Working Group Research Articles

Prevalence and associated body composition factors of sarcopenia in community-dwelling older adults

BackgroundThe objective of this investigation was to examine the frequency and determinants related to body composition of sarcopenia among aging individuals residing in the Beijing community through implementation of the diagnostic criteria for sarcopenia outlined by the 2019 Asian Working Group for Sarcopenia (AWGS).MethodsA cross-sectional examination employing multistage cluster sampling was conducted on a sample consisting of 933 individuals aged 50 years or above. The study utilized the AWGS 2019 criteria for muscle mass, muscle strength, and physical function to gauge sarcopenia. In addition, data on demographic characteristics, anthropometry, and body composition were collected. Logistic regression analysis was carried out to ascertain the relationships between sarcopenia and correlated factors.ResultsThe study found that the overall prevalence of sarcopenia was 8.3%. Sex (p < 0.001) and body mass index (BMI p < 0.001) were determined to have a significant association with the occurrence of sarcopenia. The adjusted analyses demonstrated that with each standard deviation increase in fat-free mass index (OR = 0.02 (0.01–0.05), of 95%), skeletal muscle mass (OR = 0.17 (0.12–0.25), of 95%), and other body composition indicators (including total body water 0.26 (0.2–0.35), intracellular water 0.1 (0.06–0.17), protein 0.01 (0–0.02), soft lean mass 0.35 (0.28–0.44), BMI 0.58 (0.51–0.67), body cell mass 0.21 (0.15–0.29), OR < 0.60, of 95%), the risk of sarcopenia decreased by more than 40%. Certain straightforwardly accessible anthropometric indices such as upper arm circumference (correlation coefficient 0.94 (0.9–0.97), 0.97 (0.95–1), 1.01 (0.99–1.03), respectively, of 95%), waist circumference (0.94(0.92–0.96), 1.01 (0.99–1.03), 1.02 (1–1.03), of 95%), hip circumference (0.93 (0.9–0.96), 0.99 (0.97–1.02), 1.02 (1–1.04), of 95%), waist-to-hip ratio (0.93 (0.87–1), 1.04 (1–1.08), 1 (0.97–1.03), of 95%), body fat percentage (1 (0.98–1.02), 1.02(1–1.04), 1.01 (0.99–1.02), of 95%), and phase angle (0.91 (0.89–0.93), 0.96 (0.94–0.98), 0.99 (0.98–1), of 95%) exhibited substantial correlation with skeletal muscle index, muscle strength or physical performance. However, no noteworthy link between sarcopenia and most variables associated with physical function was discovered.ConclusionsThe findings of the study highlight the prevalence of sarcopenia among the aging residents of Beijing. Certain easily measured anthropometric indices demonstrated strong correlation with muscle strength or physical performance, thereby providing an avenue for screening and diagnosing sarcopenia in older people who may not be able to undergo grip strength or physical function assessments. To investigate causal relationships, future studies employing longitudinal or interventional designs with a more comprehensive population are warranted.

Robotics: Road Ahead for Mechanical and Physical Necessities, Bridging AI and Integration Challenges

Abstract On behalf of ASME Robotics Technology Group Working Groups, this paper provides a preview of their recently published 2024 ASME Robotics Roadmap. The onset of Industry 5.0 and its coexistence with Industry 4.0 are moving robots and manufacturing from traditional automation into the ‘smart manufacturing’ realm. With conflicting priorities of productivity and safety, building mutual ‘trust’ between robots and humans requires bridging the sensing and AI with the mechanical-n-physical necessities to successfully augment the robot's awareness and intelligence. To this end, the ASME Robotics Technology Group convened several working groups to produce a robotics roadmap that embodies the mechanical engineering aspects. The roadmap was written with the aim 1) to embody mechanical and physical necessities and bridge the gaps between AI and integration challenges; 2) to identify critical trends, top-of-market challenges, and knowledge gaps; and 3) to identify opportunities in the journey – path to get there and in strengthening the mechanical engineering footprint in robotics technology. While robotics cuts across many technological areas, industry segments, and applications for the greater good, the focus is on identifying what are the enabling technologies and science needed for human-robot physical interaction and beyond physical; robot-to-robot and robot-to-(autonomous) machine collaboration; increasing robot repeatability and accuracy; space-based robotic manufacturing and assembly; human-centered manufacturing; risk and safety aspects of robotics; and what should ASME, government and industry do to advance robotics.

