bluuebunny/crossref_metadata_2025 huggingface dataset:
Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT))
Authors: Forsyth Rob , Allen Maria , Bedson Emma , Downes Alice , Gough Chris , Hartshorn Stuart , Lawton Kelly , Lyttle Mark D. , Messahel Shrouk , Mullen Niall , Raper Joseph , Rosala-Harris Anna , Taggart Leigh , Urron Jason , Walton Emily , Gamble Carrol ,   on behalf of the Paediatric Emergency Research in the United Kingdom and Ireland (PERUKI) collaborative, Tolhurst-Cleaver Meriel , Siner Sarah , Singh Anandi , Ledger Elizabeth , Harris Thomas , Amos Rachel , Downes Alice J. , Price Sally , Mikhail Maria , Alhashimi Noor
Published: May 2024

Background

Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid–base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment.

Methods

A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as ‘carbogen’.

Due to the urgent need to treat the seizure, deferred consent is used.

The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality.

Discussion

If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff.

Trial registration

EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.
Lactylation: the novel histone modification influence on gene expression, protein function, and disease
Authors: Hu Yue , He Zhenglin , Li Zongjun , Wang Yihan , Wu Nan , Sun Hongyan , Zhou Zilong , Hu Qianying , Cong Xianling
Published: May 2024

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential “writers” and “erasers” responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.
Distribution and predictors of F-18-FDG uptake values of non-malignant cervical lymph nodes in pediatric patients
Authors: Godefroy Jeremy , Godefroy Raphael , Vedder Koral , Altura Yair , Chicheportiche Alexandre , Ben-Haim Simona , Goldstein Gal
Published: May 2024

Background

F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.

Methods

191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmaxCLN), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmaxCLN was estimated using linear regression models.

Results

Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmaxCLN was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmaxCLN. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmaxCLN was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.

Conclusion

SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.

Trial was registered

In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.
Demographic and injury trends for car crash casualties hospitalized in Level I Trauma centers over two decades: data from the National Trauma Registry
Authors: Goldman Sharon , Cohen-Manheim Irit , Radomislensky Irina , Savitsky Bella ,   Israel Trauma Group, Bahouth H. , Bar A. , Braslavsky A. , Czeiger D. , Fadeev D. , Goldstein A. L. , Grevtsev I. , Hirschhorn G. , Jeroukhimov I. , Kedar A. , Klein Y. , Korin A. , Levit B. , Schrier I. , Schwarz A. D. , Shomar W. , Soffer D. , Weiss M. , Yaslowitz O. , Zoarets I. , Bodas Moran
Published: May 2024

Background

During the past two decades, there have been many changes in automotive and medical technologies, road infrastructure, trauma systems, and demographic changes which may have influenced injury outcomes. The aim of this study was to examine injury trends among traffic casualties, specifically private car occupants, hospitalized in Level I Trauma Centers (TC).

Methods

A retrospective cohort study was performed based on data from the Israel National Trauma Registry. The data included occupants of private cars hospitalized in all six Level I TC due to a traffic collision related injury between January 1, 1998 and December 31, 2019. Demographic, injury and hospitalization characteristics and in-hospital mortality were analyzed. Chi-squared (X2) test, multivariable logistic regression models and Spearman’s rank correlation were used to analyze injury data and trends.

Results

During the study period, 21,173 private car occupants (14,078 drivers, 4,527 front passengers, and 2,568 rear passengers) were hospitalized due to a traffic crash. The percentage of females hospitalized due to a car crash increased from 37.7% in 1998 to 53.7% in 2019. Over a twofold increase in hospitalizations among older adult drivers (ages 65+) was observed, from 6.5% in 1998 to 15.7% in 2018 and 12.6% in 2019. While no increase was observed for severe traumatic brain injury, a statistically significant increase in severe abdominal and thoracic injuries was observed among the non-Jewish population along with a constant decrease in in-hospital mortality.

Conclusions

This study provides interesting findings regarding injury and demographic trends among car occupants during the past two decades. Mortality among private car occupant casualties decreased during the study period, however an increase in serious abdominal and thoracic injuries was identified. The results should be used to design and implement policies and interventions for reducing injury and disability among car occupants.
Sequence spaces derived by $q_{\lambda}$ operators in $\ell _{p}$ spaces and their geometric properties
Authors: Braha Naim L. , Yaying Taja , Mursaleen Mohammad
Published: May 2024

In this paper, we establish a novel category of sequence spaces $\ell _{p}^{q_{\lambda}}$

ℓ
p

q
λ

and $\ell _{\infty}^{q_{\lambda}}$

ℓ
∞

q
λ

by utlizing q-analogue $\Lambda^{q}$

Λ
q

of Λ-matrix. Our investigation outlines several topological characteristics and inclusion results of these newly introduced sequence spaces, specifically identifying them as BK-spaces. Subsequently, we demonstrate that these novel sequence spaces are of nonabsolute type and establish their isometric isomorphism with $\ell _{p}$

