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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]

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

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..

Background: Children with inflammatory bowel disease (IBD) experience extraintestinal side effects including altered body composition, impaired muscle strength, and aerobic capacity. Exercise training may remedy these issues. Purpose: To assess the feasibility, safety, participant satisfaction, and efficacy of a training program for youth with IBD. Methods: Children with IBD completed 16 weeks of training (2 supervised + 1 home sessions per week). Feasibility was assessed by tracking recruitment, adherence, and compliance rates. Safety was assessed by tracking symptoms and adverse events. Posttraining interviews gauged satisfaction. Circulating inflammatory markers, body composition, muscle strength, aerobic fitness, and habitual physical activity were measured at baseline, midtraining (8 wk), and posttraining. Results: Eleven youth were recruited and 10 completed the study. Participants adhered to 28 (1) of 32 prescribed supervised sessions and 8 (4) of 16 prescribed home sessions. There were no adverse events, and overall feedback on training was positive. Posttraining, we observed an increase in lean mass (+2.4 [1.1] kg), bone density (+0.0124 [0.015] g·cm−2), aerobic fitness (+2.8 [5.7] mL·kg LM−1· min−1), and vigorous physical activity levels (+13.09 [8.95] min·h−1) but no change in inflammation or muscle strength. Conclusion: Supervised exercise training is feasible, safe, and effective for youth with IBD and should be encouraged. [ABSTRACT FROM AUTHOR]

BACKGROUND: Advances in plasma biomarkers to detect Alzheimers disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimers Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD. OBJECTIVES: The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individuals eligibility for AD preclinical trials. DESIGN: Pilot feasibility study with co-primary outcomes. SETTING: This pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility. PARTICIPANTS: Participants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months. MEASUREMENTS: Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [Aβ42/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study. RESULTS: 300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%-44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%-82%), with similar rates across sex (76% Female (n=57), 71% Male (n=30)) and race and ethnicity (75% URG (n=27) and 75% not from URG (n=59)). 60% (n=51) of participants with plasma biomarker results were eligible to screen for future preclinical AD trials. CONCLUSION: Electronic consent of participants through an online registry, blood sample collection at community-based centers, plasma biomarker quantification and reporting, and biomarker assessments for study eligibility were all feasible with similar engagement rates across demographic groups. Although this pilot was a small and selective sample, participants engaged and consented at higher than expected rates. We conclude that collecting blood at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version of the AlzMatch study is underway, which involves expanding invitations to additional APT Webstudy participants and clinical trial sites.

IntroductionWe elicited Vietnamese Americans' perspectives on culturally appropriate recruitment into a new research registry: Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs) Research and Education (CARE).MethodsThree focus groups were conducted with 21 Vietnamese Americans. Topics included knowledge about and experiences with research, outreach and recruitment methods for research participation and registry enrollment, and views about research incentives. Focus group transcripts were analyzed thematically.ResultsMean age of participants was 41 years (range 18-73), 57% were male, 86% were non-US born, and 81% had never participated in a research study. Themes that emerged included (1) motivations to participate in research to gain knowledge: for oneself, for family's benefit, and for the Vietnamese American community as a whole; (2) necessity of trustworthy and credible individuals/spokespersons to promote the research initiative; (3) recruitment strategies that are age-specific and culturally appropriate, and (4) importance of monetary incentives.ConclusionFindings from this study will be used to guide recruitment into and engagement with CARE among Vietnamese Americans but are also relevant for other registries aiming to diversify their participants.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of