Identity Work in Interdependent Professional Groups: The Role of a Target Identity in Enterprise Systems Implementation

Powerful new technologies in the workplace are significantly changing what employees do and how they depend on others. Key tasks that professionals regard as core to their job are automated, forcing entire professional groups to reconsider their identity within their organization. In doing so, professional groups can either feel threatened and resist new technology or develop enhanced role identities that they pursue using the technology. Our study of financial accountants and management accountants shows how managers can help employees develop enhanced role identities and become more satisfied with their jobs. Managers should ensure that each professional group has early and concrete experiences with how new technology helps them perform new, value-added tasks that are consistent with their sense of who they are as professionals in the organization. However, management must also consider how different organizational functions and professional groups will work together in light of new technology. During the technology implementation process, managers and consultants should foster intensive exchange and critical discussion among interdependent professional groups to facilitate an open renegotiation of which professional group takes on which of the existing and new organizational tasks.

Impact of Subjective Masticatory Difficulty on Malnutrition and Frailty in Community-Dwelling Older Adults.

This study evaluated the impact of masticatory difficulty on the development and progression of malnutrition, frailty, sarcopenia, and disability in community-dwelling adults, using data from the Korean Frailty and Aging Cohort Study. Participants were categorised by presence of masticatory difficulty. The Fried frailty phenotype, mini-nutritional assessments, and diagnostic criteria proposed by Asian Working Group on Sarcopenia were adopted to diagnose frailty, malnutrition, and sarcopenia respectively. Physical disabilities were measured using the Korean activities of daily living (ADL) and Korean instrumental activities of daily living (IADL) scales. A total of, 3010 participants were initially enrolled, 2864 participants remained in the study after 2 years, reflecting a 95.1% retention compliance. At baseline, the prevalence of frailty (28.0% vs. 18.1%), malnutrition (1.5% vs. 0.8%), IADL disability (10.1% vs. 7.7%), and ADL disability (10.8% vs. 8.0%) was higher among those experiencing masticatory difficulty than in those without. After 2 years, baseline masticatory difficulty was associated with the incidence of malnutrition (OR, 2.62; 95% CI, 0.99-6.90; p = 0.042) after full adjustment for confounders. However, no associations were found between baseline masticatory difficulty and the incidence of frailty, sarcopenia or physical disability over 2 years after adjustment. Additionally, masticatory difficulty did not affect the persistence or remission of malnutrition, frailty, sarcopenia, IADL disability, and ADL disability in individuals who already had these conditions at baseline. Restoring chewing function and masticatory satisfaction improves not only oral health but also contributes to overall health and promotes healthy aging in older individuals.

Regulatory Considerations for Stability Studies of Co-Processed Active Pharmaceutical Ingredient.

A co-processed active pharmaceutical ingredient (CP API) is the combination of an active pharmaceutical ingredient (API) with non-active component(s). This technology has been demonstrated to offer numerous benefits, including but not limited to improved API properties and stability. The infrastructure requirements are such that the manufacture of a CP API is typically best suited for an API facility. CP API has been regulated as either an API or as a drug product intermediate (DPI). This variability in the designation has led to ambiguities on the regulatory CMC expectations in the CP API including the stability of CP API and CP API containing products which, in turn has hampered the broader application of this technology in the pharmaceutical industry. This difference in designation also resulted in challenges to the lifecycle management of the regulatory documentation for the CMC information of the CP API.This white paper represents the proposals for the regulatory requirements on stability studies related to CP API and to drug product containing CP API by the CP API Working Group (WG) of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ). Additionally, considerations and the WG's recommendations on the stability studies of CP API from different manufacturing sites or processes and post-approval changes for product containing CP API are described.

