weight calculation for 48 patients. There were small systematic differences between ellipse fitted and derived measurements. Random differences varied between 20 week scans, early growth scans and later growth scans, so were analysed in these three groups. The 95% confidence intervals were ±6 mm (±3%), ±7 mm (±2%) and ±20 mm (±6%) for head circumference at 20 weeks, earlier growth scans and later scans, respectively; the 95% confidence intervals for abdominal circumference were ±7 mm (±5%), ±11 mm (±5%) and ±17 mm (±6%) and for estimated foetal weight were ±23 g (±6%), ±69 g (±5%) and ±311 g (±12%). Foetal circumference measurement methods are not interchangeable. The derived method should be used where size, growth and estimated foetal weight charts are based on this method.
Memantine selectively prevented the induction of dynamic allodynia by blocking Kir2.1 channel and inhibiting the activation of microglia in spinal dorsal horn of mice in spared nerve injury model
Authors: Chen Yangyang , Shi Yiqian , Wang Guoxiang , Li Yimei , Cheng Longzhen , Wang Yun
Published: March 2019

Background

Memantine is one of the important clinical medications in treating moderate to severe Alzheimer disease. The effect of memantine on preventing or treating punctate allodynia has been thoroughly studied but not on the induction of dynamic allodynia. The aim of this study is to investigate whether memantine could prevent the induction of dynamic allodynia and its underlying spinal mechanisms.

Results

(1) In in vivo spared nerve injury pain model, pretreatment with memantine at a lower dose (10 nmol, intrathecal; memantine-10) selectively prevented the induction of dynamic allodynia but not the punctate allodynia. (2) Pretreatment with either MK801-10 (MK801-10 nmol, intrathecal) or higher dose of memantine (30 nmol, intrathecal; memantine-30) prevented the induction of both dynamic and punctate allodynia. (3) Memantine-10 showed significant effect on the inhibition of the spared nerve injury-induced overactivation of microglia in spinal dorsal horn. (4) In contrast, in complete freund′s adjuvant (CFA) model, memantine-10 neither affected the CFA injection-induced activation of microglia in spinal dorsal horn nor the induction of dynamic allodynia. (5) Immunohistological studies showed Kir2.1 channel distributed widely and co-localized with microglia in the spinal dorsal horn of mice. (6) Pretreatment with either minocycline, a microglia inhibitor, or ML133, a Kir2.1 inhibitor, both selectively prevented the overactivation of microglia in spinal dorsal horn and the induction of dynamic allodynia following spared nerve injury.

Conclusion

The selective inhibitory effect on the induction of dynamic allodynia in spared nerve injury model by low dose of the memantine (memantine-10) was tightly correlated with the blockade of microglia Kir2.1 channel to suppress the microglia activation.
Prevalence of hyperplasia and cancer in endometrial polyps in women with postmenopausal bleeding: A systematic review and meta-analysis
Authors: Ghoubara Ahmed , Price Malcolm James , Fahmy Mohamed Salah El-Din , Ait-Allah Abdou Saeed , Ewies Ayman
Published: March 2019

There is wide variation in reporting the prevalence of hyperplasia and cancer in endometrial polyps in women with postmenopausal bleeding. Most studies reported heterogenous populations of pre- and postmenopausal women both symptomatic and asymptomatic, making data interpretation difficult. The aim of this work is to quantify the prevalence of hyperplasia and cancer in polyps in women with postmenopausal bleeding aiming to produce data that help inform clinical practice as whether it is safer to remove all polyps, or some women could be offered expectant management. The search terms used were Medical Subject Headings terms, text words, truncations and word variations of the words or phrases ‘endometrial polyp’ or ‘uterine polyp’ or ‘womb polyp’ and ‘postmenopause’ or ‘menopause’. Search was limited to human studies and English language articles. Studies reporting separate analysis for women with postmenopausal bleeding were included. The included articles were assessed for risk of bias using the ‘Quality in Prognosis Studies’ tool. The prevalence was estimated with a random effect model using ‘DerSimonian and Laird’ method. The pooled estimate of prevalence of hyperplasia and cancer was 9% (95% confidence interval: 6.5%–11.5%). An I2 statistic of 77.2% suggests likely substantial heterogeneity. However, adjustment for small study effects had no influence on the pooled prevalence estimate suggesting no evidence for publication bias. Sensitivity analyses showed that no study exerted a big influence on the pooled estimate. The prevalence of hyperplasia and cancer in endometrial polyps in women with postmenopausal bleeding is high enough to warrant removal for accurate histopathological diagnosis.
A systemic review and meta-analysis for prognostic values of pretreatment lymphocyte-to-monocyte ratio on gastric cancer
Authors: Li Zhigui , Xu Zhaofen , Huang Yuqian , Wang Yong , Karn Hare Ram , Zhao Rui , Cui Yaping , Zhou Yong , Wu Xiaoting
Published: March 2019

