bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of a novel polyoxazoline-based hemostatic patch in liver and spleen surgery
Authors: Roozen Edwin A. , Lomme Roger M. L. M. , Calon Nicole U. B. , ten Broek Richard P. G. , van Goor Harry
Published: March 2023

Background

A new hemostatic sealant based on a N-hydroxy-succinimide polyoxazoline (NHS-POx) polymer was evaluated to determine hemostatic efficacy and long-term wound healing and adverse effects in a large animal model of parenchymal organ surgical bleeds.

Methods

Experiment 1 included 20 pigs that were treated with two NHS-POx patch prototypes [a gelatin fibrous carrier (GFC) with NHS-POx and an oxidized regenerated cellulose (ORC) with poly(lactic-co-glycolic acid)-NHS-POx:NU-POx (nucleophilically activated polyoxazoline)], a blank gelatin patch (GFC Blank), TachoSil® and Veriset™ to stop moderate liver and spleen punch bleedings. After various survival periods (1–6 weeks), pigs were re-operated to evaluate patch degradation and parenchymal healing. During the re-operation, experiment 2 was performed: partial liver and spleen resections with severe bleeding, and hemostatic efficacy was evaluated under normal and heparinized conditions of the two previous prototypes and one additional NHS-POx patch. In the third experiment an improved NHS-POx patch (GATT-Patch; GFC-NHS-POx and added 20% as nucleophilically activated polyoxazoline; NU-POx) was compared with TachoSil®, Veriset™ and GFC Blank on punch bleedings and partial liver and spleen resections for rapid (10s) hemostatic efficacy.

Results

NHS-POx-based patches showed better (GFC-NHS-POx 83.1%, ORC-PLGA-NHS-POx: NU-POx 98.3%) hemostatic efficacy compared to TachoSil® (25.0%) and GFC Blank (43.3%), and comparable efficacy with Veriset™ (96.7%) on moderate standardized punch bleedings on liver and spleen. All patches demonstrated gradual degradation over 6 weeks with a reduced local inflammation rate and an improved wound healing. For severe bleedings under non-heparinized conditions, hemostasis was achieved in 100% for Veriset™, 40% for TachoSil and 80–100% for the three NHS-POx prototypes; similar differences between patches remained for heparinized conditions. In experiment 3, GATT-Patch, Veriset™, TachoSil and GFC Blank reached hemostasis after 10s in 100%, 42.8%, 7.1% and 14.3%, respectively, and at 3 min in 100%, 100%, 14.3% and 35.7%, respectively, on all liver and spleen punctures and resections.

Conclusions

NHS-POx-based patches, and particularly the GATT-Patch, are fast in achieving effective hemostatic sealing on standardized moderate and severe bleedings without apparent long-term adverse events.
Kai-Xin-San protects against mitochondrial dysfunction in Alzheimer’s disease through SIRT3/NLRP3 pathway
Authors: Su ShiJie , Chen Gongcan , Gao Minghuang , Zhong Guangcheng , Zhang Zerong , Wei Dongyun , Luo Xue , Wang Qi
Published: March 2023

Background

Kai-Xin-San (KXS) has been reported to have a good curative impact on dementia. The purpose of the study was to determine whether KXS might ameliorate cognitive deficits in APP/PS1 mice and to evaluate its neuroprotective mechanism.

Methods

APP/PS1 mice were employed as an AD animal model; Aβ1–42 and KXS-containing serum were used in HT22 cells. Four different behavioral tests were used to determine the cognitive ability of mice. Nissl staining was utilized to detect hippocampal neuron changes. ROS, SOD, and MDA were used to detect oxidative stress levels. Transmission electron microscopy and Western blot were used to evaluate mitochondrial morphology, mitochondrial division, and fusion state. Western blotting and immunofluorescence identified PSD95, BDNF, NGF, SYN, SIRT3, and NLRP3 inflammasome levels.

Results

The results indicated that KXS protected APP/PS1 mice against cognitive impairments. KXS suppressed neuronal apoptosis and oxidative stress among APP/PS1 mice. KXS and KXS-containing serum improved mitochondrial dysfunction and synaptic and neurotrophic factors regarding APP/PS1 mice. In addition, KXS and KXS-containing serum enhanced mitochondrial SIRT3 expression and reduced NLRP3 inflammasome expression in APP/PS1 mice.

Conclusion

KXS improves cognitive dysfunction among APP/PS1 mice via regulating SIRT3-mediated neuronal cell apoptosis. These results suggested that KXS was proposed as a neuroprotective agent for AD progression.
Individualized peer support needs assessment for families with eating disorders
Authors: Ohara Chisato , Nishizono-Maher Aya , Sekiguchi Atsushi , Sugawara Ayako , Morino Yuriko , Kawakami Junko , Hotta Mari
Published: March 2023

Background

Peer support among family members is important in cases of mental illness, but there has been limited practice or research on individual peer support specific to families taking care of patients with eating disorders (EDs). To conduct peer support activities, it is necessary to clarify the needs of families.

Objectives

The objective of this study are to identify the needs for group and individual peer support and the characteristics of family members with EDs who are willing to receive and provide individual peer support.