ℓ
p

and $\ell _{\infty}$

ℓ
∞

. Moreover, we obtain the α-, β-, and γ-duals of these sequence spaces. We further characterize the class $(\ell _{p}^{q_{\lambda}},X)$
(

ℓ
p

q
λ

,
X
)
of matrices, where X is any of the spaces $\ell _{\infty }$

ℓ
∞

, c, or $c_{0}$

c
0

. Lastly, our study delves into the exploration of specific geometric properties exhibited by the space $\ell _{p}^{q_{\lambda}}$

ℓ
p

q
λ

.
Inefficiency of laying hens farms in Benin: an input directional distance function approach
Authors: Crinot Fabrice Géraud , Adégbola Ygué Patrice , Fatunbi Abiodun Oluwole , Adéguélou Koladé Raoul
Published: May 2024

Background

In Benin, the productivity of poultry production systems is a major concern. This paper aims first to estimate the cost, technical and allocative inefficiencies of modern and traditional poultry production systems, and then to determine the factors that influence these types of inefficiencies.

Results

The study reveals significant cost inefficiencies, with just 9% and 18% of traditional and modern systems, respectively, being cost-efficient, highlighting the necessity of distinguishing production systems due to different operational requirements, particularly for modern systems. Addressing these inefficiencies requires crucial measures such as providing training, accessible credit, and mortality rate reduction to boost local production, with tailored support for small-scale farmers.

Conclusions

The poultry sector’s intense competition and the decline in local production, particularly among small-scale farmers, are primarily linked to high domestic production costs and local farmers' poor performance. Our study unveils substantial cost inefficiencies in both traditional and modern poultry farming systems, emphasizing the imperative to differentiate interventions based on their distinct operational requirements.
We are all ordinary: the shared visual narratives of daily life promote the patients’ positive attitudes toward doctors
Authors: Lyu Xiaokang , Zhang Shuyuan , Fu Chunye , Yang Min , Yang Tingting , Xie Fandi
Published: May 2024

Background

Current research on the doctor-patient relationship primarily focuses on the responsibilities of doctors, with relatively less emphasis on examining the contributions patients can make. As a result, there is an urgent demand for exploring innovative approaches that highlight the active role patients play in cultivating a robust doctor-patient relationship. The purpose of this study was to devise an intervention strategy centered around patients to enhance the doctor-patient relationship. Comics were developed to depict shared narratives encompassing challenging daily life experiences between doctors and ordinary individuals. The study aimed to assess the efficacy of this approach in cultivating positive attitudes toward doctors.

Method

A 3-group design trial was conducted in Shanghai, China. A total of 152 participants were randomly assigned to one of three conditions: the parallel presenting group (n = 51), where narratives about a doctor and an ordinary employee were presented side by side in comics; the single presenting group (n = 50), where only narratives about a doctor were presented; and the control group (n = 51). The outcomes assessed in this study encompassed changes in identification with the doctor portrayed in the comics, perceived intimacy between doctors and patients in reality, and appraisal of the doctor in a prepared doctor-patient interaction situation.

Results

The parallel presenting group exhibited significantly larger increases in identification with the doctor portrayed in the comics, perceived intimacy between doctors and patients in reality, and appraisal of the doctor in a prepared doctor-patient interaction scenario compared to the single presenting group. The observed enhancements in the appraisal of the doctor in a prepared doctor-patient interaction scenario can be attributed to the changes in identification with the doctor portrayed in the comics experienced by the participants.

Conclusion

Our study responds to the doctor-centric focus in existing research by exploring patients’ contributions to the doctor-patient relationship. Using comics to depict shared narratives, the parallel presenting group demonstrated significantly increased identification with the depicted doctor, perceived intimacy, and positive appraisal in prepared scenarios compared to the single presenting group. This underscores the effectiveness of patient-centered interventions in shaping positive attitudes toward doctors, highlighting the pivotal role patients play in fostering a resilient doctor-patient relationship.

Trial registration

Chinese Clinical Trail Registry: ChiCTR2400080999 (registered 20 February 2024; retrospectively registered).
Impact of Covid-19 lockdowns on the anthropometric development in primary school children in the Rhein-Neckar Region, Germany
Authors: Samigullin Azat , Groß Gabriel , Gählert Jana , Buchenberger Sandra , Morcos Michael , Schwertz Rainer , Öste Rickard , Siegel Erhard , Humpert Per
Published: May 2024

Background

Published data suggests that lockdowns during the COVID-19 pandemic may have negatively affected children’s weight development. This study aims to assess the prevalence of overweight and obesity after the COVID-19 lockdowns as well as anthropometric development among primary school children in the Rhein-Neckar Region, Germany.

Methods

In this cross-sectional study, schools were selected in cooperation with the local health authority to include different socioeconomic backgrounds. Participation was voluntary at school and individual level, requiring written informed consent from legal guardians. Study visits in schools were conducted between October 2021 and July 2022. Anthropometric data from nationally recommended medical examinations at 4 years (U8) and 5 years (U9), data on nutrition, physical activity, and socioeconomic data was collected using questionnaires. zBMI and weight category were calculated based on German reference data.

