bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceived Stress Predicts Subsequent Self-Reported Problems With Vision and Hearing: Longitudinal Findings From the German Ageing Survey
Authors: Wettstein Markus , Wahl Hans-Werner , Heyl Vera
Published: June 2021

Although stress is a risk factor for various diseases in later life, its role for sensory abilities in the second half of life has rarely been empirically addressed. We examined if perceived stress at baseline predicts self-reported difficulties with vision and hearing 3 years later. We also explored whether chronological age is a moderator of associations between stress and sensory difficulties. Our sample was derived from the German Ageing Survey and consisted of n = 5,085 individuals aged 40–95 years ( M = 64.01 years, SD = 10.84 years). Controlling for baseline self-reported sensory functioning, socio-demographic indicators, self-rated health and chronic diseases, greater perceived stress at baseline predicted greater self-reported difficulties with vision and hearing 3 years later. The effect of stress did not vary by age. Our findings suggest that, from middle adulthood to advanced old age, stress is a risk factor for increases in self-perceived problems with vision and hearing.
Emotions and politics of sensibilities in Latin America
Authors: Scribano Adrian
Published: June 2021

The social sciences in Latin America have always had a special connection with the study and analysis of the place of emotions in the social structuration processes. The aim of this article is to offer a synthetic exposition of some inquiries about emotions and the politics of sensibilities in Latin America, emphasizing those that are being felt in the context of the COVID-19 pandemic. To achieve this objective, first we offer a synthesis of the theoretical and methodological points that will guide the interpretation; then we draw on pre-existing inquiries and surveys which allow us to capture the state of sensibilities before and during the pandemic in the region; and finally some conclusions are presented. The work is based on a multi-method approach, where qualitative and quantitative secondary and primary data are articulated in tandem.
Duvelisib as bridge to allotransplantation in refractory peripheral T-cell lymphoma with T-follicular helper phenotype: case report
Authors: Lolli Ginevra , Casadei Beatrice , Pellegrini Cinzia , Argnani Lisa , Cocito Federica , Zinzani Pier Luigi
Published: June 2021

Objective:

Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous T-cell malignancies representing 5%–10% of aggressive lymphomas. The prognosis is poor for patients with relapsed/refractory (R/R) disease, with a median overall survival of less than 6 months and no standardized treatments. We discuss the role of the phosphatidylinositol 3-kinase (PI3K) γδ inhibitor duvelisib as bridge to allotransplantation in a patient with R/R PTCL.

Methods:

Case report.

Results:

A 55-year-old woman diagnosed with relapsed nodal PTCL with T-follicular helper phenotype received PI3K γδ inhibitor duvelisib in the context of the phase II PRIMO clinical trial. After two cycles at a dose of 75 mg twice daily, the patient achieved complete response (CR), which was subsequently consolidated with human leukocyte antigen fully matched unrelated donor allotransplantation. No major toxicities were recorded during the duvelisib treatment period or during hospitalization for allotransplantation. At the latest follow-up, the patient was alive and still in CR 10 months posttransplant.

Conclusions:

Duvelisib should be further explored as a bridge to allotransplantation in patients with R/R PTCL, given the success and low toxicity in our patient.
The problem of universals in cross-cultural studies: Insights from Sámi animal melodies (yoik)
Authors: Aubinet Stéphane
Published: June 2021

This article offers a critique of the notion of “universals” in cross-cultural studies on music and emotions based on empirical observations and philosophical arguments. The empirical material comes from experiments with songs evoking animals and belonging to the Indigenous Sámi “yoik” tradition. Participants from the Belgian Ardenne untrained to the yoik ( N = 114, age 4–79) listened to recordings and tried to guess which animal was evoked. While their scores were significantly above chance level, additional data about their own environment and relationships to animals illustrate that interpretations in terms of “universals” would obscure the interrelational processes and (productive or unproductive) “misrecognitions” at work during the experiments. By analogy, this illustrates the need for a down-to-earth approach in cross-cultural studies on music that acknowledges the creative role of experimental designs and laboratory conditions in the production of universals. This approach may imply a move away from the nature/culture divide and a renewed attention to experimental subjects in a postcolonial context, with the aim of informing us on the entanglement of human musicality in “relational places” and the productive biases these offer to relate across different environments.
Case Report: Delayed Alemtuzumab-Induced Concurrent Neutropenia and Thrombocytopenia in Relapsing-Remitting Multiple Sclerosis
Authors: Ganju Akaansha , Stock James C. , Jordan Kim
Published: June 2021