The systemic inflammation plays a crucial role in carcinogenesis and cancer progression. Pretreatment lymphocyte-to-monocyte ratio (LMR) has been suggested to be associated with clinical outcomes in various malignancies. To evaluate the prognostic significance of pretreatment LMR on gastric cancer, we conducted a comprehensive literature search in PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov (Prospero Registration No. CRD42018087263). This meta-analysis included all studies evaluating the prognostic significance of pretreatment LMR on gastric cancer. The main outcome measures included overall survival (OS), progression-free survival (PFS), and the relationship between LMR and clinicopathological features. In total, 11 studies (12 cohorts) enrolling 14,262 patients with gastric cancer were included. The pooled estimates showed that elevated pretreatment LMR was significantly associated with better OS (hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.58–0.83) and better PFS (HR: 0.71, 95% CI: 0.44–0.99). The elevated LMR was also significantly associated with young patients, female, low level of carcinoembryonic antigen (CEA), low level of carbohydrate antigen 19-9 (CA19-9), stage I–II, small tumor size, absence of lymph node metastasis, absence of vascular invasion, and absence of perineural invasion. In conclusion, the elevated pretreatment LMR predicted the better clinical outcomes in patients with gastric cancer.
Twitter-Based BIRGing: Big Data Analysis of English National Team Fans During the 2018 FIFA World Cup
Authors: Fan Minghui , Billings Andrew , Zhu Xiangyu , Yu Panfeng
Published: March 2019

Sports fans tend to associate themselves with a successful team (BIRGing), while disassociating themselves with unsuccessful teams (CORFing). This premise was applied to social media commentary within England’s matches against Croatia and Colombia during the 2018 Fédération Internationale de Football Association World Cup, uncovering that English fans tended to perform Basking in Reflected Glory (BIRG) when England was leading or victorious and tended to engage in Cutting Off Reflected Failure (CORF) when England was trailing or defeated. In Method 1, team identification, national identification with England, and sentiment were significantly higher when England was leading or victorious than when they were trailing or defeated. In Method 2, machine learning generated trending graphs to detect that English fans BIRGed when they scored against Colombia; they also BIRGed more frequently during the match with Croatia, peaking several times when they scored a goal, saved a goal, or took a free kick. However, even though CORFing (i.e., lower team identification, lower national identification, and lower sentiment) occurred when the opposing team scored, English fans still BIRGed when they were finally defeated by Croatia, likely a function of the stage the game took place (World Cup semifinal), indicating that England had nonetheless succeeded in the World Cup as a whole.
Factors Associated With a Delay in Achieving Full Knee Extension Before Anterior Cruciate Ligament Reconstruction
Authors: Gage Andrew , Kluczynski Melissa A. , Bisson Leslie J. , Marzo John M.
Published: March 2019

Background:

Arthrofibrosis commonly occurs after an acute anterior cruciate ligament (ACL) injury and following ACL reconstruction and can lead to poor outcomes. Preoperative stiffness has been shown to be associated with postoperative stiffness; however, few studies have examined predictors of preoperative delay in obtaining full knee extension.

Purpose:

To examine demographic and injury factors as predictors of time required to achieve full knee extension preoperatively in patients with an acute ACL injury.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

A total of 172 patients with an acute ACL tear at presentation (defined as ≤3 weeks from injury) who underwent magnetic resonance imaging (MRI) within 6 weeks of the injury were included in this analysis. Preoperative data included date of injury, age at injury, sex, body mass index, mechanism of injury (noncontact/contact), time from injury to surgery (days), time to achieve full extension prior to surgery (weeks), and bone bruising on MRI. Time to achieve full extension was categorized as <3 or ≥3 weeks. Unadjusted and adjusted logistic regression was used to examine predictors of delayed time to achieve full extension (≥3 vs <3 weeks). Odds ratios and 95% CIs were reported.