Results

256 children with a mean age of 8.0 years (7.1–9.3 years) were included in the study. Most participants were from households with an above average income. 5.1% of the children were overweight, 4.7% were obese, 15.6% were underweight, and 74.6% were normal weight with a mean zBMI of -0.25 (SD 1.10), which is significantly lower than the mean zBMI of the German reference population (p < 0.001). No significant changes in zBMI were observed between U8 and U9 (p = 0.16). The mean zBMI decreased by 0.17 (SD 0.72) between U9 and the study visit (p = 0.02). A zBMI decrease of 0.5 was documented for the subgroup of overweight and obese children (p = 0.028) as well as a decrease of 0.23 (SD 0.63) for the normal-weight children subgroup (p < 0.001).

Conclusions

Contrary to previous reports mean zBMI decreased significantly in the children studied. No significant changes in zBMI were observed between U8 and U9 examinations, which supports the hypothesis that the decrease in zBMI could be attributed to lockdown measures. The study was registered at clinicaltrials.gov on September 21st 2021 under the registration number NCT05077059.
Usability and accuracy of two different aortic annulus sizing software programs in patients undergoing transcatheter aortic valve replacement
Authors: Spanke Johannes , Nübel Jonathan , Hölschermann Frank , Tambor Grit , Kiessling Claudia , Kaneko Hidehiro , Haase-Fielitz Anja , Butter Christian
Published: May 2024

Background

Semi-automated software is essential for planning and prosthesis selection prior transcatheter aortic valve replacement (TAVR). Reliable data on the usability of software programs for planning a TAVR is missing. The aim of this study was to compare software programs ‘Valve Assist 2’ (GE Healthcare) and 3mensio ‘Structural Heart’ (Pie Medical Imaging) regarding usability and accuracy of prosthesis size selection in program-inexperienced users.

Methods

Thirty-one participants (n = 31) were recruited and divided into program-inexperienced users (beginners) (n = 22) and experts (n = 9). After software training, beginners evaluated 3 patient cases in 129 measurements (n = 129) using either Valve Assist 2 (n = 11) or Structural Heart (n = 11) on 2 test days (T1, T2). System Usability Scale (SUS) and ISONORM 9241/110-S (ISONORM) questionnaire were used after the test. The valve size selected by each beginner was compared with the valve size selected from expert group.

Results

Valve Assist 2 had higher SUS Score: median 78.75 (25th, 75th percentile: 67.50, 85.00) compared to Structural Heart: median 65.00 (25th, 75th percentile: 47.50, 73.75), (p < 0,001, r = 0.557). Also, Valve Assist 2 showed a higher ISONORM score: median 1.05 (25th, 75th percentile: − 0.19, 1.71) compared to Structural Heart with a median 0.05 (25th, 75th percentile: − 0.49, 0.13), (p = 0.036, r = 0.454). Correctly selected valve sizes were stable over time using Valve Assist 2: 72.73% to 69.70% compared to Structural Heart program: 93.94% to 40% (χ2 (1) = 21.10, p < 0.001, φ = 0.579).

Conclusion

The study shows significant better usability scores for Valve Assist 2 compared to 3mensio Structural Heart in program-inexperienced users.
A service evaluation study of the impact of ageless policy in a London inner-city early intervention in psychosis service
Authors: Johnston-Webber Charlotte , Gyawali Shreeya , Akyuz Elvan U. , Zlate Madalina , Nerantzis Georgios , Beauvillain Nikita , Andlauer Olivier , Gupta Susham
Published: May 2024

Background

Schizophreniform disorders tend to have an early onset. Early intervention in psychosis (EIP) services aim to provide early treatment, reduce long-term morbidity and improve social functioning. In 2016, changes to mental health policy in England mandated that the primarily youth-focused model should be extended to an ageless one, to prevent ageism; however, this was without strong research evidence.

Aims and method

An inner-city London EIP service compared sociodemographic and clinical factors between the under-35 years and over-35 years caseload cohorts utilising the EIP package following the implementation of the ageless policy.

Results

Both groups received similar care, despite the younger group having significantly more clinical morbidity and needs.

Clinical implications

Our results may indicate that service provisions are being driven by policy rather than clinical needs, potentially diverting resources from younger patients. These findings have important implications for future provision of EIP services and would benefit from further exploration.
Molecular profiling of serial liquid biopsy specimens utilizing cell free DNA (cfDNA) and circulating tumor cells (CTCs) in TBCRC041: A phase II study of alisertib in endocrine resistant metastatic breast cancer (MBC).
Authors: Giridhar Karthik , Suman Vera Jean , Tang Xiaojia , Ye Hong , Campbell Jordan , Mayer Erica L. , Karuturi Meghan Sri , Morikawa Aki , Kimmick Gretchen Genevieve , Isaacs Claudine , Young Oh Sun , Clark Amy Sanders , Park Ben Ho , Bucheit Leslie A , Tsai Jill , Ingle James N. , Goetz Matthew P. , D'assoro Antonino Bonaventura , Kalari Krishna Rani , Haddad Tufia C.
Published: May 2024