A proposed roadmap: one department of surgery’s plan for diversity, equity, and inclusion

PurposeDisparities remain in academic surgery that negatively impact our patients and our community in multiple ways. The Department of Surgery (DoS) at Oregon Health & Sciences University (OHSU) formally established a Diversity, Equity, and Inclusion (DEI) Council in 2020 to address the multifaceted etiologies of these inequities. This manuscript describes the steps taken by this council to create a more diverse, equitable, and inclusive workspace, which were guided by the framework provided in the white paper “Ensuring Equity, Diversity, and Inclusion in Academic Surgery” by West et al.MethodsThe DEI Council was constructed into four working groups: Antiracism, Gender Equity, LGBTQIA + , and Community Engagement. Each group is charged with a unique mission statement to address pertinent inequalities. Various initiatives include educational lectures, workshops, quality improvement and health advocacy projects.ResultsThe DEI Council has achieved progress by modifying hiring, promotion, and tenure policies and facilitating mentorship. Changes have been made to call expectations and lactation policies for residents and faculty who are expecting or new parents. Nine observerships and financially supported subinternships for underrepresented groups have been completed and will continue. DEI professional development modules, retreats, and monthly cultural humility discussions have been established. Cultural humility and competence of the DoS cohort has been measured through validated tools.ConclusionThere is much work ahead to achieve our DEI goals. This manuscript demonstrates progress that can be replicated and improved at other institutions as we all strive toward a more diverse, equitable, and inclusive world of academic surgery.

Teaching methodologies in calculus for engineering: a quantitative analysis

This research quantitatively analyzes worldwide university studies on teaching Differential and Integral Calculus, comparing them with the challenging Brazilian context, which historically faces high rates of failure. Following a Systematic Literature Review structure, 122 documents from different databases (Capes, Scopus, Web of Science, and Science Direct) were reviewed. The focus was placed on worldwide teaching methods for differential and integral calculus, with defined filters and inclusion/exclusion criteria for relevance. According to the results, there is a global rise in alternative and active teaching and learning methods usage. Thus, technological advancements in calculus education through software and group work are highlighted as other means to establish a more student-centric and achievement-oriented learning process. Despite the global progress in teaching calculus, the comparison with Brazil reveals the need to enhance teaching methodologies in national institutions, given the limited number of published studies exploring alternative teaching approaches.

Fixed or weight-adjusted dose in immunotherapy?

ObjectiveTo analyse the economic impact of the use of immune checkpoint inhibitors in fixed-dose regimens and to determine the potential economic savings of using weight-adjusted dosing, as well as to...

Interaction between National and Local Governments in Rural Revitalization of China

The article examines the specifics of the interaction of rural working group sent by the Communist Party of China to rural areas with local party bodies and rural self-government; analyzes the selection mechanism and staffing requirements of such groups. Rural working group are an important institutional mechanism by which the party pursues its political line in rural areas. In different historical periods, the content of work in villages and the focus of assistance have changed. Such changes reflected to a certain extent the relationship between the rights of the rural community and the state authorities, as a result of which the village management structure was in a state of constant debugging. After the completion of the formation of a moderately prosperous society in all respects, the criteria for the selection and evaluation of personnel for working group on rural development sent to villages became more stringent. Despite the symbiotic relationship between rural groups and rural "two committees" (the local government committee and the local CPC committee) from the point of view of institutional norms, the specific practice of their interaction has a number of problems, among which are blurring in the distribution of powers and responsibilities, contradictions in the motivations of the activities of workers' working group on rural development and local "two committees". In this regard, rural target groups face a twofold task. First, they must comprehensively and correctly integrate into the daily activities and life of the village in order to build harmonious relations with farmers and rural "two committees". Secondly, such groups should pay more attention to two-way communication with organizations and institutions responsible for the mission of the task force to rural areas; do not hide the difficulties in their work and inform the leadership of the structures that sent the task force to the village about the problems that arise in order to receive all the necessary sufficient assistance.

