bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-occluding Candy-Plug: Implantation Technique to Obtain False Lumen Thrombosis in Chronic Aortic Dissections
Authors: Bertoglio Luca , Bilman Victor , Rohlffs Fiona , Panuccio Giuseppe , Chiesa Roberto , Kölbel Tilo 
Published: June 2022

Purpose: To describe the implantation steps of the latest generation of candy-plug device (third CP generation [CP III]) and to illustrate its possible pitfalls by discussing a case in whom this device was employed to occlude the false lumen (FL) of a chronic type B aortic dissection. Technique: A 69 year-old male patient who underwent a frozen elephant trunk arch repair due to residual type A aortic dissection developed a FL aneurysmal degeneration limited to the descending thoracic aorta. Two thoracic stent-grafts were deployed into the true lumen up to the celiac trunk origin. Then, the FL was occluded with a self-occluding CP III device (Cook Medical, Bloomington, Indiana), placed at the same level as the distal thoracic stent-graft. The distal un-stented sleeve was pushed upward to allow immediate occlusion of its central lumen, avoiding interference with reno-visceral arteries arising from the FL. Both intraoperative transesophageal echocardiography and follow-up computed tomographic angiography scan demonstrated complete FL thrombosis. Conclusion: The introduction of CP III with its self-occluding mechanism helped to shorten and standardize the procedure. However, adjunctive steps may be needed to immediately obtain FL occlusion and avoid hampering the perfusion of vessels arising from the FL.
Pharmacokinetic Evidence of Steady and Sustained Drug Release from Long-Acting Implantable Corticosteroid Matrices for Chronic Rhinosinusitis
Authors: Ow Randall A. , Shotts Steven , Kakarlapudi Venkata , McIntyre John , Naclerio Robert M. , You Changcheng , Pappas Alexander , Brayton Lindsay , Kuang Yina , Shao James 
Published: June 2022

Background The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. Objective As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. Methods Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) ( n = 12 patients) or LYR-210 (7500 µg) ( n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. Results Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. Conclusion LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.
Peripartum disease activity in moderately and severely disabled women with multiple sclerosis
Authors: Ostrem Bridget LaMonica , Anderson Annika , Conway Sarah , Healy Brian C , Oh Jiwon , Jacobs Dina , Dobson Ruth , Graham Edith Larmon , Sadovnick A Dessa , Zimmerman Vanessa , Liu Yanqing , Bove Riley , Houtchens Maria 
Published: June 2022

Background The effects of pregnancy on multiple sclerosis (MS) inflammatory activity are not well described in women with moderate to severe disabilities. Objective To quantify the peripartum annualized relapse rate (ARR) in women with MS with an Expanded Disability Status Scale (EDSS) ≥ 3. Methods We performed a retrospective cohort study of 85 pregnancies in 74 subjects with preconception EDSS ≥ 3. We quantified peripartum ARR and tested for risk factors predictive of peripartum relapses, postpartum brain magnetic resonance imaging activity (new T2 or gadolinium-enhancing lesions), and disability worsening. Results There were 74 live births, with a 56% operative delivery rate. In subjects with relapsing-remitting MS, ARR decreased to 0.11 during the third trimester of pregnancy compared to 0.59 in the year preconception and increased to 1.22 in the 3 months postpartum. Women with a higher preconception EDSS had higher odds of postpartum relapses and clinically significant worsening of disability as compared to subjects with a lower EDSS. Conclusions Moderately to severely disabled women with MS have a lower risk of relapse during pregnancy as compared to preconception, followed by a marked increase postpartum. Further studies are needed to identify ways to reduce peripartum inflammatory activity and disability progression in women with MS with moderate to severe disability.
Comparing Types of Yoga for Chronic Low Back and Neck Pain in Military Personnel: A Feasibility Randomized Controlled Trial
Authors: Groessl Erik J , Casteel Danielle , McKinnon Symone , McCarthy Adhana , Schmalzl Laura , Chang Douglas G , Fowler Ian M , Park Crystal L 
Published: June 2022

