Search

ContextOlder adults with multimorbidity are underrepresented in clinical trials, with enrollment of Asians particularly low.ObjectiveUnderstand perspectives of US Chinese older adults regarding clinical trial participation.Study design and analysisFocus group interviews analyzed using thematic analysis.SettingCommunity/senior centers, academic health systems in Northern and Southern California, and a nationwide registry of Asian Americans/Pacific Islanders.Population studiedMandarin- and English-speaking Chinese adults aged ≥ 65 years with multimorbidity.Outcome measuresThemes related to barriers and facilitators of enrollment in clinical trials of medications.ResultsWe conducted 12 focus groups: 7 with non-US-born and 5 with US-born Chinese older adults (n = 83 total). Mean age was 74 years (SD = 5.9), 43 (51.8%) were female, and 47 (56.6%) Mandarin-speaking. US-born participants had greater educational attainment than non-US-born participants. Participants took a mean of 6.1 prescriptions (SD = 1.5). Barriers to participation in clinical trials of medications included lack of awareness of/exposure for patients and community-based Chinese physicians, preference for natural/traditional medicine, risk aversion and safety concerns, desire for privacy, and inconvenience. Trusted influences included physicians, hospitals/health systems, Asian/Chinese community centers, and family (for non-US-born participants). Suggestions to enhance participation included using language and culturally concordant materials/personnel, educating community-based Chinese physicians about clinical trials, involving patient-trusted physicians in recruitment, promoting trials on conditions common in Chinese people or for an existing condition, and financial incentives. US-born participants expressed greater understanding and willingness to join trials. All groups attributed low clinical trial enrollment to non-US-born Chinese adults.ConclusionsChinese older adults perceived obstacles to clinical trial participation that could be mitigated by involving trusted physicians in recruitment, using language and culturally concordant materials/staff, and educating patients and community-based physicians. Recognition of differences in attitudes among US- and non-US-born Chinese people may be important to tailoring recruitment strategies.

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the data safety monitoring board (DSMB) established incremental entry criteria for children aged 5 to 14.99 years with sickle cell disease (SCD) enrolling in a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation. First, the enrollment was limited to overt stroke in the first 10 participants (stage 4). Subsequently, the DSMB reviewed the interim results and expanded the eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography-defined cerebral vasculopathy (stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n = 18) and additions were made to the entry criteria that included nonneurologic morbidities (stage 2). Added eligibility criteria included the following: (1) life-threatening acute chest syndrome requiring exchange transfusion; (2) right heart catheterization confirmed pulmonary hypertension; (3) persistent systemic hypertension despite maximum medical therapy; (4) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication; and (5) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. To our knowledge, for the first time, we introduce a staged strategy for eligibility in a curative therapy trial for children with SCD concordant with 45 Code of Federal Regulations § 46.405(b). The research governance-mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials. This trial was registered at www.ClinicalTrials.gov as #NCT032635590.

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts. [ABSTRACT FROM AUTHOR]

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Given its aim to examine the impact of adversity and protective factors on childrens outcomes, the recruitment and retention of families who have a wide diversity in experiences are essential. However, the unfortunate history of inequitable treatment of underrepresented families in research and the risks with which some participants will contend (e.g., substance use) makes their recruitment and retention in social science and neuroscience research particularly challenging. This article explores strategies that the HBCD Study has developed to recruit and retain participants, including marginalized, underserved, and hard-to-reach populations, capitalizing on the extant literature and the researchers own experiences. In this paper, we address strategies to recruit and retain families within HBCD, including: 1) creating experiences that engender trust and promote relationships; 2) maintaining connections with participants over time; 3) ensuring appropriate compensation and supports; 4) considerations for study materials and procedures; and 5) community engagement. The implementation of these strategies may increase representation and inclusiveness, as well as improve the quality of the resulting data.

Black women are sorely underrepresented in studies of Alzheimers disease and related dementias (ADRD) despite higher rates of ADRD diagnoses than in non-Hispanic White women. There are many reasons for underrepresentation, including medical mistrust, limited access to clinical studies, and restrictive study inclusion criteria. These pervasive barriers to research participation are often not considered during study development and, if eventually thought of tend to be after the fact. Community-engaged research (CER) approaches are an effective method for reducing participation barriers. This article describes how CER approaches were used to develop the Black Women Inflammation and Tau Study (BWITS), a prospective study to identify biopsychosocial risk factors for ADRD in Black women. Guidelines discussed here for future ADRD research in diverse populations are informed by Community-Based Participatory Research (CBPR), the National Institute on Minority Health and Health Disparities (NIMHD), and the Patient-Centered Outcomes Research Institute (PCORI). HIGHLIGHTS: Understand the historical tragedies related to medical practices and research designs that may contribute to the underrepresentation of Black Americans in research studies today. Highlight community-engaged research approaches that effectively reduce participation barriers in minoritized groups. Review Community-Based Participatory Research, National Institute of Minority Health and Health Disparities, and the Patient-Centered Outcomes Research Institute guidelines for conducting research with minoritized communities. Describe using the three frameworks to inform the study development protocol for the Black Women Inflammation and Tau Study. Conclude by offering study design considerations that we hope can be a helpful starting point for others conducting research with minoritized communities.

Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62-0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P

IntroductionAlzheimer's disease (AD) disproportionately affects minoritized populations who remain underrepresented in AD trials.MethodsWe partnered with local nursing community-based organizations to implement a culturally tailored educational intervention and recruit Hispanic/Latino American, Filipino American, and Korean American adults aged 55 to 80 for the AHEAD study, a preclinical AD trial, at the University of California, Irvine.ResultsWe engaged 654 individuals across 21 events, leading to 71 prescreenings: 21.1% Filipino, 11.2% Hispanic/Latino, and 67.6% Korean adults. Ineligibility due to age and language barriers was common among Hispanic/Latino and Korean adults, respectively. Filipino adults often withdrew interest or were lost to follow-up. Ultimately, 25 participants enrolled: eight Filipino, two Hispanic/Latino, and 15 Korean adults. Tailored, culturally relevant content significantly contributed to the engagement success.DiscussionThis study demonstrates the value and impact of novel partnerships with health-related provider organizations that provide trusted care and access to underrepresented communities.HighlightsSix hundred and fifty four underrepresented individuals were reached, and 25 enrolled in the AHEAD 3-45 trial. Twenty-one community events were held via partnerships with nursing and community organizations. The study engaged 21% Filipino, 11% Hispanic/Latino, 68% Korean adults. Community-Based Participatory Research (CBPR) principles enhanced the recruitment process. Transparent communication and joint planning were key.

