bluuebunny/crossref_metadata_2025 huggingface dataset:
Spanish Validation of the Music in Dementia Assessment Scales
Authors: Forn Lourdes , Muñiz Sergi , Alavedra Cristina , Farràs-Permanyer Laia , Signo Sara , Bruna Olga
Published: March 2023

Music therapy has been described as a beneficial intervention for people with dementia. To provide a music therapy outcome measure, McDermott et al. (2015) developed the Music in Dementia Assessment Scales (MiDAS). The preliminary original validation indicated that MiDAS had acceptable to good psychometric properties. This study aimed to present the translation and cross-cultural adaptation of the MIDAS to the Spanish language and to show some validity sources using the Spanish version of the scale. MiDAS was adapted following the guidelines of Beaton et al. (2000), Muñiz et al. (2013) and Ridder et al. (2015), A psychometric validation study was conducted with a sample of 80 care home residents with moderate-severe dementia. Acceptable reliability values according to Cronbach’s alpha were obtained, as was good interobserver reliability at one rating time point, based on Kendall’s W test. The concurrent criterion validity values were positive, particularly in terms of the correlation coefficients of the criterion measure (specifically, the QoL-AD measures) and the item analysis, as shown by the correlation matrices. A one-factor confirmatory factor analysis (CFA) did not indicate a good fit for the obtained models, but acceptable and optimal values were observed for various parameters. The results indicate the usefulness of this tool, with sources of evidence of validity and reliability, although it is necessary to note the limitations of some of the results, as in the construct validity analysis. The MiDAS-ESP is a useful tool in clinical practice that can be used for measuring the effect of music therapy.
“I’ve Lost My Callouses:” A Phenomenological Investigation of Music Therapists Who Left the Profession
Authors: Silverman Michael J , Segall Lorna E , Edmonds Theo
Published: March 2023

Although changing industries is common for many professionals, there is a lack of research regarding why music therapists have left the profession. The purpose of this phenomenological investigation was to explore why music therapists in the United States left the profession and understand how music therapy academic and clinical training might be applied across a range of occupational opportunities. We interviewed eight music therapists who had worked in and left the profession for employment in other industries. We used interpretative phenomenological analysis to analyze transcripts and incorporated member checking and trustworthiness to verify our findings. The first theme described how there were multiple factors that contributed to the decision to leave the music therapy profession. The second theme described how participants grappled with the decision to leave the music therapy profession. Regarding why music therapists left the profession and how their education and training were related to their new industry, we used a modified social ecological model to depict four superordinate themes (supported by 11 themes) that described (1) individual and interpersonal factors contributing to the need for occupational change; (2) music therapy skills that facilitated occupational change; (3) unmet professional expectations that contributed to occupational change; and (4) desired changes to the music therapy curriculum for greater career flexibility. Constituting an idiosyncratic process for each participant, leaving the music therapy profession was a complex and multifaceted phenomenon. Implications for education and greater career flexibility, limitations of the study, and suggestions for future research are provided.
Etiology of Severe Acute Hepatitis in a Pediatric Transplant Center in Japan
Authors: Funaki Takanori , Yamada Masaki , Ide Kentaro , Ito Reiko , Shoji Kensuke , Ogimi Chikara , Imadome Ken-Ichi , Kasahara Mureo
Published: March 2023

The proportion of pediatric cases with severe acute hepatitis of unknown etiology in the coronavirus disease 2019 era was higher than that in the pre-coronavirus disease 2019 era in Japan’s largest pediatric transplant center. Further research and monitoring are essential.
Putting the “public” into public good
Authors: Cowan Mary , Kashef Shayda , Humpherson Ed
Published: March 2023

What is “public good” and why is it important to data for research and statistics? Ask people, say Mary Louise Cowan and Shayda Kashef
“I have loved, O Lord, the beauty of thy house’: Magnificence and Catholic Architecture in Ireland, 1850–1900
Authors: NicGhabhann Niamh
Published: March 2023

This article explores the deliberate invocation and communication of ideas of ‘magnificence’ by Catholic building projects across Ireland between 1850 and 1900. Through an analysis of the rhetoric and discourse surrounding the construction of three case studies in Tipperary, Limerick, and Armagh, the article identifies shared concerns with articulating architectural magnificence through drawing attention to the site, on architectural detail and formal style, and the high quality of building materials. This emphasis on magnificence is examined in terms of the need to justify and legitimate expansive and expensive building and re-building projects, which often relied heavily on fundraising from communities already under financial pressure. The symbolic importance of magnificence is also explored in the context of the increased focus on the church as the central location of Catholic life and worship in the second half of the nineteenth century. Finally, the decision by Catholics to invest in magnificent architectural styles that referenced the medieval cathedrals of France and the classical grandeur of Catholic Rome is repositioned. Rather that framing this as a diffuse architectural eclecticism, the use of these diverse historical exemplars is considered as part of the need to rebuild a ruptured Catholic architectural traditional in Ireland, and to create an architectural identity that expressed triumph over past adversity, as well as confidence in Ireland’s role in spreading the Catholic faith around the world.
Reconciling transparency, low Δ0-complexity and axiomatic weakness in undecidability proofs
Authors: Cantone Domenico , Omodeo Eugenio G , Panettiere Mattia
Published: March 2023

