bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, Aetiology, and Associated Fracture Patterns of Infraorbital Nerve Injuries Following Zygomaticomaxillary Complex Fractures: A Retrospective Analysis of 272 Patients
Authors: Dubron Kathia , Verbist Maarten , Shaheen Eman , Dormaar Titiaan Jacob , Jacobs Reinhilde , Politis Constantinus
Published: June 2021

Study Design:

Retrospective study.

Objective:

Zygomaticomaxillary complex (ZMC) fractures are common facial injuries with heterogeneity regarding aetiologies, fracture types, infraorbital nerve (ION) involvement, and treatment methods. The aim of this study was to identify associations between aetiologies, fracture types, and neurological complications. Additionally, treatment methods and recovery time were investigated.

Methods:

Medical files of 272 patients with unilateral and bilateral ZMC fractures were reviewed, whose cases were managed from January 2014 to January 2019 at the Department of Oral and Maxillofacial Surgery, University hospitals Leuven, Belgium. History of ION sensory dysfunction and facial nerve motoric dysfunction were noted during follow-up.

Results:

ION hypoaesthesia incidence was 37.3%, with the main causes being fall accidents, road traffic accidents, and interpersonal violence. Significant predictors of ION hypoaesthesia were Zingg type B fractures ( P = 0.003), fracture line course through the infraorbital canal ( P < .001), orbital floor fracture ( P < 0.001), and ZMC dislocation or mobility ( P = 0.001).

Conclusion:

Of all ZMC fractures, 37.3% exhibited ION hypoaesthesia. Only ZMC Zingg type B fractures (74.0%) were significantly more associated with ION hypoaesthesia. ION hypoesthesia was more likely (OR = 2.707) when the fracture line course ran through the infraorbital canal, and was less dependent on the degree of displacement. Neuropathic pain symptoms developed after ZMC fractures in 2.2% patients, posing a treatment challenge. Neuropathic pain symptoms were slightly more common among women, and were associated only with type B or C fractures. No other parameters were found to predict the outcome of this post-traumatic neuropathic pain condition.
Effect of negative pressure wound therapy for legs in complex wound diabetic patients: Therapeutic challenge and review
Authors: de Oliveira Leite Túlio Fabiano , Ribeiro da Silva Elpidio , Joviliano Edwaldo Edner
Published: June 2021

Diabetic foot is one of the main chronic complications caused by diabetes mellitus and can lead to limb amputation. Among the various wound treatment options, negative pressure wound therapy is a treatment modality based on vacuum-sealed drainage and vacuum-assisted closure to create a localized controlled negative pressure environment. In this case report, the patient sought medical attention and underwent surgical debridement of the dorsum of the right foot. Upon worsening of the wound condition, the patient was referred to our hospital for debridement and Renesys Smith Nephew dressing was implanted. After complete coverage of the granulation tissue without infection, elastic suturing was performed in the leg compartment to reduce the size of the dermis and epidermis graft. The patient then underwent a dermal matrix implant procedure, and an epidermis graft was removed from the ipsilateral thigh and placed on the wound. The aim of this study is to report a therapeutic challenge in an extensive wound in diabetic foot using a dressing negative pressure wound therapy and multidisciplinary treatment.
Family planning in Argentinian women with multiple sclerosis: An important yet seldom approached issue
Authors: Alonso Ricardo , Patrucco Liliana , Silva Berenice , Quarracino Cecilia , Eizaguirre María Barbara , Vrech Carlos , López Pablo , Carnero Contentti Edgar , Deri Norma , Carrá Adriana , Chercorff Aníbal , Tkachuk Verónica , Balbuena María Eugenia , Pettinicchi Juan Pablo , Tavolini Darío , Barboza Andrés , Rojas Juan I , Cristiano Edgardo , Lázaro Luciana , Garcea Orlando , Fernández Liguori Nora
Published: June 2021

Background

The purpose of this study was to assess family planning (FP) among women with multiple sclerosis (WwMS).

Methods

We invited 604 WwMS to answer a survey focused on FP: a) Temporal relationship between pregnancy and the diagnosis of multiple sclerosis; b) History of FP; c) Childbearing desire; d) Information on family planning. Comparisons between pregnancy and not pregnancy after MS, as well as, planned and unplanned pregnancy were analyzed. Multivariate and univariate analyses were used to assess the impact of independent variables and FP

Result

428 (71.7%) WwMS completed the survey. A 19.1% got pregnant after MS diagnosis and we evaluated FP in the last pregnancy, 56.1% patients had a planned pregnancy. Professional addressing FP (OR = 0.27, 95%-CI 0.08-0.92, p = 0.03) and non-injection drug treatment before pregnancy (OR = 2.88, 95%-CI 1.01-8.21, p = 0.047) were independent predictors of unplanned pregnancy in our multivariate model. Among WwMS ≤ 40 years, 48.7% had future childbearing desire. Young age (p < 0.001), PDDS <3 (p = 0.018), disease duration <5 years (p = 0.02), not childbearing before MS diagnosis (p < 0.001) and neurologist addressing family planning (p = 0.01) were significantly associated with childbearing desire.