INTRODUCTION: We evaluated preliminary feasibility of a digital, culturally-informed approach to recruit and screen participants for the Alzheimers Disease Neuroimaging Initiative (ADNI4). METHODS: Participants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12-item Everyday Cognition Scale [ECog-12]), Novoic Storyteller speech-based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non-URPs. RESULTS: Of 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty-seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog-12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level. DISCUSSION: Preliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges. HIGHLIGHTS: A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally-informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education.

PURPOSE: Global health researchers have a responsibility to conduct ethical research in a manner that is culturally respectful and safe. The purpose of this work is to describe our experiences with recruitment and retention in Pakistan, a low-middle-income country. DESCRIPTION: We draw on two studies with a combined sample of 2161 low-risk pregnant women who participated in a pilot (n = 300) and a larger (n = 1861) prospective study of psychological distress and preterm birth at one of four centers (Garden, Hyderabad, Kharadar, Karimabad) of the Aga Khan University Hospital in Karachi, Pakistan. ASSESSMENT: Challenges we encountered include economic hardship and access to healthcare; womens position in the family; safety concerns and time commitment; misconceptions and mistrust in the research process; and concerns related to blood draws. To mitigate these challenges, we developed culturally acceptable study incentives, involved family members in the decision-making process about study participation, partnered with participants obstetrician-gynecologists, accommodated off site study visits, combined research visits with regular prenatal care visits, and modified research participation related to blood draws for some women. CONCLUSION: Implementation of these mitigation strategies improved recruitment and retention success, and we are confident that the solutions presented will support future scientists in addressing sociocultural challenges while embarking on collaborative research projects in Pakistan and other low-middle-income countries.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD Study aims to reflect the sociodemographic diversity of pregnant individuals in the U.S. The study will also oversample individuals who use substances during pregnancy and enroll similar individuals who do not use to allow for generalizable inferences of the impact of prenatal substance use on trajectories of child development. Without probability sampling or a randomization-based design, the study requires innovation during enrollment, close monitoring of group differences, and rigorous evaluation of external and internal validity across the enrollment period. In this article, we discuss the HBCD Study recruitment and enrollment data collection processes and potential analytic strategies to account for sources of heterogeneity and potential bias. First, we introduce the adaptive design and enrollment monitoring indices to assess and enhance external and internal validity. Second, we describe the visit schedule for in-person and remote data collection where dyads are randomly assigned to visit windows based on a jittered design to optimize longitudinal trajectory estimation. Lastly, we provide an overview of analytic procedures planned for estimating trajectories.

IntroductionAmid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development.MethodsWe performed a conjoint experiment to compare preferences among 26 patients with mild cognitive impairment for four trial features including designs incorporating active aducanumab-control (vs. placebo), returning tau positron emission tomography (PET) results (vs. no disclosure), remote study partner participation (vs. in person), and increased risk of brain swelling (vs. lower risk). We used a generalized estimating equation to model the utility of factor levels.ResultsReturning tau PET results had the highest utility (est: 0.47; 95% confidence interval [CI]: 0.13, 0.81; P = 0.007); remote study partner participation showed a similar trend (est: 0.29; 95% CI: -0.05, 0.63; P = 0.097). Trials with active-controlled design (est: 0.01; 95% CI: -0.33, 0.35; P = 0.956) did not demonstrate utility and higher risk of brain swelling had negative utility (est: -0.64; 95% CI: -0.99, -0.30; P

IntroductionThe co-existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), or the overlap syndrome, is common and associated with a distinct pattern of nocturnal hypoxemia and worse clinical outcomes than either disease alone. Consequently, identifying who and how to treat these patients is essential.Areas coveredTreatment is recommended in all patients with OSA and symptoms or systemic hypertension, but determining symptoms attributable to OSA can be challenging in patients with COPD. Treatment should be considered in asymptomatic patients with moderate to severe OSA and COPD with pulmonary hypertension and comorbid cardiovascular and cerebrovascular disease, especially if marked hypoxic burden. CPAP is effective, but in patients with the overlap syndrome and daytime hypercapnia, high-intensity noninvasive ventilation aiming to lower PaCO2 may have additional benefits. Additionally, in those with severe resting daytime hypoxemia, supplemental oxygen improves survival and should be added to positive airway pressure. The role of alternative non-positive airway pressure therapies in the overlap syndrome needs further study.Expert opinionBoth COPD and OSA are heterogeneous disorders with a wide range of disease severity and further research is needed to better characterize and prognosticate patients with the overlap syndrome to personalize treatment.

BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Childrens Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. RESULTS: The survey was sent to 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) of those respondents had access to short-form consent forms. Full consent form translation was required at 50% of institutions, and 12% of institutional review boards restricted use of centrally translated consent forms. Forty-six percent (n = 64) of institutions reported insufficient funding to support translation costs; 19% (n = 26) had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most frequently cited barrier (56%) to obtaining consent was lack of available in-person interpreters. Forty-seven percent (n = 65) reported that recruiting persons who speak languages other than English to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak languages other than English for clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

The articles in the June issue serve not only to inform senior care pharmacists on the importance of evidence-based approaches to reduce unnecessary aspirin use, but they also underscore the urgent need for the large and rapid increase in older adult representation in clinical trials and clinical research in general. A striking analysis performed in the United States that examined the trial populations used for Medicare coverage determinations found that while the average age of a Medicare enrollee was 70.8 years old (74.7 years old for older Medicare participants), the average age of the clinical trial population patients used in technology assessments for Medicare coverage determinations was 60.1 years. Hence, the US Medicare system, one of the largest national health care purchasers for older patients in the world, has relied on non-representative data to inform medical coverage decisions.

PurposeMany survivors of rectal cancer experience persistent bowel dysfunction. There are few evidence-based symptom management interventions to improve bowel control. The purpose of this study is to describe recruitment and pre-randomization baseline sociodemographic, health status, and clinical characteristics for SWOG S1820, a trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention.MethodsSWOG S1820 aimed to determine the preliminary efficacy, feasibility, and acceptability of AIMS-RC, a symptom management intervention for bowel health, comparing intervention to attention control. Survivors with a history of cancers of the rectosigmoid colon or rectum, within 6-24 months of primary treatment completion, with a post-surgical permanent ostomy or anastomosis, and over 18 years of age were enrolled. Outcomes included total bowel function, low anterior resection syndrome, quality of life, motivation for managing bowel health, self-efficacy for managing symptoms, positive and negative affect, and study feasibility and acceptability.ResultsThe trial completed accrual over a 29-month period and enrolled 117 participants from 34 institutions across 17 states and one US Pacific territory. At baseline, most enrolled participants reported self-imposed diet adjustments after surgery, persistent dietary intolerances, and bowel discomfort post-treatment, with high levels of constipation and diarrhea (grades 1-4).ConclusionsSWOG S1820 was able to recruit, in a timely manner, a study cohort that is demographically representative of US survivors of rectal cancer. Baseline characteristics illustrate the connection between diet/eating and bowel symptoms post-treatment, with many participants reporting diet adjustments and persistent inability to be comfortable with dietary intake.ClinicaltrialsGov registration date12/19/2019.ClinicaltrialsGov identifierNCT#04205955.