In a first-order theory $\varTheta $, the decision problem for a class of formulae $\varPhi $ is solvable if there is an algorithmic procedure that can assess whether or not the existential closure $\varphi ^{\exists }$ of $\varphi $ belongs to $\varTheta $, for any $\varphi \in \varPhi $. In 1988, Parlamento and Policriti already showed how to tailor arguments à la Gödel to a very weak axiomatic set theory, referring them to the class of $\varSigma _{1}$-formulae with $(\forall \exists \forall )_{0}$-matrix, i.e. existential closures of formulae that contain just restricted quantifiers of the forms $(\forall x \in y)$ and $(\exists x \in y)$ and are writable in prenex form with at most two alternations of restricted quantifiers (the outermost quantifier being a ‘$\forall $’). While revisiting their work, we show slightly less weak theories under which incompleteness for recursively axiomatizable extensions holds with respect to existential closures of $(\forall \exists )_{0}$-matrices, namely formulae with at most one alternation of restricted quantifiers.
Psychiatry on the Stage
Authors: Berman Carol W.
Published: March 2023

Psychology and theater have often intersected in the most interesting ways to describe characters, situations, and interactions. This book presents an overview of basic psychiatric principles applied to plays from the Greeks to Shakespeare to modern times. Included are illustrative vignettes. Technical terms are fully explained so that everyone may enjoy this book. Neuroscience is in the process of discovering how the brain longs for patterns that are found in theater and other art forms. Theatergoers may be enhancing their brains while they enjoy themselves. Practitioners in psychiatry are always referring to literature and drama to understand patients better. For instance, the Oedipal complex, a basic building block of psychoanalysis, was first illustrated in Sophocles’s Oedipus Rex. Sigmund Freud derived his understanding of psychiatric complexes from his familiarity with Greek mythology.
A uniform spherical goat (problem): explicit solution for homologous collapse’s radial evolution in time
Authors: Slepian Zachary , Philcox Oliver H E
Published: March 2023

The homologous collapse from rest of a uniform density sphere under its self gravity is a well-known toy model for the formation dynamics of astronomical objects ranging from stars to galaxies. Equally well-known is that the evolution of the radius with time cannot be explicitly obtained because of the transcendental nature of the differential equation solution. Rather, both radius and time are written parametrically in terms of the development angle θ. We here present an explicit integral solution for radius as a function of time, exploiting methods from complex analysis recently applied to the mathematically similar ‘geometric goat problem.’ Our solution can be efficiently evaluated using a Fast Fourier Transform and allows for arbitrary sampling in time, with a simple python implementation that is $\sim \, 100\times$ faster than using numerical root-finding to achieve arbitrary sampling. Our explicit solution is advantageous relative to the usual approach of first generating a uniform grid in θ, since this latter results in a non-uniform radial or time sampling, less useful for applications such as generation of sub-grid physics models. This solution is also of interest because it is the e = 1 case of Kepler’s equation. Our subsequent work extends the method here to produce a general one for solving Kepler’s equation, which turns out to be faster than any other currently extant.
Tandem organic solar cells with 20.6% efficiency enabled by reduced voltage losses
Authors: Wang Jianqiu , Zheng Zhong , Bi Pengqing , Chen Zhihao , Wang Yafei , Liu Xiaoyu , Zhang Shaoqing , Hao Xiaotao , Zhang Maojie , Li Yongfang , Hou Jianhui
Published: March 2023

Large voltage losses are the main obstacle for achieving high efficiency in organic solar cells (OSCs). Here we construct ternary OSCs by introducing an asymmetric small molecule acceptor AITC into PBDB-TCl : BTP-eC9 system and demonstrate the effectiveness in simultaneously decreasing energy disorder and non-radiative voltage losses. It is found that the introduction of AITC can modify domain size and increase the degree of crystallinity, which enhances open-circuit voltage and power conversion efficiency (19.1%, certified as 18.9%). Inspiringly, an output efficiency of 20.6% of the constructed tandem OSCs based on PBDB-TCl : AITC : BTP-eC9 ternary active layer output a recorded efficiency of 20.6% (certified as 20.3%), which is the highest value in OSCs field to date. This work demonstrates that decreasing the voltage losses by ternary strategy and constructing of tandem architecture are effective approaches towards improving photovoltaic performance.
Engaging youth and parents in clinical pediatric research: A case-based example
Authors: Martin Elise G , Rasiah Jananee , Claassen Curtis S , Waywitka Jennifer , Merritt Anne M , Pringsheim Tamara M , Shearer Kathleen A , Tsang Vivian W L , Stevens Katherine E , Sheehan-Klassen Cole E , Suddaby Perle , Orr Serena L
Published: March 2023

Background

Youth and parent engagement is a key component of clinical research. There are many ways to actively and meaningfully engage youth and parents as integral members of research teams, for example, through ad-hoc committees, advisory councils, or as co-leads on projects. When youth and parents are actively and meaningfully engaged in research projects, they share knowledge from their lived experiences to improve the quality and relevance of research.