Analyzing Bilateral Trade Dynamics between Azerbaijan and Pakistan: A Robust Least Squares Regression Approach

&lt;p class="MsoNormal" style="margin-top: 12pt; text-align: justify;"&gt;&lt;span lang="EN-US" style="font-family: 'times new roman', times, serif; font-size: 14pt;"&gt;The diplomatic relations between Azerbaijan and Pakistan have undergone significant development since the late 1990s. Despite some studies focusing on diplomatic and political relations, the economic dimension of this partnership has not been systematically covered. In this paper, a robust least squares (RLS) approach is used to model bilateral trade between the two countries and identify statistically significant determinants, including economic, institutional, and cultural factors, after analyzing the main economic and subsectoral trade dynamics of both countries. The results reveal that Azerbaijan's imports from Pakistan are significantly associated with the country's higher income and market size, while Pakistan's elevated exchange rate and trade costs hinder bilateral trade. In addition, Pakistan's rising manufacturing output increases exports to Azerbaijan but decreases imports from Azerbaijan. Among institutional determinants, government effectiveness, the trade freedom index (TFI), and political stability play significant roles in bilateral trade. Lastly, it was found that cultural proximity increases Pakistani exports to Azerbaijan but not imports from Azerbaijan. The analysis also indicates that domestic savings stimulate Pakistani exports. These findings underscore the complex nature of bilateral trade between Azerbaijan and Pakistan and highlight the need for institutional arrangements to harmonize trade flows and boost welfare gains from trade. The results may be of great importance to intergovernmental working groups, domestic policymakers, and businesses.&lt;/span&gt;&lt;/p&gt;

Evaluating the Effectiveness of Collaborative Strategic Reading on EFL Female University Students' Reading Comprehension

This study aimed to evaluate the feasibility and effectiveness of Collaborative Strategic Reading (CSR) in improving reading comprehension among second-year female English as a Foreign Language university students. A mixed-methods approach was employed, involving quantitative pretest and posttest assessments and qualitative feedback from students and teachers. The study included 61 participants divided into three groups, with each group undergoing CSR sessions over eight weeks. Pretest and posttest scores were analyzed using paired-sample t-tests and regression analysis to determine the statistical significance of the changes in participants’ reading comprehension. This study found that CSR significantly contributed to reading comprehension. Additionally, the regression analysis showed that CSR intervention significantly predicted posttest scores, confirming the substantial positive impact of CSR on reading comprehension. The findings from the semi-structured interviews revealed that most students found the CSR sessions to be useful and enjoyed working in groups. Teachers reported significant improvements in students' reading skills and engagement with enhanced classroom dynamics. However, challenges such as resource allocation and the need for continuous teacher training were also identified. Thus, CSR is an effective and feasible instructional strategy for enhancing reading comprehension among English as a Foreign Language students. The findings of the current study highlight CSR's potential to improve academic performance and foster a collaborative learning environment, as well as have implications for reading instruction and learning. Further research is recommended to explore the long-term effects of CSR and its applicability in different educational settings.

Knowledge among clinical personnel on the impact of hemolysis using blood gas analyzers.

In the light of a rapidly increasing use of POCTblood gas testing, where tests and interpretation are performed by non-laboratory personnel, the objective was toinvestigate the knowledge among personnel in the Nordic countries using blood gas analyzers with focus on the interference from hemolysis. Information was obtained from a self-developed, pre-tested online questionnaire. The questions covered demographic information about the respondents and specific questions on handling of and knowledge about blood gas analyses and the impact of hemolysis. The questionnaire was distributed by e-mail to relevant colleagues on behalf of theNordic preanalytical scientific working group under the Nordic Federation of Clinical Chemistry. A total of 117 respondents completed the questionnaire. 62.7 % respondents both used the analyzer and interpreted the results. 59.6 % respondents did not know to which degree the blood gas analyzer can identify hemolysis. 4.4 % answered that all levels or high levels of hemolysis can be detected. 3.9 % considered the result valid despite hemolysis if it is released from the instrument. 73.7 % of all respondents knew that hemolysis alters potassium measurements, while knowledge about the effect on PaO2 and bicarbonate measurements were more divergent. The knowledge about blood gas analyzers with focus on the interference from hemolysis is sparse among non-laboratory personnel using the blood gas analyzers. This emphasizes the need for better education and competence management, which perhaps is even more important for these analyses than for other point-of-care tests.