Conclusions

This research highlights that pregnancy remains an important concern among WwMS.
Recent Smoking History Is Not Associated with Adverse 30-Day Standardized Postoperative Outcomes following Microsurgical Reconstructive Procedures of the Upper Extremity
Authors: Oleru Olachi O. , Shah Neil V. , Zhou Peter L. , Sedaghatpour Dillon , Mistry Jaydev B. , Wham Bradley C. , Kurtzman Joey , Mithani Suhail K. , Koehler Steven M.
Published: June 2021

Background: Upper extremity (UE) microsurgical reconstruction relies upon proper wound healing for optimal outcomes. Cigarette smoking is associated with wound healing complications, yet conclusions vary regarding impact on microsurgical outcomes (replantation, revascularization, and free tissue transfer). We investigated how smoking impacted 30-day standardized postoperative outcomes following UE microsurgical reconstruction. Methods: Utilizing the National Surgical Quality Improvement Program, all patients who underwent (1) UE free flap transfer (n = 70) and (2) replantation/revascularization (n = 270) were identified. For each procedure, patients were stratified by recent smoking history (current smoker ≤1-year preoperatively). Baseline demographics and standardized 30-day complications, reoperations, and readmissions were compared between smokers and nonsmokers. Results: Replantation/revascularization patients had no differences in sex, race, or body mass index between smokers (n = 77) and nonsmokers. Smokers had a higher prevalence of congestive heart failure (5.2% vs 1.0%, P = .036) and nonsmokers were more often on hemodialysis (15.6% vs 10.4%, P = .030). Free flap transfer patients had no differences in age, sex, or race between smokers (n = 14) and nonsmokers. Smokers had a longer length of stay (6.6 vs 4.2 days, P = .001) and a greater prevalence of chronic obstructive pulmonary disorder (COPD; 7.1% vs 0%, P = .044). Recent smoking was not associated with increased odds of any 30-day minor and major standardized surgical complications, readmissions, or reoperations following UE microsurgical reconstruction via free flap transfer or replantation/revascularization. Baseline diagnosis of COPD was also not a predictor of adverse 30-day outcomes following free flap transfer. Conclusion: Recent smoking history was not associated with any 30-day adverse outcomes following UE microsurgical reconstruction via replantation/revascularization or free flap transfer. In light of these findings, further investigation is warranted, with particular focus on adverse events specific to free flaps and replantation/revascularization.
All-Inside Anterior Cruciate Ligament Reconstruction Using an Anterior Half of the Peroneus Longus Tendon Autograft
Authors: Bi Mingguang , Zhao Chen , Zhang Qiong , Cao Li , Chen Xinji , Kong Mingxiang , Bi Qing
Published: June 2021

Background:

The peroneus longus tendon (PLT) has been used as a graft in many orthopaedic surgical procedures because of its comparable biomechanical strength with the native anterior cruciate ligament (ACL). Despite its potential, few studies have been performed to investigate the clinical reliability of ACL reconstruction using a PLT autograft.

Purpose:

To assess the clinical outcomes and donor-site morbidity of ACL reconstruction using an anterior half of the PLT (AHPLT) autograft in patients with an isolated ACL injury.

Study Design:

Case series; Level of evidence, 4.

Methods:

Between January 2016 and January 2017, a total of 21 patients with an isolated ACL injury underwent all-inside single-bundle ACL reconstruction using an AHPLT autograft. Knee stability was assessed using the Lachman test, pivot-shift test, and KT-2000 arthrometer (side-to-side difference) with 134-N anterior force and at 30° of knee flexion. Knee function was evaluated using the International Knee Documentation Committee score, Lysholm score, and Tegner score. Donor-site morbidity was assessed using ankle eversion and plantarflexion strength as well as the American Orthopaedic Foot & Ankle Society scoring system and the Foot and Ankle Disability Index.

Results:

At a mean final follow-up of 40.1 months (range, 36-48 months), the KT-2000 arthrometer side-to-side difference was significantly lower compared with preoperatively (1.1 ± 0.62 vs 7.0 ± 2.18 mm, respectively; P < .001). The mean preoperative International Knee Documentation Committee, Lysholm, and Tegner scores were 52.0 ± 8.27, 50.9 ± 8.50, and 1.8 ± 0.87, respectively, increasing significantly to 94.2 ± 2.61, 95.2 ± 2.64, and 6.8 ± 1.50, respectively, at final follow-up ( P < .001 for all). All patients had grade 5 muscle strength in ankle eversion and plantarflexion at the donor site, with mean American Orthopaedic Foot & Ankle Society and Foot and Ankle Disability Index scores of 96.8 and 97.6, respectively. No complications or reoperations occurred.

