bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of routine blood alcohol tests and ICD-10-AM coding of alcohol involvement for major trauma patients
Authors: Lau Georgina , Gabbe Belinda J , Mitra Biswadev , Dietze Paul M , Braaf Sandra , Beck Ben 
Published: September 2021

Background: Alcohol use is a key preventable risk factor for serious injury. To effectively prevent alcohol-related injuries, we rely on the accurate surveillance of alcohol involvement in injury events. This often involves the use of administrative data, such as International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) coding. Objective: To evaluate the completeness and accuracy of using administrative coding for the surveillance of alcohol involvement in major trauma injury events by comparing patient blood alcohol concentration (BAC) with ICD-10-AM coding. Method: This retrospective cohort study examined 2918 injury patients aged ≥18 years who presented to a major trauma centre in Victoria, Australia, over a 2-year period, of which 78% ( n = 2286) had BAC data available. Results: While 15% of patients had a non-zero BAC, only 4% had an ICD-10-AM code suggesting acute alcohol involvement. The agreement between blood alcohol test results and ICD-10-AM coding of acute alcohol involvement was fair ( κ = 0.33, 95% confidence interval: 0.27–0.38). Of the 341 patients with a non-zero BAC, 82 (24.0%) had ICD-10-AM codes related to acute alcohol involvement. Supplementary factors Y90 Evidence of alcohol involvement determined by blood alcohol level codes, which specifically describe patient BAC, were assigned to just 29% of eligible patients with a non-zero BAC. Conclusion: ICD-10-AM coding underestimated the proportion of alcohol-related injuries compared to patient BAC. Implications: Given the current role of administrative data in the surveillance of alcohol-related injuries, these findings may have significant implications for the implementation of cost-effective strategies for preventing alcohol-related injuries.
Epidemiology of Spine Injuries in National Collegiate Athletic Association Men’s Wrestling Athletes
Authors: Brinkman Joseph C. , Tummala Sailesh V. , McQuivey Kade S. , Hassebrock Jeffrey D. , Pagdilao Christian , Makovicka Justin L. , Chhabra Anikar 
Published: September 2021

Background: Spine injuries are common in collegiate wrestlers and can lead to reinjury, persistent pain, and time lost from participation. Purpose: To describe the epidemiology of spine injuries in National Collegiate Athletic Association (NCAA) wrestlers between academic years 2009 to 2010 and 2013 to 2014. Study Design: Descriptive epidemiology study. Methods: The incidence and characteristics of spine injuries were identified utilizing the NCAA–Injury Surveillance Program database. Spine injuries were assessed for injury type, injury mechanism, time of season, event type, recurrence, participation restriction, and time lost from participation. Rates of injury were calculated as the number of injuries divided by the total number of athlete-exposures (AEs). Injury rate ratios (IRRs) were calculated for event type and time of season, and results with 95% confidence intervals that did not include 1.0 were considered statistically significant. Results: There were an estimated 2040 spine injuries reported in the database over the 4-year period, resulting in an injury rate of 0.71 per 1000 AEs. Spine injuries were over twice as likely to occur in competitions as in practices (IRR, 2.02; 95% confidence interval, 1.10-3.69). More injuries occurred in both the preseason (0.94 per 1000 AEs) and the postseason (1.12 per 1000 AEs) compared with the regular season (0.55 per 1000 AEs). Contact injuries (42%) were the most common mechanism of injury, and brachial plexus injury (20%) was the most common diagnosis. Only 1.3% of injuries required surgery, and athletes most commonly returned to sport within 24 hours (33%) or within 6 days (25%). Conclusion: This investigation found an overall injury rate of 0.71 per 1000 AEs in wrestling athletes between academic years 2009 to 2010 and 2013 to 2014. The majority of these injuries were new, and athletes most commonly returned to sport within 24 hours. The injury rate was highest in competition, and both the preseason and the postseason showed a higher injury rate than that in season. Efforts to improve injury prevention and management should be informed by these findings.
Systemic antiplatelet agents and anticoagulants in eyes with branch retinal vein occlusion
Authors: Singh Pali P. , Borkar Durga S. , Robbins Cason B. , Kim Jane S. , Birnbaum Faith , Gomez-Caraballo Maria , Thomas Akshay S. , Fekrat Sharon 
Published: September 2021