BACKGROUNDThe inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.METHODSInterviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.RESULTSInvestigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.CONCLUSIONProactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial..

Whether age impacts the recently demonstrated survival benefit of microaxial flow pump (mAFP) treatment in patients with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock (CS) is unknown. The purpose of this study was to assess the impact of age on mortality and complication rates in patients with STEMI-related CS randomized to standard care or mAFP on top of standard care. This is a secondary analysis of the Danish-German Cardiogenic Shock (DanGer Shock) trial, an international, multicenter, open-label trial, in which 355 adult patients with STEMI-related CS were randomized to receive an mAFP (Impella CP) plus standard care or standard care alone. The primary outcome of 180-day all-cause mortality is analyzed according to age and intervention. From lowest to highest age quartile, the median ages (range) were 54 years (Q1-Q3: 31-59 years), 65 years (Q1-Q3: 60-69 years), 73 years (Q1-Q3: 70-76 years), and 81 years (Q1-Q3: 77-92 years). There were no differences in blood pressure, lactate level, left ventricular ejection fraction, or shock severity at randomization across age groups. Mortality increased from lowest to highest quartile (31%, 47%, 61%, and 73%, respectively; log-rank P < 0.001), with an adjusted OR for death at 180 days of 7.85 (95% CI: 3.37-19.2; P < 0.001) in the highest quartile compared to the lowest. The predicted risk of mortality was higher in the standard-care group until approximately 77 years, after which the predicted risk became higher in the mAFP group (P = 0.20). In patients <77 years, a reduced 180-day mortality was observed in patients randomized to the mAFP (OR: 0.45; 95% CI: 0.28-0.73; P = 0.001), opposed to patients aged ≥77 years (OR: 1.52; 95% CI: 0.57-4.08; P = 0.40), P for interaction = 0.028. Complications were more frequent in the mAFP group, but there were no apparent differences in incidence of complications across all ages. This exploratory secondary analysis of the DanGer Shock trial demonstrates that older patients with STEMI-related CS experience high mortality and may not attain the same benefit from routine treatment with an mAFP as younger patients. Incorporating age as a factor in patient selection may enhance the overall benefit of this therapy. (Danish Cardiogenic Shock Trial [DanShock]; NCT01633502) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Revision rhinoplasty is a complex issue that involves in-depth listening to patients, gaining patients trust, understanding their psychology, and managing patients expectations and a detailed analysis of deformities. This study aim to measure the satisfaction levels of patients who will undergo revision rhinoplasty surgery and to reveal the main factors that determine satisfaction. Methods: The medical records of patients who underwent revision rhinoplasty surgery from January 2021 to April 2022 were obtained from the data system of our institute. SCHNOS (Standardized Cosmesis and Health Nasal Outcomes Survey) questionnaire, consisting of 10 questions and revealing the functional and aesthetic status of the nose, was applied to the patients. Thus, the patients' satisfaction with the operation was revealed through their responses to the survey before and after the surgery. Results: When the pre- and post-operative SCHNOS scores of the patients were compared, it was determined that there was a significant decrease in the scores in the other groups, except those who were > 50 years old, those who had 4–5 operations, and those who had a history of psychiatric disease requiring medication use. Within subgroup analysis, the decrease in SCHNOS-Obstruction and SCHNOS-Cosmetic scores was statistically significant in those aged between 18 and 29 and 30–39 years, in those with both genders, in those with 2–3 operations, in those with aesthetic + functional reasons for the need for revision, and in those without a history of psychiatric illness requiring drug use. Conclusions: This study highlights the complexities of septorhinoplasty, particularly in revision surgeries, where achieving optimal cosmetic results is challenging. While patients generally report improved satisfaction and reduced symptoms, factors like age, psychiatric history, and the balance of aesthetic and functional expectations significantly influence satisfaction levels. Level of evidence: Not ratable [ABSTRACT FROM AUTHOR]

Representativeness in randomized clinical trials remains a critical concern, affecting the external validity of trial results, equitable access to the risks and benefits of research participation, and public trust in clinical research. Although representative participation by members of groups traditionally underrepresented in clinical trials is just a surrogate for true diversity, equity, inclusion, and belonging in clinical trials, it can be quantified, allowing stakeholders to add empirical rigor to diversity, equity, inclusion, and belonging efforts. Multiple ways to measure representativeness have been proposed, including the participation-to-prevalence ratio, raw participation proportions or numbers for relevant subgroups, and enrollment fraction for relevant subgroups. These methods have strengths and weaknesses and may be appropriate to report in certain circumstances, depending on why stakeholders seek to assess representativeness. Stakeholders—including regulatory agencies, journal editors, clinical trial investigators, and trial sponsors—may use quantitative measures of representativeness to establish trial enrollment standards, monitor equitable participation in ongoing trials, and condition funding or drug or device approval on achieving specific representativeness targets. However, using quantitative measures of representativeness in this way could have unintended consequences, including researchers "gaming" recruitment strategies to meet target numbers, overlooking nuanced variations within communities, and potentially incentivizing problematic and exploitative recruitment strategies. Although no single method of measuring representativeness offers a comprehensive solution for increasing diversity, equity, inclusion, and belonging in all randomized clinical trials, a carefully designed, multifaceted approach to measuring representativeness may provide stakeholders with useful perspectives for measuring progress in increasing the diversity of clinical trial participation. For stakeholders seeking a single number to assess the representativeness of a trial enrolling patients with a disease state with well-delineated demographics, the participation-to-prevalence ratio is ideal; however, for a more nuanced view of representativeness, the combination of enrollment fraction in subgroups of relevance plus a full report of the demographics of patients approached for enrollment may be more appropriate. [ABSTRACT FROM AUTHOR]