Conclusion:

All-inside ACL reconstruction using an AHPLT autograft produced good functional scores and stability without obvious ankle-site morbidity.
The Mental Health Effects of Cumulative Lifetime Violence in Men: Disruptions in the Capacity to Connect with Others and Finding Ways to Reengage
Authors: Taylor Petrea Lea , O’Donnell Susanne , Wuest Judith , Scott-Storey Kelly , Vincent Charlene , Malcom Jeannie
Published: June 2021

We report qualitative findings of our Men’s Violence Gender and Health Study, a multiple method study using a sequential design in which we explored the mental health manifestations of cumulative lifetime violence in men. Survey results revealed that higher cumulative lifetime violence scores were significantly associated with higher scores on depression, post-traumatic stress disorder, and anxiety in a community sample of men ( n = 685) living in Eastern Canada. To obtain a deeper understanding of men’s scores, we used an interpretive description approach to analyze data derived from 32 participant interviews. The main mental health manifestation of cumulative lifetime violence is perceptual interference, a sense of being disconnected or detached from others. This is managed by rectifying detachment, a process that includes efforts to gain connections with others. Findings suggest mental health needs in men with cumulative lifetime violence contradict gender role expectations to be stoic. Implications for nurses are explored.
Parent-Child Attachment: A Principle-Based Concept Analysis
Authors: Ali E. , Letourneau N. , Benzies K.
Published: June 2021

Introduction

Extensive evidence indicates that the quality of parent-child attachment is related to later socio-emotional and physical health outcomes. Yet, despite its clinical relevance, the parent-child attachment concept has been inconsistently applied across the disciplines of nursing, medicine and psychology and is often conflated with parent-child bonding in nursing literature.

Objectives

To provide readers with a critical analysis of the concept of parent-child attachment. Using a principle-based concept analysis, we clarify how parent-child attachment is understood from a multidisciplinary perspective to advance the use of this concept in nursing practice. Concept Description: Attachment is an affectionate, mutually satisfying relationship between a child and a caregiver that serves the purpose of making the child feel safe, secure, and protected.

Discussion

In this principle-based concept analysis, each definitional (i.e., epistemological, pragmatic, linguistic, and logical) principle contributes to an understanding of the strengths and limitations of the state of science about this concept. The discussion highlights how applying the concept of parent-child attachment security may offer exciting and promising opportunities for nursing clinical work with families.

Conclusion

The understanding of the concept of parent-child attachment differs among disciplines of nursing, medicine and psychology and offers exciting and promising opportunities for clarity and collaborative, multi-disciplinary work.
Reimagining Isolated Literacy Classrooms as Interdependent Networks: Tracing Rituals, Repetitions, and Technologies
Authors: Kleekamp Monica C.
Published: June 2021

Recent literacy scholarship increasingly seeks to center and value the literacies of systematically marginalized youth in response to deficit-oriented narratives that locate oppressed communities as incompetent or delayed. Often, this reframing leans on a contextualization of literacies as culturally, historically, and socially situated acts that people do. Located alongside recent literacy research combatting racism, homophobia, transphobia, linguicism, xenophobia, and the invisibilizing of indigenous peoples, this piece reimagines the active and rich literacies produced in an isolated (i.e., self-contained) special education literacy classroom. While theoretically utilizing situated literacies, this article also directly responds to critiques of situated literacies as too human-centric, an especially relevant criticism for classrooms with students who have complex support needs. Actor-network theory, as a theoretical and methodological lens, provides entry into the analysis of human and nonhuman actors collectively producing intricate literacy events during a curricular exploration of inclusive picturebooks (i.e., texts featuring main characters with lived dis/ability experiences). Findings presented trace two literacy events animated by actors such as students, technologies, rituals, and repetitions. Implications for this research argue for future theoretical and pedagogical framings of literacies as inherently interdependent productions, not just in isolated special education classrooms but all literacy classrooms. This shift moves away from illusive discourses of independence and autonomy and toward understandings of all literacies as interdependently shaped by endless network actors.
Post-colonial conservation of colonial built heritage in Hong Kong: A statistical analysis of historic building grading
Authors: Chau KW , Lai Lawrence WC , Chua Mark H
Published: June 2021

Based on government appointed specialists’ (Antiquities Advisory Board or AAB’s) assessments of the heritage value of more than 1400 heritage items in the Hong Kong Special Administrative Region, we found no evidence of nationalistic bias against British or Japanese built military heritage buildings and structures after the handover of Hong Kong to China in July 1997. We also found no evidence of bias in favour of imperial Chinese architecture in the postcolonial period. Incidentally, we found some evidence that suggests AAB’s assessments of heritage value for military heritage buildings and structures have increased while those for imperial Chinese architecture have decreased after 1997, which is somewhat puzzling and merits further investigation. The reasons for the results are discussed in terms of the governance of the AAB as a government appointed committee.
Surgical Macular Hole Closure Without a Gas Tamponade
Authors: Grant Scott , Adrean Sean D.
Published: June 2021

Purpose:

This work aims to evaluate the outcomes of a series of macular hole (MH) surgical procedures in patients who had pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peel and without gas tamponade.