Purpose: The purpose of this study was to investigate the effect of systemic antiplatelet agents and anticoagulants on the structural and functional outcomes of eyes with branch retinal vein occlusion (BRVO). Methods: A retrospective longitudinal cohort study was performed on BRVO patients evaluated at a single tertiary care referral center between 2009 and 2017. Medical records were reviewed for antiplatelet agent and anticoagulant use including aspirin, clopidogrel, warfarin, rivaroxaban, apixaban, or dabigatran prior to BRVO onset. In addition, optical coherence tomography (OCT) parameters, clinical outcomes, and treatment patterns were also recorded. Results: A total of 354 BRVO eyes were identified with a mean follow-up time of 36 months. Antiplatelet or anticoagulant use was associated with presence of cystoid macular edema (CME) at presentation after controlling for potential confounding variables in a multivariate logistic regression. Multivariate regression also revealed an association between foveal hemorrhage at presentation and use of antiplatelet or anticoagulant medications. There were no significant differences in visual acuity or prevalence of CME at the final visit in those with antiplatelet/anticoagulant use compared to those not on these agents. Conclusion: Although the use of systemic antiplatelet or anticoagulant agents was associated with increased prevalence of CME and foveal hemorrhage at presentation of BRVO, the use of these medications was not associated with different visual or structural outcomes at the final visit.
Multiparameter phenotyping of platelet reactivity for stratification of human cohorts
Authors: Dunster Joanne L. , Bye Alexander P. , Kriek Neline , Sage Tanya , Mitchell Joanne L. , Kempster Carly , Batista Joana , McKinney Harriet , Thomas Patrick , Jones Chris I. , Downes Kate , Unsworth Amanda J. , Gibbins Jonathan M. 
Published: September 2021

Abstract
Accurate and comprehensive assessment of platelet function across cohorts of donors may be key to understanding the risk of thrombotic events associated with cardiovascular disease, and, hence, to help personalize the application of antiplatelet drugs. However, platelet function tests can be difficult to perform and analyze; they also can be unreliable or uninformative and poorly standardized across studies. The Platelet Phenomic Analysis (PPAnalysis) assay and associated open-source software platform were developed in response to these challenges. PPAnalysis utilizes preprepared freeze-dried microtiter plates to provide a detailed characterization of platelet function. The automated analysis of the high-dimensional data enables the identification of subpopulations of donors with distinct platelet function phenotypes. Using this approach, we identified that the sensitivity of a donor’s platelets to an agonist and their capacity to generate a functional response are distinct independent metrics of platelet reactivity. Hierarchical clustering of these metrics identified 6 subgroups with distinct platelet phenotypes within healthy cohorts, indicating that platelet reactivity does not fit into the traditional simple categories of “high” and “low” responders. These platelet phenotypes were found to exist in 2 independent cohorts of healthy donors and were stable on recall. PPAnalysis is a powerful tool for stratification of cohorts on the basis of platelet reactivity that will enable investigation of the causes and consequences of differences in platelet function and drive progress toward precision medicine.
Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma
Authors: Ferrari Nicola , Ward George , Gewinner Christina , Davis Matthew P. , Jueliger Simone , Saini Harpreet , Munck Joanne , Smyth Tomoko , Ferraldeschi Roberta , Keer Harold , Lyons John , Sims Martin J. 
Published: September 2021