1037

Background: TBCRC041, a randomized phase 2 trial of alisertib (A) ± fulvestrant (F) in women with HR+/HER2- MBC demonstrated promising clinical activity for alisertib (1). Interrogation of baseline (PreC1) and end of cycle 1 (EOC1) cfDNA and CTCs may identify biomarkers associated with response to A±F. Methods: Plasma cfDNA was sequenced using the Guardant INFINITY platform, which includes genomic and methylated tumor fraction (mTF) analysis. Pathogenic variants were determined using publicly available databases and Mayo Clinic annotation pipelines. CTCs were identified as nucleated, EpCAM+/ cytokeratin+/ CD45- cells and assessed for ER/HER2 staining (RareCyte, Seattle). PFS was defined as the time from randomization to progression or death. EOC1-PFS differs from PFS as time starts at C2D1. Stratified log-rank tests and conditional Cox modeling were used to assess whether PFS or EOC1-PFS differed by mutations in ESR1 or PIK3CA, pre-CTC ≥ 5, or mTF>1%. Results: Of the 91 eligible pts, 84 progressed, and 73 were deceased. In the 86 pts with PreC1-cfDNA results, variants were identified in ESR1 (42; 48.8%), PIK3CA (36; 41.9%), AKT1 (7; 8.1%), PTEN(7; 8.1%), BRCA1 (4; 4.7%), and BRCA2 (7; 8.1%). Pts with a PIK3CAmut had significantly decreased PFS (HR 1.8; 95%CI: 1.1 -2.9, p=0.014) but not by ESR1mut status (p=0.583). PreC1 and EOC1-mTF were determined for 78 and 76 pts, respectively. PreC1-mTF was 0-1% in 21; 1.1-10.0% in 27; and 10.1-100% in 30. mTF levels remained between 0-1% in 17 pts fell to 0-1% in 11 pts, and was 0-1% in 5 pts without a preC1-mTF determination. PFS did not differ with respect to PreC1-mTF (p=0.210), but EOC1-PFS was worse in pts with mTF >1% (HR 3.0; 95%CI: 1.6 -5.2, p<0.001). PreC1 and EOC1-CTC were determined for 78 and 76 pts. 36 (46.2%) pts had a PreC1 CTC count ≥ 5. EOC1-CTC levels remained at (n=17) or increased to (n=1) ≥ 5 and was ≥ 5 in 2 pts without a preC1-CTC determination. EOC1-PFS was not significantly different for EOC1-CTC ≥ 5 (p=0.065), but was significantly decreased in pts with PreC1-CTC≥5 (HR=1.8; 95%CI: 1.1-3.0; p=0.018). Broader cfDNA NGS panel and CTC-derived ER/HER2 staining results will be presented at the meeting. Conclusions: Among patients receiving A±F, PFS varied based on the PIK3CAmutation status. cfDNA and CTC assessment PreC1 and EOC1 provided complementary information. Further validation in larger datasets is needed. 1. JAMA Oncol 2023;9:815. Clinical trial information: NCT02860000 .
Rapid survey assessment: Barriers and facilitators to mammogram completion in English and Spanish-speaking patients in a federally qualified health center (FQHC) setting.
Authors: Anderson Daniela , Ellingwood Jamie , Halvorsen Allison , Tarricone Anne , Lam Helen , Lee Nita Karnik
Published: May 2024

1587

Background: Mammography has decreased breast cancer mortality in the US by 40% since the 1980s; yet disparities in screening and outcomes persist in underserved populations. Many studies note language as a barrier to screening with lower mammogram completion amongst Spanish-speaking patients versus those with English language proficiency. At our health center, Spanish-speaking patients were more likely to complete screening mammography compared to patients with English proficiency (53% vs 31% in 2022). To understand this pattern and barriers and facilitators to breast cancer screening, we conducted a mixed methods rapid assessment survey as part of a quality improvement initiative. Methods: We developed a patient bilingual survey measuring knowledge, attitudes, and behaviors about breast cancer prevention and screening. We identified consecutive female patients (age 40-75 years) and extracted baseline demographic data from the electronic medical record. Surveys were distributed via our health center’s patient messaging service and responses stored on a secure platform. Data analysis included descriptive statistics, chi-squared testing between groups and qualitative analysis to identify common themes from free-text answers. Results: The overall response rate was 14% (N=732/5,332) in 30 days. Of the surveys completed, 37% were in Spanish. Spanish-speaking patients more strongly regarded mammography as safe and effective compared to English-speaking patients (p<0.001). Spanish-speaking patients were more likely to view getting a mammogram as a priority (79% vs 65% p<0.001) and noted speaking about breast cancer prevention in their communities more often (p<0.006) as an important factor. Spanish-speaking patients primarily cited cost, scheduling, and language (p<0.05) as barriers to mammogram completion, while English-speaking patients cited time constraints, transportation, and discomfort (p<0.05) more frequently. Spanish-speaking patients were more likely to prefer speaking with a trusted community member or attending health fairs than English-speaking patients (P<0.05). Conclusions: Our study demonstrates differences in attitudes, behaviors, and perceived barriers to mammography in English vs Spanish-speaking patients. The increased mammogram completion rate in Spanish-speaking patients may reflect more positive attitudes about screening and more discussion in the community amongst Spanish-speaking patients queried. Reported barriers to screening differed and will guide targeted QI interventions. We demonstrated feasibility and patient engagement in a diverse population using a message system built into our EHR in an FQHC setting. This survey study allows us to elevate patient voices, better understand gaps and preferences, and better tailor future interventions for cancer screening.
Improving ethnic and racial diversity in biomarker-driven clinical trials: A proof of concept with the BASECAMP-1 master prescreening study of patients with high-risk solid tumors with human leukocyte antigen-A*02 (HLA-A*02) loss of heterozygosity (LOH).
Authors: Smith Caleb Joshua , Simeone Diane M. , Grierson Patrick , Kirtane Kedar , Morelli Maria Pia , Patel Sandip Pravin , Ulrickson Matthew L. , Dahiya Saurabh , Park Jong Chul , Specht Jennifer M. , Fakih Marwan , Liechty Kirstin B. , Tebbets Jessica , Welch John Sutton , Go William Y. , Maloney David G. , Maus Marcela Valderrama , Ng Eric Wai-Choi , Hecht J. Randolph
Published: May 2024