Methods

We describe a case-based example of engaging youth and parent research partners when co-designing a questionnaire to assess preferences for pediatric headache treatments, from both a researcher and youth/parent perspective. We also summarize best practices in patient and family engagement from the literature and pertinent guidelines to assist researchers with integrating patient and family engagement into their studies.

Results

As researchers, we felt that the integration of a youth and parent engagement plan into our study significantly altered and strengthened questionnaire content validity. We encountered challenges throughout the process and detailed these experiences to help educate others about challenge mitigation and best practices in youth and parent engagement. As youth and parent partners, we felt that engaging in the process of questionnaire development was an exciting and empowering opportunity, and that our feedback was valued and integrated.

Conclusions

By sharing our experience, we hope to catalyze thought and discussion around the importance of youth and parent engagement in pediatric research, with the goal of stimulating more appropriate, relevant, and high-quality pediatric research and clinical care in the future.
Low-frequency noise mitigation and bandgap engineering using seismic metamaterials for terrestrial gravitational wave observatories
Authors: Oh John J
Published: March 2023

Gravitational waves have become one of the most important observational methods for studying the Universe since their first detection. However, ground-based observatories have an inherent barrier to their detection frequency band due to the seismic and gravity gradient noises near the perturbation of the surroundings. A recent intriguing development of artificial structures for media called metamaterial is opening a new branch of wave mechanics and its application in various fields, in particular suggesting a novel way of mitigating noises by controlling the media structure for propagating waves. In this paper, we propose a novel framework for handling noises in ground-based gravitational wave detectors by using wave mechanics under metamaterial media. Specifically, we suggest an application of the bandgap engineering technique for mitigating the underground effects of acoustic noises resulting from seismic vibration in the KAGRA gravitational wave observatory.
Adult Attachment and Personal Recovery in Clients With a Psychotic Disorder
Authors: van Bussel E M M , Wierdsma A I , van Aken B C , Willems I E M G , Mulder C L
Published: March 2023

Background

Personal recovery has become a key objective in the treatment of clients with a psychotic disorder. So far it has been established that the two attachment dimensions, ie, anxious and avoidant, are negatively associated with subjective well-being, self-esteem and hope. This study is the first to explore whether attachment styles are related to personal recovery in this population.

Aims

To study the effects of anxious and avoidant attachment on personal recovery in a population with a psychotic disorder.

Method

This cross-sectional study is part of the UP’s multicenter cohort study on recovery from psychotic disorders, in which 265 participants are currently included. Attachment was assessed using the Psychosis Attachment Measure, including the anxious and avoidant attachment dimensions. Personal recovery was measured using the Recovering Quality of Life-10 (ReQOL-10) and the Individual Recovery Outcomes Counter (I.ROC). Regression analysis was used to investigate the effect of attachment on personal recovery.

Results

We found negative effects of the anxious attachment style on the total scores of the ReQoL-10 (b = −4.54, SE = 0.69, β = β0.37) and the I.ROC (b = −5.21, SE = 0.89, β = −0.32). Although there were also negative effects of the avoidant attachment style on the total scores of the ReQoL-10 (b = −3.08, SE = 0.93, β = −0.18) and the I.ROC (b = −4.24, SE = 1.24, β = −0.19), these were less pronounced.

Conclusion

Results show that both forms of insecure attachment (anxious and avoidant) are related to poorer personal recovery in clients with a psychotic disorder.
Centres of excellence in Latin America: how do these differ from other experiences?
Authors: Corilloclla Terbullino Pavel Gabriel
Published: March 2023

Centres of excellence (CoEs), as boundary-spanning structures between universities and firms, have been promoted and studied mainly in developed countries, while some Latin American countries have recently launched CoE programmes. This study explores how CoEs in Chile and Peru have been working in terms of their internal structures and interactions. It draws upon a conceptual framework that encompasses the distinction between contexts for and channels of university–industry linkages (UILs), the defining features of CoEs, their differences with other schemes and innovation intermediaries, and the patterns shown by CoEs in developed countries. Applying this framework to analyse two CoEs, we found that these fit into the concept of contexts for UILs and differ substantially from research and technology organisations. We also found that Chilean and Peruvian CoEs share certain commonalities with their counterparts in developed countries, albeit they also show sharp differences, which have both academic and policy implications.
Racial differences in upper airway collapsibility and loop gain in young adult males
Authors: Puri Shipra , Panza Gino S , Kissane Dylan , Jones Steven , Reck Kevin , Lin Ho-Sheng , Badr M Safwan , Mateika Jason H
Published: March 2023

Study Objectives

Previous studies reported that the apnea–hypopnea index was similar in young adult Black and White participants. However, whether this similarity reflects an analogous combination of apneas and hypopneas is unknown. Likewise, the physiological mechanisms underlying this similarity has not been explored.