Abstract
Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. Tolinapant has demonstrated evidence of single-agent clinical activity in relapsed/refractory peripheral TCL and cutaneous TCL. To investigate the mechanism of action underlying the single-agent activity observed in the clinic, we have used a comprehensive translational approach integrating in vitro and in vivo models of TCL confirmed by data from human tumor biopsies. Here, we show that tolinapant acts as an efficacious immunomodulatory molecule capable of inducing complete tumor regression in a syngeneic model of TCL exclusively in the presence of an intact immune system. These findings were confirmed in samples from our ongoing clinical study showing that tolinapant treatment can induce changes in gene expression and cytokine profile consistent with immune modulation. Mechanistically, we show that tolinapant can activate both the adaptive and the innate arms of the immune system through the induction of immunogenic forms of cell death. In summary, we describe a novel role for IAP antagonists as immunomodulatory molecules capable of promoting a robust antitumor immune response in TCL.
Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted
Authors: Rubinstein Jeremy D. , Zhu Xiang , Leemhuis Thomas , Pham Giang , Ray Lorraine , Emberesh Sana , Jodele Sonata , Thomas Shawn , Cancelas Jose A. , Bollard Catherine M. , Hanley Patrick J. , Keller Michael D. , Grimley Olivia , Clark Diana , Clark Teri , Lindestam Arlehamn Cecilia S. , Sette Alessandro , Davies Stella M. , Nelson Adam S. , Grimley Michael S. , Lutzko Carolyn 
Published: September 2021

Abstract
Infection with adenoviruses is a common and significant complication in pediatric patients after allogeneic hematopoietic stem cell transplantation. Treatment options with traditional antivirals are limited by poor efficacy and significant toxicities. T-cell reconstitution is critical for the management of adenoviral infections, but it generally takes place months after transplantation. Ex vivo–generated virus-specific T cells (VSTs) are an alternative approach for viral control and can be rapidly generated from either a stem cell donor or a healthy third-party donor. In the context of a single-center phase 1/2 clinical trial, we treated 30 patients with a total of 43 infusions of VSTs for adenoviremia and/or adenoviral disease. Seven patients received donor-derived VSTs, 21 patients received third-party VSTs, and 2 received VSTs from both donor sources. Clinical responses were observed in 81% of patients, with a complete response in 58%. Epitope prediction and potential epitope identification for common HLA molecules helped elucidate HLA restriction in a subset of patients receiving third-party products. Intracellular interferon-γ expression in T cells in response to single peptides and response to cell lines stably transfected with a single HLA molecule demonstrated HLA-restricted CD4+ T-cell response, and these results correlated with clinical outcomes. Taken together, these data suggest that VSTs are a highly safe and effective therapy for the management of adenoviral infection in immunocompromised hosts. The trials were registered at www.clinicaltrials.gov as #NCT02048332 and #NCT02532452.
Treatment of allosensitized patients receiving allogeneic transplantation
Authors: Ciurea Stefan O. , Al Malki Monzr M. , Kongtim Piyanuch , Zou Jun , Aung Fleur M. , Rondon Gabriela , Chen Julianne , Taniguchi Michiko , Otoukesh Salman , Nademanee Auayporn , Forman Stephen J. , Champlin Richard , Gendzekhadze Ketevan , Cao Kai 
Published: September 2021

Abstract
Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P &lt; .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA &gt; 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA &lt; 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.
Racial and ethnic enrollment disparities and demographic reporting requirements in acute leukemia clinical trials
Authors: Hantel Andrew , Luskin Marlise R. , Garcia Jacqueline S. , Stock Wendy , DeAngelo Daniel J. , Abel Gregory A. 
Published: September 2021

Abstract
Data regarding racial and ethnic enrollment diversity for acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) clinical trials in the United States are limited, and little is known about the effect of federal reporting requirements instituted in the late 2000s. We examined demographic data reporting and enrollment diversity for ALL and AML trials in the United States from 2002 to 2017, as well as changes in reporting and diversity after reporting requirements were instituted. Of 223 AML trials and 97 ALL trials with results on ClinicalTrials.gov, 68 (30.5%) and 51 (52.6%) reported enrollment by both race and ethnicity. Among trials that reported race and ethnicity (AML, n = 6554; ALL, n = 4149), non-Hispanic (NH)-Black, NH-Native American, NH-Asian, and Hispanic patients had significantly lower enrollment compared with NH-White patients after adjusting for race-ethnic disease incidence (AML odds ratio, 0.68, 0.31, 0.75, and 0.83, respectively; ALL odds ratio, 0.74, 0.27, 0.67, and 0.64; all, P ≤ .01). The proportion of trials reporting race increased significantly after implementation of the reporting requirements (44.2% to 60.2%; P = .02), but race-ethnicity reporting did not (34.8% to 38.6%; P = .57). Reporting proportions according to number of patients enrolled increased significantly after the reporting requirements were instituted (race, 51.7% to 72.7%; race-ethnicity, 39.5% to 45.4%; both, P &lt; .001), and relative enrollment of NH-Black and Hispanic patients decreased (AML odds ratio, 0.79 and 0.77; ALL odds ratio, 0.35 and 0.25; both P ≤ .01). These data suggest that demographic enrollment reporting for acute leukemia trials is suboptimal, changes in diversity after the reporting requirements may be due to additional enrollment disparities that were previously unreported, and enrollment diversification strategies specific to acute leukemia care delivery are needed.
Cancer risk in patients with sleep apnoea following adherent 5-year CPAP therapy
Authors: Justeau Grégoire , Bailly Sebastien , Gervès-Pinquié Chloé , Trzepizur Wojciech , Meslier Nicole , Goupil François , Pigeanne Thierry , Launois Sandrine , Leclair-Visonneau Laurene , Masson Philippe , Bizieux-Thaminy Acya , Racineux Jean-Louis , Gozal David , Gagnadoux Frédéric 
Published: September 2021