Alemtuzumab is an anti-CD52 monoclonal antibody used to treat relapsing-remitting multiple sclerosis following failure of second-line medications. It is administered intravenously in 2 treatment sequences 1 year apart. This drug is frequently associated with mild infusion reactions within days of administration, increased infection risk, and long term adverse events from secondary autoimmunity. Alemtuzumab-induced serious immune-mediated thrombocytopenia (ITP) is well-reported and occurred in 1.0-2.2% of participants in initial phase 2 and 3 trials for multiple sclerosis. Significant neutropenia, however, is rare and was only observed in 0.1% of study participants. Delayed neutropenia and/or ITP is thought to occur from secondary autoimmunity. Few case reports have described severe neutropenia occurring beyond 2 months of last alemtuzumab dose. We present an unusual case of delayed combined neutropenia and thrombocytopenia that occurred 15 months after the second infusion of alemtuzumab. The patient was asymptomatic and presented following discovery of neutropenia and thrombocytopenia during routine laboratory studies. The patient responded to steroids initially and was discharged, although outpatient cell counts subsequently revealed recurrent neutropenia and ITP. The adverse drug reaction probability (Naranjo) scale was completed and showed probable likelihood that the adverse event was alemtuzumab-related. Long term screening for delayed hematologic abnormalities, at least 4 years after initial dose, is necessary when using alemtuzumab. Greater research is needed to understand the mechanism of drug-associated neutropenia.
Taxes for public libraries: Arguments about library district management from the perspective of residents
Authors: Suzuki Issei , Koizumi Masanori
Published: June 2021

Economic pressure on public library budgets has risen since the late-20th century as government funding has declined. Under increasing financial pressure, creating a procedure for how public libraries can provide fulfilling services to residents is one of the essential issues in public library management. As a result, library districts are receiving much attention as a management model in response to financial deterioration of public sectors in the United States. Library districts are special-purpose local governments that have a tax levy and bond authority for library management. Recent studies have demonstrated that library districts’ revenues are more stable over the long term than those of other legal bases, such as general-purpose local governments and non-profit organizations in the United States. However, it is not easy to form a library district because it involves a tax increase for residents. Nevertheless, the number of library districts has increased since the late-20th century. Why do voters allow a tax levy for library management? In this study, we examined the opinions of residents through a qualitative content analysis, using the voters’ pamphlets distributed to residents at the time of the referendum for forming the library district. Specifically, we analyzed opinions of both voters in favor and opposed to creating a library district and identified their preferences. Our research results showed that residents held a common understanding of the significance of public libraries in the community. The debate revolved around how much burden the residents were willing to accept to provide library services.
Teachers’ perceived information literacy self-efficacy
Authors: Shonfeld Miri , Aharony Noa , Nadel-Kritz Noa
Published: June 2021

The aim of this research was to examine the factors that might correlate with variables that may explain teachers’ perceptions of their information literacy self-efficacy level. The study was conducted among 101 teachers during the 2018 academic year. It used the following questionnaires: information literacy self-efficacy level, being a digital newcomer/native, personality variables taken from the Big Five model, mastery of computer applications, personal characteristics, and participation in a digital program. Researchers used a quantitative methodology. Findings present a correlation between teachers’ perceptions of their information literacy self-efficacy level and openness to experience and neuroticism, teachers’ level of digital skills, and teachers’ participation in a digital program. We propose that the ministry of education should focus on developing pre-service teachers’ and teachers’ information literacy skills, thus enhancing their information literacy self-efficacy.
Assessing the Rotation of the First Metatarsal on Computed Tomography Scans: A Systematic Literature Review
Authors: Najefi Ali-Asgar , Malhotra Karan , Patel Shelain , Cullen Nicholas , Welck Matthew
Published: June 2021

Background:

Hallux valgus is a multiplanar deformity that is often treated on the basis of 2-dimensional (2D) parameters and radiographs. Recurrence rates after surgical correction remain high, and failure to correct pronation of the metatarsal is increasingly stipulated as being part of the problem. Multiple methods of assessing metatarsal pronation have been proposed.

Methods:

We performed a systematic literature review identifying studies that measured metatarsal pronation and torsion on computed tomography (CT) scans. Specific methodology, patient groups, results, and reliability assessments were all reported.

Results:

We identified 14 studies that fulfilled the inclusion criteria. Eleven studies measured 2D values on CT scan, and 3 studies used computer-based 3-dimensional (3D) modeling and artificial intelligence systems to help calculate pronation. Metatarsal pronation angle, α angle, sesamoid rotation angle, and measurements for torsion were the most commonly used methods. All angles and measurements were performed as 2D measurements, but the metatarsal pronation angle was also performed with 3D modeling. Reliability and reproducibility of the α angle and metatarsal pronation angle were excellent, despite being performed on studies with small numbers.

Conclusion:

Multiple methods have been reported to demonstrate first metatarsal pronation on CT, of which the α angle and the metatarsal pronation angle are the most pragmatic and useful in a clinical setting. Further work is needed to further validate the reliability of these measurements in larger series and to identify normal pronation and metatarsal torsion on weightbearing imaging. Further work is required to determine whether addressing pronation reduces recurrence rates and improves outcomes in surgery for hallux valgus.