Background Chronic low back pain (cLBP) and chronic neck pain (cNP) are highly prevalent conditions and common reasons for disability among military personnel. Yoga and other mind-body interventions have been shown to safely decrease pain and disability in persons with cLBP and/or cNP but have not been adequately studied in active duty military personnel. The objective of this study was to examine the feasibility and acceptability of delivering 2 types of yoga (hatha and restorative) to a sample of active-duty military personnel with cLBP/cNP. Methods Military personnel with cLBP and/or cNP (n = 49; 59% men) were randomized to either hatha or restorative yoga interventions. Interventions consisted of in-person yoga 1-2x weekly for 12 weeks. Feasibility and acceptability were measured by rates of recruitment, intervention attendance, attrition, adverse events, and satisfaction ratings. Health outcomes including pain and disability were measured at baseline, 12 weeks, and 6 months. Means and effect sizes are presented. Results Recruitment was completed ahead of projections. Over 90% of participants agreed or strongly agreed that they enjoyed participation, liked the instructor, and would like to continue yoga. Retention rates were 86% and 80% at 12 week and 6 month assessments, respectively. Intervention attendance was adequate but lower than expected. There were small to moderate reductions in back-pain related disability, pain severity and pain interference, and improvements in quality of life, grip strength, and balance. In general, effects were larger for those who attended at least 50% of intervention classes. Participants with cNP tended to have smaller outcome improvements, but conclusions remain tentative given small sample sizes. Conclusions Results demonstrate feasibility for conducting a randomized controlled comparative effectiveness trial of yoga for cLBP and cNP among active duty military personnel. Acceptability was also established. Ongoing work will enhance the intervention for cNP and establish feasibility at another military facility in preparation for a fully-powered comparative effectiveness trial. ClinicalTrials #NCT03504085; registered April 20, 2018.
Variation in General Dentists’ Patterns of Sealant Use in Children with Elevated Caries Risk
Authors: McKernan S.C. , Momany E.T. , Sukalski J.M.C. , Jones M.P. , Damiano P.C. , Kuthy R.A. 
Published: June 2022

Introduction: Strong evidence supports use of dental sealants to prevent tooth decay, and professional guidelines recommend use in children with elevated caries risk. However, not all children indicated for sealants receive this preventive intervention, even when they use routine dental care. Objective: The aim of this study was to explore the extent to which dentists’ use of sealants varied in pediatric patients with elevated caries risk. Methods: Claims and enrollment data from a private dental program were used to identify a cohort of 6- to 17-y-olds with elevated caries risk (N = 27,677) and general dentists (N = 818) who provided services to the children. Children were identified as having elevated caries risk based on history of restorative treatment over a 5-y period (2010–2014). The 2 outcomes of interest were whether a dentist provided any sealants to children with elevated risk and, if so, the extent to which these were used during a 2-y observation period (2013–2014). A 2-stage hurdle model was used for multivariable analysis to identify dentist characteristics associated with sealant use. Results: Over the observation period, 13.3% (n = 109) of dentists did not provide any sealants to their elevated risk patients from the study cohort. Logistic regression found that female dentists were significantly more likely to have used sealants (odds ratio = 2.27); dentist age and practice in an isolated small rural town were negatively associated with any sealant use. However, among dentists who did place sealants (n = 709), female dentists, older dentists, dentists in solo practice, and those working full-time were significantly more likely to provide sealants to a child. Overall, substantial variation in practitioners’ use of sealants was observed. Conclusion: This is the first study to explore provider-level variation in sealant use, representing a critical step in future efforts to increase routine use of sealants by dentists and eliminate oral health disparities. Knowledge Transfer Statement: Findings from this study can be used to design targeted policy and behavioral interventions to increase sealant use by general dentists. This study provides foundational evidence for future research that explores motivation and barriers to routine use of preventive dental interventions by clinicians.
Single-cell multiomics reveal the scale of multilayered adaptations enabling CLL relapse during venetoclax therapy
Authors: Thijssen Rachel , Tian Luyi , Anderson Mary Ann , Flensburg Christoffer , Jarratt Andrew , Garnham Alexandra L. , Jabbari Jafar S. , Peng Hongke , Lew Thomas E. , Teh Charis E. , Gouil Quentin , Georgiou Angela , Tan Tania , Djajawi Tirta M. , Tam Constantine S. , Seymour John F. , Blombery Piers , Gray Daniel H. D. , Majewski Ian J. , Ritchie Matthew E. , Roberts Andrew W. , Huang David C. S. 
Published: June 2022