PELATIHAN STEAM UNTUK MEMBANGUN KREATIVITAS DAN INOVASI ANAK SD DI SDN 1 PERAMPUAN KABUPATEN LOMBOK BARAT

STEAM (Science, Technology, Engineering, Arts and Mathematics) training at SDN 1 Perampuan, West Lombok, aims to improve the creativity, innovation and critical thinking skills of grade 4 students. Through an interactive and practical approach, this training involves students in experiments simple and collaborative projects, allowing them to integrate various disciplines. This activity will be carried out in September 2024 using observation, experimentation, collaborative projects and feedback-based evaluation methods. Initial observations are carried out to identify learning needs and challenges, followed by preparation of materials and tools. The training involved an introduction to basic STEAM concepts, simple experiments such as building a mini volcano, technology development through basic coding, and the integration of art and mathematics in bridge design. Each session features a collaborative project, where students work in groups to apply the knowledge they have gained. Evaluation is carried out through project presentations and providing feedback to improve and enhance student skills. The results of the training showed high student enthusiasm, as well as increased understanding of basic STEAM concepts. Final project evaluations provide constructive feedback, encouraging students to continue learning and applying STEAM concepts in everyday life. With the support of the STEAM guidebook, this training is expected to have a long-term impact on educational development in the West Lombok area, preparing students to face future challenges with the necessary 21st century skills.

Performance, Democracy, and the Commune in the Black Sheep Revolution

This article analyzes cultural production in theaters across three pivotal historical moments from the 1980s to the present, including the theater as ruins, refuge, and resistance. It begins with the theater in ruins as depicted in the 1986 film, The Black Sheep, by the legendary playwright, director, and filmmaker, Román Chalbaud, in which a commune of artists, outcasts, and misfits squat in the theater, taking shelter from a storm of state-sponsored neoliberal austerity, corruption, and persecution in the pre-Chávez era of Venezuela. The article then turns to the work of community groups during Chávez-led revolutionary reforms to recuperate abandoned theaters as vital spaces for democratic assembly through municipal government programs. The last section of the article juxtaposes the advanced democratization of theaters and cultural production in Caracas during the Maduro era with a phase of violent street mobilizations in middle-class and wealthy sectors of the city (known as guarimbas), to raise questions about the role of the media as an intervening character in global theaters of illusion. Where the spotlight shifts in location from stages to streets, and the street to the screen, the actual conditions of democratized access are happening behind the unlit marquis, a global majority operating in an ‘underground’ commune in the same scenario as the film. Except in this case, the military-media arm of the US polices the ‘streets’ of the global media commons to malign the Bolivarian Revolution as a black sheep political project. The conclusion points to the media’s role in promoting a dangerous misperception of reality by erasing the constituent power of a revolutionary society and the perpetuation of violence against them.

Implementing FAIR data principles in the IPCC seventh assessment cycle: Lessons learned and future prospects

Every five to seven years, the Intergovernmental Panel on Climate Change (IPCC) convenes the climate science community to assess the latest knowledge on climate change relevant to policy-makers. This generally takes the form of Assessment Reports (AR) covering the scientific basis of climate change, its impacts and future risks, and options for adaptation and mitigation. With each cycle, these reports have grown in scope, length, number of referenced papers, and underpinning datasets. During the sixth assessment cycle, a large-scale collective effort went into archiving digital products assessed and generated through the IPCC process. The main objectives driving this initiative are making IPCC’s work more transparent, improving the reproducibility and reusability of the assessment outcomes, better utilization of the services of the IPCC Data Distribution Centre (DDC), and, more generally, compliance with best practices in open science. This paper expands on the motivations for the curation and preservation of digital objects in the IPCC. It gives an overview of how FAIR (Findable, Accessible, Interoperable, Reusable) and open data principles have been implemented in practice and explores some of the successes and setbacks of the AR6 experience. It concludes with recommendations for consolidation and expansion of the approach for AR7. These include a tighter integration of digital curation activities in the IPCC timeline and workflows, better support of IPCC authors and contributors through early training and use of suitable software, improved standardization and harmonization of data and software handling across Working Groups (WGs), and close collaboration with key external data providers and research organizations.