BackgroundIncreasing evidence suggests that obstructive sleep apnoea (OSA) contributes to cancer risk; however, limited data are available on the impact of continuous positive airway pressure (CPAP) therapy on cancer incidence. We aimed to determine whether adherence to CPAP therapy is associated with a reduction in all-cancer incidence compared with nonadherent patients with OSA.MethodsThe study relied on data collected by the multicentre Pays de la Loire Sleep Cohort study, linked to health administrative data, so as to identify new-onset cancer. We included patients who were prescribed CPAP for OSA, with no history of cancer before the diagnostic sleep study or during the first year of CPAP. Patients with documented CPAP use for ≥4 h per night were defined as adherent. Those who discontinued or used CPAP <4 h per night constituted the nonadherent group. A propensity score inverse probability of treatment weighting analysis was performed to assess the effect of CPAP adherence on cancer risk.ResultsAfter a median (interquartile range) follow-up of 5.4 (3.1–8.0) years, 437 (9.7%) out of 4499 patients developed cancer: 194 (10.7%) in the nonadherent group (n=1817) and 243 (9.1%) in adherent patients (n=2682). The final weighted model showed no significant impact of CPAP adherence on all-cause cancer risk (subdistribution hazard ratio 0.94, 95% CI 0.78–1.14).ConclusionsAdherence to CPAP therapy in OSA patients was not associated with a reduction in all-cancer incidence. Whether adherent CPAP therapy of OSA might reduce the risk of specific cancer sites should be further evaluated.
Nintedanib in progressive interstitial lung diseases: data from the whole INBUILD trial
Authors: Flaherty Kevin R. , Wells Athol U. , Cottin Vincent , Devaraj Anand , Inoue Yoshikazu , Richeldi Luca , Walsh Simon L.F. , Kolb Martin , Koschel Dirk , Moua Teng , Stowasser Susanne , Goeldner Rainer-Georg , Schlenker-Herceg Rozsa , Brown Kevin K. 
Published: September 2021

BackgroundThe primary analysis of the INBUILD trial showed that in subjects with progressive fibrosing interstitial lung diseases (ILDs), nintedanib slowed the decline in forced vital capacity (FVC) over 52 weeks. We report the effects of nintedanib on ILD progression over the whole trial.MethodsSubjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice, were randomised to receive nintedanib or placebo. Subjects continued on blinded randomised treatment until all subjects had completed the trial. Over the whole trial, mean±sdexposure to trial medication was 15.6±7.2 and 16.8±5.8 months in the nintedanib and placebo groups, respectively.ResultsIn the nintedanib (n=332) and placebo (n=331) groups, respectively, the proportions of subjects who had ILD progression (absolute decline in FVC ≥10% predicted) or died were 40.4% and 54.7% in the overall population (hazard ratio (HR) 0.66, 95% CI 0.53–0.83; p=0.0003) and 43.7% and 55.8% among subjects with a usual interstitial pneumonia (UIP)-like fibrotic pattern on high-resolution computed tomography (HRCT) (HR 0.69, 95% CI 0.53–0.91; p=0.009). In the nintedanib and placebo groups, respectively, the proportions who had an acute exacerbation of ILD or died were 13.9% and 19.6% in the overall population (HR 0.67, 95% CI 0.46–0.98; p=0.04) and 15.0% and 22.8% among subjects with a UIP-like fibrotic pattern on HRCT (HR 0.62, 95% CI 0.39–0.97; p=0.03).ConclusionBased on data from the whole INBUILD trial, nintedanib reduced the risk of events indicating ILD progression.
Cross-talk of inflammatory mediators and airway epithelium reveals the cystic fibrosis transmembrane conductance regulator as a major target
Authors: Simões Filipa B. , Kmit Arthur , Amaral Margarida D. 
Published: September 2021