In large transdisciplinary research teams finding the balance between using the most appropriate and needed measures for data collection and minimising participant burden is often a significant challenge. This paper aims to describe the development process for selecting a set of determinants of physical activity behaviours in 9–12 years old children. An internal small group (n = 8) worked iteratively with an external large group of experts and stakeholders (n = 30-50) in three steps: 1) External input – Identification through expert opinion; 2) Internal input – Identification and selection via a systematized approach; 3) External validation of the selected measures. During these steps, 113 measures were first identified, then scored, sorted, and selected using evidence-building practices such as systematic literature reviews, peer-review, and consensus discussions. Eighteen measures were agreed and included in the core measures toolkit (child and caregiver questionnaires). In conclusion, pragmatism, implementation concerns, and the experts' experience were key in this process. This process may be considered as a reference to others involved in the challenge of selecting measures in their research. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether radiation therapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH) in patients with left breast cancer. One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation–manual plan (MD–MP). A total of 104 of 136 plans were selected for RP model training. A total of 32 of 136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation–RapidPlan (AD–RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. Two RP models were established for post–breast-conserving surgery (BCS) and post-modified radical mastectomy. There were no significant differences in most of the dosimetric parameters between the MD–MP and AD–RP. The heart doses of the 2 plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P <.05) and moderately correlated in patients after postmodified radical mastectomy (0.46 ≤ r ≤ 0.58, P <.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the 2 surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH. [ABSTRACT FROM AUTHOR]

Introduction: The impact of sex bias in medical research is a matter of significant relevance and importance especially in the modern age. Despite notable improvements in sex equity across various societal fields, disparities in sex representation persist within clinical and pharmacological research. The objective of this article is to investigate the sex bias within Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia, a southern European region. Methods: A retrospective study that analyses data from final reports of Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia from 2015 to 2021. Disease categories and specific diseases, obtained from the Global Data Exchange, were evaluated for sex bias, comparing female participation to female prevalence. Results: There were 1,06,399 participants, including 43,778 female participants (42.5%). A significant underrepresentation of females was observed across various disease categories. Notably, in 12 out of 19 categories (63.2%), a pronounced female underrepresentation (sex bias ≤ 0.05) was evident, particularly in the categories of HIV/AIDS and sexually transmitted infections (sex bias = −0.5659). Furthermore, 11 categories (57.9%) also demonstrated significant female underrepresentation, with the same notable categories, HIV/AIDS and sexually transmitted infections (sex bias = −0.4439). When examining specific diseases, significant female underrepresentation was observed in 13 out of 29 diseases (46.4%), especially in HIV (sex bias = −0.4781). The overall findings indicate that the degree of sex bias was notably less favorable for females in numerous disease categories and specific conditions. Conclusion: Our study has demonstrated a significant sex bias within observational studies, mirroring patterns observed in clinical trials. Importantly, our findings highlight a pervasive underrepresentation of women across various disease categories and specific conditions. Despite efforts to promote both sexes inclusivity, our results emphasize the persistent challenges in achieving balanced sex representation in study populations. Furthermore, the absence of categorization of diseases based on male and female prevalence poses a significant challenge in accessing pertinent data, particularly concerning the sex distribution of specific diseases. [ABSTRACT FROM AUTHOR]