Methods

60 Black and 48 White males completed the study. After matching for age and body mass index, 41 participants remained in each group. All participants completed a sleep study. Subsequently, standard sleep indices along with loop gain and the arousal threshold were determined. In addition, airway collapsibility (24 of 60 and 14 of 48 participants) and the hypoxic ventilatory response during wakefulness (30 of 60 and 25 of 48 participants) was measured.

Results

The apnea–hypopnea index was similar in Blacks and Whites (p = .140). However, the index was comprised of more apneas (p = .014) and fewer hypopneas (p = .025) in Black males. These modifications were coupled to a reduced loop gain (p = .0002) and a more collapsible airway (p = .030). These differences were independent of whether or not the groups were matched. For a given hypoxic response, loop gain was reduced in Black compared to White males (p = .023).

Conclusions

Despite a similar apnea–hypopnea index, more apneas and fewer hypopneas were evident in young adult Black compared to White males. The physiological mechanisms that contribute to these events were also different between groups. Addressing these differences may be important when considering novel therapeutic approaches to eliminate apnea in Black and White participants.
Exploring research team members’ and trial participants’ perceptions of acceptability and implementation within one videoconference-based supportive care program for individuals affected by systemic sclerosis during COVID-19: a qualitative interview study
Authors: Wurz Amanda , Ellis Kelsey , Duchek Delaney , Bansal Mannat , Carrier Marie-Eve , Tao Lydia , Dyas Laura , Kwakkenbos Linda , Levis Brooke , El-Baalbaki Ghassan , Rice Danielle B , Wu Yin , Henry Richard S , Bustamante Laura , Harb Sami , Hebblethwaite Shannon , Patten Scott B , Bartlett Susan J , Varga John , Mouthon Luc , Markham Sarah , Thombs Brett D , Culos-Reed S Nicole ,   SPIN-CHAT Patient Advisory Team,   Program Facilitators
Published: March 2023

The SPIN-CHAT Program was designed to support mental health among individuals with systemic sclerosis (SSc; commonly known as scleroderma) and at least mild anxiety symptoms at the onset of COVID-19. The program was formally evaluated in the SPIN-CHAT Trial. Little is known about program and trial acceptability, and factors impacting implementation from the perspectives of research team members and trial participants. Thus, the propose of this follow-up study was to explore research team members’ and trial participants’ experiences with the program and trial to identify factors impacting acceptability and successful implementation. Data were collected cross-sectionally through one-on-one, videoconference-based, semi-structured interviews with 22 research team members and 30 purposefully recruited trial participants (Mage = 54.9, SD = 13.0 years). A social constructivist paradigm was adopted, and data were analyzed thematically. Data were organized into seven themes: (i) getting started: the importance of prolonged engagement and exceeding expectations; (ii) designing the program and trial: including multiple features; (iii) training: research team members are critical to positive program and trial experiences; (iv) offering the program and trial: it needs to be flexible and patient-oriented; (v) maximizing engagement: navigating and managing group dynamics; (vi) delivering a videoconference-based supportive care intervention: necessary, appreciated, and associated with some barriers; and (vii) refining the program and trial: considering modification when offered beyond the period of COVID-19 restrictions. Trial participants were satisfied with and found the SPIN-CHAT Program and Trial to be acceptable. Results offer implementation data that can guide the design, development, and refinement of other supportive care programs seeking to promote psychological health during and beyond COVID-19.
The implementation of ask-advise-connect in a federally qualified health center: a mixed methods evaluation using the re-aim framework
Authors: Shorey Fennell Bethany , Cottrell-Daniels Cherell , Hoover Diana Stewart , Spears Claire A , Nguyen Nga , Piñeiro Bárbara , McNeill Lorna H , Wetter David W , Vidrine Damon J , Vidrine Jennifer I
Published: March 2023

Ask-Advise-Connect (AAC) efficiently links smokers in healthcare settings with evidence-based Quitline-delivered tobacco treatment through training clinic staff to systematically ask patients about smoking status, advise smokers to quit, and connect patients with state Quitlines using the electronic health record. This study utilized a mixed-methods approach, guided by the RE-AIM framework, to evaluate the implementation of AAC in a Federally Qualified Health Center (FQHC). AAC was implemented for 18 months at a FQHC serving primarily low-socioeconomic status (SES) Latinos and Latinas. Results are presented within the RE-AIM conceptual framework which includes dimensions of reach, effectiveness, adoption, implementation, and maintenance. Quantitative patient-level outcomes of reach, effectiveness, and Impact were calculated. Post-implementation, in-depth interviews were conducted with clinic leadership and staff (N = 9) to gather perceptions and inform future implementation efforts. During the implementation period, 12.0% of GNHC patients who reported current smoking both agreed to have their information sent to the Quitline and were successfully contacted by the Quitline (Reach), 94.8% of patients who spoke with the Quitline enrolled in treatment (Effectiveness), and 11.4% of all identified smokers enrolled in Quitline treatment (Impact). In post-implementation interviews assessing RE-AIM dimensions, clinic staff and leadership identified facilitators and advantages of AAC and reported that AAC was easy to learn and implement, streamlined existing procedures, and had a positive impact on patients. Staff and leadership reported enthusiasm about AAC implementation and believed AAC fit well in the clinic. Staff were interested in AAC becoming the standard of care and made suggestions for future implementation. Clinic staff at a FQHC serving primarily low-SES Latinos and Latinas viewed the ACC implementation process positively. Findings have implications for streamlining clinical smoking cessation procedures and the potential to reduce tobacco-related disparities.
Econometric evaluation of implementing a behavioral health integration intervention in primary care settings
Authors: Nagykaldi Zsolt , Littenberg Benjamin , Bonnell Levi , Breshears Ryan , Clifton Jessica , Crocker Abigail , Hitt Juvena , Kessler Rodger , Mollis Brenda , Miyamoto Robin E S , van Eeghen Constance
Published: March 2023