Level of Evidence:

Level III, retrospective cohort study.
Phronesis (Practical Wisdom) as a Type of Contextual Integrative Thinking
Authors: Kristjánsson Kristján , Fowers Blaine , Darnell Catherine , Pollard David
Published: June 2021

Coinciding with the recent psychological attention paid to the broad topic of wisdom, interest in the intellectual virtue of phronesis or practical wisdom has been burgeoning within pockets of psychology, philosophy, professional ethics, and education. However, these discourses are undercut by frequently unrecognized tensions, lacunae, ambivalences, misapplications, and paradoxes. While a recent attempt at conceptualizing the phronesis construct for the purpose of psychological measurement offers promise, little is known about how phronesis develops psychologically, what motivates it, or how it can be cultivated. Many psychologists aspire to make sense of wise thinking without the contextual, affective, and holistic/integrative resources of phronesis. This article explores some such attempts, in particular, a new “common model” of wisdom. We argue for the incremental value of the phronesis construct beyond available wisdom accounts because phronesis explains how mature decision-making is motivated and shaped by substantive moral aspirations and cognitively guided moral emotions. We go on to argue that, in the context of bridging the gap between moral knowledge and action, phronesis carries more motivational potency than wisdom in the “common model.” The phronesis construct, thus, embodies some unique features that psychologists studying wise decision-making ignore at their peril.
Caesarean Scar Endometriosis May Require Abdominoplasty
Authors: Bartłomiej Barczyński , Małgorzata Sobstyl , Karolina Frąszczak , Anna Sobstyl
Published: June 2021

Endometriosis is defined as an ectopic presence of endometrium-like tissue outside uterine cavity, which most commonly involves intraperitoneal organs. However, one of the less frequent forms of the disease is abdominal wall endometriosis usually developing in surgical scars following obstetric and gynaecological surgeries involving uterine cavity entering, that is, caesarean section, myomectomy or hysterectomy. In this case report we present a case of a patient with extensive caesarean scar endometriosis, who required complex surgical management. Successful surgical treatment involved not only radical tumour resection and application of mesh in postoperative hernia prevention but also adequate wound closure ensuring satisfactory cosmetic results, which was most challenging. The abdominal wall defect could not be sutured by traditional technique, thus polypropylene mesh was used and partial abdominoplasty was performed. The wound healed without complication and 24-month follow-up showed no evidence of local recurrence and satisfactory cosmetic result. In case of extensive endometrial abdominal wall tumours surgical treatment may involve application of advanced plastic surgery techniques, like abdominoplasty or skin/musculocutaneous flaps transposition.
COVID times make ‘deep listening’ explicit: changing the space between interviewer and participant
Authors: ’t Hart Dorinda
Published: June 2021

This article draws on the research project Post-abortion narratives shared by Perth women via face-to-face interviews. The project was subsequently disrupted by the arrival of COVID-19 in Perth, Australia, making it necessary to conduct interviews via video call. The experience of using an online platform to conduct interviews became an opportunity to consider more carefully the practice of ‘deep listening’. This kind of listening involves creating an emotional connection with the participant so that the interviewer is able to hear multiple layers of meaning and context. It includes listening mixed with perception in which one can hear the emotions of the other. In a paradigm where the interview is seen as an interaction between two embodied individuals and the interviewer herself is the instrument of research, this article examines the communication that occurs in the space between two co-present, embodied individuals and explicates the practice of deep listening. While interviewing via video call is an excellent tool, I argue that a layer of meaning is removed by the technological medium, which impacts the researcher relationship and thus the ability to listen deeply.
An expert review on breaking barriers in severe asthma in Brazil: Time to act
Authors: Pitrez Paulo Márcio , Giavina-Bianchi Pedro , Rizzo José Ângelo , Souza-Machado Adelmir , Garcia Guilherme Freire , Pizzichini Marcia Margaret Menezes
Published: June 2021

Currently, Brazil lacks a national asthma management program and is burdened with nearly 200,000 hospitalizations due to the disease per year and approximately 5 deaths per day. The purpose of this article was to analyze the current issues surrounding severe asthma in Brazil, as the status of diagnosis and treatment is largely unknown, and to provide feasible recommendations to elicit imminent action. A panel of Brazilian medical experts in the field of severe asthma was provided with a series of relevant questions to address prior to a multi-day conference. Within this conference, each narrative was discussed and edited by the entire group. Through numerous rounds of discussion consensus was achieved. In order to overcome barriers to adequate asthma treatment, this panel recommends specific initiatives that can be implemented in the short-term to decrease the burden of severe asthma in Brazil. With increasing healthcare costs and limited resources globally, there is an opportunity to implement these recommendations in other countries in order to achieve adequate asthma care. Severe asthma is a heterogeneous and complex disease with various phenotypes that requires strict attention for diagnosis and management. Although this disease affects only a small proportion of the population with asthma, it poses a great burden to healthcare systems. Thus, barriers to diagnosis, treatment, and management should be overcome as quickly and efficiently as possible.
Gender Essentialism in Chinese Reality TV: A Case Study of You Are So Beautiful
Authors: Peng Altman Yuzhu
Published: June 2021