Background: Renal replacement therapy (RRT) plays a crucial role in managing acute pancreatitis (AP). This study aimed to develop and evaluate predictive models for determining the need for RRT among patients with AP in the intensive care unit (ICU). Methods: A retrospective selection of patients with AP was made from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version V2.0). The cohort was randomly divided into a training set (447 patients) and a validation set (150 patients). The least absolute shrinkage and selection operator (LASSO) regression cross-validation method was utilized to identify key features for model construction. Using these features, four machine learning (ML) algorithms were developed. The optimal model was visualized and clarified using SHapley Additive exPlanations (SHAP) and presented as a nomogram. Results: The mean age of the cohort was 59.17 years, with an average Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 17.55. Acute kidney injury (AKI) was observed in 52.43% of patients with AP, and 9.05% required RRT. After feature selection, four of 41 clinical factors were ultimately chosen for use in model construction. The Lasso-Logistic Regression (Lasso-LR) model showed a high discriminative ability to predict RRT risk in patients with AP, with an area under the receiver operating characteristic (AUROC) of 0.955 (95% CI 0.924–0.987) in the training set. In the validation set, it maintained its discriminative performance, achieving an AUROC of 0.985 (95% CI 0.970–1.000). Calibration curves indicated an excellent fit in both sets (Brier scores: 0.039 and 0.032, respectively), suggesting high consistency. Decision curve analysis (DCA) highlighted the Lasso-LR model's significant clinical utility in predicting RRT likelihood in patients with AP. Conclusions: Developed via the LASSO regression cross-validation method, the Lasso-LR model significantly excels in predicting the requirement for RRT in patients with AP, demonstrating its potential for clinical application. [ABSTRACT FROM AUTHOR]

Background: Regulatory bodies have recently approved chimeric antigen receptor (CAR)-T cell therapies for patients with multiple myeloma (MM), but the treatment process involves complex decision making. To support the introduction of these therapies, we aimed to establish consensus expert opinion on best practices of all aspects of the management of patients with MM undergoing CAR-T cell therapy in Australia. Methods: We conducted a modified RAND/UCLA two-round Delphi panel informed by a systematic literature review (SLR). The SLR included evidence from clinical practice guidelines, interventional trials, and observational studies for CAR-T cell therapy for patients with MM, to synthesize methodological aspects of CAR-T cell therapy related to patient management. The Delphi panel comprised eight hematologists from across Australia, each with significant experience directly treating patients using CAR-T therapy or referring patients for CAR-T cell therapy. Panelists completed the surveys electronically, and attended a virtual meeting held before the second-round questionnaire to discuss the first-round questionnaire responses. Consensus was defined a priori as at least 70% agreement on survey questions. Results: The SLR identified 22 interventional or observational studies and 5 clinical practice guidelines reporting on selection and management of patients with MM treated with CAR-T cell therapy from various global regions. The Delphi panel reached consensus on practices related to patient referral, screening, selection, prioritization, treatments requiring wash-out, bridging therapy, lymphodepletion, infusion, and post-infusion monitoring and management. Most consensus results aligned with consistently recommended practices within guidelines included in the SLR. Consensus was not reached for statements related to specific screening practices and post-treatment monitoring, suggesting differing opinions on the specific best practices to implement. Conclusion: Our Delphi panel established expert consensus on key considerations for patient selection, administrative processes, and aftercare for patients with MM in Australia undergoing CAR-T therapy. This will guide the development of clinical practice guidelines which are relevant and feasible to Australian health systems. [ABSTRACT FROM AUTHOR]

Simple Summary: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising yet invasive treatment for patients with peritoneal carcinomatosis. Given the procedure's complexity and associated risks, careful patient selection is critical to achieving optimal outcomes. Historically, age 70 was used as a strict cutoff for eligibility, limiting access for older adults. However, modern approaches focus on evaluating additional factors, such as comorbidities, frailty, and functional status, recognizing that age alone may not determine a patient's ability to tolerate treatment. Despite this shift, the influence of age on outcomes—such as recovery, readmission rates, and survival—remains underexplored. This study aims to investigate the role of age in CRS-HIPEC outcomes, refining patient selection criteria and guiding postoperative care strategies. The findings will inform clinical decisions and support the development of tailored treatment approaches for individuals undergoing CRS-HIPEC. Introduction: Peritoneal carcinomatosis presents significant treatment challenges. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers a promising therapeutic approach. Patient selection remains critical, and the role of age as an exclusion criterion requires further investigation. This study evaluates whether age influences postoperative outcomes in CRS-HIPEC patients. Methods: A retrospective review of a prospective comprehensive database of 271 CRS-HIPEC procedures performed between 2018 and 2023 was conducted. Logistic regression assessed the relationship between age and postoperative outcomes. Age groups (18–44, 45–69, ≥70 years) were compared based on demographic data, primary tumor site, Peritoneal Cancer Index scores, and key outcome measures. Results: Across the different age groups, there were no significant differences in PCI scores, recurrence, disease-free survival, 30-day morbidity, or mortality. Length of stay was longer in older patients (p = 0.009). Patients aged ≥70 had higher readmission rates (p = 0.041) and were more often discharged to transitional care facilities (p = 0.001). Older patients were also more likely to experience Clavien–Dindo grade III or higher complications (p = 0.008). Logistic regression confirmed these findings. Continuous age analysis yielded similar results and revealed significant differences in race and primary organ involvement. Conclusions: Age is not a significant predictor of 30-day morbidity, mortality, or survival outcomes in patients undergoing CRS-HIPEC. However, older patients require closer attention to discharge planning and readmission risk management. This study highlights the importance of comprehensive patient assessment beyond age and underscores the need for further research to better understand factors influencing outcomes in this population. [ABSTRACT FROM AUTHOR]

Introduction Neuroblastoma is the most common extracranial solid tumor in childhood. The data on the treatment experience with 131 iodine-meta-iodo-benzyl-guanidine (131 I-mIBG) and clinical outcome data are meager from India. Objectives This article studies the efficacy and treatment outcomes in patients treated with 131 I-mIBG in high-risk neuroblastoma. Materials and Methods The study group consisted of 201 consecutive patients (aged between 1 and 15 years) with biopsy-proven neuroblastoma who underwent 131 I-mIBG scans from 2012 to 2022. The majority of these children had a disease that was inoperable or had poor response to chemotherapy. Patients with positive scintigraphy were considered for therapy with 131 I-mIBG. The findings were analyzed and correlated with the final diagnosis and outcomes obtained from survival during follow-up and reviewing patient records. Results Thirty-nine children, 22 males and 17 females, with a median age of 4 years had positive 131 I-mIBG scintigraphy. Intra-abdominal primary lesions and osseous lesions were the most common sites of uptake on 131 I-mIBG scan. Of these, 13 had upfront chemotherapy and 26 had surgery followed by chemotherapy. All the patients underwent therapy with 131 I-mIBG. Fourteen patients had multiple therapies while the remaining 25 had only one therapy. Eight patients had no follow-up, and 13 had disease relapse. The remaining 18 had regression of disease which was confirmed by follow-up 131 I-mIBG scintigraphy and with bone scintigraphy in patients with osseous metastases. Conclusion 131 I-mIBG scintigraphy should be preferred in intermediate and high-risk neuroblastoma to know the extent of the disease and also for patient selection for early therapy with 131 I-mIBG. It holds significant utility in the management of metastatic neuroblastoma, facilitating palliative pain relief and tumor size reduction in inoperable or metastatic disease. [ABSTRACT FROM AUTHOR]