Integrated behavioral health (IBH) is an approach to patient care that brings medical and behavioral health providers (BHPs) together to address both behavioral and medical needs within primary care settings. A large, pragmatic, national study aimed to test the effectiveness and measure the implementation costs of an intervention to improve IBH integration within primary care practices (IBH-PC). Assess the time and cost to practices of implementing a comprehensive practice-level intervention designed from the perspective of clinic owners to move behavioral service integration from co-location toward full integration as part of the IBH-PC study. IBH-PC program implementation costs were estimated in a representative sample of 8 practices using standard micro-econometric evaluation of activities outlined in the implementation workbook, including program implementation tasks, remote quality improvement coaching services, educational curricula, and learning community activities, over a 24-month period. The total median cost of implementing the IBH-PC program across all stages was $20,726 (range: $12,381 - $60,427). The median cost of the Planning Stage was $10,258 (range: $4,625 - $14,840), while the median cost of the Implementation Stage was $9,208 (range: $6,017 – 49,993). There were no statistically significant differences in practice or patient characteristics between the 8 selected practices and the larger IBH-PC practice sample (N=34). This study aimed to quantify the relative costs associated with integrating behavioral health into primary care. Although the cost assessment approach did not include all costs (fixed, variable, operational, and opportunity costs), the study aimed to develop a replicable and pragmatic measurement process with flexibility to adapt to emerging developments in each practice environment, providing a reasonable ballpark estimate of costs associated with implementation to help guide future executive decisions.
“No Excuses Anymore”: Substance Use Screening and Treatment for Justice-involved Youth
Authors: Goldman Paula N. , Hull Ilana , Wilson J. Deanna
Published: March 2023

Objective

The aim of this study was to present best practices for substance use disorder (SUD) screening and treatment in the juvenile justice setting.

Methods

Semistructured qualitative interviews, informed by the Capability-Opportunity-Motivation-Behavior Model, were conducted with medical and behavioral health providers with experience caring for justice-involved youth. Interviews were analyzed using thematic and content analysis to elucidate best practices and identify facilitators and barriers affecting implementation of evidence-based substance use screening and treatment.

Results

We interviewed 14 participants from 12 unique institutions and 9 states. All participants described the populations in their facilities as predominately male and minoritized, with substance use being an exceedingly common problem. Eight main themes emerged from analysis of the barriers and facilitators discussed by participants. These included the importance of (1) ensuring substance use–specific training for all team members, (2) integrating medical and behavioral health care, (3) addressing staff reticence and stigma, (4) building an institutional culture that supports screening and treatment, (5) dedicating adequate resources with respect to time, staffing, and funding, (6) formalizing and standardizing screening and treatment protocols, (7) engaging youth using trauma-informed approaches that emphasize youth strengths and autonomy, and (8) collaborating with multidisciplinary teams and community partners to maximize linkage to follow-up care after release.

Conclusions

Our findings highlight an urgent need for improved implementation of evidence-based, developmentally appropriate substance use treatment for justice-involved youth. Although the majority of participants screen youth, they described variable implementation of behavioral health interventions and limited provision of on-site withdrawal management and treatment using medications for SUD.
Effects of Sacubitril–Valsartan in Patients With Various Types of Heart Failure: A Meta-analysis
Authors: Zhang Hongyu , Huetteman Abigail T. , Reyes Eduardo A. , Appelbaum Jonathan S.
Published: March 2023