AbstractVenetoclax (VEN) inhibits the prosurvival protein BCL2 to induce apoptosis and is a standard therapy for chronic lymphocytic leukemia (CLL), delivering high complete remission rates and prolonged progression-free survival in relapsed CLL but with eventual loss of efficacy. A spectrum of subclonal genetic changes associated with VEN resistance has now been described. To fully understand clinical resistance to VEN, we combined single-cell short- and long-read RNA-sequencing to reveal the previously unappreciated scale of genetic and epigenetic changes underpinning acquired VEN resistance. These appear to be multilayered. One layer comprises changes in the BCL2 family of apoptosis regulators, especially the prosurvival family members. This includes previously described mutations in BCL2 and amplification of the MCL1 gene but is heterogeneous across and within individual patient leukemias. Changes in the proapoptotic genes are notably uncommon, except for single cases with subclonal losses of BAX or NOXA. Much more prominent was universal MCL1 gene upregulation. This was driven by an overlying layer of emergent NF-κB (nuclear factor kappa B) activation, which persisted in circulating cells during VEN therapy. We discovered that MCL1 could be a direct transcriptional target of NF-κB. Both the switch to alternative prosurvival factors and NF-κB activation largely dissipate following VEN discontinuation. Our studies reveal the extent of plasticity of CLL cells in their ability to evade VEN-induced apoptosis. Importantly, these findings pinpoint new approaches to circumvent VEN resistance and provide a specific biological justification for the strategy of VEN discontinuation once a maximal response is achieved rather than maintaining long-term selective pressure with the drug.
European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases
Authors: Korevaar Daniël A. , Colella Sara , Fally Markus , Camuset Juliette , Colby Thomas V. , Hagmeyer Lars , Hetzel Juergen , Maldonado Fabien , Morais Antonio , Ravaglia Claudia , Spijker René , Tomassetti Sara , Troy Lauren K. , Verschakelen Johny A. , Wells Athol U. , Tonia Thomy , Annema Jouke T. , Poletti Venerino 
Published: June 2022

BackgroundIn patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD.MethodsThe ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied.ResultsIn patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required.ConclusionsTBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly “very low”.
Impact of wait times for treatment on clinical outcomes in patients with obstructive sleep apnoea: protocol for a randomised controlled trial
Authors: Thornton Christina S. , Povitz Marcus , Tsai Willis H. , Loewen Andrea H. , Ip-Buting Ada , Kendzerska Tetyana , Flemons W. Ward , Fraser Kristin L. , Hanly Patrick J. , Pendharkar Sachin R. 
Published: June 2022

BackgroundObstructive sleep apnoea (OSA) is a common chronic condition that is associated with significant morbidity and economic cost. Prolonged wait times are increasingly being recognised as a barrier to diagnosis and treatment of many chronic diseases; however, no study to date has prospectively evaluated the impact of wait times on health outcomes in OSA.ObjectiveThe purpose of this study is to determine whether treatment outcomes for individuals with OSA differ between patients managed using an expeditedversusstandard pathway.MethodsA pragmatic randomised controlled trial design will be used with a target sample size of 200 adults. Participants with clinically significant uncomplicated OSA will be recruited through referrals to a large tertiary care sleep centre (Calgary, AB, Canada) and randomised to either early management (within 1 month) or usual care (∼6 months) with a 1:1 allocation using a concealed computer-generated randomisation sequence. The primary outcome will be adherence to positive airway pressure (PAP) therapy at 3 months after treatment initiation. Secondary outcomes will include change in sleepiness, quality of life, patient satisfaction, and patient engagement with therapy from baseline to 3 months after PAP initiation, measured using validated questionnaires and qualitative methods.Anticipated resultsThis study will determine whether expedited care for OSA leads to differences in PAP adherence and/or patient-reported outcomes. More broadly, the findings of this study may improve the understanding of how wait time reductions impact health outcomes for other chronic diseases.
Real-life burden of hospitalisations due to COPD exacerbations in Spain
Authors: Izquierdo José Luis , Rodríguez José Miguel , Almonacid Carlos , Benavent María , Arroyo-Espliguero Ramón , Agustí Alvar 
Published: June 2022

BackgroundPatients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation of symptoms (ECOPD) that may eventually require hospitalisation due to several, often overlapping, causes. We aimed to analyse the characteristics of patients hospitalised because of ECOPD in a real-life setting using a “big data” approach.MethodsThe study population included all patients over 40 years old with a diagnosis of COPD (n=69 359; prevalence 3.72%) registered from 1 January 2011 to 1 March 2020 in the database of the public healthcare service (SESCAM) of Castilla-La Mancha (Spain) (n=1 863 759 subjects). We used natural language processing (Savana Manager version 3.0) to identify those who were hospitalised during this period for any cause, including ECOPD.ResultsDuring the study 26 453 COPD patients (38.1%) were hospitalised (at least once). Main diagnoses at discharge were respiratory infection (51%), heart failure (38%) or pneumonia (19%). ECOPD was the main diagnosis at discharge (or hospital death) in 8331 patients (12.0% of the entire COPD population and 31.5% of those hospitalised). In-hospital ECOPD-related mortality rate was 3.11%. These patients were hospitalised 2.36 times per patient, with a mean hospital stay of 6.1 days. Heart failure was the most frequent comorbidity in patients hospitalised because of ECOPD (52.6%).ConclusionsThis analysis shows that, in a real-life setting, ECOPD hospitalisations are prevalent, complex (particularly in relation to heart failure), repetitive and associated with significant in-hospital mortality.
Trends and predictors of specialist assessments in oral corticosteroid treated asthma among young adults
Authors: Skov Inge Raadal , Madsen Hanne , Andersen Jacob Harbo , Pottegård Anton , Davidsen Jesper Rømhild 
Published: June 2022