This article provides a feminist analysis of Chinese reality TV, using the recent makeover show— You Are So Beautiful (你怎么这么好看) as a case study. I argue that the notion of gender essentialism is highlighted in the production of You Are So Beautiful, which distances the Chinese show from its original American format— Queer Eye. This phenomenon is indicative of how existing gender power relations influence the production of popular cultural texts in post-reform China, where capitalism and authoritarianism weave a tangled web. The outcomes of the research articulate the interplay between post-socialist gender politics and reality TV production in the Chinese context.
A Novel Application of the Schema Therapy Mode Model for Social Anxiety Disorder: A Naturalistic Case Study
Authors: Penney Erika S. , Norton Alice R.
Published: June 2021

Social Anxiety Disorder (SAD) is a condition defined by an excessive and persistent fear of negative evaluation in social or performance situations. Whilst Cognitive Behaviour Therapy (CBT) is the gold standard treatment, not all individuals with SAD respond to CBT. The Schema Therapy Mode Model is frequently applied to chronic and hard-to-treat conditions and therefore may be applicable for SAD individuals who are non-responders to CBT. This case study describes how the Mode Model was successfully used to treat a woman in her 20s who presented with excessive fears of negative evaluation and pervasive social avoidance. Experiential techniques, such as chair dialogues and imagery rescripting, resulted in cognitive modification of negative core beliefs, reduced experiential discomfort and increased engagement in social and relational activities. This case offers a preliminary indication that the Schema Therapy Mode Model may be an effective treatment for socially anxious individuals and that further theoretical and empirical study in this area is warranted.
The Potential of Advanced Placement to Improve College Outcomes and Narrow Racial/Ethnic and Socioeconomic Disparities
Authors: Phillips Sarah Fierberg , Lane Brett
Published: June 2021

The U.S. economy requires a highly educated workforce, yet too few black, Latino, and low-income students attend, persist, and graduate from college. The present study examines the college outcomes of participants in a model Advanced Placement® (AP) intervention to shed light on its effectiveness and determine whether improving AP participation and performance is a promising strategy for closing persistent racial/ethnic and socioeconomic disparities in college outcomes. Findings suggest the college outcomes of program participants are better than those of similar students statewide while also highlighting variation within and across subgroups. At the same time, they confirm that AP participation and performance predict college outcomes and suggest that improving AP participation and performance among low-income white, black, and Latino students could be a useful strategy for closing persistent racial/ethnic and socioeconomic disparities in college outcomes.
Elevated glycohemoglobin is linked to critical illness in COVID-19: a retrospective analysis
Authors: Windham Samuel , Wilson Melissa P. , Fling Connor , Sheneman David , Wand Taylor , Babcock Lyndsey , MaWhinney Samantha , Erlandson Kristine M.
Published: June 2021

Background:

Several studies have explored hospitalization risk factors with the novel coronavirus disease 2019 (COVID-19) infection. Our goal was to identify clinical characteristics outside of laboratory or radiologic data associated with intubation or death within 7 days of admission.

Methods:

The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed COVID-19 were included. Demographics, comorbidities, and select medications were collected by chart abstraction. Missing height for calculating body mass index (BMI) was imputed using the median height for patients’ sex and race/ethnicity. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression and a minimax concave penalty (MCP) regularized logistic regression explored prediction.

Results:

Participants had a mean [standard deviation (SD)] age 55 (17), BMI 30.9 (8.2), 55% were male and 80% were ethnic/racial minorities. Increasing age [aOR: 1.24 (1.07, 1.45) per 10 years], higher BMI (aOR 1.03 (1.00, 1.06), and poorly controlled diabetes [hemoglobin A1C (HbA1c) ⩾ 8] (aOR 2.26 (1.24, 4.12) were significantly ( p < 0.05) associated with greater odds of intubation or death. Female sex [aOR: 0.63, 95% CI (0.40, 0.98); p value = 0.043] was associated with lesser odds of intubation or death. The odds of death and/or intubation increased 19% for every 1 unit increase in HbA1c value [OR: 1.19 (1.01, 1.43); p = 0.04]. Our final MCP model included indicators of A1C ⩾ 8, age > 65, sex, and minority status, but predicted intubation/death only slightly better than random chance [area under the receiver operating characteristic curve (AUC) = 0.61 (0.56, 0.67)].