Results:

Time to achieve full extension was early (<3 weeks) in 98 patients and delayed (≥3 weeks) in 74 patients. The average time to achieve full extension was 7 days in the early group and 32.5 days in the delayed group. Delayed time to achieve full extension was associated with increased lateral femoral condyle (LFC) bruising compared with early time to achieve extension (82.8% vs 66.7%, respectively; P = .03). No other statistically significant predictors were found after adjustment for age, sex, body mass index, and mechanism of injury.

Conclusion:

Acute ACL injuries associated with LFC bone bruising seen on MRI are more likely to result in reduced extension prior to ACL reconstruction. These injuries should be identified and addressed by an appropriate preoperative rehabilitation program, and surgery should be delayed to avoid risking arthrofibrosis postoperatively by reconstructing a knee with less than full extension.
Mathematics and Reading Develop Together in Young Children: Practical and Policy Considerations
Authors: Purpura David J. , Litkowski Ellen C. , Knopik Valerie
Published: March 2019

Early mathematics and reading skills underlie later school and career success. Yet, many children struggle to acquire these skills at the same rate as their peers. Often, these challenges are interrelated because both domains share basic underlying factors. Although research considers the development and instruction of these two domains together, practice and policy efforts lag behind, often treating these as completely independent domains. Here, we review the empirical basis for linking mathematics and reading: domain-specific and domain-general connections, neurobiological underpinnings, and shared genetic and environmental factors. Furthermore, we recommend enhanced national policies and practices that place mathematics alongside reading campaigns and integrate the two. Future work should also support empirically based instructional tools for both domains and develop links across instructional efforts.
Reading Comprehension Research: Implications for Practice and Policy
Authors: Elleman Amy M. , Oslund Eric L.
Published: March 2019

Reading comprehension is one of the most complex cognitive activities in which humans engage, making it difficult to teach, measure, and research. Despite decades of research in reading comprehension, international and national reading scores indicate stagnant growth for U.S. adolescents. In this article, we review the theoretical and empirical research in reading comprehension. We first explore different theoretical models for comprehension and then focus on components shown to be important across models that represent potential targets for instruction. In the last part of the article, we consider solutions for translating research to practice and policies for improving instruction. Improving reading scores will require a concerted and collaborative effort by researchers, educators, and policy makers with a focus on long-term solutions. An early and sustained focus on developing background knowledge, vocabulary, inference, and comprehension monitoring skills across development will be necessary to improve comprehension.
Subscapularis in Reverse Total Shoulder Arthroplasty
Authors: Bigdon Sebastian F , Bolliger Lilianna , Albers Christoph E , Collin Philippe , Zumstein Matthias A
Published: March 2019

The use of reverse total shoulder arthroplasty (RSA) is becoming increasingly popular, but many biomechanical aspects are poorly understood. Particularly, the role and function of the subscapularis following RSA are unclear. Several clinical and biomechanical studies have analyzed its role in range of motion and stability. There is some evidence that the subscapularis is beneficial for stability but may reduce range of motion. This review provides an overview of the current literature, which suggests that the subscapularis may have a more important role in RSA than originally thought.
Patient-reported distress can aid clinical decision-making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort
Authors: Stewart Iain , McKeever Tricia , Braybrooke Rebecca , Oballa Eunice , Simpson Juliet K. , Maher Toby M. , Marshall Richard P. , Lukey Pauline T. , Fahy William A. , Jenkins Gisli , Saini Gauri
Published: March 2019

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease. We aimed to determine if patient response to a palliative assessment survey could predict disease progression or death.

We undertook a cross-sectional study in a UK clinical cohort of incident cases. Rasch-based methodology provided a disease distress value from an abridged 11-item model of the original 45-item survey. Distress values were compared with measures of lung function. Disease progression or mortality alone was predicted at 12 months from survey completion, with risk of death assessed at 3, 6 and 12 months.

Disease distress values were negatively correlated with lung function (r=−0.275 for the percentage predicted diffusing capacity of the lung for carbon monoxide). Expected survey scores computed from distress values could distinguish disease progression (n=8.8, p=0.004) and death (n=10.2, p=0.002) from no disease progression (n=6.9). Actual survey scores predicted disease progression and death with an area under the curve of 0.60 and 0.64, respectively. Each point increment in actual score increased risk of 12-month mortality by 10%; almost 43% of people scoring above 18 did not survive beyond 105 days.