VET leaders’ collaborative problem-solving skills: insights from a professionals’ master’s degree program

Vocational education and training (VET) structures are ecosystems bound to collaboration. As VET leaders’ roles become increasingly diverse and demanding, challenges must be addressed through collaborative efforts within teams. Leaders’ collaborative problem-solving (CPS) skills remain unexplored despite the importance of CPS in VET settings. This single case study investigates the CPS skills that VET leaders use in addressing tasks and challenges in an educational setting. Postgraduate students in a professional master’s degree program with several years of work experience in VET leadership positions served as study participants. We utilised content analysis on video data of participants engaging in group work on an assignment that required them to give both constructed responses and creative solutions. The study also analysed VET leaders’ self-reflections on their CPS skills collected through a survey tool. Our results revealed that despite participants’ similar professional profiles, their performance in CPS varied significantly. Older participants seemed to have better self-reflection skills, and experienced professionals could allocate cognitive resources to more complex strategic and meta-cognitive processes. This study can be used as a roadmap for targeted professional development programs aiming to improve CPS skills and for informed decisionmaking in choosing professionals for pivotal leadership positions.

Comparative Study on Associations Between Lung Cancer Prognosis and Diagnostic Criteria Set by the European Palliative Care Research Collaboration and the Asian Working Group for Cachexia.

Cachexia is a poor prognostic factor in many advanced cancers. Cachexia diagnostic criteria of the European Palliative Care Research Collaboration (EPCRC) may underestimate cachexia in Asians; therefore, new criteria have been proposed by the Asian Working Group for Cachexia (AWGC). We compared both criteria to determine differences in diagnostic rates and their association with lung cancer prognosis. This single-center, retrospective cohort study considered lung cancer outpatients receiving chemotherapy. Survival was analyzed using Kaplan-Meier curves and log-rank tests. The association between cachexia diagnosis and prognosis was examined for each set of criteria using a Cox proportional hazards model. C-statistic analysis was performed to compare the discriminative power for prognosis. Among the 106 participants analyzed (median age, 75 [71-79] years; 75 males [70.8%]; 91 [85.9%] with performance status [PS] 0-1), 58 (54.7%) and 77 (72.6%) cachexia cases were diagnosed using the EPCRC and AWGC criteria, respectively. The latter encompassed all but one patient diagnosed using the EPCRC criteria. Patients with cachexia had a significantly poorer prognosis according to both criteria (EPCRC, p = 0.002; AWGC, p = 0.001). Both criteria had almost equal discriminative power for prognosis (EPCRC, C-statistic = 0.658; AWGC, C-statistic = 0.658). CRP in the AWGC criteria was most strongly related to prognosis. Cachexia was an independent poor prognostic factor in lung cancer patients receiving chemotherapy under the AWGC and EPCRC criteria, both of which had similar prognostic discriminatory power. Among CRP, anorexia, and grip strength, elevated CRP may be the most prognostically relevant parameter in the AWGC criteria.

Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma.

Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified. Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).