Conclusion:

In a hospitalized patient cohort with COVID-19, worsening control of diabetes as evidenced by higher HbA1c was associated with increased risk of intubation or death within 7 days of admission. These results complement and help clarify previous associations found between diabetes and acute disease in COVID-19. Importantly, our analysis is missing some known predictors of severity in COVID-19. Our predictive model had limited success, suggesting unmeasured factors contribute to disease severity differences.
Sustained Online Amplification of COVID-19 Elites in the United States
Authors: Gallagher Ryan J. , Doroshenko Larissa , Shugars Sarah , Lazer David , Foucault Welles Brooke
Published: June 2021

In the absence of clear, consistent guidelines about the COVID-19 pandemic in the United States, many people use social media to learn about the virus, public health directives, vaccine distribution, and other health information. As people individually sift through a flood of information online, they collectively curate a small set of accounts, known as crowdsourced elites, that receive disproportionate attention for their COVID-19 content. However, these elites are not all created equal: not all accounts have received the same attention during the pandemic, and various demographic and ideological groups have crowdsourced their own elites. Using a mixed-methods approach with a panel of Twitter users in the United States over the first year of the COVID-19 pandemic, we identify COVID-19 crowdsourced elites. We distinguish sustained amplification from episodic amplification and demonstrate that crowdsourced elites vary across demographics with respect to race, geography, and political alignment. Specifically, we show that different subpopulations preferentially amplify elites that are demographically similar to them, and that they crowdsource different types of elite accounts, such as journalists, elected officials, and medical professionals, in different proportions. In light of this variation, we discuss the potential for using the disproportionate online voice of crowdsourced COVID-19 elites to equitably promote public health information and mitigate misinformation across networked publics.
Increased Stress, Declining Mental Health: Emerging Adults’ Experiences in College During COVID-19
Authors: Halliburton Amanda E. , Hill Michele B. , Dawson Bryan L. , Hightower Jennifer M. , Rueden Hailey
Published: June 2021

The COVID-19 pandemic altered the college experience and substantially impacted emerging adults’ navigation of this life stage. This concurrent mixed-methods study used an online survey, distributed to a southeastern university shortly after the transition to remote learning, to explore and understand college-attending emerging adults’ experiences during COVID-19. A total of 1,220 students ( Mage = 20.9) participated, and the diversity of the demographics was largely consistent with the university population. Participants completed questionnaires about psychopathology and COVID-related stressors, and they were given an opportunity to provide feedback to the university about the adjustment to COVID-19. The most common stressors included loss of routine, lack of social contact, and work/finances. Approximately two-thirds of participants reported anxiety and depression symptoms in the moderate to severe range, and about one-third reported suicidality. The authors discuss the implications of these findings for the ongoing crisis and offer recommendations for universities and college counselors.
Outpatient Shoulder Arthroplasty—A Systematic Review
Authors: Allahabadi Sachin , Cheung Edward C , Hodax Jonathan D , Feeley Brian T , Ma Chunbong B , Lansdown Drew A
Published: June 2021

Objective

Recent reports have shown that outpatient shoulder arthroplasty (SA) may be a safe alternative to inpatient management in appropriately selected patients. The purpose was to review the literature reporting on outpatient SA.

Methods

A systematic review of publications on outpatient SA was performed. Included publications discussed patients who were discharged on the same calendar day or within 23 hours from surgery. Articles were categorized by discussions on complications, readmissions, and safety, patient selection, pain management strategies, cost effectiveness, and patient and surgeon satisfaction.

Results

Twenty-six articles were included. Patients undergoing outpatient SA were younger and with a lower BMI than those undergoing inpatient SA. Larger database studies reported more medical complications for patients undergoing inpatient compared to outpatient SA. Articles on pain management strategies discussed both single shot and continuous interscalene blocks with similar outcomes. Both patients and surgeons reported high levels of satisfaction following outpatient SA, and cost analysis studies demonstrated significant cost savings for outpatient SA.

Conclusion

In appropriately selected patients, outpatient SA can be a safe, cost-saving alternative to inpatient care and may lead to high satisfaction of both patients and physicians, though further studies are needed to clarify appropriate utilization of outpatient SA.
Innovative EC8-compliant solutions for selection of the optimum retrofitting scheme of buildings with special characteristics
Authors: Skalomenos Konstantinos A , Morfidis Konstantinos E , Lekidis Vassilios A , Anagnostopoulos Stavros A
Published: June 2021

This article presents the seismic assessment and retrofit design of an existing old building in Greece of great regional importance. The Building is the “Administration building of Kalamata” located in the city of Kalamata, capital of the Messinia Prefecture. The Building, the largest in the city, is a seven-floor reinforced concrete (r/c) structure with a basement built in 1974. The seismic assessment procedure is based on the provisions of the EN 1998-3 code and the Greek code for structural interventions “KAN.EPE.,” introducing several novelties that give solutions to difficult practical problems with respect to the modeling, the analysis methods, and performance evaluation framework. The article presents details of the Building’s modeling, description of the analyses, and the corresponding results, as well as the most efficient retrofitting schemes that fulfill the safety demands (i.e. performance level B or “Life safety” and performance level C or “Collapse prevention” according to KAN.EPE.), considering cost and minimal disturbance both for the superstructure and foundation interventions. While considering the various intervention solutions, it proceeds with new simplified ways that optimize the proposed solution. As such, it can be used as a paradigm for finding clever, practical, and at the same time economical solutions. An interesting characteristic of the Building is that it has been strengthened already after the damaging earthquake of 1986, but the new usage requirements raised questions about the adequacy of that earlier strengthening. Last, but not least, it must be mentioned that this building is unique in the sense that the main earthquake record (a strong motion accelerogram) obtained during the damaging 1986 Kalamata earthquake was at its basement. This record is also used for the assessment.
Stoppingversuscontinuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study)
Authors: Moore Wendy C. , Kornmann Oliver , Humbert Marc , Poirier Claude , Bel Elisabeth H. , Kaneko Norihiro , Smith Steven G. , Martin Neil , Gilson Martyn J. , Price Robert G. , Bradford Eric S. , Liu Mark C.
Published: June 2021

Background

The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.