Method

A cross-sectional questionnaire survey was conducted for family members with EDs recruited via the Internet. The questionnaires included demographic information on respondents and their patients, questions about the need for family peer support, interest in offering peer support, and social resources. All participants were given the General Health Questionnaire (GHQ-12), the Zarit Caregiver Burden Interview (J-ZBI_8), and the Anorectic Behavior Observation Scale (ABOS).

Results

Out of 314 respondents, 87.3% believed that a group peer support system was necessary, whereas 56.7% believed that an individual peer support system was necessary. As to whether they want to use individual peer support, 70 (22.4%) stated “Extremely YES” and 99 (31.7%) stated “Moderately YES.” Family members who were willing to receive individual peer support used more social resources and had higher scores on the GHQ and J-ZBI_8. Regarding the provision of peer support, 38 (12.2%) responded “very interested and willing to provide it if possible” and 87 (27.9%) responded “interested and willing to study.” Those with a high willingness to provide peer support used more social resources and had lower ABOS scores; however, 38 respondents (45.7%) exceeded the GHQ mental health screening cutoff (3/4).

Conclusion

Family members with ED had a strong need for family peer support Those willing to receive individual peer support suffered from poor mental health and high burden of care. Family members willing to provide peer support tended to have patients whose EDs symptoms had already improved, but their own mental health was not necessarily good. Training for potential peer supporters is needed to implement peer support.
Access to mental health and addiction services for youth and their families in Ontario: perspectives of parents, youth, and service providers
Authors: Kourgiantakis Toula , Markoulakis Roula , Lee Eunjung , Hussain Amina , Lau Carrie , Ashcroft Rachelle , Goldstein Abby L. , Kodeeswaran Sugy , Williams Charmaine C. , Levitt Anthony
Published: March 2023

Background

Canadian youth (aged 16–24) have the highest rates of mental health and addiction concerns across all age groups and the most unmet health care needs. There are many structural barriers that contribute to the unmet mental health care needs of youth including lack of available and appropriate services, high costs, long wait times, fragmented and siloed services, lack of smooth transition between child and adult services, stigma, racism, and discrimination, as well as lack of culturally appropriate treatments. Levesque et al. (2013) developed a framework to better understand health care access and this framework conceptualizes accessibility across five dimensions: (1) approachability, (2) availability, (3) affordability, (4) appropriateness, and (5) acceptability. The purpose of this study was to explore access to addiction and mental health services for youth in Ontario, Canada from the perspectives of youth, parents, and service providers.

Methods

This qualitative study was a university-community partnership exploring the experiences of youth with mental health concerns and their families from the perspectives of youth, caregivers, and service providers. We conducted semi-structured interviews and used thematic analysis to analyze data.

Results

The study involved 25 participants (n = 11 parents, n = 4 youth, n = 10 service providers). We identified six themes related to structural barriers impacting access to youth mental health and services: (1) “The biggest barrier in accessing mental health support is where to look,” (2) “There’s always going to be a waitlist,” (3) “I have to have money to be healthy,” (4) “They weren’t really listening to my issues,” (5) “Having more of a welcoming and inclusive system,” and (6) “Health laws aren’t doing what they need to do.”

Conclusion

Our study identified five structural barriers that map onto the Levesque et al. healthcare access conceptual framework and a sixth structural barrier that is not adequately captured by this model which focuses on policies, procedures, and laws. The findings have implications for policies and service provisions, and underline the urgent need for a mental health strategy that will increase access to care, improve mental health in youth, decrease burden on parents, and reduce inequities in mental health policies and services.
RET signaling in breast cancer therapeutic resistance and metastasis
Authors: Pecar Geoffrey , Liu Simeng , Hooda Jagmohan , Atkinson Jennifer M. , Oesterreich Steffi , Lee Adrian V.
Published: March 2023

RET, a single-pass receptor tyrosine kinase encoded on human chromosome 10, is well known to the field of developmental biology for its role in the ontogenesis of the central and enteric nervous systems and the kidney. In adults, RET alterations have been characterized as drivers of non-small cell lung cancer and multiple neuroendocrine neoplasms. In breast cancer, RET signaling networks have been shown to influence diverse functions including tumor development, metastasis, and therapeutic resistance. While RET is known to drive the development and progression of multiple solid tumors, therapeutic agents selectively targeting RET are relatively new, though multiple multi-kinase inhibitors have shown promise as RET inhibitors in the past; further, RET has been historically neglected as a potential therapeutic co-target in endocrine-refractory breast cancers despite mounting evidence for a key pathologic role and repeated description of a bi-directional relationship with the estrogen receptor, the principal driver of most breast tumors. Additionally, the recent discovery of RET enrichment in breast cancer brain metastases suggests a role for RET inhibition specific to advanced disease. This review assesses the status of research on RET in breast cancer and evaluates the therapeutic potential of RET-selective kinase inhibitors across major breast cancer subtypes.
Insights of different analytical approaches for estimation of budesonide as COVID-19 replication inhibitor in its novel combinations: green assessment with AGREE and GAPI approaches
Authors: Hammouda Mohammed E. A. , El-Masry Amal A. , El-Ashry Saadia M. , El-Wasseef Dalia R.
Published: March 2023

Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous estimation of BUD epimers in the presence of AZL with excellent efficiency in a relatively short chromatographic run (< 9 min). The separation of BUD epimers with AZL was carried out on a C18column using acetonitrile: phosphate buffer of pH 3.5 adjusted by 0.2 M orthophosphoric acid (40:60, v/v) as a mobile phase, UV detection at 230 nm and a flow rate of regulated at 2 mL/min. Besides, three spectrophotometric methods were applied for the simultaneous determination of the provided mixture adopting zero order, first order derivative, and ratio first derivative approaches. The Zero-order spectrophotometry was used for the determination of AZL in presence of BUD, where BUD shows no absorbance at 290 nm. The first derivative amplitude at 265 nm (1D265) (zero-crossing of AZL) and the ratio of first derivative amplitudes at 270 nm (1DD270) using 10.0 µg mL−1AZL as divisor was chosen for the simultaneous determination of BUD in the presence of AZL in the binary mixture. The proposed methods were found to be rectilinear in the concentration range of (0.4–40.0 µg mL−1) and (0.05–40.0 µg mL−1) for BUD and AZL, respectively in the HPLC method. Whereas the concentration range for AZL in the zero-order method was (1.0–35.0 µg mL−1) and for BUD in the first derivative and ratio derivative method was (6.0–20.0 µg mL−1). Validation of the suggested approaches according to the ICH criteria was performed. Furthermore, to ensure the proposed approaches' greenness, The AGREE and GAPI metrics were utilized, and the afforded results revealed an excellent greenness of the proposed approaches.
Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments
Authors: Zhang Xiaohua , Du Qian , Chen Guiyuan , Jiang Yiyuan , Huang Kai , Li Linghao , Tong Dewen , Huang Yong
Published: March 2023

The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, responsible for severe economic losses to the swine industry worldwide. The interferon-inducible GTPase guanylate-binding protein 1 (GBP1) exhibits antiviral immunity. Our findings show that there is a robust upregulation in the expression of porcine GBP1 during PRV infection. GBP1 knockout promotes PRV infection, while GBP1 overexpression restricts it. Importantly, we found that GBP1 impeded the normal structure of actin filaments in a GTPase-dependent manner, preventing PRV virions from reaching the nucleus. We also discovered that viral US3 protein bound GBP1 to interfere with its GTPase activity. Finally, the interaction between US3 and GBP1 requires US3 serine/threonine kinase activity sites and the GTPase domain (aa 1 to 308) of GBP1. Taken together, this study offers fresh perspectives on how PRV manipulates the host’s antiviral immune system.
Off-grid DOA estimation using improved root sparse Bayesian learning for non-uniform linear arrays
Authors: Shen Jiajun , Gini Fulvio , Greco Maria Sabrina , Zhou Tian
Published: March 2023

This paper concerns direction of arrival (DOA) estimation based on a sparse Bayesian learning (SBL) approach. We address two inherent problems of this class of DOA estimation methods: (i) a predefined dictionary can generate off-grid problems to a SBL DOA estimator; (ii) a parametric prior generally enforces the solution to be sparse, but the existence of noise can greatly affect the sparsity of the solution. Both of these issues may have a negative impact on the estimation accuracy. In this paper, we propose an improved root SBL (IRSBL) method for off-grid DOA estimation that adopts a coarse grid to generate an initial dictionary. To reduce the bias caused by dictionary mismatch, we integrate the polynomial rooting approach into the SBL method to refine the spatial angle grid. Then, we integrate a constant false alarm rate rule in the SBL framework to enforce sparsity and improve computational efficiency. Finally, we generalize the IRSBL method to the case of non-uniform linear arrays. Numerical analysis demonstrates that the proposed IRSBL method provides improved performance in terms of both estimation accuracy and computational complexity over the most relevant existing method.
The association of asthma duration with body mass index and Weight-Adjusted-Waist index in a nationwide study of the U.S. adults
Authors: Han Xiaoxiao , He Xiaofang , Hao Gui , Cao Lifang , Qi Yinliang , Han Kexing
Published: March 2023

Backgrounds

The association between obesity and asthma has been of interest, but whether the duration of asthma has an effect on obesity is still limitedly studied.

Aim

The purpose of this study was to investigate the association between asthma duration and obesity-related indexes, where obesity-related indexes include Body mass index (BMI) and Weight-adjusted-waist index (WWI).

Methods

Data from National Health and Nutrition Examination Survey (NHANES) 2009–2018 were obtained to conduct this cross-sectional study. Duration of asthma was used as the independent variable and obesity-related indexes as the response variables. Multiple linear regression was used to assess the association between the independent variable and the response variables, and subsequently smoothed curve fitting and threshold effect analysis were performed to clarify whether there was a nonlinear correlation between the independent variable and the response variables. Finally, subgroup analysis was conducted to find sensitive populations.

Results

A total of 9170 participants were included in the analysis. Asthma duration was statistically different between the two groups when all participants were grouped by median WWI (Q1 < 11.65, Q2 ≥ 11.65) (P < 0.001), but not by median BMI (Q1 < 31.8, Q2 ≥ 31.8) (P = 0.130). There was a positive association between asthma duration and WWI [β = 0.016, 95% CI (0.016, 0.017)], but a negative one with BMI [β = − 0.098, 95% CI (− 0.112, − 0.085)], and the correlations between the independent and response variables became more pronounced with increasing asthma duration (P for trend < 0.01). In addition, there were nonlinear relationships between asthma duration with BMI and WWI (log likelihood ratio < 0.001), with the best valid inflection points for asthma duration being 2 years (with WWI as the response variable) and 3 years (with BMI as the response variable), respectively. In the subgroup analysis, the positive association between asthma duration and WWI was more pronounced in the participants who were male, aged less than 40 years, and had asthma onset before 12 years of age. In contrast, when BMI was used as the response variable, the negative association between it and asthma duration was more pronounced among participants of female, aged 60 years or older, and with asthma onset less than 12 years of age.