We performed a meta-analysis investigating the efficacy and adverse effects of sacubitril–valsartan in various types of heart failure including more recent studies and a larger sample size. We conducted an electronic search through Cochrane, Web of Science, PubMed, and Embase. Included studies were randomized controlled trials analyzing the efficacy of sacubitril–valsartan compared with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) in patients with heart failure. Fourteen trials were included. Pooled estimates were analyzed using RevMan 5.4.1. The odds ratio (OR) of hospitalization from worsening heart failure that compared sacubitril–valsartan with control was 0.70 (95% CI, 0.51–0.97; P = 0.03) in patients with heart failure with reduced ejection fraction (HFrEF) with a relative risk reduction (RRR) of 24.3% and absolute risk reduction (ARR) of 3.4%. In patients with heart failure with midrange (HFmEF) and preserved (HFpEF) ejection fraction, the OR was 0.80 (95% CI, 0.71–0.90; P = 0.0001) with RRR of 14.5% and ARR of 3.3%. There was a significant reduction in cardiovascular deaths (OR = 0.79; 95% CI, 0.70–0.89; P = <0.0001) and all-cause mortality (OR = 0.84; 95% CI, 0.75–0.94; P = 0.002) in patients with HFrEF, with no significant differences in patients with HFmEF and HFpEF. Hospitalization rate was significantly reduced in patients taking sacubitril–valsartan across all analyzed cohorts. Sacubitril–valsartan significantly reduced the risk of all-cause mortality and cardiovascular death in patients with HFrEF but not in patients with HFmEF/HFpEF. These findings support sacubitril–valsartan use in reducing hospitalization of patients with HFmEF and HFpEF. More studies should be performed to further analyze the efficacy of sacubitril–valsartan in patients with HFmEF/HFpEF.
Humoral response to two doses of the mRNA-1273 vaccine in Taiwanese liver transplant recipients unaffected by antimetabolites: A single-institute experience
Authors: Huang Wei , Lai Chia-Yu , Liu Hsiao-Tien , Chen Yi-Ju , Tsai Hui-Chu , Liu Po-Yu , Cheng Shao-Bin
Published: March 2023

Background

Data on the immunogenicity of mRNA vaccines in solid transplant recipients are emerging; however, data on liver transplant recipients of Taiwanese ethnicity remain limited.

Methods

We recruited 33 Taiwanese liver transplant recipients who received two doses of the Moderna mRNA-1273 vaccine and obtained blood samples for the semiquantitative determination of antibodies to the severe acute respiratory syndrome coronavirus 2 S protein RBD (receptor-binding domain) 2 weeks after each vaccination. The participants were also required to note any adverse events 1 week after the booster vaccination.

Results

Antibody response after the priming and booster doses of the mRNA-1273 vaccine was 50% and 100%, respectively. The participants were further stratified into optimal (n = 27, >250 U/mL) and inadequate (n = 6, <250 U/mL) response groups according to the upper limit of the numeric antibody titer. A shorter time after transplantation and lower estimated glomerular filtration rate were significantly associated with an inadequate titer. The postvaccination humoral response seemed unaffected by use of antimetabolites. No severe adverse events were reported.

Conclusions

The postvaccination immunogenicity of Taiwanese liver transplant recipients was satisfactory, whereas the reactogenicity to the novel vaccine was minimal.
Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers
Authors: Yoo Changhoon , Javle Milind M. , Verdaguer Mata Helena , de Braud Filippo , Trojan Jörg , Raoul Jean-Luc , Kim Jin Won , Ueno Makoto , Lee Choong-kun , Hijioka Susumu , Cubillo Antonio , Furuse Junji , Azad Nilofer , Sato Masashi , Vugmeyster Yulia , Machl Andreas , Bajars Marcis , Bridgewater John , Oh Do-Youn , Borad Mitesh J.
Published: March 2023

Background and Aims:

Biliary tract cancers are rare, heterogeneous cancers with poor prognoses. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, was evaluated in patients with locally advanced/metastatic chemorefractory biliary tract cancers.

Approach and Results:

This multicenter, single-arm, open-label, phase 2 study (NCT03833661) enrolled adults with locally advanced or metastatic biliary tract cancer that was intolerant to or had failed first-line systemic platinum-based chemotherapy. Patients received 1200 mg bintrafusp alfa intravenously Q2W. The primary endpoint was confirmed objective response according to Response Evaluation Criteria in Solid Tumors 1.1 assessed by IRC. Secondary endpoints included duration of response, durable response rate, safety, progression-free survival, and overall survival.

Between March 2019 and January 2020, 159 patients were enrolled. Median follow-up was 16.1 (range, 0.0–19.3) months; 17 patients (10.7%; 95% CI: 6.4%–16.6%) achieved an objective response. Median duration of response was 10.0 (range, 1.9–15.7) months; 10 patients (6.3%; 95% CI: 3.1%–11.3%) had a durable response (≥6 mo). Median progression-free survival was 1.8 months (95% CI: 1.7–1.8 mo); median overall survival was 7.6 months (95% CI: 5.8–9.7 mo). Overall survival rates were 57.9% (6 mo) and 38.8% (12 mo). Grade ≥3 adverse events occurred in 26.4% of patients, including one treatment-related death (hepatic failure). Frequent grade ≥3 adverse events included anemia (3.8%), pruritus (1.9%), and increased alanine aminotransferase (1.9%).

