bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2
Authors: Deodhar Atul , Gladman Dafna , Bolce Rebecca , Sandoval David , Park So Young , Leage Soyi Liu , Nash Peter , Poddubnyy Denis 
Published: August 2023

Background: Psoriatic arthritis (PsA) is a chronic inflammatory condition predominantly affecting the peripheral joints. However, some patients with PsA can experience axial involvement which is manifested with back pain and associated with increased burden of illness. Objectives: The aim of this post hoc analysis was to determine the efficacy of ixekizumab (IXE) up to 52 weeks in reducing axial symptoms in PsA patients, presenting with axial manifestations. Design: This was a post hoc analysis of two pooled phase III clinical trials. Methods: Patients with axial manifestations, from two placebo-controlled, randomized, double-blind, phase III trials (SPIRIT-P1 and SPIRIT-P2), were defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 (Q2; back pain)] total score ⩾4 and average of BASDAI Q5 + Q6 (morning stiffness) ⩾4 at baseline. For this post hoc analysis, the efficacy of IXE was evaluated at weeks 16, 24, and 52 using separate BASDAI questions (including back pain and morning stiffness), total BASDAI and modified BASDAI (mBASDAI; without Q3), Ankylosing Spondylitis Disease Activity Score (ASDAS), and 50% improvement in BASDAI (BASDAI50) response. Treatment comparisons were performed using logistic regression and analysis of covariance model for categorical and continuous end points, respectively. Results: In the post hoc analysis among PsA patients with axial manifestations at baseline ( N = 313), improvements in back pain and morning stiffness at weeks 16 and 24 were significantly greater in patients receiving IXE versus placebo (both p < 0.001). Improvements in BASDAI individual scores and total scores, mBASDAI, and ASDAS were significantly greater in patients receiving IXE compared with placebo. Similarly, significantly more IXE-treated patients achieved BASDAI50 at weeks 16 and 24 versus placebo. The effect of IXE was sustained at week 52. Similar effects were observed in sensitivity analyses subgroups. Conclusion: IXE is effective in improving axial symptoms in patients with active PsA presenting with axial manifestations.
Identifying the potential impact of a multidisciplinary outpatient antimicrobial therapy program in an area of high social vulnerability
Authors: Tan Karen K. , Hino Garret , Zhou Anna Y. , Al-Fayiz Hadeel , Rodriguez Sasha , Abdul-Mutakabbir Jacinda C. 
Published: August 2023

Background: Outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) are common practice in the management of infectious diseases (IDs). However, providing OPAT/COpAT can pose significant challenges pre- and post-discharge, particularly in vulnerable patient populations. Objectives: The objective of this study is to assess outpatient complications related to OPAT/COpAT in patients discharged with a home health services referral and to identify pre- and post-discharge intervention opportunities and the associated cost-savings that could be achieved with a multidisciplinary ID team-run OPAT/COpAT program. Design/methods: This is a retrospective cohort study of patients who were discharged with OPAT/COpAT through home health services over a 3-month study period. Data on potential pre-discharge interventions and post-discharge complications were recorded. Results: Medication-related issues were the most common pre-discharge complications, accounting for more than 50% of identified intervention opportunities. More than half of the included patients experienced at least one documented outpatient complication post-discharge with peripherally inserted central catheter-line-related complication (20.7%) being the most common issue. Using previously published cost-estimates, the implementation of a designated pre- and post-discharge OPAT/COpAT program could have saved over $100,000 over the 3-month study period. Conclusion: A multidisciplinary OPAT/COpAT program located in a high social vulnerable area can help reduce complications related to a patient’s antimicrobial therapy. Medication-related issues represent a major area for potential intervention. Our findings suggest that a multidisciplinary ID team will have ample opportunities to improve the transition of care, at both pre- and post-discharge, for patients requiring antimicrobial therapy.
Development of the Tool to Empower Parental Telling and Talking (TELL Tool): A digital decision aid intervention about children's origins from donated gametes or embryos
Authors: Hershberger Patricia E. , Gallo Agatha M. , Adlam Kirby , Driessnack Martha , Grotevant Harold D. , Klock Susan C. , Pasch Lauri , Gruss Valerie 
Published: August 2023