Methods

COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary end-point: time to first clinically significant exacerbation; secondary end-points: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline) and blood eosinophil count ratio to COMET baseline. Safety was assessed.

Results

Patients stopping (n=151)versuscontinuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio 1.61, 95% CI 1.17–2.22; p=0.004) and decrease in asthma control (hazard ratio 1.52, 95% CI 1.13–2.02; p=0.005), and higher blood eosinophil counts at week 52 (270versus40 cells·µL−1; ratio (stoppingversuscontinuing) 6.19, 95% CI 4.89–7.83; p<0.001). Differences in efficacy outcomes between groups were observed when assessed from week 12 (16 weeks after last mepolizumab dose). Exacerbations requiring hospitalisation/emergency department visit were rare. Adverse events in patients continuing mepolizumab were consistent with previous studies. For patients who stopped mepolizumab, the safety profile was consistent with other eosinophilic asthma populations.

Conclusion

Patients who stopped mepolizumab had an increase in exacerbations and reduced asthma controlversusthose who continued.
Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold
Authors: Franciosi Alessandro N. , Fraughen Daniel , Carroll Tomás P. , McElvaney Noel G.
Published: June 2021

Alpha-1 antitrypsin deficiency (AATD) is the only readily identifiable monogenic cause of COPD. To date the only condition-specific treatment for AATD-associated COPD is weekly administration of intravenous plasma-purified human alpha-1 antitrypsin (IV-AAT). Uncertainties regarding which AATD genotypes should benefit from IV-AAT persist. IV-AAT is costly and involves weekly administration of a plasma product. Much of the risk stratification has been centred around the long-accepted hypothesis of a “putative protective threshold” of 11 µM (0.57 g·L−1) AAT in serum. This hypothesis has become central to the paradigm of AATD care, although its derivation and accuracy for defining risk of disease remain unclear.

We reviewed the literature and examined the association between the 11 µM threshold and clinical outcomes to provide context and insight into the issues surrounding this topic.

We found no data demonstrating an increased risk of COPD dependent on the 11 µM threshold. Moreover, an abundance of recent clinical data examining this threshold refutes the hypothesis. Conversely, the use of 11 µM as a treatment target in appropriate ZZ individuals is supported by clinical evidence, although more refined dosing regimens are being explored.

Continued use of the 11 µM threshold as a determinant of clinical risk is questionable, perpetuates inappropriate AAT-augmentation practices, may drive increased healthcare expenditure and should not be used as an indicator for commencing treatment.

Genotype represents a more proven indicator of risk, with ZZ and rare ZZ-equivalent genotypes independently associated with COPD. New and better risk assessment models are needed to provide individuals diagnosed with AATD with reliable risk estimation and optimised treatment goals.
Prognostic factors for adverse outcomes in patients with COVID-19: a field-wide systematic review and meta-analysis
Authors: Bellou Vanesa , Tzoulaki Ioanna , van Smeden Maarten , Moons Karel G.M. , Evangelou Evangelos , Belbasis Lazaros
Published: June 2021

Introduction

The individual prognostic factors for coronavirus disease 2019 (COVID-19) are unclear. For this reason, we aimed to present a state-of-the-art systematic review and meta-analysis on the prognostic factors for adverse outcomes in COVID-19 patients.

Methods

We systematically reviewed PubMed from 1 January 2020 to 26 July 2020 to identify non-overlapping studies examining the association of any prognostic factor with any adverse outcome in patients with COVID-19. Random-effects meta-analysis was performed, and between-study heterogeneity was quantified using I2statistic. Presence of small-study effects was assessed by applying the Egger's regression test.

Results

We identified 428 eligible articles, which were used in a total of 263 meta-analyses examining the association of 91 unique prognostic factors with 11 outcomes. Angiotensin-converting enzyme inhibitors, obstructive sleep apnoea, pharyngalgia, history of venous thromboembolism, sex, coronary heart disease, cancer, chronic liver disease, COPD, dementia, any immunosuppressive medication, peripheral arterial disease, rheumatological disease and smoking were associated with at least one outcome and had >1000 events, p<0.005, I2<50%, 95% prediction interval excluding the null value, and absence of small-study effects in the respective meta-analysis. The risk of bias assessment using the Quality in Prognosis Studies tool indicated high risk of bias in 302 out of 428 articles for study participation, 389 articles for adjustment for other prognostic factors and 396 articles for statistical analysis and reporting.