Methods:

Patients from a retina specialty clinic who had MHs were identified for this interventional case series. Patients with small MHs were offered inclusion into the trial. Patients with larger MHs were excluded. They underwent standard 3-port PPV and ILM peel without gas or air to treat small MHs. The main outcomes that we measured were closure of MH and visual results.

Results:

Small MHs in 5 patients were managed with PPV and ILM peel alone. The average preoperative hole size at its narrowest width was 227 µm (range, 173-294 µm). Four of 5 patients (80%) had successful hole closure without a gas tamponade and improved vision; 1 patient did not have hole closure and was treated with an in-office gas bubble to close the hole. The average preoperative vision at 3 months was 20/80– (54 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and improved to 20/30–2 (73 ETDRS letters) in the 4 patients whose MHs were closed with surgery without a gas bubble. This was statistically significant ( P = .003). The hole that did not close initially without gas tamponade was the largest in the series.

Conclusions:

Patients with small MHs can be successfully treated with a vitrectomy and ILM peel alone without a gas tamponade.
Ischemia Developing in a Fibrotic Finger Following the Use of Anesthetic With Epinephrine, Salvaged by Hyperbaric Oxygen Therapy
Authors: Engwall Abigail J. , Oakes Tannur C. , Torabi Mohammad , Schank Kyle J. , Kuhns Benjamin W. , Haan Pam , Clarkson James H. W.
Published: June 2021

Background:

The use of epinephrine for hand surgery has been rising over the past decade following the popularization of Wide Awake Local Anesthetic No Tourniquet (WALANT). Traditional teaching from the 20th century forbade the use of epinephrine claiming it could induce digital ischemia, yet trial data now contradicts this assumption.

Purpose:

Digital ischemia after epinephrine injection cases are important to report because epinephrine is being used increasingly in finger anesthesia. We wish to communicate to a growing number of hand surgeons who may be new to WALANT that epinephrine may have adverse effects in a fibrotic poorly perfused environment which is salvageable by hyperbaric oxygen therapy (HBOT).

Case presentation:

A 22-year-old male sustained a crush injury resulting in right index phalanx fracture. Acute open reduction with K wire fixation was performed under WALANT using 1% lidocaine with 1:100,000 epinephrine. After removal of wires, he was found to require elective open reduction and internal fixation with bone graft for delayed union, which was performed tension free using general anesthetic plus bupivacaine and 1:200,000 epinephrine. Despite mild congestion, phentolamine was not acutely administered when it might have been justified. The patient presented to the clinic five days later with blistering ischemic necrosis of the pulp, which was salvaged by HBOT.

This case of digital ischemia following a crush injury with fibrotic scarring treated with lidocaine and epinephrine is reported as a warning to other hand surgeons performing WALANT. Epinephrine should be used with caution for digital blocks associated with scarred or fibrotic tissue and phentolamine should be used to reverse acute ischemia. HBOT can still salvage compromised tissue once the subacute process of ischemic necrosis has begun.
Political ecology and the Foucault effect: A need to diversify disciplinary approaches to ecological management?
Authors: Nustad Knut G , Swanson Heather
Published: June 2021

While explicitly Foucauldian analyses have declined in recent years in the social sciences, Foucault’s ideas continue to strongly influence scholars’ approaches to power, governance and the state. In this article, we explore how Foucauldian concepts shape the work of political ecologists and social scientists working on environmental management, multispecies ethnography and the Anthropocene – often in an unrecognized way. We argue that – regardless of whether or not Foucault’s work is explicitly cited – his legacy of linking scientific projects, population management and state control continues to have an outsized impact on thinking in these fields. It is time, we assert, to directly consider how such theoretical inheritances are affecting the shape of political ecology, in particular, and the social sciences, more generally. How, we ask, are Foucauldian traditions at once enabling and constraining more-than-human scholarship? In this article, we explore the contributions and limitations of Foucauldian approaches in environmental contexts through empirical attention to trout introduction and management efforts in South Africa. Our overall aim is to call for a deeper conversation about how scholars working on environmental topics engage the science-governance nexus. The article ends with proposing landscape, as a material enactment of more-than-human politics, as a useful analytical category to this end.
Powering racial capitalism: Electricity, rate-making, and the uneven energy geographies of Atlanta
Authors: Luke Nikki
Published: June 2021