Introduction: The primary objective of this study was to evaluate the impact of vaginal uterosacral plication on urge symptoms and quality of life in a cohort of patients with uterosacral ligament insufficiency and urge symptoms. Methods: A total of 40 female patients were included in the study, and their posterior fornix was supported with gauze to simulate the surgical procedure. Uterosacral plication was applied to patients who experienced a decrease in urinary incontinence, nocturia, a sense of urgency, and a decrease in urge urinary incontinence symptoms or complete recovery. Images of the bladder, bladder neck, urethra, and symphysis pubis were obtained preoperatively and 1 year postoperatively. POP-Q staging was also performed, and patients completed the Overactive Bladder Evaluation Form (OAB-V8) and the Incontinence Impact Questionnaire Short Form (ICIQ-SF). Results: Results from the OAB-V8 questionnaire showed that postoperative nocturia scores improved by 72.1% compared to preoperative scores, and the need to urinate at night and waking up scores improved by 68.3%. The mean bladder neck thickness and the mean detrusor thickness were significantly decreased from 10 to 9.2 (p < 0.0001) and from 8.7 to 6.4 (p < 0.0001), respectively. The ICIQ-SF questionnaire scores showed a 68.4% improvement in urinary incontinence affecting daily life after the operation. Conclusion: This study adds to the clinical evidence that uterosacral ligament support improves symptoms of overactive bladder syndromes, including urgency and nocturia. The use of pelvic floor ultrasound and the apical tamponade test is important in patient selection for the correct indication. [ABSTRACT FROM AUTHOR]

Traditional treatments for localized prostate cancer include radical prostatectomy or radiation therapy but pose challenges due to treatment related side effects, namely erectile dysfunction and urinary incontinence. In recent years, focal therapy has emerged as a viable treatment option for localized low-intermediate risk prostate cancer in carefully selected patients. Short and medium-term studies show acceptable cancer control outcomes and reduced morbidity when comparing focal therapy to whole gland treatment for prostate cancer, however there is paucity of long-term studies. Here we review focal ablative therapies commonly used, discuss the role of imaging in monitoring treatment, and summarize oncologic outcomes based on studies to date. [ABSTRACT FROM AUTHOR]

Background: Pancreatic surgery is still associated with significant morbidity. In a simultaneously increasingly ageing population with elevated morbidity, the risk stratification and indications for surgery are of particular importance. Objective: Assessment of the impact of multimorbidity of patients on the postoperative outcome after pancreatic surgery. Material and methods: Evaluation and summary of the available literature. Results: The postoperative morbidity after pancreatic surgery remains high. Relevant comorbidities, such as liver cirrhosis, cardiac and pulmonary diseases and advanced renal insufficiency enormously increase the risk of perioperative morbidity and mortality; however, in high-volume centers with appropriate expertise in pancreatic surgery the mortality is below 5%. Conclusion: Pancreatic surgery with severe comorbidity can be safely performed in centers with proven expertise. Nevertheless, a careful interpretation of the indications and good patient selection are essential for the postoperative outcome. [ABSTRACT FROM AUTHOR]

Background: Many factors, including some related to the patient, implant selection, and the surgeon's skill and expertise, likely contribute to the risk of THA revision. However, surgeon factors have not been extensively analyzed in national joint replacement registries, and there is limited insight into their potential as a confounding variable for revision outcomes; for example, if surgeons with higher revision rates choose more successful prostheses, would this alone reduce their revision rate? Questions/purposes: This study used Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) data for patients receiving primary THA for a diagnosis of osteoarthritis to answer the following questions: (1) Will the difference in revision rates among surgeons change or disappear when only procedures performed with the best prostheses or prostheses that have been identified as having higher revision rates are considered? (2) Is the benefit associated with using the best-performing prostheses different among surgeons with different revision rates? (3) Do the reasons for revision differ between surgeons with higher rates of revision compared with surgeons with lower rates of revision? Methods: All primary THA procedures performed and recorded in the AOANJRR for osteoarthritis from September 1, 1999, to December 31, 2022, were considered for inclusion. Each THA prosthesis used was categorized per the AOANJRR as superior-performing, middle-performing, or identified as having a higher rate of revision by the AOANJRR benchmarking process. Surgeons who had performed at least 50 procedures and had a recorded 2-year cumulative percent revision (CPR) were included. After applying these restrictions, the study consisted of 302,066 procedures performed by 476 known surgeons. For the primary outcome measure of all-cause revision, we examined the variation in all-cause revision rates across individual surgeons when different classes of devices were used to assess whether differences between surgeons persisted when accounting for prosthesis selection. For the purposes of descriptively comparing reasons for revision between surgeons with higher-than-average or lower-than-average risk of revision, surgeons were classified into quartiles and outcomes compared when these surgeons used the same class of prosthesis. Results: The difference in rates of revision among surgeons remained even after accounting for the effects of the prosthesis used. For any given surgeon, identified prostheses were associated with higher revision rates compared with both superior-performing prostheses (HR 1.73 [95% CI 1.57 to 1.92]; p < 0.01) and medium-performing prostheses (HR 1.31 [95% CI 1.20 to 1.43]; p < 0.01). All surgeons demonstrated a lower revision rate when using a superior-performing prosthesis, but the difference was greatest for surgeons with the highest rates of revision. Surgeons with the lowest rates of revision had a 19-year CPR of 3.9% (95% CI 3.0% to 5.0%) when using a superior-performing prosthesis compared with 5.4% (95% CI 4.0% to 7.3%) for procedures in which an identified prosthesis was used. Surgeons with the highest rates of revision had a 19-year CPR of 10.9% (95% CI 8.6% to 13.8%) when using a superior-performing prosthesis, and this increased to 20.4% (95% CI 18.0% to 23.1%) for procedures in which an identified prosthesis was used. The reasons for revision differ between surgeons, with causes of revision likely preventable and not related to the prosthesis choice being apparent for surgeons with high revision rates. Conclusion: The choice of implant and the surgeon performing the index procedure both affected the risk of revision as well as the reasons for revision. Surgeons could improve the survivorship of the arthroplasties they perform by choosing implants identified by registries as having lower revision rates. Acceptance of the fact that surgeons have different revision rates is needed, and detailed analysis is required to explain why surgeons with high revision rates have increased rates of likely preventable revisions, and outside of prosthesis choice, how revision rates can be lowered. The influence of training, fellowship completion, ongoing education, patient selection, indications for surgery, and factors underlying prosthesis decision-making should be assessed. The surgeon performing THA is an important confounder that should be considered in future registry analyses. Level of Evidence: Level III, therapeutic study. [ABSTRACT FROM AUTHOR]