1604

Background: Diversity in clinical studies is essential to address health disparities, but racial and ethnic minorities are often underrepresented in clinical studies, especially in precision medicine studies using genetic data (1). BASECAMP-1 (NCT04981119) is an ongoing prescreening study to identify patients with unresectable advanced or metastatic solid tumors and tumor-associated HLA-A*02 LOH for the EVEREST-1 and -2 Tmod chimeric antigen receptor T-cell therapy trials. When enrollment began in 2021, eligibility for Part 1 was restricted to patients with germline HLA-A*02:01 based on preclinical data. Additional analysis revealed the blocker in the Tmod construct had activity across HLA-A*02 subtypes (Mock, et al. Mol Ther Oncolytics.2022). Eligibility for Part 1 was then expanded to all HLA-A*02 subtypes, allowing enrollment of more diverse patient populations. HLA-A*02 allele subtypes vary by ethnicity and race; the frequency of HLA-A*02:01 is 96% in non-Hispanic Whites, but ranges from 53% to 73% in other ethnicities and races. The frequency of all other HLA-A*02 allele subtypes (HLA-A*02:XX) is <5% in non-Hispanic Whites but up to 66% in other ethnicities and races (2,3). Methods: Patients eligible for BASECAMP-1 were identified at United States study sites. All patients screened before January 16, 2024, for Part 1 were included for demographic and central lab HLA-A typing. The % increase in eligibility and % of heterozygous HLA-A*02 patients with HLA-A*02:XX were calculated by ethnicity and race. Results: A total of 1124 patients were screened for germline HLA-A*02 typing; 431 patients were HLA-A*02:01 heterozygous, of whom 37 (9%) were Hispanic, 14 (3%) African American (AA), 2 (<1%) American Indian or Alaska Native, 17 (4%) Asian or Pacific Islander (API), and 324 (75%) non-Hispanic White (Table). The eligibility expansion identified 62 patients with HLA-A*02:XX heterozygosity, of whom 6 (10%) were Hispanic, 6 (10%) AA, 19 (31%) API, and 25 (40%) non-Hispanic White. Conclusions: By expanding enrollment to include HLA-A*02:XX, 16% more Hispanic, 43% more AA, and 112% more API patients were identified, improving the diversity in this trial compared with that of initial enrollment. 1. Aldrighetti, et al. JAMA Netw Open 2021. 2. Ellis, et al. Human Immunol. 2000. 3. Gragert, et al. Human Immunol.2013. Clinical trial information: NCT04981119 . [Table: see text]
Unveiling inequities in representation: Racial disparities in supportive care breast cancer clinical trial enrollment.
Authors: Reyes Kevin R , Lau Bryan Hill-Fung , Tang Felicia , Gardner Bianca , Cui Kathleen , Trejo Evelin , Velazquez Manana Ana I.
Published: May 2024