We define a short questionnaire that can score disease distress and predict prognosis, thus assisting clinical decision-making in progressive fibrosis.
Treatable traits: a new paradigm for 21st century management of chronic airway diseases: Treatable Traits Down Under International Workshop report
Authors: McDonald Vanessa M. , Fingleton James , Agusti Alvar , Hiles Sarah A. , Clark Vanessa L. , Holland Anne E. , Marks Guy B. , Bardin Philip P. , Beasley Richard , Pavord Ian D. , Wark Peter A.B. , Gibson Peter G.
Published: March 2019

“Treatable traits” have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each individual to improve outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.
The management of post-traumatic stress disorder and associated pain and sleep disturbance in refugees
Authors: Lies July , Jones Lester , Ho Roger
Published: March 2019

More than 68 million people worldwide have been forcibly displaced and one-third of these are refugees. This article offers an overview of the current literature and reviews the epidemiology and evidence-based psychological and pharmacological management of post-traumatic stress disorder (PTSD), sleep disturbance and pain in refugees and asylum seekers. It also considers the relationship between sleep disturbance and PTSD and explores concepts of pain in relation to physical and psychological trauma and distress. During diagnosis, clinicians must be aware of ethnic variation in the somatic expression of distress. Treatments for PTSD, pain and sleep disturbance among refugees and asylum seekers are essentially the same as those used in the general population, but treatment strategies must allow for cultural and contextual factors, including language barriers, loss of freedom and threat of repatriation.

LEARNING OBJECTIVES

After reading this article you will be able to:

•

recognise the challenges faced by the large number of refugees worldwide

•

understand the relationship between PTSD, sleep disturbance and pain in refugees

•

broadly understand the evidence for psychological and pharmacological therapy for treating PTSD, sleep disturbance and pain in refugees.

DECLARATION OF INTEREST

None.
ARAMIS: Efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Fizazi Karim , Shore Neal D. , Tammela Teuvo , Ulys Albertas , Vjaters Egils , Polyakov Sergey , Jievaltas Mindaugas , Luz Murilo , Alekseev Boris Y. , Kuss Iris , Kappeler Christian , Snapir Amir , Sarapohja Toni , Smith Matthew Raymond
Published: March 2019

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Background: Delaying metastases for nmCRPC patients, while minimizing the risk of adverse events, is an important treatment goal. Darolutamide, a structurally unique androgen receptor (AR) antagonist, is being evaluated for the treatment of advanced prostate cancer. The ARAMIS trial studied the efficacy and safety of darolutamide in nmCRPC patients. Methods: This double-blind, placebo-controlled phase III trial randomized nmCRPC patients in a 2:1 ratio to receive darolutamide 600 mg (two 300 mg tablets) twice-daily or placebo, while continuing androgen deprivation therapy. Patients were stratified by prostate-specific antigen doubling time (≤6 months or >6 months) and use of osteoclast-targeted therapy. The primary endpoint was metastasis-free survival (MFS), with independent central review of radiographic imaging every 16 weeks. Secondary endpoints include overall survival (OS), times to pain progression (assessed by Brief Pain Inventory), first cytotoxic chemotherapy and first symptomatic skeletal event, as well as safety profile. Results: In total, 1,509 patients were randomized (955 to darolutamide, 554 to placebo). Median MFS was 40.4 months with darolutamide vs 18.4 months with placebo (hazard ratio [HR] 0.41; 95% confidence interval [CI] 0.34–0.50; 2-sided p<0.0001). OS showed a trend in favor of darolutamide (HR 0.71, 95% CI 0.50–0.99, 2-sided p=0.045), as did time to pain progression (HR 0.65; 95% CI 0.53–0.79; 2-sided p<0.0001). Other secondary and exploratory efficacy endpoints also favored darolutamide. Incidences of treatment-emergent adverse events (AEs) with ≥5% frequency or grade 3–5 were comparable between darolutamide and placebo arms; none except fatigue occurred in >10%. Discontinuation rates due to AEs were 8.9% with darolutamide and 8.7% with placebo. Grouped terms for AEs noted with other AR inhibitors (including fracture, falls, seizures, weight decrease, hypertension, and cognitive disorder) showed minimal or no difference in incidence between study arms. Conclusion: Among men with nmCRPC, MFS was significantly longer with darolutamide than with placebo with a low incidence of treatment-related AEs in this asymptomatic patient population. Clinical trial information: NCT02200614.
Cost-effectiveness of metastasis-directed therapy in the setting of oligometastatic hormone-sensitive prostate cancer.
Authors: Parikh Neil Rohit , Nickols Nicholas George , Rettig Matthew , King Christopher R. , Raldow Ann C. , Steinberg Michael L. , Tran Phuoc T. , Kishan Amar Upadhyaya
Published: March 2019