Aim: The faecal immunochemical test (FIT) is now widely used in English primary care to triage people who exhibit signs or symptoms of colorectal cancer (CRC). National guidelines for FIT implementation were based on data that acknowledged limitations. This study examines FIT accuracy in primary care patients with low‐ and high‐risk symptoms of CRC. Methods: This study describes a retrospective cohort study in South Yorkshire, UK (n = 2029). Consecutive symptomatic adult patients in primary care undergoing a FIT between 01/04/2021 and 30/04/2021 were assessed. A threshold > 10 μg Hb/g was defined as a positive FIT result. Lower gastrointestinal tract (LGI) investigations were the reference standard. Follow‐up over 24 months was used to identify serious colorectal diseases (CRC, high‐risk polyps and inflammatory bowel disease [IBD]). Results: Five hundred and fifteen (25.4%) patients had a positive FIT. The CRC prevalence was 1.2% (24/2029). Nineteen (79.1%) of the 24 CRC cases had NG12 symptoms, with two (8.3%) having a negative FIT. For CRC detection, FIT showed 91.7% sensitivity (95% CI: 71.5%–98.5%), 75.4% specificity (95% CI: 73.4%–77.2%), 4.3% positive predictive value (PPV) (95% CI: 2.8%–6.5%) and 99.9% negative predictive value (NPV) (95% CI: 99.5%–99.97%). Combining CRC, high‐risk polyps and IBD increased PPV and specificity but decreased sensitivity and NPV. Conclusions: In primary care, FIT safely triages patients having at‐risk CRC risk symptoms. Negative FIT results indicate a low likelihood of CRC and supports safety‐netting interventions. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusions The subcutaneous implantable cardioverter defibrillator (S‐ICD) is an alternative to a transvenous ICD in patients who meet the criteria for ICD implantation without concurrent need for cardiac pacing. The objective of this study is to examine the rates of and indications for S‐ICD removal and extraction.A retrospective analysis of all patients who underwent S‐ICD implantation between 2010 and 2022 at a single multihospital healthcare system was performed. The primary endpoint was S‐ICD removal or extraction. Patient and device characteristics were abstracted from the electronic medical record. Univariate and multivariate analyses were completed to determine factors associated with S‐ICD extraction.A total of 372 patients (69.5% male; 48.6 ± 14.4 years old) underwent S‐ICD implantation during the study period. There were 22 (5.9%) patients (81.8% male; 52.1 ± 13.2 years old) who underwent S‐ICD extraction over a median follow‐up period of 4.4 [2.0−6.5] years. The median length of time between implantation and extraction was 39.6 [8.3−64.6] months. The most common indications for S‐ICD extraction were the need for bradycardia pacing (frequency among extractions, 18.2%), infection (22.7%), and inappropriate shocks due to oversensing (22.7%). A smoking history and higher body mass index were independently associated with S‐ICD extraction.The overall rate of S‐ICD extraction over 4.4 [2.0−6.5] years was 5.9%, with the most common indications for extraction being the need for bradycardia pacing, infection, and inappropriate shocks due to oversensing. A smoking history and high body mass index are associated with increased rates of S‐ICD extraction. With appropriate patient selection for the S‐ICD, the need to remove the device after implantation is low. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Clinical Considerations Conclusion Clinical Significance This case report illustrates a clinical scenario of a patient with insufficient crowns, gold onlays and localized tooth pain in the posterior teeth, treated with partial and full coverage lithium disilicate restorations.A female patient presented in the clinics, complaining about tooth pain and unesthetic metal restorations. After a thorough examination, diagnosis and treatment plan, the existing restorations were removed, and a defect‐oriented preparation was done to preserve as much as possible of the remaining tooth structure. Final partial and full coverage lithium disilicate restorations were delivered. After a 10‐year follow‐up no biological complications were observed. Nevertheless, one major chipping was observed in one of the upper molars. This technical complication was resolved with the fabrication of a new ceramic restoration.Lithium disilicate ceramic posterior full‐ or partial‐coverage restorations are a reliable and predictable treatment option not only for the replacement of tooth structure lost due to caries but also for the replacement of insufficient restorations.The following key factors are to be considered to pursue long‐term success with ceramic restorations: patient selection, minimal invasive tooth preparation, appropriate material selection and cementation. Nevertheless, complications are to be expected, and the patient should be informed accordingly. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of mental health disorders in the United Kingdom necessitates the exploration of novel treatment modalities. This study aimed to assess the feasibility and acceptability of conducting a randomised controlled trial (RCT) evaluating the efficacy of four osteopathic interventions on psychophysiological and mental health outcomes. Methods: A mixed-methods feasibility study with an explanatory sequential design was implemented. The quantitative phase involved randomising 42 participants into four intervention groups: (1) high-velocity and articulation techniques (HVAT), (2) soft-tissue massage (STM), (3) craniosacral therapy (CST), and (4) a combination approach. Primary outcome measures encompassed recruitment rate, assessment duration, questionnaire completion, intervention attrition, and adverse events. Secondary outcomes included validated assessments of depression, anxiety, stress, psychological flexibility, heart rate variability (HRV), and interoception, administered pre- and post-intervention. Analysis of variance (ANOVA) was employed to evaluate pre-post intervention changes. The qualitative phase comprised semi-structured interviews analysed using thematic analysis. Results: The study achieved a recruitment rate of 21 eligible participants per month, with 54.8% of respondents meeting eligibility criteria. All 33 participants who completed the study underwent interventions and assessments within the allocated one-hour timeframe, with full questionnaire completion. The attrition rate was 21%. No adverse events were reported. Qualitative analysis revealed positive participant experiences, with themes highlighting good practitioner communication, intervention accessibility, and increased bodily awareness. Some participants found the questionnaire battery burdensome. Exploratory quantitative analyses showed variations in effects across interventions for heart rate variability, interoceptive accuracy, and mental health measures, but these results should be interpreted cautiously due to the small sample size. Conclusions: This study provides evidence supporting the feasibility and acceptability of a larger-scale RCT investigating osteopathic interventions for individuals presenting with mild psychological symptoms. The preliminary findings suggest potential efficacy in improving mental health outcomes, warranting further investigation. Trial registration NCT05674071, registered 06/01/2023. [ABSTRACT FROM AUTHOR]