1605

Background: Supportive care is an integral part of breast cancer survivorship care. However, not much is known if there is adequate representation of racial minorities in supportive care breast cancer (BC) clinical trials (CTs). Methods: We conducted a systematic review of supportive care CTs for patients with BC using Covidence. A search of clinicaltrials.gov identified 2695 CTs, of which 173 met inclusion criteria. The SEER database was used as a racial distribution data reference for patients with BC. One-sample proportion tests were performed to assess adequacy in racial representation among supportive care CTs and by intervention type. Results: Of 173 supportive care CTs, 133 (77%) trials reported race-specific data. Characteristics of supportive care CTs based on intervention type and race are shown (Table). Although no statistically significant differences in frequencies of Black participants in supportive BC CTs overall were observed compared to the US population (11% vs 12%, p= 0.40), they were underrepresented in symptom management CTs specifically (8% vs 12%, p= 0.004). When stratified based on diet/physical activity CTs, Black participants were overrepresented in the study population (18% vs 11%, p= <0.001). Asian participants were underrepresented in the overall study population compared to the US population (5% vs 7%, p= 0.01). However, within psycho-oncology CTs, there was an overrepresentation of Asian participants in the study population (21% vs 7%, p = <0.001). No significant differences in enrollment frequencies of Black and Asian participants were found in cognitive health, complementary and alternative medicine, education/communication, and sexual health interventional CTs. Conclusions: Our findings highlight inadequate representation of Asian participants in supportive care BC CTs and Black participants in symptom management CTs. This study is limited in that ethnicity was not included in this analysis. Strategies are needed to promote recruitment of diverse individuals in these settings so that we can more accurately generalize findings from supportive care BC CTs. [Table: see text]
Assessing survival effects of persistent poverty and payer status in non-elderly adults with lung or breast cancer.
Authors: Eom Kirsten Yuna , Davidoff Amy J.
Published: May 2024

1608

Background: Persistent poverty (PP), defined as area poverty ≥20% over 30 years has been associated with increased cancer incidence and worse survival. We examined 1) whether residing in a PP area has larger survival effects than areas with similar contemporary poverty rates; 2) whether adjusting for sociodemographics and payer status reduces PP effects; and 3) whether effects differ for relatively poor (lung and bronchus, LCa) vs good prognosis (female breast; BrCa) cancers. Methods: We used Surveillance, Epidemiology, and End Results (SEER) data linked to Medicaid and Medicare enrollment records (2007-2013), with census-tract level indicators for PP and current poverty (CP) as of 2010. We selected adults aged 19-64, diagnosed with LCa or BrCa. We created a hierarchical poverty status measure (PP, CP>20%, CP 10-20%, CP <10%). Primary payer at diagnosis (SEER) was edited using Medicaid and Medicare enrollment records. Covariates include patient sociodemographics (including age, race, sex (LCa only), marital status), rurality, and region. We used Cox proportional hazard models to estimate effects of poverty status and payer on survival, starting with a limited Model I (poverty status, rurality, and cancer stage), adding sociodemographics, region, and diagnosis year (Model II), plus primary payer (Model III). Results: Among LCa (BrCa) 8.8% (5.3%) of 70,964 (246,405) patients lived in PP areas, with 19.1% (13.7%) in areas with CP >20%; primary payers included 51.9% (75.0%) private, 28.7% (16.9%) Medicaid, and 3.1% (1.1%) uninsured. For both cancers, adjusted hazard of death increased with increasing poverty levels; PP areas showed the highest risk (table). The magnitude of the poverty gradient was smaller for LCa vs BrCa. Adjusting for sociodemographic measures and primary payer reduced the magnitude of poverty status effects, particularly for BrCa. Conclusions: We observed significant but distinct associations of poverty status, including PP, with survival for non-elderly adults with LCa and BrCa. With better prognosis, BrCa patients have longer exposure to PP, which may increase the impact on outcomes. Person-level characteristics and health insurance are also key factors affecting care access and survival. These results highlight the need to consider both area context and personal socioeconomic characteristics when targeting and evaluating interventions to enhance survival outcomes. [Table: see text]
Potentially inappropriate medications and their association with frailty, unplanned hospitalizations, and mortality in patients with cancer treated in the national U.S. Veterans Affairs Healthcare System.
Authors: La Jennifer , Hshieh Tammy , Hamparsumian Anahid , Zwolinski Robert , Wood Jameson , Dharne Mayuri , Gaziano J. Michael , Brophy Mary T. , Do Nhan , Munshi Nikhil C. , Driver Jane A. , Abel Gregory A. , Fillmore Nathanael , DuMontier Clark
Published: May 2024