147

Background: Androgen deprivation therapy (ADT) has historically been used as the backbone of treatment in patients with newly-diagnosed hormone-sensitive metastatic prostate cancer. However, recent literature has suggested the potential utility of metastasis-directed therapy (MDT) in a subset of patients with oligometastatic prostate cancer (OPC), potentially allowing for ADT-free survival. Methods: A cost-effectiveness analysis was performed comparing (1) ADT upfront versus (2) MDT followed by salvage ADT in patients with asymptomatic hormone-sensitive OPC. MDT was delivered via stereotactic body radiation therapy (SBRT) over 3 fractions. ADT consisted of Lupron injections every 3 months. Costs were calculated from a payor’s perspective based on Medicare CPT codes, CLAB fee schedule, and ASP drug prices. ADT-free survival was modeled based on results from STOMP trial; costs of retreatment were not considered in the MDT arm. Based on prior literature, health utility was assumed to be 0.9 without ADT, and 0.82 with ADT. Given paucity of long-term data on survival effect of MDT with delayed ADT, both arms were assumed to have identical long-term disease transition state probabilities. Results: Total cost of ADT upfront vs. MDT + salvage ADT was $3,430 vs. $9,434 at 1 year, and $10,289 vs. $13,806 at 3 years. Compared to ADT alone, MDT + salvage ADT showed improvements in quality-adjusted life years (QALYs) of 0.07 and 0.15 at 1 and 3 years respectively, translating to incremental cost-effectiveness ratio (ICER) of $85,385/QALY at 1 year and $24,118/QALY at 3 years. Conclusions: Using a willingness-to-pay ICER threshold of $100,000/QALY, MDT with SBRT is shown to be a cost-effective option compared to ADT alone in patients with OPC, particularly when utilizing a longer follow-up time period.
Outcomes of the miltuximab first in human trial and proposed study design for a phase I trial 89Zr/177Lu theranostic trial.
Authors: Campbell Douglas , Sabanathan Dhanusha , Gurney Howard , Gillatt David , Trifunovic Marko , Poursoultan Pirooz , Ho Shon Kevin , Mackay Tiffany , Bailey Dale L , Roach Paul , Walsh Brad
Published: March 2019

261

Background: Miltuximab is a chimeric antibody targeting Glypican-1 which is overexpressed in prostate cancer. Miltuximab has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. Methods: Metastatic patients (prostate, pancreatic and bladder) were dosed with unlabelled Miltuximabfollowed by the infusion of 1 mg/250MBq 67Ga-Miltuximab. Patients underwent whole body gamma and SPECT/CT scans up to 144 hours post-infusion. Standard of care imaging was performed at least 14 days before and after participation. Safety was evaluated by an external monitoring committee. Total organ exposure was determined by dosimetry of whole-body gamma scans. Antibody pharmacokinetics were also determined. Results: 12 patients were enrolled into the trial. Miltuximabwas well tolerated and did not elicit any drug-related adverse reactions. Liver and spleen uptake of 67Ga-Miltuximabwas observed from 30 min to 72 hours post dose. Pre-infusion of unlabelled Miltuximab resulted in reduced liver accumulation and increased distribution in the rest of the body. Miltuximab targeting to sites of active progressive disease was observed in certain prostate cancer patients who had failed enzalutamide treatment. Dosimetry analysis combined with antibody pharmacokinetic data was used to establish safe dose limits for a Phase 1 study. Conclusions: This study is the first in human for Miltuximaband demonstrates its potential for further clinical evaluation as a theranostic in prostate cancers and formed the basis for a Phase I imaging and therapy study planned for 2019. This study will use 89Zr-labelled Miltuximab to screen eligible patients and confirm tumour localisation, followed by treatment with 177Lu-labelled Miltuximab. Clinical trial information: ACTRN12616000787482.
PEAX: Men with metastatic castrate-resistant prostate cancer (mCRPC) treated with either sipuleucel-T (SIP-T), enzalutamide (ENZA) or abiraterone acetate (ABI) undergoing cardiopulmonary exercise testing (CPET).
Authors: Harrison Michael Roger , Khouri Michel , Armstrong Andrew J. , Zhang Tian , McNamara Megan Ann , Anand Monika , Bratt Ellen , Hood Hillary , Coyne Brian , Wu Yuan , Healy Patrick , George Daniel J.
Published: March 2019