Introduction: Knowledge of the natural and temporal course of a disease is important when deciding if an intervention is appropriate. In the case of Ménière's disease (MD), there is some evidence that attacks diminish over time, but the topic remains controversial. A conservative approach to surgery is usually followed in northern Europe, and leads to strict patient selection before considering surgery. Here, we describe the evolution of vertigo attacks among a group of intractable MD patients in whom surgery was considered. Methods: Retrospective cohort study in a Ménière's disease expert center. Patients with definite unilateral Ménière's disease and persisting vertigo attacks despite treatment with intratympanic steroid injections were included. All patients had been waitlisted for participation in a planned trial assessing non-ablative surgery. They were waitlisted between June 2016 and June 2021 without undergoing the surgical intervention. In September 2022, data were collected from patient's files and follow-up telephone interviews were conducted to assess the evolution of their vertigo attacks. Results: Thirty-five patients (54% male, mean age of onset 52 years, 51% right sided) were included in the analysis. Twenty-five patients (71%) eventually declined surgery. Of the 33 patients with complete information on vertigo attacks, 21 (64%) were free of vertigo attacks upon data collection, after a median disease duration of 5.3 years. Patients who did undergo surgery, had longer duration of disease than patients who did not. Discussion: Even in a population with intractable MD, most patients will experience relief of symptoms over time. On one hand, active treatment may accelerate relief of symptoms, but on the other hand, non-ablative therapies are of debatable effect and ablative intervention carries a risk of life long side effects. Therefore, any active intervention should be carefully considered. [ABSTRACT FROM AUTHOR]