1620

Background: We previously operationalized the NCCN list of high-risk medications in older adults into a measurable scale—Geriatric Oncology Potentially Inappropriate Medications (GO-PIMs)—to aid oncology teams in identifying PIMs and understand their impact (1). This scale revealed that PIMs were prevalent and associated with frailty in older patients with blood cancers. The current study aims to evaluate the ability of GO-PIMs to identify high-risk medications and their impact in patients with both solid and liquid tumors managed in a large national healthcare system. Methods: We performed a retrospective cohort study using data from the national Veterans Affairs (VA) Cancer Registry and electronic health record, including all veterans newly diagnosed with a solid or liquid malignancy in the years 2000-2023.The number of GO-PIMs for each patient were measured among outpatient pharmacy prescriptions in the 90 days preceding the initial diagnosis date (the index date). We evaluated the association of PIMs with baseline frailty (the electronic Veterans Affairs-Frailty Index [VA-FI], categorized as nonfrail [0-0.2], mildly frail [>0.2-0.3], and moderate-to-severely frail [>0.3]), time to unplanned hospitalization, and mortality in multivariable models adjusting for age, gender, cancer type and stage, Charlson comorbidity index, and socioeconomic factors (rurality, area deprivation index, and history of homelessness). Results: Among 307,487 newly diagnosed patients (median age 68.5, IQR 62.1-75.8; most common cancers: prostate [20.5%], lung [23.1%], GI [21.3%]), GO-PIMs were prevalent (39% patients with ≥1 GO-PIM). The most common classes of PIMs were SSRIs (12.4%); opioids (10.7%); benzodiazepines (9.5%), and corticosteroids (9.5%). Each additional PIM increased the odds of being mild or moderate-to-severely frail at diagnosis by 65%, controlling for all covariates (ordinal regression adjusted OR [aOR] 1.65, 95% CI 1.63-1.66). Increasing number of PIMs was also associated with a higher hazard of unplanned hospitalization (Cox regression aHR 1.04, 95% CI 1.04-1.05) and death (Cox regression aHR 1.05, 95% CI 1.05-1.06), controlling for frailty and all covariates. Conclusions: Independently of cancer type and stage, comorbidity, and other covariates, increasing PIMs identified by the GO-PIMs scale was associated with an increased risk of frailty at diagnosis, unplanned hospitalization in follow-up, and death. We are implementing the GO-PIMs scale in a clinician-facing application that will automate real-time detection of PIMs and recommendations for oncology teams in routine clinical practice. 1. Hshieh and DuMontier et al., J Natl Compr Canc Netw, 2022.
Effect of a 12-week remote exercising program (ExIOnc) on quality of life and symptoms of older patients with cancer in Brazil.
Authors: Bergerot Paulo Gustavo , Bergerot Cristiane Decat , Silva Jonas Ribeiro Gomes , Franca Marcos V S , Lages Dr. Paulo Sergio , Vargas Pivato de Almeida Daniel , Paes Marcio Almeida , Fuzita William Hiromi , Buso Daniel Sobreira de Oliveira , Azeredo Andressa Cardoso , Fernandes Cristiano Menezes , Matos Neto Joao Nunes , Buso Murilo , Buso Murilo , Dale William , Schmitz Kathryn , Florez Narjust , Soto Pérez de Celis Enrique
Published: May 2024

1623

Background: Leading organizations, including ASCO, recommend physical activity for patients with cancer. However, numerous barriers hinder patients from maintaining regular physical activity, particularly among older adults, who have lower participation in exercise programs. This study aims to evaluate the effects of a 12-week supervised remote exercise program on the health-related quality of life (HRQOL) of older patients with cancer (aged ≥65) undergoing treatment in Brazil. Methods: This was a single-arm pilot study evaluating a remote physical activity program which combined supervised and remote exercise. Eligible patients were contacted through WhatsApp for the initial assessment and received guidance on weekly exercises. The Vedius platform was employed to demonstrate proper home exercise techniques. The prescribed regimen consisted of 3-5 hours per week (4-6 days a week), encompassing both resistance and aerobic exercise. Outcome measures included overall HRQOL (FACT-G, scale 0-108) and symptom assessment (ESAS). Assessments were conducted at baseline and after 12 weeks. Descriptive statistics were calculated, and linear mixed models were employed to analyze changes from before to after the intervention. Results: Out of 46 approached patients, 41 patients were enrolled, with a median age of 70 years (range 65-88). Of the participants, 56.1% were female, 70.7% were white, and 58.2% were married, with 53.5% holding a college degree. The most common cancer types were breast (26.8%), genitourinary (22.0%), and lung (17.1%), all diagnosed at advanced stages. A significant improvement was observed in overall HRQOL (MT1=83.2 to MT2=94.4, P=0.001). Improvements were also seen in the severity of various symptoms, including pain (MT1=1.6 to MT2=0.7, P=0.001), fatigue (MT1=3.8 to MT2=1.3, P=0.001), nausea (MT1=0.8 to MT2=0.2, P=0.01), depression (MT1=2.6 to MT2=0.8, P=0.001), anxiety (MT1=3.2 to MT2=1.2, P=0.001), drowsiness (MT1=1.8 to MT2=0.4, P=0.001), and appetite (MT1=2.2 to MT2=0.6, P=0.001). Conclusions: This study demonstrates a positive impact of a 12-week remote physical activity program on HRQOL and symptom management for older patients with cancer, and set the stage for future randomized trials. Despite the challenges posed by cancer treatment, incorporating such programs into patient care could be an effective strategy to enhance overall well-being and mitigate treatment-related symptoms.
Accelerated epigenetic aging and risk of chemotoxicity in older adults with early breast cancer.
Authors: Ji Jingran , Sun Can-Lan , LeVee Alexis Ann , Sedrak Mina S.
Published: May 2024