In this paper, I bring together scholarship on racial capitalism and critical energy studies to investigate how electrification contributes to racialized uneven development. I work toward a theory of racialized electricity capital as a state-supported circuit of accumulation through corporate provision of electricity, which is basic need essential to everyday life. I develop a case study of the electrification of Atlanta, Georgia to examine the historical–geographical formation of the relationship between the city’s electric utility, Georgia Power, and the state agency that regulates the Company, the Georgia Public Service Commission. I ask how regulation functioned simultaneously to expand and differentiate electricity consumption across Atlanta and in so doing reinforce a racialized labor hierarchy and unequal access to affordable electricity. This case study emphasizes the importance of analyzing the central role of the state in allowing and perpetrating systems of energy provision that create racialized and gendered poverty. Drawing from the most recent hearings regulating electricity rates before the Commission in 2019, I bring to the fore the work of energy equity activists leading a campaign to Fight the Hike who enact demands for racial justice and a democratic energy system.
Integrating Social Entrepreneurship Literature Through Teaching
Authors: Addae Angela E. , Ellenwood Cheryl
Published: June 2021

As boundaries between the business and social sectors dissolve, social entrepreneurship has emerged as a phenomenon that bridges two worlds previously divided. Now, social entrepreneurs embrace market-based tools to address society’s greatest challenges. Coinciding with the growth of the sector, students and researchers have sought to understand development, growth strategies, and the practical challenges related to social entrepreneurship. In turn, universities have bolstered social entrepreneurship education by creating academic offerings that emphasize business, social impact, and innovation. Still, social entrepreneurship education remains in its infancy. Courses are as varied as the field itself, and instructors routinely rely on their professional backgrounds and networks to develop curricula that explore the field’s multifaceted character. Thus, social entrepreneurship courses are diverse across disciplines, and the academic literature theorizing the phenomenon is similarly emergent. As social entrepreneurship courses combine theoretical insights with experiential learning in a myriad of ways, aligning theoretical insights with necessary core competencies presents a challenge. To address this dilemma, we highlight the importance of employing theory-driven concepts to develop core competencies in social entrepreneurship students. In doing so, we review key threshold concepts in the social entrepreneurship literature and suggest how instructors might link theoretical insights to practical skill sets.
The Effects of Megaproject Social Responsibility on Participating Organizations
Authors: Ma Hanyang , Sun Daxin , Zeng Saixing , Lin Han , Shi Jonathan J.
Published: June 2021

This study focuses on the effects of megaproject social responsibility (MSR) on participating organizations’ performance. Using a survey of the participating organizations in Chinese megaprojects, this study reveals that the impact of MSR on a participant’s performance goes beyond the scope of the current megaproject. The empirical results indicate that MSR positively affects both financial and social performance of the participating organizations. The interactions of primary stakeholders weaken the positive effects of MSR on both financial and social performance, whereas the interactions of secondary stakeholders strengthen the positive effects of MSR on social performance.
CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease
Authors: Hecker Judith S. , Hartmann Luise , Rivière Jennifer , Buck Michèle C. , van der Garde Mark , Rothenberg-Thurley Maja , Fischer Luise , Winter Susann , Ksienzyk Bianka , Ziemann Frank , Solovey Maria , Rauner Martina , Tsourdi Elena , Sockel Katja , Schneider Marie , Kubasch Anne S. , Nolde Martin , Hausmann Dominikus , Paulus Alexander C. , Lützner Jörg , Roth Andreas , Bassermann Florian , Spiekermann Karsten , Marr Carsten , Hofbauer Lorenz C. , Platzbecker Uwe , Metzeler Klaus H. , Götze Katharina S.
Published: June 2021

Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA). THA-derived hip bones serve as a major source of healthy hematopoietic cells in experimental hematology. We prospectively investigated frequency and clinical associations of CH in 200 patients without known hematologic disease who were undergoing THA. Prevalence of CH was 50%, including 77 patients with CH of indeterminate potential (CHIP, defined as somatic variant allele frequencies [VAFs] ≥2%), and 23 patients harboring CH with lower mutation burden (VAF, 1% to 2%). Most commonly mutated genes were DNMT3A (29.5%), TET2 (15.0%), and ASXL1 (3.5%). CHIP is significantly associated with lower hemoglobin, higher mean corpuscular volume, previous or present malignant disease, and CVD. Strikingly, we observed a previously unreported association of CHIP with autoimmune diseases (AIDs; multivariable adjusted odds ratio, 6.6; 95% confidence interval, 1.7-30; P = .0081). These findings underscore the association between CH and inflammatory diseases. Our results have considerable relevance for managing patients with OA and AIDs or mild anemia and question the use of hip bone–derived cells as healthy experimental controls.
Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding
Authors: Saavedra Belén , Mambuque Edson , Nguenha Dinis , Gomes Neide , Munguambe Shilzia , García Juan Ignacio , Izco Santiago , Acacio Sozinho , Murias-Closas Adrià , Cossa Marta , Losada Irene , Pernas-Pardavila Hadrián , Oliveras Laura , Theron Grant , García-Basteiro Alberto L.
Published: June 2021

Aims

We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF (“Xpert”) and Xpert MTB/RIF Ultra (“Ultra”) using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique.

Methods

Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificityviatheir recategorisation to negative (in all and just among those previously treated individuals).