Conclusions:

Although this study did not meet its prespecified primary endpoint, bintrafusp alfa demonstrated clinical activity as second-line treatment in this hard-to-treat cancer, with durable responses and a manageable safety profile.
Epigenetic regulation of HBV-specific tumor-infiltrating T cells in HBV-related HCC
Authors: You Maojun , Gao Yanan , Fu Junliang , Xie Runze , Zhu Zhenyu , Hong Zhixian , Meng Lingzhan , Du Shunda , Liu Junliang , Wang Fu-Sheng , Yang Pengyuan , Chen Liang
Published: March 2023

Background and Aims:

HBV shapes the T-cell immune responses in HBV-related HCC. T cells can be recruited to the nidus, but limited T cells participate specifically in response to the HBV-related tumor microenvironment and HBV antigens. How epigenomic programs regulate T-cell compartments in virus-specific immune processes is unclear.

Approach and Results:

We developed Ti-ATAC-seq. 2 to map the T-cell receptor repertoire, epigenomic, and transcriptomic landscape of αβ T cells at both the bulk-cell and single-cell levels in 54 patients with HCC. We deeply investigated HBV-specific T cells and HBV-related T-cell subsets that specifically responded to HBV antigens and the HBV + tumor microenvironment, respectively, characterizing their T-cell receptor clonality and specificity and performing epigenomic profiling. A shared program comprising NFKB1/2-, Proto-Oncogene, NF-KB Sub unit, NFATC2-, and NR4A1-associated unique T-cell receptor-downstream core epigenomic and transcriptomic regulome commonly regulated the differentiation of HBV-specific regulatory T-cell (Treg) cells and CD8 + exhausted T cells; this program was also selectively enriched in the HBV-related Treg-CTLA4 and CD8-exhausted T cell-thymocyte selection associated high mobility subsets and drove greater clonal expansion in HBV-related Treg-CTLA4 subset. Overall, 54% of the effector and memory HBV-specific T cells are governed by transcription factor motifs of activator protein 1, NFE2, and BACH1/2, which have been reported to be associated with prolonged patient relapse-free survival. Moreover, HBV-related tumor-infiltrating Tregs correlated with both increased viral titer and poor prognosis in patients.

Conclusions:

This study provides insight into the cellular and molecular basis of the epigenomic programs that regulate the differentiation and generation of HBV-related T cells from viral infection and HBV + HCC unique immune exhaustion.
Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection
Authors: Jackson Carl-Christian A. , Newland Jason , Dementieva Nataliia , Lonchar Julia , Su Feng-Hsiu , Huntington Jennifer A. , Bensaci Mekki , Popejoy Myra W. , Johnson Matthew G. , De Anda Carisa , Rhee Elizabeth G. , Bruno Christopher J.
Published: March 2023

Background:

Ceftolozane/tazobactam, a cephalosporin–β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

Methods:

This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

Results:

The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: −14.3; 95% confidence interval: −26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: −19.1; 95% confidence interval: −30.18 to −2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol.

Conclusion:

Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.
Secondary single-piece toric posterior chamber intraocular lens fixation
Authors: Pandit Rahul T.
Published: March 2023

The intended axis of fixation of a dislocated TECNIS single-piece toric posterior chamber intraocular lens (PC IOL) is identified, and a marker is placed 40 degrees counterclockwise to this axis. A polypropylene suture on a straight needle is passed 2.5 mm posterior to the limbus through a scleral flap at this meridian and into the bore of the needle inserted through a paracentesis at the opposite margin, then the needle is retracted, reinserted, and captured through a second needle inserted through the scleral flap adjacent to the first suture pass, leaving a loop of suture outside of the paracentesis. The haptic of the PC IOL is externalized through another paracentesis made at the scleral flap margin. The loop of suture is pulled into the anterior chamber and out of the latter paracentesis. A cow-hitch knot is fastened around the haptic, which is then repositioned, while the suture is tightened until the PC IOL is in its final aligned position.
Cell-free DNA as a prognostic and predictive biomarker in resectable distal common bile duct cancer
Authors: Shyr Bor-Shiuan , Chen Shih-Chin , Shyr Yi-Ming , Wang Shin-E , Shyr Bor-Uei
Published: March 2023

Background:

Cell-free DNA (cfDNA) as an oncological biomarker has drawn much attention in recent years, but very limited effort has been made to investigate the prognostic values of cfDNA in distal common bile duct (CBD) cancer.

Methods:

Plasma cfDNA was measured in 67 patients with resectable distal CBD cancer. Survival outcomes and the correlation of cfDNA with other conventional prognostic factors were determined.

Results:

cfDNA levels were significantly higher in female patients, and those with poor tumor differentiation, abnormal serum carcinoembryonic antigen (CEA) level, and stage III cancer. The significant prognostic factors included a high cfDNA level (>8955 copies/mL), abnormal serum CEA level, stage III cancer, and positive resection margins. Compared with patients with high cfDNA level, those with lower cfDNA level (≤8955 copies/mL) had significantly better overall survival outcomes (74.4% vs 100% and 19.2% vs 52.6%, for 1- and 5-year survival rates, respectively, p = 0.001). The cfDNA level, perineural invasion, CEA level, and radicality were identified as independent prognostic factors for distal CBD cancer after multivariate analysis.