Airway inflammation, mucus hyperproduction and epithelial remodelling are hallmarks of many chronic airway diseases, including asthma, COPD and cystic fibrosis. While several cytokines are dysregulated in these diseases, most studies focus on the response of airways to interleukin (IL)-4 and IL-13, which have been shown to induce mucus hyperproduction and shift the airway epithelium towards a hypersecretory phenotype.We hypothesised that other cytokines might induce the expression of chloride (Cl−) channels/transporters, and regulate epithelial differentiation and mucus production. To this end, fully differentiated human airway basal cells (BCi-NS1.1) were treated with cytokines identified as dysregulated in those diseases, namely IL-8, IL-1β, IL-4, IL-17A, IL-10 and IL-22, and tumour necrosis factor-α.Our results show that the cystic fibrosis transmembrane conductance regulator (CFTR) is the main Cl−channel modulated by inflammation, in contrast to transmembrane protein 16A (TMEM16A), whose levels only changed with IL-4. Furthermore, we identified novel roles for IL-10 and IL-22 by influencing epithelial differentiation towards ciliated cells and away from pulmonary ionocytes. In contrast, IL-1β and IL-4 reduced the number of ciliated cells while increasing club cells. Interestingly, while IL-1β, IL-4 and IL-10 upregulated CFTR expression, IL-4 was the only cytokine that increased both its function and the number of CFTR-expressing club cells, suggesting that this cell type may be the main contributor for CFTR function. Additionally, all cytokines assessed increased mucus production through a differential upregulation of MUC5AC and MUC5B transcript levels.This study reveals a novel insight into differentiation resulting from the cross-talk of inflammatory mediators and airway epithelial cells, which is particularly relevant for chronic airway diseases.
Acceptability of capnography-assisted respiratory therapy: a new mind–body intervention for COPD
Authors: Norweg Anna Migliore , Skamai Anne , Kwon Simona C. , Whiteson Jonathan , MacDonald Kyle , Haas Francois , Collins Eileen G. , Goldring Roberta M. , Reibman Joan , Wu Yinxiang , Sweeney Greg , Pierre Alicia , Troxel Andrea B. , Ehrlich-Jones Linda , Simon Naomi M. 
Published: September 2021

Dyspnoea self-management is often suboptimal for patients with COPD. Many patients with COPD experience chronic dyspnoea as distressing and disabling, especially during physical activities. Breathing therapy is a behavioural intervention that targets reducing the distress and impact of dyspnoea on exertion in daily living.Using a qualitative design, we conducted interviews with 14 patients after they participated in a novel mind–body breathing therapy intervention adjunct, capnography-assisted respiratory therapy (CART), combined with outpatient pulmonary rehabilitation. Comprehensive CART consisted of patient-centred biofeedback, tailored breathing exercises, a home exercise programme and motivational interviewing counselling. We assessed participants’ perceptions and reported experiences to gauge the acceptability of CART and refine CART based on feedback. Constant comparative analysis was used to identify commonalities and themes.We identified three main themes relating to the acceptability and reported benefits of CART: (1) self-regulating breathing; (2) impact on health; and (3) patient satisfaction. Our findings were used to refine and optimise CART (i.e.its intensity, timing and format) for COPD.By addressing dysfunctional breathing behaviours and dysregulated interoception, CART offers a promising new paradigm for relieving dyspnoea and related anxiety in patients with COPD.