Conclusions

In US adults, asthma duration might cause changes in obesity-related indexes. Longer asthma duration might cause weight loss, but might increase the risk of abdominal obesity.
α-Synuclein conformers reveal link to clinical heterogeneity of α-synucleinopathies
Authors: Schmitz Matthias , Candelise Niccolò , Canaslan Sezgi , Altmeppen Hermann C. , Matschke Jakob , Glatzel Markus , Younas Neelam , Zafar Saima , Hermann Peter , Zerr Inga
Published: March 2023

α-Synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfolded α-synuclein (αSyn), referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions (Papp–Lantos bodies). Even though the specific cellular distribution of aggregated αSyn differs in PD and DLB patients, both groups show a significant pathological overlap, raising the discussion of whether PD and DLB are the same or different diseases. Besides clinical investigation, we will focus in addition on methodologies, such as protein seeding assays (real-time quaking-induced conversion), to discriminate between different types of α-synucleinopathies. This approach relies on the seeding conversion properties of misfolded αSyn, supporting the hypothesis that different conformers of misfolded αSyn may occur in different types of α-synucleinopathies. Understanding the pathological processes influencing the disease progression and phenotype, provoked by different αSyn conformers, will be important for a personalized medical treatment in future.
LINP1 represses unfolded protein response by directly inhibiting eIF2α phosphorylation to promote cutaneous squamous cell carcinoma
Authors: Liang Xiaoting , Liu Jieyu , Liu Xingyuan , Jin Yi , Xu Minna , Han Zhenyu , Wang Ke , Zhang Chunting , Zou Fei , Zhou Liang
Published: March 2023

Background

Endoplasmic reticulum stress (ER stress) may destroy endoplasmic reticulum homeostasis (ER homeostasis) and leads to programmable cell death. Unfolded protein response (UPR) originally stimulated by ER stress is critical for the survival of tumor cells through trying to re-establish ER homeostasis as an adaption to harsh microenvironment. However, mechanisms involving key regulators in modulating UPR remain underexplored.

Methods

The expression of LINP1 in cutaneous squamous cell carcinoma (cSCC) tissues and cell lines was assessed. Subsequently, LINP1 was knocked out, knocked down or overexpressed in cSCC cells. CCK-8 assays, colony forming assays, transwell migration assays and invasiveness measurement by matrigel-coated transwell were performed to examine the role of LINP1 in cSCC development through gain-of-function and loss-of-function experiments. Transcriptomic sequencing (RNA-Seq) was conducted and indicated the key downstream signaling events regulated by LINP1 including UPR and apoptosis signaling. Furthermore, the direct interaction between LINP1 and eIF2α to modulate UPR and apoptosis was confirmed by RNA pulldown, RNA immunoprecipitation (RIP), ChIP-qPCR and in vitro phosphorylation assays.

Results

In this study, LncRNA in non-homologous end joining pathway 1 (LINP1) was identified to be one of the top ten highest-expressed LncRNAs in cSCC, the second most common cancer in the world. Functional studies using in vitro and in vivo models revealed that LINP1 functions as an oncogene to promote cell proliferation, colony formation, migration and invasiveness while inhibiting cell apoptosis in cSCC. Transcriptomic sequencing after knockdown of LINP1 indicated LINP1 negatively regulates UPR-related pathways involving key effectors for activating UPR and the apoptosis following the prolonged UPR. Mechanistic study showed LINP1 physically interacts with eIF2α to inhibit its phosphorylation for avoiding unmitigated UPR. Loss of LINP1 followed by enhanced eIF2α phosphorylation led to overactivated UPR and induced DDIT3 expression, contributing to ER stress-induced apoptosis and suppression of cSCC development.

Conclusions

Our findings demonstrate a novel regulatory hierarchy of UPR by demonstrating LINP1 as a critical modulator for eIF2α phosphorylation and a suppressor of UPR-mediated apoptosis, which suggests a novel therapeutic target for cSCC treatment.
The effect of short-term preoperative nutritional intervention for cleft surgery eligibility
Authors: Mikhail Shady , Chattopadhyay Lily , DiBona Melissa , Steppling Charlotte , Kwadjo Dede , Ramamonjisoa Anjaramamy , Gallardo Wendy , Almendarez Fatima , Sylvester Beau , Rosales Samanta , Nthalika Ibrahim , Collier Zachary J. , Magee William , Auslander Allyn
Published: March 2023

Background

Children with orofacial clefts are highly susceptible to malnutrition, with severe malnutrition restricting their eligibility to receive safe surgery. Ready-to-use therapeutic foods (RUTF) are an effective treatment for malnutrition; however, the effectiveness has not been demonstrated in this patient population prior to surgery. We studied the effectiveness of short-term RUTF use in transitioning children with malnutrition, who were initially ineligible for surgery, into surgical candidates.