Within the past decade, there have been multiple innovations in the field of nerve surgery. In this review, we highlight critical changes and innovations that have helped advance the field and present opportunities for further study. This includes the modification and clarification of the classification schema for nerve injuries which informs prognosis and treatment, and a refined understanding and application of electrodiagnostic studies to guide patient selection. We provide indications for operative intervention based on this nerve injury classification and propose strategies best contoured for varying injury presentations at differing time points. Lastly, we discuss new developments in surgical techniques and approaches based on these advancements. [ABSTRACT FROM AUTHOR]

Purpose: To study the prioritization effects of the of COVID‐19 pandemic on Swedish cataract surgery using a national healthcare registry with high coverage. Setting: A study from the Swedish National Cataract Register (NCR), involving all patients undergoing cataract surgery in Sweden during 2019–2022 – before, during and after the COVID‐19 pandemic. Results: With the pandemic outbreak, the number of cataract surgeries fell by 22% in 2020 (15 369 procedures), albeit with large regional differences (−43% to +58%). The numbers recovered in 2021, and in 2022, a new top notation was seen (n = 149 952). On a national level, the patients were younger (−0.46 years, p < 0.001), with a larger proportion of less difficult cases (p < 0.001) and the proportion of males was higher (p < 0.001) during the pandemic, but all these variables also differed substantially between different regions and clinics. Conclusion: A national registry with high coverage can map the consequences of an event disrupting elective surgery in detail. During the COVID‐19 pandemic, the impact on Swedish cataract surgery varied largely between different regions, clinics, and healthcare providers, leading to inequality in the availability of surgery. These differences likely owed to variations in healthcare policy approaches in different parts of the country. The present study shows that outcomes at one clinic or region cannot be extrapolated to larger regions under these circumstances. It actualizes the need to aim for a healthcare on equal terms, but it also shows a system that delivers care to many despite difficult times. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this retrospective study was to collect epidemiological, clinical, laboratory, imaging, management, and follow-up data on cases of alveolar echinococcosis (AE) diagnosed and/or followed up within the Namur Hospital Network (NHN) in order to gather information on the challenges, pitfalls, and overall experience in the diagnosis and treatment of AE. Methods: EchiNam was a multicenter retrospective study. Patients diagnosed and/or treated for probable or confirmed AE in the NHN between 2002 and 2023 were included in the study. Patient selection was based on diagnosis codes, laboratory results, and albendazole (ABZ) dispensing. Results: A total of 22 AE cases were retrieved, of which four were classified as probable and 18 as confirmed cases. Nine patients were either asymptomatic or had symptoms attributed to another disease. Clinical examination yielded pathologic findings in 10 patients. The median duration from the first AE-suggestive laboratory abnormalities to diagnosis was 176 days, and the median duration from the first AE-related imaging abnormalities to diagnosis was 133 days. Overall, 12 patients underwent surgical resection, with only four achieving complete lesion resection. Nine patients experienced ABZ-related adverse effects, with temporary ABZ discontinuation in five. Conclusion: Due to various factors such as a long incubation period and a lack of awareness among Belgian physicians, AE is often diagnosed at advanced disease stages. Treatment then becomes more complex or even suboptimal, resulting in prolonged therapy, higher risk of adverse effects, significantly impaired quality of life, poor prognosis, and higher mortality rates. Measures should be taken to achieve early diagnosis in endemic areas. [ABSTRACT FROM AUTHOR]

• HHT patients with low grade right-to-left shunt (RLS) at screening TTCE do not develop pulmonary arteriovenous malformations-related complications during long-term follow-up. • RLS rarely increases to grades ≥ 2 in HHT patients with initial grades 0–1 RLS at TTCE. • Extending rescreening to a period greater than 5 years could be justified in HHT patients without RLS at screening (grade 0). To describe the incidence of pulmonary arteriovenous malformations (PAVM)-related complications, right-to-left shunt (RLS) progression at transthoracic contrast echocardiography (TTCE) and development of treatable PAVM during long-term follow-up in hereditary hemorrhagic telangiectasia (HHT) patients with RLS grades 0–1 at screening TTCE. Observational prospective study including adult HHT patients with grades 0–1 RLS at screening TTCE. Those requiring previous embolization of PAVM were excluded. PAVM-related complications and RLS progression during follow-up were recorded. 183 patients were followed-up during 5.6 [IQR: 3.3–8.2] years. Seven (3.8 %) patients developed potentially PAVM-related complications, although all of them were considered unrelated to HHT after multidisciplinary assessment. Among 84 patients with a follow-up TTCE, RLS progressed to grades ≥2 in eight (9.5 %). Among patients with grade 0 RLS at screening, 31.6 % evolved to grade 1 RLS during follow-up and none progressed to grade ≥ 2. Among patients with grade 1 RLS at screening, RLS increased in 17.4 %, by one grade in most cases, and two (2.4 %) patients developed treatable PAVM. Grade 1 RLS and a higher epistaxis severity score were associated with RLS progression. In HHT patients with grades 0–1 RLS at screening, PAVM-related complications are rare. No patient with grade 0 RLS showed an increase in RLS of more than one grade on TTCE. Among patients with grade 1 RLS, rescreening every 5 years should be recommended because treatable PAVM can develop; follow-up with TTCE could be an alternative, as it would allow a better selection of patients for chest CT. [ABSTRACT FROM AUTHOR]

Copyright of Plastic Surgery is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Our study explores the utilization of objective tools for preoperative assessment of elderly patients by Emergency General Surgeons (EGS). Methods: A descriptive cross-sectional survey was conducted via the European Society for Trauma and Emergency Surgery (ESTES) Research Committee. EGS were invited through the ESTES members’ mailing list and social media platforms. The survey included two sections: (1) clinical scenarios involving elderly patients with varying chronic conditions, and (2) participant characteristics. Data collection lasted 12 weeks, with reminders sent every 4 weeks. Statistical analyses were performed using Microsoft Excel and EasyMedStat. Results: One hundred and seven surgeons responded to the survey. Median respondent age was 41 years, with a male prevalence (72.9%). Most participants were from Europe (85%). Key-findings included that 62.6% reported using one or more risk assessment tools (RATs), while 35.5% used one or more frailty scores. Additionally, 4.7% were unaware of any RATs, and 35.5% were unaware of any frailty scores. Decision-making strategies leveraging personal experience with minimal impact from RATs predominated. Conclusions: Preoperative risk assessment tool and frailty score use for elderly patients requiring emergency surgery remains limited among ESTES surgeons. Our study highlights the need for focused education and tool workflow integration to improve risk stratification, decision-making and outcomes. Institutional approaches coupled with targeted educational interventions using implementation science principles are recommended to bridge this knowledge-to-action gap. Future research should focus on developing comprehensive, user-friendly tools and evaluating their impact on patient-centered outcomes. [ABSTRACT FROM AUTHOR]