Conclusions

Our findings could be used for prognostic model building and guide patient selection for randomised clinical trials.
Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study
Authors: Darley David Ross , Ma Jin , Huszti Ella , Ghany Rasheed , Hutcheon Michael , Chow Chung-Wai , Tikkanen Jussi , Keshavjee Shaf , Singer Lianne Gail , Martinu Tereza
Published: June 2021

Rationale

The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (DLCOcor) measures gas movement across the alveolar–capillary interface. We hypothesised thatDLCOcoris a sensitive measure of injurious allograft processes disrupting this interface.

Objectives

To determine the prognostic significance of theDLCOcortrajectory on chronic lung allograft dysfunction (CLAD) and survival.

Methods

A retrospective analysis was conducted of all bilateral lung transplant recipients at a single centre, between January 1998 and January 2018, with one or moreDLCOcormeasurements. Low baselineDLCOcorwas defined as the failure to achieve aDLCOcor>75% predicted. Drops inDLCOcorwere defined as >15% below recent baseline.

Results

1259 out of 1492 lung transplant recipients were included. The median (range) time to peakDLCOcorwas 354 (181–737) days and the mean±sdDLCOcorwas 80.2±21.2% pred. Multivariable analysis demonstrated that low baselineDLCOcorwas significantly associated with death (hazrd ratio (HR) 1.68, 95% CI 1.27–2.20; p<0.001). Low baselineDLCOcorwas not independently associated with CLAD after adjustment for low baseline forced expiratory volume in 1 s or forced vital capacity. AnyDLCOcordeclines ≥15% were significantly associated with death, independent of concurrent spirometric decline. Lower percentage predictedDLCOcorvalues at CLAD onset were associated with shorter post-CLAD survival (HR 0.75 per 10%-unit change, p<0.01).

Conclusion

Low baselineDLCOcorand post-transplant declines inDLCOcorwere significantly associated with survival, independent of spirometric measurements. We propose thatDLCOcortesting may allow identification of a subphenotype of baseline and chronic allograft dysfunction not captured by spirometry. There may be benefit in routine monitoring ofDLCOcorafter lung transplantation to identify patients at risk of poor outcomes.
Genetically increased circulating FUT3 level leads to reduced risk of idiopathic pulmonary fibrosis: a Mendelian randomisation study
Authors: Nakanishi Tomoko , Cerani Agustin , Forgetta Vincenzo , Zhou Sirui , Allen Richard J. , Leavy Olivia C. , Koido Masaru , Assayag Deborah , Jenkins R. Gisli , Wain Louise V. , Yang Ivana V. , Lathrop G. Mark , Wolters Paul J. , Schwartz David A. , Richards J. Brent
Published: June 2021

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal fibrotic interstitial lung disease. Few circulating biomarkers have been identified to have causal effects on IPF.

Methods

To identify candidate IPF-influencing circulating proteins, we undertook an efficient screen of circulating proteins by applying a two-sample Mendelian randomisation (MR) approach with existing publicly available data. For instruments, we used genetic determinants of circulating proteins which residecisto the encoded gene (cis-single nucleotide polymorphisms (SNPs)), identified by two genome-wide association studies (GWASs) in European individuals (3301 and 3200 subjects). We then applied MR methods to test if the levels of these circulating proteins influenced IPF susceptibility in the largest IPF GWAS (2668 cases and 8591 controls). We validated the MR results using colocalisation analyses to ensure that both the circulating proteins and IPF shared a common genetic signal.

Results

MR analyses of 834 proteins found that a 1 sdincrease in circulating galactoside 3(4)-l-fucosyltransferase (FUT3) and α-(1,3)-fucosyltransferase 5 (FUT5) was associated with a reduced risk of IPF (OR 0.81, 95% CI 0.74–0.88; p=6.3×10−7and OR 0.76, 95% CI 0.68–0.86; p=1.1×10−5, respectively). Sensitivity analyses including multiplecis-SNPs provided similar estimates both for FUT3 (inverse variance weighted (IVW) OR 0.84, 95% CI 0.78–0.91; p=9.8×10−6and MR-Egger OR 0.69, 95% CI 0.50–0.97; p=0.03) and FUT5 (IVW OR 0.84, 95% CI 0.77–0.92; p=1.4×10−4and MR-Egger OR 0.59, 95% CI 0.38–0.90; p=0.01). FUT3 and FUT5 signals colocalised with IPF signals, with posterior probabilities of a shared genetic signal of 99.9% and 97.7%, respectively. Further transcriptomic investigations supported the protective effects ofFUT3for IPF.

Conclusions

An efficient MR scan of 834 circulating proteins provided evidence that genetically increased circulating FUT3 level is associated with reduced risk of IPF.
Lung function trajectory and biomarkers in the Tasmanian Longitudinal Health Study
Authors: Bui Dinh S. , Agusti Alvar , Walters Haydn , Lodge Caroline , Perret Jennifer L. , Lowe Adrian , Bowatte Gayan , Cassim Raisa , Hamilton Garun S. , Frith Peter , James Alan , Thomas Paul S. , Jarvis Debbie , Abramson Michael J. , Faner Rosa , Dharmage Shyamali C.
Published: June 2021

Background and objective

Different lung function trajectories through life can lead to COPD in adulthood. This study investigated whether circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories.