Methods

A cohort of patients from Ghana, Honduras, Malawi, Madagascar, Nicaragua, and Venezuela enrolled in a nutrition program were followed by Operation Smile from June 2017 to January 2020. Age, weight, and length/height were tracked at each visit. Patients were included until they were sufficiently nourished (Z >  = -1) with a secondary outcome of receiving surgery. The study was part of a collaborative program between Operation Smile (NGO), Birdsong Peanuts (peanut shellers and distributors), and MANA Nutrition (RUTF producer).

Results

A total of 556 patients were recruited between June 2017 and January 2020. At baseline 28.2% (n = 157) of patients were diagnosed with severe, 21.0% (n = 117) moderate, and 50.7% (n = 282) mild malnutrition. 324 (58.3%) presented for at least one return visit. Of those, 207 (63.7%) reached optimal nutrition status. By visit two, the mean z-score increased from -2.5 (moderate) to -1.7 (mild) (p < 0·001). The mean time to attain optimal nutrition was 6 weeks. There was a significant difference in the proportion of patients who improved by country(p < 0.001).

Conclusion

Malnutrition prevents many children with orofacial clefts in low- and middle-income countries from receiving surgical care even when provided for free. This creates an even larger disparity in access to surgery. In an average of 6 weeks with an approximate cost of $25 USD per patient, RUTF transitioned over 60% of patients into nutritionally eligible surgical candidates, making it an effective, short-term preoperative nutritional intervention. Through unique partnerships, the expansion of cost-effective, large-scale nutrition programs can play a pivotal role in ensuring those at the highest risk of living with unrepaired orofacial clefts receive timely and safe surgical care.
Vitamin D deficiency in Ukraine: current evidence
Authors: Grygorieva N. V. , Solonenko T. Yu. , Musiienko A. S. , Bystrytska M. A.
Published: March 2023

Background

Data from numerous studies demonstrate the high frequency of vitamin D deficiency (VDD) and insufficiency (VDI) in many countries worldwide that depend on age and sex, seasons, country, and concomitant pathology. This research aimed to study vitamin D status in the Ukrainian population during 2016–2022 years depending on age, sex, month, and year of the observation, and compare the results with the data of previous Ukrainian epidemiologic studies.

Methods

In a single-center cohort study, we analyzed the serum total 25-hydroxyvitamin D (25(OH)D) level in 7,418 subjects aged 20–99 years. The analysis was performed depending on age, sex, month, season, and year of the observation. Also, we compared the results with the data of previous Ukrainian studies. 25(OH)D level was measured using the electrochemiluminescence method.

Results

The mean serum 25(OH)D level in the total group was 31.0 [22.3–41.1] ng/mL, the lowest level was in the age group 90–99 years old. No gender differences were found in 25(OH)D levels, except the one for the women aged 60–69 years old who had higher vitamin D levels compared to male parameters. 41.6% of the subjects had an optimal (> 30–50 ng/mL) 25(OH)D level, 27.3% had VDI, and 19.5% had a VDD. The suboptimal and high serum concentration of 25(OH)D (> 50–100 ng/mL) was found in 11.4% of the subjects. Also, we established the increase of serum 25(OH)D level from 2016 to 2022 with the highest values in 2020–2022. Seasonal variations of 25(OH)D concentration confirmed the highest index in autumn (33.0 [24.0–42.4] ng/mL) and the lowest one in the spring (28.5 [19.7–38.7] ng/mL) with the highest 25(OH)D level in September and the lowest one in March.

Conclusion

Our results confirmed a decrease in VDD and VDI in 2020–2022 in the Ukrainian population compared to the previous years (2016–2019) and previous Ukrainian studies with similar age and seasonal particularities. It may be the consequence of an improvement in public awareness of global vitamin D deficiency, its positive skeletal and extra-skeletal effects, as well as more intensive vitamin D supplementation due to the COVID-19 pandemic in the recent years.
The Debriefing Assessment in Real Time (DART) tool for simulation-based medical education
Authors: Baliga Kaushik , Halamek Louis P. , Warburton Sandra , Mathias Divya , Yamada Nicole K. , Fuerch Janene H. , Coggins Andrew
Published: March 2023

Background

Debriefing is crucial for enhancing learning following healthcare simulation. Various validated tools have been shown to have contextual value for assessing debriefers. The Debriefing Assessment in Real Time (DART) tool may offer an alternative or additional assessment of conversational dynamics during debriefings.

Methods

This is a multi-method international study investigating reliability and validity. Enrolled raters (n = 12) were active simulation educators. Following tool training, the raters were asked to score a mixed sample of debriefings. Descriptive statistics are recorded, with coefficient of variation (CV%) and Cronbach’s α used to estimate reliability. Raters returned a detailed reflective survey following their contribution. Kane’s framework was used to construct validity arguments.

Results

The 8 debriefings (μ = 15.4 min (SD 2.7)) included 45 interdisciplinary learners at various levels of training. Reliability (mean CV%) for key components was as follows: instructor questions μ = 14.7%, instructor statements μ = 34.1%, and trainee responses μ = 29.0%. Cronbach α ranged from 0.852 to 0.978 across the debriefings. Post-experience responses suggested that DARTs can highlight suboptimal practices including unqualified lecturing by debriefers.