Objective This study aimed to create and develop a well-designed, theoretically driven, evidence-based, digital, decision Tool to Empower Parental Telling and Talking (TELL Tool) prototype. Methods This developmental study used an inclusive, systematic, and iterative process to formulate a prototype TELL Tool: the first digital decision aid for parents who have children 1 to 16 years of age and used donated gametes or embryos to establish their families. Recommendations from the International Patient Decision Aids Standards Collaboration and from experts in decision aid development, digital health interventions, design thinking, and instructional design guided the process. Results The extensive developmental process incorporated researchers, clinicians, parents, children, and other stakeholders, including donor-conceived adults. We determined the scope and target audience of the decision aid and formed a steering group. During design work, we used the decision-making process model as the guiding framework for selecting content. Parents’ views and decisional needs were incorporated into the prototype through empirical research and review, appraisal, and synthesis of the literature. Clinicians’ perspectives and insights were also incorporated. We used the experiential learning theory to guide the delivery of the content through a digital distribution plan. Following creation of initial content, including storyboards and scripts, an early prototype was redrafted and redesigned based on feedback from the steering group. A final TELL Tool prototype was then developed for alpha testing. Conclusions Detailing our early developmental processes provides transparency that can benefit the donor-conceived community as well as clinicians and researchers, especially those designing digital decision aids. Future research to evaluate the efficacy of the TELL Tool is planned.
Effectiveness of the non-face-to-face comprehensive elderly care application “smart silver care” for community-dwelling elderly: A randomized controlled trial
Authors: Hong Dahye , Lee Seon Heui 
Published: August 2023

Background Quality of life for the elderly has become an important issue, and services aimed at improving it have typically been provided face-to-face. However, coronavirus disease 2019 has limited the use of face-to-face services, and the need to convert such systems to online interfaces has emerged. Objective This study evaluates the effectiveness of a non-face-to-face comprehensive elderly care application called “Smart Silver Care.” Methods This study was designed as a randomized controlled trial. Sixty community-dwelling elderly individuals were randomly assigned to experimental and control groups in a 1:1 ratio. The participants participated in the “Smart Silver Care” intervention using a tablet and smartwatch based on the programs we provided. The participants performed five tasks, five days a week, consisting of physical, emotional, and cognitive programs. Participants could communicate with the researchers in real-time from their homes, and the researchers could remotely supervise their performance. Results We found positive effects on the relevant scales testing fall risk (Activities-Specific Balance Confidence [ABC] Scale, p = 0.028; Timed Up and Go [TUG] test, p = 0.001). However, there was no time × group interaction between the experimental and control groups on the relevant scales for depression and quality of life (Short Form-Geriatric Depression Scale [SGDS]-K: p = 0.225; EuroQol five-dimension five-level [EQ-5D-5L], p = 0.172). While the SGDS-K and EQ-5D-5L did not show statistical significance, we found improvement trends in the experimental group. Conclusions The findings of this study show that Smart Silver Care significantly improved the participants’ TUG and ABC scores in community-dwelling elderly, and a qualitative evaluation confirmed that it could be conveniently used by the elderly. Thus, Smart Silver Care offers a feasible intervention to improve the quality of life of the elderly, including physical aspects.
Why Didn’t You Walk Yesterday? Factors Associated With Slow Early Recovery After Adult Spinal Deformity Surgery
Authors: Kazarian Gregory S. , Lovecchio Francis , Merrill Robert , Clohisy John , Zhang Bo , Du Jerry , Jordan Yusef , Pajak Anthony , Knopp Rachel , Kim David , Samuel Justin , Elysee Jonathan , Akosman Izzet , Shahi Pratyush , Johnson Mitchell , Schwab Frank J. , Lafage Virginie , Kim Han Jo 
Published: August 2023