Results

1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90–0.98)versus0.88 (96% CI 0.82–0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71–0.93)versus0.63 (96% CI 0.48–0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95–0.97)versus0.98 (96% CI 0.97–0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22–0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252)versus2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort.

Conclusion

These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios.
The sputum transcriptome better predicts COPD exacerbations after the withdrawal of inhaled corticosteroids than sputum eosinophils
Authors: Ditz Benedikt , Sarma Aartik , Kerstjens Huib A.M. , Liesker Jeroen J.W. , Bathoorn Erik , Vonk Judith M. , Bernal Victor , Horvatovich Peter , Guryev Victor , Caldera Saharai , Langelier Chaz , Faiz Alen , Christenson Stephanie A. , van den Berge Maarten
Published: June 2021

Introduction

Continuing inhaled corticosteroid (ICS) use does not benefit all patients with COPD, yet it is difficult to determine which patients may safely sustain ICS withdrawal. Although eosinophil levels can facilitate this decision, better biomarkers could improve personalised treatment decisions.

Methods

We performed transcriptional profiling of sputum to explore the molecular biology and compared the predictive value of an unbiased gene signatureversussputum eosinophils for exacerbations after ICS withdrawal in COPD patients. RNA-sequencing data of induced sputum samples from 43 COPD patients were associated with the time to exacerbation after ICS withdrawal. Expression profiles of differentially expressed genes were summarised to create gene signatures. In addition, we built a Bayesian network model to determine coregulatory networks related to the onset of COPD exacerbations after ICS withdrawal.

Results

In multivariate analyses, we identified a gene signature (LGALS12,ALOX15,CLC,IL1RL1,CD24,EMR4P) associated with the time to first exacerbation after ICS withdrawal. The addition of this gene signature to a multiple Cox regression model explained more variance of time to exacerbations compared to a model using sputum eosinophils. The gene signature correlated with sputum eosinophil as well as macrophage cell counts. The Bayesian network model identified three coregulatory gene networks as well as sex to be related to an earlyversuslate/nonexacerbation phenotype.

Conclusion

We identified a sputum gene expression signature that exhibited a higher predictive value for predicting COPD exacerbations after ICS withdrawal than sputum eosinophilia. Future studies should investigate the utility of this signature, which might enhance personalised ICS treatment in COPD patients.
Development and validation of a mouse model of contemporary cannabis smoke exposure
Authors: Fantauzzi Matthew F. , Cass Steven P. , McGrath Joshua J.C. , Thayaparan Danya , Wang Peiyao , Stampfli Martin R. , Hirota Jeremy A.
Published: June 2021

Cannabis is widely used for both recreational and medicinal purposes. Inhalation of combusted cannabis smoke is the most common mode of drug consumption, exposing the lungs to the pharmacologically active ingredients, including tetrahydrocannabinol (THC) and cannabidiol (CBD). While the relationship between cannabis smoke exposure and compromised respiratory health has yet to be sufficiently defined, previous investigations suggest that cannabis smoke may dysregulate pulmonary immunity. Presently, there exist few preclinical animal models that have been extensively validated for contemporary cannabis smoke exposure.

 To address this need, we developed a mouse model with readouts of total particulate matter, serum cannabinoid and carboxyhaemoglobin levels, lung cellular responses, and immune-mediator production.

 Using a commercially available smoke exposure system and a cannabis source material of documented THC/CBD composition, we exposed mice to a mean±sdtotal particulate matter of 698.89±66.09 µg·L−1and demonstrate increases in serum cannabinoids and carboxyhaemoglobin. We demonstrate that cannabis smoke modulates immune cell populations and mediators in both male and female BALB/c mice. This modulation is highlighted by increases in airway and lung tissue macrophage populations, including tissue-resident alveolar macrophages, monocyte-derived alveolar macrophages, and interstitial macrophage subpopulations. No changes in airway or lung tissue infiltration of neutrophils were observed. Immune-mediator analysis indicated significant upregulation of macrophage-derived chemokine, thymus and activation-regulated chemokine, and vascular endothelial growth factor within the lung tissue of cannabis smoke-exposed mice.

 This accessible and reproducible smoke-exposure model provides a foundation to explore the impact of chronic cannabis exposures and/or co-exposures with pathogens of clinical relevance, such as influenza.
Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough
Authors: Ludbrook Valerie J. , Hanrott Kate E. , Kreindler James L. , Marks-Konczalik Joanna E. , Bird Nick P. , Hewens Debbie A. , Beerahee Misba , Behm David J. , Morice Alyn , McGarvey Lorcan , Parker Sean M. , Birring Surinder S. , Smith Jaclyn
Published: June 2021

Objective

Airway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel activation causes ATP release from airway cells, and it is hypothesised that a TRPV4-ATP-P2X3 axis contributes to chronic cough. An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough.