1624

Background: Older adults with breast cancer have considerable heterogeneity in their risk of chemotoxicity; two people with the same chronological age have different risks of chemotoxicity. This heterogeneity in chemotoxicity may be due to older adults having variable rates of biological aging. Some older adults age faster biologically compared with their chronological age (i.e., accelerated epigenetic aging [AEA]), while others do not. AEA is a blood biomarker of aging, but its utility as a biomarker of chemotoxicity is unknown. Here, we evaluated the association between AEA and risk of chemotoxicity in older adults with early breast cancer. Methods: In a prospective multicenter study of 397 women age >65 with stage I-III breast cancer treated with neo/adjuvant chemo, we extracted genomic DNA from blood to estimate the participant’s rate of biological aging at baseline (prior to chemotherapy). Using two established epigenetic clocks (AgeAccelGrim and DunedinPACE), we classified individuals as either having AEA or not (dichotomized as a yes/no variable) for each clock. Our primary endpoint was grade 3+ chemotoxicity (yes/no, yes defined as any grade 3+ toxicity attributed to chemo). Using multivariable logistic regression, we examined the association between AEA and grade 3+ chemotoxicity, adjusting for sociodemographic, geriatric, and clinical covariates. Results: The median (range) pretreatment chronological age was 70 (65-85), AgeAccelGrim was -0.88 (-10.4-15.7), and DunedinPACE was 1.03 (0.69-1.45). Of the 397 women, 31 (8%) had AEA per AgeAccelGrim, 63 (16%) had AEA per DunedinPACE, and 184 (46%) experienced grade 3+ chemotoxicity. Women who had evidence of AEA as measured by AgeAccelGrim (≥6.83 years, adjusted OR = 2.73, 95% CI 1.17-6.41, p = 0.02) or DunedinPACE (≥1.17 biological years per chronological year, adjusted OR = 2.20, 95% CI 1.18-4.10, p = 0.01) had greater odds of having grade 3+ chemotoxicity compared to women without AEA (AgeAccelGrim <6.83 or DunedinPACE <1.17, respectively). Conclusions: In this cohort of older women with early breast cancer, those with pre-chemo AEA had increased odds of chemotoxicity compared to women without any evidence of AEA. Future research is needed to examine whether measures of biological age can be translated to the clinical care of older patients with breast cancer. Clinical trial information: NCT01472094 . [Table: see text]
Multi-cancer early detection (MCED) test performance in cancer survivors.
Authors: Marinac Catherine , O'Donnell Elizabeth , Shaknovich Rita , Clarke Christina A. , Walia Guneet , Chung Karen , Farese Jennifer , Lopatin Margarita , Fung Eric T. , Venstrom Jeffrey M. , Klein Eric A. , Karlitz Jordan J.
Published: May 2024

1628

Background: Cancer survivors (CS) are at risk for recurrent or new primary tumors in any organ, but there is lack of clear guidance and options for long-term surveillance. We analyzed the performance of a blood-based MCED test that detects cancer-specific methylation patterns and predicts cancer signal origin (CSO) in CS in the PATHFINDER study (PF; NCT04241796). Methods: PF enrolled6662 participants (pts) ≥50 yr without clinical suspicion of cancer; 6578 samples were analyzed with a refined MCED test. Pts were stratified by CS status (treated cancer >3 yr prior to study vs no prior cancer); in CS, prior cancer type and time from diagnosis were recorded. Cancers diagnosed during PF were classified as recurrent or new primaries. Positive predictive value (PPV), number needed to screen (NNTS), and CSO accuracy were assessed. Results: CS comprised 25% (1609/6578) of pts analyzed; 73% were female. Median age was 66 yr; age at prior diagnosis was 8% <40, 22% 40-49, 70% ≥50 yr. Most common prior cancers were breast (749, 47%), melanoma (163, 10%) and prostate (141, 9%). A higher proportion of pts with cancer diagnosis was observed in CS vs those with no prior cancer (Table). Among 20 CS with cancer signal detected, 10 cancers were diagnosed in 9 pts; 5 recurrent (all metastatic breast) and 5 new primaries (uterine stage 1 [found as incidental lesion on imaging during MCED-triggered workup for recurrent breast cancer], sarcoma stage 2, ovarian stage 3, lymphoma and CRC stage 4). During 1-yr follow-up in those with negative MCED result, new cancer diagnoses in CS included 13 recurrences (all local) and 15 new primaries. Of the 13 new primaries with known stage, 46% were stage 1 (2 breast, 1 melanoma, 1 thyroid, 1 lymphoma, 1 lung), 31% stage 2 (2 lymphomas, 1 melanoma, 1 breast), 15% stage 3 (1 pancreas, 1 pleural mesothelioma), and 7% stage 4 (1 prostate). Yield, PPV, NNTS, and CSO accuracy were similar in CS and no prior cancer group. Years between MCED cancer detection and prior cancer in CS was 4-11 for recurrent and 8-15 for new primaries. Most (4/5) new primaries were cancers with no USPSTF-recommended screenings. Conclusions: The MCED test detected both cancer recurrences and new primaries in CS for whom multiple years had elapsed since their original diagnosis, potentially expanding surveillance options for this patient group. Cancers in CS not detected by MCED were predominantly early stage. Test performance was similar in those with and without a cancer history. Clinical trial information: NCT04241796 . [Table: see text]