Study Design This is a retrospective case-control study. Objectives The objectives of this study are to identify (1) risk factors for delayed ambulation following adult spinal deformity (ASD) surgery and (2) complications associated with delayed ambulation. Methods One-hundred and ninety-one patients with ASD who underwent posterior-only fusion (≥5 levels, LIV pelvis) were reviewed. Patients who ambulated with physical therapy (PT) on POD2 or later (LateAmb, n = 49) were propensity matched 1:1 to patients who ambulated on POD0-1 (NmlAmb, n = 49) based on the extent of fusion and surgical invasiveness score (ASD-S). Risk factors, as well as inpatient medical complications were compared. Logistic regressions were used to identify risk factors for late ambulation. Results Of the patients who did not ambulate on POD0-1, 32% declined participation secondary to pain or dizziness/fatigue, while 68% were restricted from participation by PT/nursing due to fatigue, inability to follow commands, nausea/dizziness, pain, or hypotension. Logistic regression showed that intraoperative estimated blood loss (EBL) >2L (OR = 5.57 [1.51-20.55], P = .010) was independently associated with an increased risk of delayed ambulation, with a 1.25 times higher risk for every 250 mL increase in EBL ( P = .014). Modified 5-Item Frailty Index (mFI-5) was also independently associated with delayed ambulation (OR = 2.53 [1.14-5.63], P = .023). LateAmb demonstrated a higher hospital LOS (8.4 ± 4.0 vs 6.2 ± 2.6, P < .001). The LateAmb group trended toward an increase in medical complications on POD3+ (14.3% vs 26.5%, P = .210). Conclusions EBL demonstrates a dose-response relationship with risk for delayed ambulation. Delayed ambulation increases LOS and may impact medical complications.
Early Childhood Caries Intervention in Aboriginal Australian Children: A Cross-in Randomized Trial
Authors: Ju X. , Mittinty M.N , Smithers L. , Jamieson L. 
Published: August 2023

Introduction: Early childhood caries (ECC) is the strongest predictor of dental caries in adulthood. Indigenous children have higher levels of ECC compared with non-Indigenous children. The study aimed to estimate the efficacy of an ECC intervention among Aboriginal Australian children. Methods: Baby Teeth Talk was an outcome assessor-blinded, closed-cohort cross-in randomized controlled trial conducted in South Australia, Australia. We randomly allocated 448 women pregnant with an Aboriginal child to either an immediate (II) or delayed (DI) intervention group between January 2011 and May 2012. The immediate intervention comprised (1) provision of dental care to mothers during pregnancy; (2) application of fluoride varnish to teeth of children at ages 6, 12; and 18 mo; (3) motivational interviewing delivered in conjunction; and (4) anticipatory guidance. Mothers/children in the DI group received the same intervention commencing when the child was 24 mo of age. The outcomes were assessed by the number of decayed, missing, and filled teeth (dmft) in children aged 24, 36, and 60 mo. Regression-based approaches with generalized linear mixed effect (log-Poisson) model characterized the mean dmft to estimate risk ratios (RRs) and 95% confidence intervals (95% CIs). Results: A total of 223 participants were randomly allocated to the II group and 225 to the DI group. Three hundred sixty-five children (178 II, 187 DI) received at least 1 dental clinical examination at 24, 36, and 60 mo of follow-up. The mean dmft was lower in the II group (0.48, 1.32, and 2.06) than in the DI group (0.82, 1.90, and 3.29) at each time point, respectively. The direct ECC intervention effect was to prevent/decrease dental decay experience (dmft) occurrence by 84% (RR = 1.84, 95% CI: 1.20–2.48) after adjusting for all covariates. Conclusions: Our analysis indicated that the time-varied ECC intervention had immediate and longer-term effects on the prevention of ECC among Indigenous Australian children. Knowledge Transfer Statement: The study aimed to estimate the efficacy of an early childhood caries (ECC) intervention among Aboriginal Australian children. The findings indicated that the culturally appropriate ECC intervention is effective for the preventive of ECC and can be used by clinicians, educators, and policy makers when planning an ECC intervention, so as to prevent and reduce ECC and meet identified oral health needs across the Australian population, which is important for preventive dental care.
Exploiting the CD200-CD200R immune checkpoint axis in multiple myeloma to enhance CAR T-cell therapy
Authors: Tang Yan , Liu Wei , Kadu Siddhant , Johnson Omar , Hasanali Zainul S. , Kelly Andre , Shestov Alexander , Pajarillo Raymone , Greenblatt Eli , Holmes Matthew , Wang Li-Ping , Shih Natalie , O’Connor Roddy S. , Ruella Marco , Garfall Alfred L. , Allman David , Vogl Dan T. , Cohen Adam , June Carl H. , Sheppard Neil C. 
Published: August 2023