281

Background: Both ENZA and ABI are associated with significant toxicity to the cardiovascular-musculoskeletal system and physical side effects. However whether they cause a decline in cardiorespiratory fitness (CRF), as conventional ADT does, has not been studied. We hypothesized that men treated with ENZA or ABI would have a significant decline in CRF, whereas those treated with SIP-T would not. Methods: Men starting standard of care (SOC) ENZA or ABI for asymptomatic or minimally symptomatic mCRPC were treated per institutional standards. SIP-T (SOC) is the control arm. Primary endpoint is change in VO2peak from baseline to week 21 by CPET. Secondary endpoints include measurement of functional status by patient reported outcomes (FACT-P, FACIT-Fatigue) and physician reported outcomes (ECOG PS, AEs). Results: In this single-site, prospective, parallel group, observational study, 28 pts completed the baseline and week 21 CPET and secondary assessments. Median age was 68 years; 86% were white. Two-thirds of pts had ECOG PS 0; the rest had PS 1. 93% were nonsmokers. Intention to treat analyses for mean 21-week change from baseline with a 95% confidence interval (CI) for each assessment by arm are presented in the Table. Conclusions: Unexpectedly, there was great heterogeneity in 21-week ΔVO2peak within each therapy group. Reasons for heterogeneity will be explored and correlated with baseline variables, clinical status, and questionnaire data. A low percentage of patients exercised regularly. Larger trials of exercise training interventions in this setting are warranted. Clinical trial information: NCT02353715. [Table: see text]
ATM mutation is associated with shorter overall survival in relapsed/advanced urothelial cancer.
Authors: Yin Ming , Grivas Petros , Mortazavi Amir , Monk Paul , Emamekhoo Hamid , Holder Sheldon L. , Drabick Joseph J. , Pal Sumanta K. , Woo Michele Sue-Ann , Dexter Jin , Vasekar Monali K. , Joshi Monika
Published: March 2019

370

Background: Somatic mutations of ATM are frequently found in UC and have been associated with a better response to cisplatin-based neoadjuvant chemotherapy. However, we previously showed ATM mutations were associated with a short survival in UC (PMID: 29682192 ). In this study, we focused on prognostic values of mutations in ATM in tumors of patients with relapsed or advanced (TxN2-3M0-1) UC through three independent datasets. Methods: 81 UC pts who underwent FoundationOne genomic sequencing (315 cancer-related genes) were used as a discovery dataset. Results were then validated in additional 91 pts with UC who received FoundationOne test (collected separately) and 129 relapsed/advanced UC patients selected from 412 TCGA bladder cohort. Fisher Exact test was used to determine difference of ATM mutation rates. Logistic regression analysis was performed to calculate odds ratio (OR) and 95% confidence interval (CI). Overall survival (OS) was measured from time of initial diagnosis and Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% CI. Results: The median ages of the 3 cohorts were 65 (44–84), 65 (21–91) and 67 (45–-90). The majority of pts were Caucasians (86.4%, 75.8% and 81.4%) and ever smokers (77.8%, 67% and 76.7%). ATM mutations were present in 14.8% (12/81), 11% (10/91) and 6.2% (8/129) of the three cohorts (Fisher Exact, p = 0.118). In all three groups of pts, ATM mutations consistently correlated with a significantly shorter OS (Discovery: HR = 2.25, 95% CI, 1.03–4.89, p = 0.041; Validation 1: HR = 3.15, 95% CI, 1.17–8.44, p = 0.023; and Validation 2: HR = 2.17, 95% CI, 0.99–4.75, p = 0.051). In 144 pts treated with cisplatin or carboplatin pooled from the three cohorts, ATM mutations correlated with a non-significantly higher objective response rate (OR = 1.54, 95% CI 0.44–5.35, p = 0.5), but were still associated with a poorer survival (HR = 1.95, 95% CI 1.00–3.83, p = 0.05). Conclusions: These results suggest that ATM mutations may be considered as a negative prognostic biomarker in relapsed/advanced UC pts. Further studies are required to determine the underlying mechanisms.