Conclusion

The DART demonstrated acceptable reliability and may have a limited role in assessment of healthcare simulation debriefing. Inherent complexity and emergent properties of debriefing practice should be accounted for when using this tool.
Early identification of treatment non-response in first-episode psychosis
Authors: Wold Kristin Fjelnseth , Ottesen Akiah , Camilla Bärthel Flaaten , Johnsen Erik , Lagerberg Trine Vik , Romm Kristin Lie , Simonsen Carmen , Ueland Torill , Widing Line , Åsbø Gina , Melle Ingrid
Published: March 2023

Background

Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery—no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups.

Methods

Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the “Remission in Schizophrenia Working Group” criteria and TR on adaptations of the “Treatment Response and Resistance in Psychosis” (TRRIP) working group criteria.

Results

97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects.

Conclusion

The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.
Survival in Black and non-Black patients with metastatic prostate cancer.
Authors: Cheranda Nina , Luo Suhong , Sanfilippo Kristen Marie , Eisen Seth A , Schoen Martin W.
Published: March 2023

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Background: In the general population, Black men have greater incidence, lower five-year survival, and higher mortality due to prostate cancer when compared to white men. However, in clinical trials and studies of metastatic castrate resistant prostate cancer (mCRPC) in the Veterans Health Affairs (VHA) that excluded chemotherapy, Black men have longer overall survival (OS). We sought to analyze outcomes of Black men treated with androgen receptor targeting agents (ARTAs) abiraterone (AA) and enzalutamide (ENZ) in the VHA. Methods: Patients initially treated with AA or ENZ for mCRPC from May 2011 to June 2017 were identified within the VHA. Racial cohorts of Black and non-Black were determined from patient charts. ANOVA, Kaplan-Meier, and Cox proportional hazards modeling were used to assess the association between overall survival and covariates, including treatment, age, Charlson Comorbidity Index, body-mass index, PSA, year of treatment, prior docetaxel therapy, hemoglobin, creatinine clearance, bilirubin, and albumin at start of treatment. Results: Of 11,027 patients treated for mCRPC with ARTAs, 2550 (23.1%) were identified as Black. Black patients were significantly younger (72.6 vs. 75.8 years, p<0.001), had higher median PSA (60.3 vs. 37.0, p<0.001) and higher Charlson comorbidity index (4.5 vs. 3.9, p<0.001) with lower mean BMI (27.7 vs. 28.4, p<0.001) and higher rates of cardiovascular disease (62.0% vs. 59.8%, p=0.044) and diabetes (45.8% vs. 34.1%, p<0.001). Docetaxel was given more frequently to Black veterans both prior to ARTA (24.7% vs. 16.9%, p<0.001) and at any time (43.1% vs. 31.3%, p<0.001). Black men had a median 2.0 months longer OS than non-Black men (22.0 vs. 20.0, p<0.001) and decreased mortality in unadjusted models (HR 0.89, 95% CI 0.85-0.94) and multivariable models (aHR 0.76, 95% CI 0.72-0.80). Black veterans had longer OS with ENZ compared to AA (24.5 vs. 21.3 months, p<0.001) and decreased mortality (HR 0.83, 95% CI 0.75-0.92) in unadjusted models. However, there was no difference in OS between ENZ and AA in neither multivariable models in all Black men (aHR 0.95, 95% CI 0.85-1.05) nor Black men with cardiovascular disease or diabetes (n=1912, aHR 0.91, 95% CI 0.80-1.03). Conclusions: In the VHA, which provides more equitable access to care, Black men have longer OS with ARTAs compared to non-Black men and increased use of chemotherapy. Importantly, Black men are significantly younger (>3 years) when treated for mCRPC, with higher PSA, and higher rates of comorbid diseases.
Main reasons of choice of formulation and route of triptorelin treatment initiated in patients with prostate cancer (PCa): TALISMAN study.
Authors: Thiery-Vuillemin Antoine , Crehange Gilles , Lebret Thierry , Pello Leprince Ringuet Nathalie , Perrot Valérie , Rigaud Jerome
Published: March 2023

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Background: Modalities of use of androgen deprivation therapy (ADT), like triptorelin, in real life, at the era of new strategies in advanced stages, lack of recent data. Our purpose here was to describe main reasons of choice of formulation and route (F&R) of triptorelin treatment (Tt) declared by the physician. Patient comorbidities, cancer aggressiveness and physician habits may influence their choices. Methods: Initiated in 2020, a prospective, multicenter, non-interventional study is ongoing in France (TALISMAN, NCT04593420). Patients with histologically confirmed PCa, eligible for ≥ 12-month triptorelin Tt within its label were enrolled. Interim analysis of baseline data was planned when 50% of 786 planned patients were enrolled. Modalities of use, including F&R of triptorelin prescribed [monthly intramuscular (1mIM), every 3 months subcutaneous (3mSC) or intramuscular (3mIM), every 6 months intramuscular (6mIM)], were described. Results: 509 patients were included in the interim analysis. Overall population was presented at ASCO-GU22. Subgroups of F&R are presented here. Main F&R prescribed was 3mSC (70.7%). Main baseline parameters in F&R subgroups are presented (except for 1mIM, 4 patients (0.8%)). 31 patients had missing F&R data and were not included in subgroups. 62.1% of patients overall received at least one concomitant systemic Tt for comorbidity at baseline (58.2% in 3mIM, 61.7% in 3mSC and 6mIM). 18.6% and 13.0% of patients overall received, respectively, platelet aggregation inhibitor and anticoagulant; they were 20.9% and 13.8% in 3mSC, 7.3% and 5.5% in 3mIM, 18.5% and 11.1% in 6mIM. Conclusions: Main reason of choice of F&R of triptorelin was physician preferred F&R (47.7%); noticeable reasons included anticoagulants for the choice of 3mSC, planned total duration of Tt for 3mIM and 6mIM, and potential impact on compliance for 6mIM. As the covid pandemic may change the management of patients with prostate cancer, longer acting formulations may become more attractive. Clinical trial information: NCT04593420 . [Table: see text]
Patient perceptions regarding the process of obtaining oral prostate cancer medications.
Authors: Schwartz Eric B , Furgal Allison , Widmer Gina , Caram Megan Veresh , Veenstra Christine M
Published: March 2023