BackgroundRepeated oral corticosteroid use indicates uncontrolled disease among asthma patients, and referral for asthma specialist assessment is recommended. We aimed to describe trends and predictors associated with specialist contacts among young adults with asthma and repeated oral corticosteroid use.MethodsIndividuals aged 18–45 years with two or more dispensed asthma medication prescriptions and two dispended oral corticosteroid prescriptions (including short-term and long-term treatments) within 12 months during 1999–2018 were identified by use of Danish healthcare registers. The frequency of specialist contacts within 1 year of follow-up was assessed among individuals without previous specialist contacts within 5 years of inclusion. Factors associated with specialist contact were identified using logistic regression models. Furthermore, oral corticosteroid prescriber sources were assessed.ResultsFor the 11 223 individuals included, 2444 (22%) had previous specialist-contact care within 5 years prior of inclusion, and additionally 926 (8.3%) within 1 year of follow-up. Among those without previous specialist contacts (n=8779), the frequency of incident specialist contacts within 1 year of follow-up increased from 6.3% in 1999 to 18% in 2017. Factors associated with incident specialist contacts included dispensing ≥12 short-acting β-agonist canisters and previous asthma-related emergency department visits and hospitalisations. The majority of oral corticosteroid prescriptions at baseline (71%) were prescribed by general practitioners, although with decreasing proportions from 1999 to 2018.ConclusionsThe majority (70%) of young adults with asthma and repeated oral corticosteroid use do not seem to receive specialist assessment in Denmark. This highlights a potential room for improvement in the patient referral pathway for at-risk asthma patients.
Increased monocyte level is a risk factor for radiological progression in patients with early fibrotic interstitial lung abnormality
Authors: Achaiah Andrew , Lyon Paul , Fraser Emily , Saunders Peter , Hoyles Rachel , Benamore Rachel , Ho Ling-Pei 
Published: June 2022

BackgroundInterstitial lung abnormalities (ILA) are specific spatial patterns on computed tomography (CT) scan potentially compatible with early interstitial lung disease. A proportion will progress; management involves risk stratification and surveillance. Elevated blood monocyte levels have been shown to associate with progression of idiopathic pulmonary fibrosis. The aims of the present study were: 1) to estimate the proportion of “early fibrotic” (EF)-ILAs (reticular±ground-glass opacities, excluding traction bronchiectasis and honeycombing) on CT scans of patients attending all-indications thoracic CTs, and proportion demonstrating radiological progression; and 2) to explore association between peripheral blood leukocyte levels and ILA progression.MethodsWe analysed all thoracic CT reports in individuals aged 45–75 years performed between January 2015 and December 2020 in one large teaching hospital (Oxford, UK) to identify patient CT reports consistent with EF-ILA. CT-contemporaneous blood leukocyte counts were examined to explore contribution to progression and all-cause mortality, using multivariate Cox regression.Results40 711 patients underwent thoracic CT imaging during this period. 1259 (3.1%) demonstrated the EF-ILA pattern (mean±sdage 65.4±7.32 years; 735 (47.8%) male). EF-ILA was significantly associated with all-cause mortality (hazard ratio 1.87, 95% CI 1.25–2.78; p=0.002). 362 cases underwent at least one follow-on CT. Radiological progression was observed in 157 (43.4%) cases: increase in reticulation n=51, new traction bronchiectasis n=84, honeycombing n=22. Monocyte count, neutrophil count, monocyte:lymphocyte ratio, neutrophil:lymphocyte ratio and “systemic inflammatory response index” were significantly associated with radiological progression.Conclusion3.1% of subjects requiring thoracic CT during a 6-year period demonstrated EF-ILA. Monocyte levels and blood leukocyte-derived indexes were associated with radiological progression and could indicate which patients may require closer follow-up.