Clinical Benefits and Utility of Pretherapeutic DPYD and UGT1A1 Testing in Gastrointestinal Cancer

To date, the clinical benefit and utility of implementing a DPYD/UGT1A1 pharmacogenetic-informed therapy with fluoropyrimidines and/or irinotecan have not been prospectively investigated. To examine clinically relevant toxic effects, hospitalizations, and related costs while preserving treatment intensity and efficacy outcomes in patients with gastrointestinal cancer. This nonprespecified secondary analysis stems from Pre-Emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE), a multicenter, controlled, open, block-randomized, crossover implementation trial conducted from March 7, 2017, to June 30, 2020, and includes data from Italy according to a sequential study design. The study population included 563 patients (intervention, 252; control [standard of care], 311) with gastrointestinal cancer (age ≥18 years) who were eligible for fluoropyrimidine and/or irinotecan treatment. Data analysis for the present study was performed from May 27 to October 10, 2024. Participants with actionable variants (DPYD*2A, DPYD*13, .DPYD c.2846A>T, and DPYD c.1236G>A for fluoropyrimidines, and UGT1A1*28, UGT1A1*6, and UGT1A1*27 for irinotecan) received drug or dose adjustments based on Dutch Pharmacogenetics Working Group recommendations. The primary outcome was clinically relevant toxic effects (National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥4 hematologic, grade ≥3 nonhematologic, or causing hospitalization, fluoropyrimidines and/or irinotecan causally related). Secondary outcomes included hospitalization rates, toxic effect management costs, intensity of treatment, quality-adjusted life-years, and 3-year overall survival. Overall, 1232 patients were enrolled in Italy, with 563 included in this analysis (317 [56.3%] men; median age, 68.0 [IQR, 60.0-75.0] years). In the intervention arm, carriers of any actionable genotype exhibited a 90% lower risk of clinically relevant toxic effects compared with the control arm (odds ratio, 0.1; 95% CI, 0.0-0.8; P = .04). They also presented higher toxic effect management costs per patient ($4159; 95% CI, $1510-$6810) compared with patients in the intervention arm ($26; 95% CI, 0-$312) (P = .004) and a higher rate of hospitalization (34.8% vs 11.8%; P = .12). The differences were not significant among all patients. Three-year overall survival did not differ significantly between arms, while quality-adjusted life-years significantly improved in the intervention arm. The pharmacogenetics-informed approach did not manifest a detrimental effect on treatment intensity in actionable genotype carriers. In this secondary analysis of PREPARE, pretreatment application of DPYD- and UGT1A1-guided treatment appeared to increase safety and reduce hospitalizations and related costs in patients with gastrointestinal cancer. Clinical benefit did not appear to be affected. ClinicalTrials.gov Identifier: NCT03093818.

Reirradiation Practice in Gynecological Cancer: Insights from a National Survey in Spain.

Given the lack of standardisation in gynecological cancer reirradiation, the Gyneacologial Radiation Oncology (GINECOR) working group on behalf of the Spanish Society of Radiation Oncology (SEOR), works towards to inquire the current state of reirradiation practices among the radiation oncology departments in Spain. An online 37-question survey was sent to all GINECOR members, representing most Spanish centers. The survey addressed general aspects of reirradiation, including experience, reirradiation sites, and techniques used. It included seven clinical case scenarios on reirradiation, and a final section on technical aspects of external beam radiotherapy (EBRT) and brachytherapy (BT) treatment. Descriptive statistics were used for data analysis. Out of 58 centers, 29 responded, with 51.7% performing ≥ 5 reirradiation cases annually. While most centers offer multiple techniques, only 16/29 have access to BT. For in-field local relapse with surgery contraindicated, 79.3% performed BT in endometrial cancer, but only 27.5% treated with BT in cervical cancer recurrence. In this case, 17.2% used SBRT. For endometrial and cervical cancer, 44.8% and 65.4% of centers prescribed doses based on organ-at-risk tolerance, respectively. For pelvic wall/parametrial in-field relapse, 46.4% of the centres reirradiated with stereotactic body radiotherapy (SBRT), and 32.1% with BT. In nodal reirradiation, SBRT was preferred by 90% of centers. Variability was observed in target volume definitions for EBRT and proton therapy. Reirradiation for gynecological cancer remains unstandardized, presenting significant challenges in clinical practice. To improve reirradiation protocols in gynecological cancer, the GINECOR working group is currently conducting a systematic review and formulating Delphi recommendations.