Conclusion:

Circulating cfDNA levels play a significant role in predicting the prognosis and survival outcome for resectable distal CBD cancer. Furthermore, acting as a promising liquid biopsy, cfDNA could serve as a prognostic and predictive biomarker in combination with current conventional markers to improve diagnostic and prognostic efficacy.
Effect of low-frequency repetitive transcranial magnetic stimulation as adjunctive treatment for insomnia patients under hypnotics: A randomized, double-blind, sham-controlled study
Authors: Lin Wei-Chen , Chen Mu-Hong , Liou Ying-Jay , Tu Pei-Chi , Chang Wen-Han , Bai Ya-Mei , Li Cheng-Ta , Tsai Shih-Jen , Hong Chen-Jee , Su Tung-Ping
Published: March 2023

Background:

Pharmacotherapy of insomnia is prescribed often but may be complicated by drug dependence. Cognitive-behavioral therapy for insomnia is effective, but requires time to take effect. Repetitive transcranial magnetic stimulation (rTMS) is effective for depression but of uncertain benefit for insomnia. We studied low-frequency rTMS of the left dorsal medial prefrontal cortex (DMPFC) as an adjunctive therapy of insomnia.

Methods:

We recruited 60 patients with insomnia, of whom 49 completed the study. We applied 1 Hz rTMS to the DMPFC in the experimental group (n = 36) and sham coil for the placebo group (n = 13). Outcome measures included objective polysomnography (PSG) and subjective Pittsburgh Sleep Quality Index (PSQI). All participants were requested to continue prescribed pharmacotherapy.

Results:

After 10 sessions of low-frequency DMPFC-rTMS, the experimental group demonstrated a reduction of duration of wake after sleep onset (WASO) from 75.4 (±53.3) to 51.2 (±75.1) min (p = 0.011). Sleep efficiency (SE) increased from 74.6% (±15.6) to 80.8% (±13.8) (p = 0.004). The sham group experienced improved SE from 79.4% (±30.7) to 88.9% (±5.6) (p = 0.039). After controlling for baseline PSG parameters and hypnotic dosage, the sham group exhibited better effects of sleep onset latency and SE than the rTMS group but no difference on PSQI.

Conclusion:

Although the effects of rTMS and sham coil on insomnia were similar (which implied significant placebo effect), low-frequency DMPFC-rTMS might offer a safe, non-invasive, and useful adjunctive therapy of insomnia by reducing WASO. The DMPFC may represent a new target for future rTMS insomnia studies.
Fatalities Involving Substance Use Among US Oil and Gas Extraction Workers Identified Through an Industry Specific Surveillance System (2014–2019)
Authors: Ramirez-Cardenas Alejandra , Wingate Kaitlin C. , Pompei Richard , King Bradley , Scott Kenneth A. , Hagan-Haynes Kyla , Chosewood L. Casey
Published: March 2023

Objective

Characteristics of oil and gas extraction (OGE) work, including long hours, shiftwork, fatigue, physically demanding work, and job insecurity are risk factors for substance use among workers. Limited information exists examining worker fatalities involving substance use among OGE workers.

Methods

The National Institute for Occupational Safety and Health’s Fatalities in Oil and Gas Extraction database was screened for fatalities involving substance use from 2014 through 2019.

Results

Twenty-six worker deaths were identified as involving substance use. Methamphetamine or amphetamine was the most common substances (61.5%) identified. Other contributing factors were lack of seatbelt use (85.7%), working in high temperatures (19.2%), and workers’ first day with the company (11.5%).

Conclusions

Employer recommendations to mitigate substance use–related risks in OGE workers include training, medical screening, drug testing, and workplace supported recovery programs.
Improving Surgical Delays Related to Pediatric Preoperative Pregnancy Testing
Authors: Alexander Morgan B. , Newsome Cassandra F. , Paton Elizabeth A. , Rhodes Leslie N.
Published: March 2023

Introduction

Preoperative pregnancy status is a vital measure necessary for patient safety. At our institution, missing or delayed pregnancy test results, measured by human chorionic gonadotropin (HCG) levels, were identified as a contributing factor to surgical delays.

Methods

A quality improvement project was initiated in 2020 at a free-standing children’s hospital after missing or delayed HCG results were identified as a cause of surgical delays. A team was created to specifically evaluate this problem and devise an intervention. As a result, an automatically generated HCG test order was established to address surgical delays associated with missing or delayed HCG test results. The automatic order is triggered when the patient’s initial admission order is activated. For female patients 9 through 11 years of age, an order is automatically generated only if the admitting physician answers “No” to the question “Is the patient premenses?” when prompted. The system automatically generates an order for all female patients greater than 12 years of age regardless of menstruation.

Results

Pre-intervention data revealed approximately 6% of surgical cases were delayed because of pregnancy test results; post-intervention data revealed approximately 2.6% of surgical cases were delayed because of pregnancy test results.

Conclusion

Initiation of an automatically generated HCG test order helped achieve the overall goal of reducing surgical delays linked to missing or delayed HCG results. Continued education and collective efforts are underway to help ensure the automatic order’s continued success.