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Background: Various oral therapies exist and have improved outcomes for men with prostate cancer. These agents are expensive and put patients at risk for financial toxicity. Although assistance mechanisms exist to offset these costs, navigating through assistance can be complicated and places excess burdens on patients. We conducted a survey of men prescribed oral therapies for prostate cancer to assess financial toxicity and perceptions on the process of obtaining oral cancer medications for prostate cancer. Methods: Patients with prostate cancer who had been prescribed abiraterone, enzalutamide, apalutamide or darolutamide at our institution in the six months prior to survey distribution were identified. Those with an email address were eligible for inclusion and sent a survey. Financial toxicity was assessed using the FACIT-COST score. Perceptions of the process of obtaining medication were assessed with a novel measure, which included questions regarding affordability, delays in care and ease of obtaining medications. We assessed bivariate associations between financial variables and financial toxicity measures. Results: Of 238 patients identified, 188 had a listed email address. Response rate was 28% of eligible patients (n = 53). Among respondents, 53% reported household income < $100,000 and 32% > $100,000, 15% declined to answer. A total of 41% utilized commercial insurance, 23% Medicare D, 28% an alternative Medicare program, 2% Medicaid and 4% had no prescription coverage. Monthly costs were between $100 and $1000 for 15% of patients and > $1000 for 6%. A total of 25% of patients considered their medication somewhat or very unaffordable; 13% were somewhat or not at all confident about affording their medication in the future; 6% reported delays in starting; 15% found the initial process of obtaining their medication somewhat or very stressful; 9% reported ongoing stress about affording their medications. Those with monthly cost > $100 were less likely to consider their medication affordable (p = 0.001). Those with commercial insurance were least likely to perceive delays in care (p = 0.024). Primary insurance type but no other variable was associated with difference in COST score with those who had commercial insurance reporting less financial toxicity than those with Medicare. Conclusions: The costs of oral prostate cancer medications are a concern for many men with prostate cancer. In a survey at our institution, many patients have high costs, despite the availability of financial assistance. In addition, many reported distress and uncertainty related to the process of obtaining their prostate cancer medications. Our survey was limited by small sample size and low response rate utilizing email as primary contact. We expect that many patients without access to email would be those at higher risk of financial toxicity. Further studies will aim to recruit patients directly in clinics.
Effect of cerebral dopamine metabolism genetic polymorphism on patient-reported quality-of-life (QOL): An analysis of the E3805 CHAARTED trial.
Authors: Gupta Arjun , Chen Yu-Hui , Sweeney Christopher , Jarrard David Frazier , Plimack Elizabeth R. , Gartrell Benjamin Adam , Carducci Michael Anthony , Hussain Maha H. A. , Garcia Jorge A. , Cella David , DiPaola Robert S. , Morgans Alicia K.
Published: March 2023

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Background: QOL outcomes have been associated with specific genetic variants in neurotransmitter metabolism. One such variant associated with reduced symptoms in placebo studies is in the rs4680 SNP of Carboxy-O-Methyltransferase (COMT). This variant is associated with reduced COMT enzymatic activity, higher cerebral dopamine levels, and improved mood. The interaction between this germline variant and cancer-directed treatment on QOL is undefined. A priori, we hypothesized that the COMT rs4680 SNP would be associated with better pain and QOL patient reported outcomes (PROs), than wildtype (WT) COMT within the E3805 CHAARTED Trial. Methods: E3805 compared docetaxel + androgen deprivation therapy (ADT+D) vs ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC). PROs were collected at baseline, 3, 6, 9, and 12 months. Blood samples were genotyped prior to treatment. We compared PROs between patients with COMT WT vs rs4680 SNP within treatment arms longitudinally. PROs include Brief Pain Inventory (BPI) classified as: no (0), minimal (1), or more (≥2) pain, and BPI interference (range 0-10, 0= no pain or interference), and the Functional Assessment of Cancer Therapy-Prostate (FACT-P, higher score= better QOL, clinically important difference (CID)= 6). Descriptive statistics were used to characterize QOL over time. Fisher’s exact test, Wilcoxon rank sum test and mixed effects models were used to evaluate the associations between SNP and QOL in each arm. Results: Of 790 participants, 550 with SNP data were included. In the ADT+D arm, SNPs were not associated with PROs at any time point. In contrast, in the ADT alone arm, when compared to WT, rs4680 was associated with less pain at 3 months, less interference at 3, 6 and 9 months, and better QOL at 6 months (met criteria for CID). Conclusions: The rs4680 SNP, often associated with higher cerebral dopamine levels and improved QOL, was associated with less pain and superior QOL among patients with mHSPC treated with ADT, but not chemohormonal therapy. This is the first hypothesis driven genotyping study to demonstrate that genetics are associated with QOL in patients with cancer, especially when treatment does not cause profound symptoms. Clinical trial information: NCT00309985 . [Table: see text]
Developing a novel patient-reported outcome measure for patients with prostate cancer receiving radionuclide therapy: The FACT-RNT.
Authors: Gudenkauf Lisa M. , Chavez Melody , Maconi Melinda , Geiss Carley , Seyedroudbari Ameen , Thin Pan , Hoogland Aasha , Nguyen Kathleen , Oswald Laura B. , Jim Heather S.L. , El-Haddad Ghassan , Fendler Wolfgang Peter , Herrmann Ken , Cella David , Czernin Johannes , Hofman Michael S , Dicker Adam P. , Calais Jeremie , Tagawa Scott T. , Gonzalez Brian D.
Published: March 2023