Background and objective: Voluntary blood donations remain a major concern in the Democratic Republic of Congo, increasing morbidity and mortality due to shortages of safe blood. Local studies show low rates of recruitment and retention of voluntary donations, as well as a high attrition rate of former donors. The psychosocial factors involved in deciding to become and remain a voluntary blood donor in sub-Saharan Africa remain poorly understood. Our study therefore aimed to explore the motivational factors and perceptions involved in voluntary blood donation in South Kivu. Materials and methods: We conducted 20 individual interviews, and three focus group discussions were conducted with a total of 26 volunteer donors. As a way of triangulation, two additional focus-groups were held with 19 non-donors. The individual interviews were analysed thematically, using a starting list of 3 predefined units of analysis, namely: initiation, maintenance, and cessation of voluntary blood donation. The data was analysed inductively within these predefined units of analysis to generate possible factors of motivation that were then presented and further discussed during the focus-groups discussions with donors and non-donors. Results: Fear presented as a factor influencing the decisions to donate blood either positively or negatively, from recruitment to maintenance to cessation of donation. Other motivational factors were found to be linked to the perceived meaning of voluntary donation, such as the meaning given to the blood voluntary donation and material or non-material expectations. Our results suggest that expectations for material rewards are still high in the context of poverty. Conclusion: In conclusion, many motivational factors may act as incentives or barriers to voluntary blood donation, including high expectations towards the transfusion system. Local particularities need to be considered when promoting voluntary blood donation. The fear of being abused by the system needs to be addressed, by enhancing accessibility to transfusions. [ABSTRACT FROM AUTHOR]

PURPOSE: Immune checkpoint inhibitors (ICIs) are now first-line therapy for most patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and cetuximab is most often used as subsequent therapy. However, data describing cetuximab efficacy in the post-ICI setting are limited. METHODS: We performed a single-institution retrospective analysis of patients with R/M HNSCC treated with cetuximab, either as monotherapy or in combination with chemotherapy, after receiving an ICI. We extracted objective response rate (ORR), duration of treatment (DOT), and overall survival (OS) and compared them on the basis of patient characteristics. Multivariable models assessed associations between patient and tumor characteristics and outcomes. RESULTS: We identified 70 patients treated with cetuximab after an ICI. The mean age was 67.6 years, with 60% having virus-associated HNSCC. Overall, the ORR was 21.4%, the median DOT was 1.9 months, and the median OS was 6.3 months. Patients receiving cetuximab with chemotherapy had a higher ORR (27.7% v 8.7%) and longer median DOT but similar OS compared with monotherapy. Virus-independent HNSCC had higher ORR (28.6% v 10.7%), longer DOT (3.3 v 1.2 months; hazard ratio [HR], 0.47 [95% CI, 0.25 to 0.90]), and longer OS (8.1 v 4.6 months; HR, 0.40 [95% CI, 0.19 to 0.83]). In multivariable models, virus-independent disease and negative smoking history were associated with improved OS. Concurrent chemotherapy, age, and sex were not associated with differences in OS. When assessing genomic data, TP53 mutations were associated with improved DOT (HR, 0.33 [95% CI, 0.15 to 0.70]) and OS (HR, 0.38 [95% CI, 0.17 to 0.86]). CONCLUSION: Cetuximab-based therapy shows limited efficacy in R/M HNSCC post-ICI, although outcomes were better in virus-independent HNSCC and nonsmokers. The findings may improve prognostication and patient selection for cetuximab after ICI in R/M HNSCC. [ABSTRACT FROM AUTHOR]

For over a century, radiotherapy has revolutionised cancer treatment. Technological advancements aim to deliver high doses to tumours with increased precision while minimising off-target effects to organs at risk. Despite advancements such as image-guided, high-precision radiotherapy delivery, long-term toxic effects on healthy tissues remain a great clinical challenge. In this Review, we summarise common mechanisms driving acute and long-term side-effects and discuss monitoring strategies for radiotherapy survivors. We explore ways to mitigate toxic effects through novel technologies and proper patient selection and counselling. Additionally, we address policies and management strategies to minimise the severity and impact of toxicity during and after treatment. Finally, we examine the potential advantages of emerging technologies and innovative approaches to improve conformity, accuracy, and minimise off-target effects. [ABSTRACT FROM AUTHOR]

Existing prognostic models are useful for estimating the prognosis of lung adenocarcinoma patients, but there remains room for improvement. In the current study, we developed a deep learning model based on histopathological images to predict the recurrence risk of lung adenocarcinoma patients. The efficiency of the model was then evaluated in independent multicenter cohorts. The model defined high- and low-risk groups successfully stratified prognosis of the entire cohort. Moreover, multivariable Cox analysis identified the model defined risk groups as an independent predictor for disease-free survival. Importantly, combining TNM stage with the established model helped to distinguish subgroups of patients with high-risk stage II and stage III disease who are highly likely to benefit from adjuvant chemotherapy. Overall, our study highlights the significant value of the constructed model to serve as a complementary biomarker for survival stratification and adjuvant therapy selection for lung adenocarcinoma patients after resection. [ABSTRACT FROM AUTHOR]

Throughout the COVID-19 pandemic, underserved populations, such as racial and ethnic minority communities, were disproportionately impacted by illness and death. Ensuring people from diverse backgrounds have the ability to participate in clinical trials is key to advancing health equity. We sought to analyze the spatial variability in locations of COVID-19 trials sites and to test associations with demographic correlates. All available and searchable COVID-19 studies listed on ClinicalTrials.gov until 04/04/2022 and conducted in the United States were extracted at the trial-level, and locations were geocoded using the Microsoft Bing API. Publicly available demographic data were available at the county level for national analysis and the census tract level for local analysis. Independent variables included eight racial and ethnic covariates, both sexes, and twelve age categories, all of which were population-normalized. The county-level, population-normalized count of study site locations, by type, was used as the outcome for national analysis, thereby enabling the determination of demographic associations with geospatial availability to enroll as a participant in a COVID-19 study. Z-scores of the Getis-Ord Gi statistic were used as the outcome for local analysis in order to account for areas close to those with clinical study sites. For both national (p < 0.001) and local analysis (p = 0.006 for Los Angeles, p = 0.030 for New York), areas with greater proportions of men had significantly fewer studies. Sites were more likely to be found in counties with higher proportions of Asian (p < 0.001) and American Indian or Alaska Native residents (p < 0.001). Areas with greater concentrations of Black or African American residents had significantly lower concentrations of observational (p < 0.001) and government-sponsored COVID-19 studies (p = 0.003) in national analysis and significantly fewer concentrations of study sites in both Los Angeles (p < 0.001) and New York (p = 0.007). Though there appear to be a large number of COVID-19 studies that commenced in the US, they are distributed unevenly, both nationally and locally. [ABSTRACT FROM AUTHOR]