Methods

A two-period randomised, double blinded, placebo-controlled crossover study was designed with interim analyses for futility and sample size adjustment. Refractory chronic cough patients received either GSK2798745 or placebo once daily for 7 days with a washout between treatments. Pharmacokinetic samples were collected for analysis of GSK2798745 at end of study. The primary end-point was total cough counts assessed objectively during day-time hours (10 h) following 7 days of dosing.

Results

Interim analysis was performed after 12 participants completed both treatment periods. This showed a 32% increase in cough counts on Day 7 for GSK2798745 compared to placebo; the pre-defined negative criteria for the study were met and the study was stopped. At this point 17 participants had been enrolled (mean 61 years; 88% female), and 15 had completed the study. Final study results for posterior median cough counts showed a 34% (90% credible interval: −3%, +85%) numerical increase for GSK2798745 compared to placebo.

Conclusion

There was no evidence of an anti-tussive effect of GSK2798745. The study design allowed the decision on lack of efficacy to be made with minimal participant exposure to the investigational drug.
Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (1): specific signatures of stromal, glandular and luminal epithelial cells
Authors: Chankeaw Wiruntita , Lignier Sandra , Richard Christophe , Ntallaris Theodoros , Raliou Mariam , Guo Yongzhi , Plassard Damien , Bevilacqua Claudia , Sandra Olivier , Andersson Göran , Humblot Patrice , Charpigny Gilles
Published: June 2021

Background

A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle.

Results

In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process.

Conclusion

The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.
Morphologic and molecular correlates of EZH2 as a predictor of platinum resistance in high-grade ovarian serous carcinoma
Authors: Reid Brett M. , Vyas Shraddha , Chen Zhihua , Chen Ann , Kanetsky Peter A. , Permuth Jennifer B. , Sellers Thomas A. , Saglam Ozlen
Published: June 2021

Background

Enhancer of zesta homologue 2 (EZH2) is an essential component of polycomb repressive complex 2 (PRC2) that contributes to tumor progression and chemo-resistance. The aim of this study was to comprehensively assess the prognostic value of EZH2 across the morphologic and molecular spectra of high-grade serous ovarian carcinoma (HGSOC) by utilizing both immunohistochemistry (IHC) and proteogenomic technologies.

Methods

IHC of EZH2 was performed using a tissue microarray of 79 HGSOC scored (+/−) for lymphovascular invasion (LVI), tumor-infiltrating lymphocytic aggregates ≥1 mm (TIL) and architectural growth patterns. The association of EZH2 H-score with response to therapy and overall survival was evaluated by tumor features. We also evaluated EZH2 transcriptional (RNA sequencing) and protein (mass spectrometry) expression from bulk tumor samples from 336 HGSOC from The Cancer Genome Atlas (TCGA). EZH2 expression and co-expression networks were compared by clinical outcomes.

Results

For HGSOC without TIL (58%), EZH2 expression was almost 2-fold higher in platinum resistant tumors (P = 0.01). Conversely, EZH2 was not associated with platinum resistance among TIL+ HGSOC (P = 0.41). EZH2 expression was associated with reduced survival for tumors with LVI (P = 0.04). Analysis of TCGA found higher EZH2 expression in immunoreactive and proliferative tumors (P = 6.7 × 10− 5) although protein levels were similar across molecular subtypes (P = 0.52). Both mRNA and protein levels of EZH2 were lower in platinum resistant tumors although they were not associated with survival. Co-expression analysis revealed EZH2 networks totaling 1049 mRNA and 448 proteins that were exclusive to platinum sensitive or resistant tumors. The EZH2 network in resistant HGSOC included CARM1 which was positively correlated with EZH2 at both mRNA (r = 0.33, p = 0.003) and protein (r = 0.14, P = 0.01) levels. Further, EZH2 co-expression with CARM1 corresponded to a decreased prognostic significance of EZH2 expression in resistant tumors.

Conclusions

Our findings demonstrate that EZH2 expression varies based on its interactions with immunologic pathways and tumor microenvironment, impacting the prognostic interpretation. The association between high EZH2 expression and platinum resistance in TIL- HGSOC warrants further study of the implications for therapeutic strategies.
Perceived consequences of healthcare service decentralization on access, affordability and quality of care in Khartoum locality, Sudan
Authors: Noory Bandar , Hassanain Sara , Edwards Jeffrey , Lindskog Benedikte V.
Published: June 2021

Background

Decentralization of healthcare services has been widely utilized, especially in developing countries, to improve the performance of healthcare systems by increasing the access and efficiency of service delivery. Experiences have been variable secondary to disparities in financial and human resources, system capacity and community engagement. Sudan is no exception and understanding the perceived effect of decentralization on access, affordability, and quality of care among stakeholders is crucial.

Methods

This was a mixed method, cross-sectional, explorative study that involved 418 household members among catchment areas and 40 healthcare providers of Ibrahim Malik Hospital (IBMH) and Khartoum Teaching Hospital (KTH). Data was collected through a structured survey and in-depth interviews from July–December 2015.