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Background: The field of targeted radionuclide therapy (RNT) for prostate cancer (PC) is growing rapidly with recent FDA approval of the first lutetium-177-PSMA-ligand. Commonly used patient-reported outcome (PRO) measures were originally designed to assess the impacts of traditional therapies (e.g., chemotherapy, surgery). We aimed to develop the first PRO measure for PC patients receiving RNT. Methods: We used a multi-step approach based on input from experts and patients. We identified symptoms and toxicities potentially relevant in the context of RNT for PC from a literature review of published trials and interviews with PC patients who had received RNT, caregivers of RNT recipients, and clinicians. We identified items to include in the measure from the Functional Assessment of Chronic Illness Therapy (FACIT) item library. Finally, we reviewed, refined, and finalized the new measure. Results: Potentially relevant symptoms/toxicities were identified by reviewing published trials (e.g., xerostomia, nausea). Interviews with PC patients who received RNT (n=29), caregivers (n=14), and clinicians (n=11) yielded additional symptoms/toxicities (e.g., fatigue, constipation). After selecting a broad and comprehensive list of items from the FACIT item library, we refined the list based on input from 9 experts in the field of RNTs and PROs from 5 institutions. Patients who received RNT for PC (n=11) reviewed the draft measure and confirmed items were relevant to RNT recipients and comprehensible. This resulted in a brief 15-item measure deemed by key stakeholders to be relevant and useful in the context of RNT for PC. Conclusions: The FACT-RNT (Functional Assessment of Cancer Therapy – Radionuclide Therapy) is a PRO new measure for RNT recipients developed through multi-step collaboration with patients, caregivers, clinicians, and international experts. The FACT-RNT can be used in RNT clinical trials and real-world settings.
Optimising bone health management in advanced prostate cancer: A comparative cohort study.
Authors: Waton Anthony , Prichard Rachel , Navarro Rodriquez Carolina , Hannaway Nicola , Azzabi Ashraf , Chandler Robert , Frew John A. , Jiang Xue Yan , Pearson Rachel , Pedley Ian
Published: March 2023

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Background: Survival in prostate cancer is increasing due to advances in hormonal therapy. The recommended duration of Androgen Deprivation Therapy (ADT) is 18 months or more for patients with Non-Metastatic (NM) high risk disease, and lifelong in Metastatic disease. ADT is, however, an independent risk factor for osteoporosis, a disease characterised by low Bone Mineral Density (BMD) and subsequent increased risk of fractures, which can lead to significant disability and early death. In patients with advanced prostate cancer, it is therefore recommended that BMD is assessed yet there remains no established national guidance on how bone health should be managed. Methods: In total, 515 case notes for patients with newly diagnosed advanced hormone sensitive prostate cancer were retrospectively reviewed for assessment of bone health management. Our data analysis included a comparison of outcomes between patient cohorts managed at a dedicated Cancer Bone Health Unit (CBHU) and the Northern centre for Cancer Care (Oncology Centre, OC). Results: 1) Baseline characteristics: The cohorts were well balanced in terms of age and cancer stage. Data was available for 410 patients in the CBHU and 105 in the OC. Median age was 75 (range 59-94) in the CBHU and 71 (range 46-86) in the OC. The majority of patients had metastatic disease and were therefore receiving lifelong ADT. 2) Fracture incidence: was consistently higher in the OC (p<0.001). The most common fractures were hip, spine and wrist. Median time to first fracture in the CBHU was 112 (range 2 to 240) vs 83 weeks (8 to 229) in the OC (p=0.252). 3) Survival: for all patients 2 years after ADT commenced was 96.7% in the CBHU vs 91.8% in the OC (HR 0.321, 95% CI 0.19-0.55, p<0.001). Median survival has not yet been reached. Conclusions: This comparative analysis suggests that a strategy of standardised bone health management within a CBHU is associated with reduced fracture incidence and may delay time to first fracture compared with clinician discretion in an OC. Additionally the data suggests that this strategy also improves survival at 2 years in patients with NM high risk disease. Bone health strategies for prostate cancer should be implemented within hospital trusts to provide standardised care across the region. This could reduce costs associated with fractures and improve quality of life for patients who avoid fractures through timely introduction of treatment. The Northern Cancer Alliance (NCA) has recently approved guidance on the management of bone health in prostate cancer, and implementation has since commenced.