Abstract
Patients with multiple myeloma (MM) treated with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T cells usually relapse with BCMA+ disease, indicative of CAR T-cell suppression. CD200 is an immune checkpoint that is overexpressed on aberrant plasma cells (aPCs) in MM and is an independent negative prognostic factor for survival. However, CD200 is not present on MM cell lines, a potential limitation of current preclinical models. We engineered MM cell lines to express CD200 at levels equivalent to those found on aPCs in MM and show that these are sufficient to suppress clinical-stage CAR T-cells targeting BCMA or the Tn glycoform of mucin 1 (TnMUC1), costimulated by 4-1BB and CD2, respectively. To prevent CD200-mediated suppression of CAR T cells, we compared CRISPR-Cas9–mediated knockout of the CD200 receptor (CD200RKO), to coexpression of versions of the CD200 receptor that were nonsignaling, that is, dominant negative (CD200RDN), or that leveraged the CD200 signal to provide CD28 costimulation (CD200R-CD28 switch). We found that the CD200R-CD28 switch potently enhanced the polyfunctionality of CAR T cells, and improved cytotoxicity, proliferative capacity, CAR T-cell metabolism, and performance in a chronic antigen exposure assay. CD200RDN provided modest benefits, but surprisingly, the CD200RKO was detrimental to CAR T-cell activity, adversely affecting CAR T-cell metabolism. These patterns held up in murine xenograft models of plasmacytoma, and disseminated bone marrow predominant disease. Our findings underscore the importance of CD200-mediated immune suppression in CAR T-cell therapy of MM, and highlight a promising approach to enhance such therapies by leveraging CD200 expression on aPCs to provide costimulation via a CD200R-CD28 switch.
Severe asthma trajectories in adults: findings from the NORDSTAR cohort
Authors: von Bülow Anna , Hansen Susanne , Sandin Patrik , Ernstsson Olivia , Janson Christer , Lehtimäki Lauri , Kankaanranta Hannu , Ulrik Charlotte , Aarli Bernt Bøgvald , Geale Kirk , Tang Sheila Tuyet , Wolf Maija , Backer Vibeke , Hilberg Ole , Altraja Alan , Backman Helena , Lúdvíksdóttir Dóra , Björnsdóttir Unnur Steina , Kauppi Paula , Sandström Thomas , Sverrild Asger , Yasinska Valentyna , Kilpeläinen Maritta , Dahlén Barbro , Viinanen Arja , Bjermer Leif , Bossios Apostolos , Porsbjerg Celeste 
Published: August 2023

BackgroundThere is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma.MethodsWe conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. We identified adult patients with severe asthma in 2018 according to the European Respiratory Society/American Thoracic Society definition and used latent class analysis to identify trajectories of asthma severity over a 10-year retrospective period from 2018.ResultsAmong 169 128 asthma patients, we identified 4543 severe asthma patients. We identified four trajectories of severe asthma that were labelled as: trajectory 1 “consistently severe asthma” (n=389 (8.6%)), trajectory 2 “gradual onset severe asthma” (n=942 (20.7%)), trajectory 3 “intermittent severe asthma” (n=1685 (37.1%)) and trajectory 4 “sudden onset severe asthma” (n=1527 (33.6%)). “Consistently severe asthma” had a higher daily inhaled corticosteroid dose and more prevalent osteoporosis compared with the other trajectories. Patients with “gradual onset severe asthma” and “sudden onset severe asthma” developed type 2-related comorbidities concomitantly with development of severe asthma. In the latter group, this primarily occurred within 1–3 years preceding onset of severe asthma.ConclusionsFour distinct trajectories of severe asthma were identified illustrating different patterns of progression of asthma severity. This may eventually enable the development of better preventive management strategies in severe asthma.
Management of systemic to pulmonary shunts and elevated pulmonary vascular resistance
Authors: Linder Alexandra N. , Hsia Jill , Krishnan Sheila V. , Bacha Emile A. , Crook Sarah , Rosenzweig Erika B. , Krishnan Usha S. 
Published: August 2023