Objectives: The feasibility of corticosteroid withdrawal (CW) for Takayasu arteritis (TAK) remains uncertain. Two autoantibodies (Abs) are identified against endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) in TAK, determining its three subgroups. This study aimed to evaluate CW using tocilizumab (TCZ) and its association with the Ab profile. Methods: This prospective study, lasted for 24 weeks, included patients with relapsed but stable TAK. Scheduled tapering of prednisolone (PSL) was performed with subcutaneous TCZ (CW at week 20). The primary endpoint was the difference in type A remission, defined by CW and the absence of inflammatory signs, according to the Ab profile at week 24. Results: Twenty patients were included and 18 patients with a mean PSL dose of 4.9 ± 2.8 mg/day were analysed. Anti-EPCR Ab-positive (E+), anti-SR-BI Ab-positive (S+), and double-negative (DN) groups included four (22.2%), eight (44.4%), and six (33.3%) patients, respectively. At week 24, the mean PSL dose was 2.0 ± 2.7 mg/day. Type A remission was observed in eight patients (44.4%), with significant differences based on the Ab profile: E+ (three patients, 75%), S+ (five patients, 62.5%), and DN (zero patients, 0%) (P=0.018). Besides, age, disease duration, PSL dose, type V arterial lesion, arterial dilation, and C-reactive protein >0.01 mg/dL were identified as risks for CW failure. Conclusion: CW using TCZ was achieved in 44.4% of patients with TAK relapse and was significantly higher in E+ and S+ patients. CW can be a feasible target, and the precise selection of patients is critical. [ABSTRACT FROM AUTHOR]

Background: Disorders of consciousness (DoC) in non-traumatic ICU-patients are often treated with amantadine, although evidence supporting its efficacy is limited. Methods: This retrospective study analyzed non-traumatic DoC-patients treated with amantadine between January 2016 and June 2021. Data on patient demographics, clinical characteristics, treatment specifications, and outcomes were extracted from electronic medical records. Patients were classified as responders if their Glasgow Coma Scale (GCS) improved by ≥3 points within 5 days. Good outcome was defined as a modified Rankin Scale (mRS) of 0–2. Machine learning techniques were used to predict response to treatment. Results: Of 442 patients (mean age 73.2 ± 10.7 years, 41.0% female), 267 (60.4%) were responders. Baseline characteristics were similar between groups, except that responders had lower baseline GCS (7 [IQR 5–9] vs. 8 [IQR 5–10], p = 0.030), better premorbid mRS (2 [IQR 1–2] vs. 2 [IQR 1–3], p < 0.001) and fewer pathological cerebral imaging findings (45.7% vs. 61.1%, OR 0.56, 95% CI: 0.36–0.86, p = 0.008). Responders exhibited significantly lower mortality at discharge (13.5% vs. 27.4%, OR 0.41, 95% CI: 0.25–0.67, p < 0.001) and follow-up (16.9% vs. 32.0%, OR 0.43, 95% CI: 0.24–0.77, p = 0.002). Good outcomes were more frequent in responders at follow-up (4.9% vs. 1.1%, OR 6.14, 95% CI: 1.35–28.01, p = 0.004). In multivariate analysis higher premorbid mRS (OR 0.719, 95% CI 0.590–0.875, p < 0.001), pathological imaging results (OR 0.546, 95% CI 0.342–0.871, p = 0.011), and experiencing cardiac arrest (OR 0.542, 95% CI 0.307–0.954, p = 0.034) were associated with lower odds of response. Machine learning identified key predictors of response, with the Stacking Classifier achieving the highest performance (accuracy 64.5%, precision 66.6%, recall 64.5%, F1 score 61.3%). Conclusion: This study supports the potential benefits of intravenous amantadine in non-traumatic DOC-patients. Higher premorbid mRS, and pathological cerebral imaging were key predictors of non-response, offering potential avenues for patient selection and treatment customization. Findings from this study informed the design of our ongoing prospective study, which aims to further evaluate the long-term efficacy of amantadine. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) significantly impacts healthcare systems due to high rates of hospital bed utilization and readmission rates. Chronic HF often leads to frequent hospitalizations due to recurrent exacerbations and a decline in patient health status. Intravenous (IV) diuretic administration is essential for treating worsening HF. Emerging strategies include home-based IV diuretic therapy administration; however, limited practical implementation guidance is available. This scoping review aims to summarize the literature on home IV diuretic administration for HF patients, focusing on the interventions' characteristics, and facilitators and barriers to its implementation. Methods: This review followed the scoping review framework proposed by Arksey and O'Malley and PRIMSA-ScR. A comprehensive search was conducted across six databases (CINAHL, the Cochrane Library, EMBASE, MEDLINE, PsychINFO and Scopus) and grey literature to identify English studies from inception to April 13, 2024. Two independent reviewers screened articles and resources for inclusion and data was extracted using a form created by the authors in Covidence. Results: The search yielded 2,049 results, with nine studies meeting the inclusion criteria. Studies varied in design, including feasibility, pilot, observational, and pre/post-intervention evaluations. The majority were conducted in European countries, with sample sizes ranging from 12 to 96 patients receiving home IV diuretics for HF. Key implementation challenges include appropriate patient selection, IV cannulation competency of healthcare providers, and multi-disciplinary and multi-agency collaboration. Conclusions: Evidence on home IV diuretic administration practices for HF management remains limited. However, this scoping review suggests that commonalities across studies could form the basis for developing standard protocols in outpatient settings. Despite the lack of formal evidence-based guidelines, the findings also suggest that tailored, community-specific approaches and safe infusion guidance documents could enhance the efficacy and scalability of home IV diuretic therapy. Future research should focus on refining these strategies and exploring diuretic escalation methods beyond traditional acute care administration to optimize patient outcomes. [ABSTRACT FROM AUTHOR]