Methods

The Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their forced expiratory volume in 1 s (FEV1) trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (n=720) defined as never-smokers with an average FEV1trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories.

Results

Results showed that CC16 levels (an anti-inflammatory protein) were lower and C-reactive protein (CRP) (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 (0.63–0.98) per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07, 95% CI: 1.00–1.13, per unit increase). Levels of CC16 (area under the curve (AUC)=0.69, 95% CI: 0.56–0.81, p=0.002), CRP (AUC=0.63, 95% CI: 0.53–0.72, p=0.01) and the combination of both (AUC=0.72, 95% CI: 0.60–0.83, p<0.001) were able to discriminate between the AD and ND trajectories. Other quantified biomarkers (interleukin (IL)-4, IL-5, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)) were not significantly different between AD, ND and controls.

Conclusions

Circulating levels of CRP and CC16 measured in late adulthood identify different lung function trajectories (ADversusND) leading to COPD at age 53 years.
Upper airway symptoms associate with the eosinophilic phenotype of COPD
Authors: Obling Nicolai , Backer Vibeke , Hurst John R. , Bodtger Uffe
Published: June 2021

Background

There is growing evidence that upper airway symptoms coexist with lower airway symptoms in COPD. Still, the prevalence and impact of upper airway disease on the nature and course of COPD remain unclear. We aimed to describe this in a cross-sectional study.

Methods

We examined a cohort of COPD patients with pulmonary function tests, induced sputum, blood eosinophils, atopy tests and computed tomography (CT) of the paranasal sinuses. Lower airway symptoms were assessed using the COPD Assessment Test (CAT), and upper airway symptoms were assessed using the nasal subdomain of the 22-item Sino Nasal Outcome Test (SNOT22nasal). We recruited patients from five sites in Denmark and Sweden. We excluded patients with a history of asthma.

Findings

In total, 180 patients (female 55%, age 67±8 years, forced expiratory volume in 1 s (FEV1%) 52.4±16.6, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage: A: 18%, B: 54%, C: 3%, D: 25%) were included in the study. Seventy-four patients (41%) reported high upper airway symptoms (UAS, defined as SNOT22nasal≥6) with a median score of 10 (IQR 8–13). Patients with high UAS reported higher CAT scores (17.4±7.5versus14.9±6.6, p<0.05) and displayed higher fractions of eosinophils in blood (median 3.0% (IQR 1.6–4.2%)versus2.3% (IQR 1.4–3.1%), p<0.05) and in induced sputum (median 1.8% (IQR 0.3–7.1%)versusmedian 0.5% (IQR 0–1.7%), p<0.05). No differences in atopy, CT findings or exacerbation rates were observed.

Conclusion

COPD patients with upper airway disease showed increased evidence of eosinophilic disease and increased lower airway symptom burden.
Lung diffusing capacity for nitric oxide measured by two commercial devices: a randomised crossover comparison in healthy adults
Authors: Radtke Thomas , de Groot Quintin , Haile Sarah R. , Maggi Marion , Hsia Connie C.W. , Dressel Holger
Published: June 2021

In Europe, two commercial devices are available to measure combined single-breath diffusing capacity of the lung for nitric oxide (DLNO) and carbon monoxide (DLCO) in one manoeuvre. Reference values were derived by pooling datasets from both devices, but agreement between devices has not been established.

We conducted a randomised crossover trial in 35 healthy adults (age 40.0±15.5 years, 51% female) to compareDLNO(primary end-point) between MasterScreen™ (Vyaire Medical, Mettawa, IL, USA) and HypAir (Medisoft, Dinant, Belgium) devices during a single visit under controlled conditions. Linear mixed models were used adjusting for device and period as fixed effects and random intercept for each participant.

Difference inDLNObetween HypAir and MasterScreen was 24.0 mL·min−1·mmHg−1(95% CI 21.7–26.3). There was no difference inDLCO(−0.03 mL·min−1·mmHg−1, 95% CI −0.57–0.12) between devices while alveolar volume (VA) was higher on HypAir compared to MasterScreen™ (0.48 L, 95% CI 0.45–0.52). Disparity in the estimation ofVAand the rate of NO uptake (KNO=DLNO/VA) could explain the discrepancy inDLNObetween devices. Disparity in the estimation ofVAand the rate of CO uptake (KCO=DLCO/VA) per unit ofVAoffset each other resulting in negligible discrepancy inDLCObetween devices. Differences in methods of expiratory gas sampling and sensor specifications between devices likely explain these observations.

These findings have important implications for derivation ofDLNOreference values and comparison of results across studies. Until this issue is resolved, reference values, established on the respective devices, should be used for test interpretation.