BackgroundRepair of systemic to pulmonary shunts is timed to prevent the development of irreversible pulmonary vascular disease, including in patients with other factors contributing to pulmonary hypertension. This study assessed outcomes of an individualised strategy for managing patients with mild–moderately elevated pulmonary vascular resistance (PVR) deemed borderline eligible for repair.MethodsA retrospective chart review was conducted of patients with systemic to pulmonary shunts and baseline indexed PVR (PVRi) ≥3 WU·m2treated at a single centre from 1 January 2005 to 30 September 2019. Data included demographics, World Health Organization functional class (WHO FC), medications and haemodynamic data at baseline and serial follow-up.Results30 patients (18 females) met criteria for inclusion. Median age at diagnosis of pulmonary arterial hypertension was 1.3 years (range 0.03–54 years) and at surgery was 4.1 years (range 0.73–56 years). Median follow-up time was 5.8 years (range 0.2–14.6 years) after repair. Most patients received at least one targeted pulmonary arterial therapy prior to repair and the majority (80%) underwent fenestrated shunt closure. There was a significant decrease in mean pulmonary arterial pressure (mPAP) (p<0.01), PVRi (p=0.0001) and PVR/systemic vascular resistance (p<0.01) between baseline and preoperative catheterisation and a decrease in PVRi (p<0.005), mPAP (p=0.0001) and pulmonary to systemic flow ratio (p<0.03) from baseline to most recent catheterisation. WHO FC improved from FC II–III at baseline to FC I post repair in most patients (p<0.003).ConclusionsIn carefully selected patients with systemic to pulmonary shunts and elevated PVR considered borderline for operability, the use of preoperative targeted therapy in conjunction with fenestrated or partial closure of intracardiac shunts is associated with improvement in WHO FC and clinical outcomes.
The Influence of Crystallographic Orientation and Grain Boundary on Nanoindentation Behavior of Inconel 718 Superalloy Based on Crystal Plasticity Theory
Authors: Zhu Wenbo , Yuan Guangjian , Tan Jianping , Chang Shuai , Tu Shantung 
Published: August 2023

AbstractThe crystal plasticity finite element method (CPFEM) is widely used to explore the microscopic mechanical behavior of materials and understand the deformation mechanism at the grain-level. However, few CPFEM simulation studies have been carried out to analyze the nanoindentation deformation mechanism of polycrystalline materials at the microscale level. In this study, a three-dimensional CPFEM-based nanoindentation simulation is performed on an Inconel 718 polycrystalline material to examine the influence of different crystallographic parameters on nanoindentation behavior. A representative volume element model is developed to calibrate the crystal plastic constitutive parameters by comparing the stress-strain data with the experimental results. The indentation force-displacement curves, stress distributions, and pile-up patterns are obtained by CPFEM simulation. The results show that the crystallographic orientation and grain boundary have little influence on the force-displacement curves of the nanoindentation, but significantly influence the local stress distributions and shape of the pile-up patterns. As the difference in crystallographic orientation between grains increases, changes in the pile-up patterns and stress distributions caused by this effect become more significant. In addition, the simulation results reveal that the existence of grain boundaries affects the continuity of the stress distribution. The obstruction on the continuity of stress distribution increases as the grain boundary angle increases. This research demonstrates that the proposed CPFEM model can well describe the microscopic compressive deformation behaviors of Inconel 718 under nanoindentation.