Results

Access, affordability and quality of healthcare services were all perceived as worse, compared to before decentralization was implemented. Reported affordability was found to be 53 and 55% before decentralization compared to 24 to 16% after decentralization, within KTH and IBMH catchment areas respectively, (p = 0.01). The quality of healthcare services was reported to have declined from 47 and 38% before decentralization to 38 and 28% after, in KTH and IBMH respectively (p = 0.02). Accessibility was found to be more limited, with services being accessible before decentralization approximately 59 and 52% of the time, compared to 41 and 30% after, in KTH and IBMH catchment areas respectively, (p = 0.01).

Accessibility to healthcare was reported to have decreased secondary to facility closures, reverse transference of services, and low capacity of devolved facilities. Lastly, privatized services were reported as strengthened in response to this decentralization of healthcare.

Conclusions

The deterioration of access, affordability and quality of health services was experienced as the predominant perception among stakeholders after decentralization implementation. Our study results suggest there is an urgent need for a review of the current healthcare policies, structure and management within Sudan in order to provide evidence and insights regarding the impact of decentralization.
Situational analysis of diabetic retinopathy treatment Services in Ghana
Authors: Mensah-Debrah Agatha , Amissah Arthur Kwesi Nyan , Kumah David Ben , Akuffo Kwadwo Owusu , Osei Duah Isaiah , Bascaran Covadonga
Published: June 2021

Background

Although the equitable distribution of diabetic retinopathy (DR) services across Ghana remains paramount, there is currently a poor understanding of nationwide DR treatment services. This study aims to conduct a situation analysis of DR treatment services in Ghana and provide evidence on the breadth, coverage, workload, and gaps in service delivery for DR treatment.

Methods

A cross-sectional study was designed to identify health facilities which treat DR in Ghana from June 2018 to August 2018. Data were obtained from the facilities using a semi-structured questionnaire which included questions identifying human resources involved in DR treatment, location of health facilities with laser, vitreoretinal surgery and Anti–vascular endothelial growth factor therapy (Anti-VEGF) for DR treatment, service utilisation and workload at these facilities, and the average price of DR treatment in these facilities.

Results

Fourteen facilities offer DR treatment in Ghana; four in the public sector, seven in the private sector and three in the Christian Health Association of Ghana (CHAG) centres. There was a huge disparity in the distribution of facilities offering DR services, the eye care cadre, workload, and DR treatment service (retinal laser, Anti-VEGF, and vitreoretinal surgery). The retinal laser treatment price was independent of all variables (facility type, settings, regions, and National Health Insurance Scheme coverage). However, settings (p = 0.028) and geographical regions (p = 0.010) were significantly associated with anti-VEGF treatment price per eye.

Conclusion

Our results suggest a disproportionate distribution of DR services in Ghana. Hence, there should be a strategic development and implementation of an eye care plan to ensure the widespread provision of DR services to the disadvantaged population as we aim towards a disadvantaged population as we aim towards a universal health coverage.
The referral of patients to smoking cessation counselling: perceptions and experiences of healthcare providers in general practice
Authors: van Westen-Lagerweij Naomi A. , Meeuwsen Elisabeth G. , Croes Esther A. , Meijer Eline , Chavannes Niels H. , Willemsen Marc C.
Published: June 2021

Background

Few European smokers receive professional counselling when attempting to quit smoking, resulting in suboptimal success rates and poor health outcomes. Healthcare providers in general practice play an important role in referring smokers to smoking cessation counselling. We chose the Netherlands as a case study to qualitatively explore which factors play a role among healthcare providers in general practice with regard to referral for smoking cessation counselling organised both inside and outside general practice.

Methods

We conducted four focus groups and 18 telephone interviews, with a total of 31 healthcare providers who work in general practice. Qualitative content analysis was used to identify relevant factors related to referral behaviours, and each factor was linked to one of the three main components of the COM-B behaviour model (i.e., capability, opportunity and motivation) as well as the six sub-components of the model.

Results

Dutch healthcare providers in general practice typically refer smokers who want to quit to counselling inside their own general practice without actively discussing other counselling options, indicating a lack of shared decision making. The analysis showed that factors linked to the COM-B main components ‘capability’ and ‘opportunity’, such as healthcare providers’ skills and patients’ preferences, play a role in whether patients are referred to counselling inside general practice. Factors linked to all three COM-B components were found to play a role in referrals to counselling outside general practice. These included (knowledge of) the availability and quality of counselling in the region, patients’ requests, reimbursement, and sense of urgency to refer. The identified factors can both act as barriers and facilitators.

Conclusions

The findings of this research suggest that more smokers can be reached with smoking cessation counselling if implementation interventions focus on: (i) equipping healthcare providers with the knowledge and skills needed to refer patients; (ii) creating more opportunities for healthcare providers to refer patients (e.g., by improving the availability and reimbursement of counselling options); and (iii) motivating healthcare providers to discuss different counselling options with patients.