Background and Aims Severe tricuspid regurgitation is associated with increased mortality rates, but benefit of its correction and ideal timing are not clearly determined. This study aimed to identify patient subsets who might benefit from the surgery. Methods In TRIGISTRY, an international cohort study of consecutive patients with severe isolated functional tricuspid regurgitation (33 centres, 10 countries), survival rates up to 10 years were compared between patients who underwent isolated tricuspid valve surgery (repair or replacement) and those conservatively managed, overall and according to TRI-SCORE category (low: ≤3, intermediate: 4–5, and high: ≥6). Results One thousand and two hundred seventeen were managed conservatively, and 551 underwent isolated tricuspid valve surgery (200 repairs and 351 replacements). TRI-SCORE distribution was 33% low, 32% intermediate, and 35% high. At 10 years, survival rates were similar between surgical and conservative management [41% vs. 36%; hazard ratio (HR).97; 95% confidence interval (CI).88–1.08, P =.57]. Surgery improved survival compared with conservative management in the low TRI-SCORE category (72% vs. 44%; HR.27; 95% CI.20–.37, P <.0001), but not in the intermediate (36% vs. 37%; HR 1.17; 95%CI.98–1.40, P =.09) or high categories (20% vs. 24%; HR 1.06; 95% CI.91–1.25, P =.45). Both repair and replacement improved survival in the low TRI-SCORE category (84% and 61% vs. 44%; HR.11; 95% CI.06–.19, P <.0001, and HR.65; 95% CI.47–.90, P =.009). Repair showed benefit in the intermediate category (59% vs. 37%; HR.49; 95% CI.35–.68, P <.0001) while replacement was possibly harmful (25% vs. 37%; HR 1.43; 95% CI 1.18–1.72, P =.0002). Conclusions Higher survival rates were observed with repair than replacement and benefit of intervention declined as TRI-SCORE increased with no benefit of any type of surgery in the high TRI-SCORE category. These results emphasize the importance of timely intervention and patient selection to achieve the best outcomes and the need for randomized controlled trials. [ABSTRACT FROM AUTHOR]

Patients with metastatic triple-negative breast cancer (TNBC) show variable responses to PD-1 inhibition. Efficient patient selection by predictive biomarkers would be desirable but is hindered by the limited performance of existing biomarkers. Here, we leveraged in silico patient cohorts generated using a quantitative systems pharmacology model of metastatic TNBC, informed by transcriptomic and clinical data, to explore potential ways to improve patient selection. We evaluated and quantified the performance of 90 biomarker candidates, including various cellular and molecular species, at different cutoffs by a cutoff-based biomarker testing algorithm combined with machine learning-based feature selection. Combinations of pretreatment biomarkers improved the specificity compared to single biomarkers at the cost of reduced sensitivity. On the other hand, early on-treatment biomarkers, such as the relative change in tumor diameter from baseline measured at two weeks after treatment initiation, achieved remarkably higher sensitivity and specificity. Further, blood-based biomarkers had a comparable ability to tumor-or lymph node-based biomarkers in identifying a subset of responders, potentially suggesting a less invasive way for patient selection. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion Research shows that medical students are graduating with inadequate teaching on diverse patients and insufficient experience of working with diverse patient groups. The inclusion of patients from diverse groups is necessary in healthcare teaching to ensure medical students are adequately prepared for practice. In this study, we explored the perspectives of General Practitioner (GP) tutors on the recruitment of diverse volunteer patients for medical student primary clinical care placements. In particular, we focused on the current representation of diverse volunteer patients, barriers affecting their inclusion and recommendations to help with this.Focus groups were carried out with GP tutors involved in the recruitment of volunteer patients from one region in the United Kingdom. Transcripts were analysed using Thematic Analysis.Participants acknowledged the importance of ensuring that medical students have clinical experience in assessing and managing patients from diverse populations, but most did not actively think about the diversity of the patients they were recruiting. Instead, recruitment was driven by the need to cover the curriculum and teaching requirements.To ensure that students' learning was not diminished and recognising time was a significant factor, participants automatically discounted certain patients from being a volunteer patient. They acknowledged that they did not feel comfortable identifying patients based on their demographics and were more likely to invite patients who had been volunteer patients before.Suggested solutions to overcome the factors affecting the recruitment of diverse patients are presented. Patient populations will continue to become more diverse, and therefore, medical schools must prepare their students for this and encourage GP tutors to make a conscious effort to recruit diverse patient volunteers for teaching. [ABSTRACT FROM AUTHOR]

Since their initial approval as single agent therapy for multiply relapsed/refractory Hodgkin lymphoma (HL), the PD-1 inhibitors nivolumab and pembrolizumab have been incorporated into second-line salvage regimens, and they are being investigated in upfront therapy of newly diagnosed patients. As second-line therapy in combination with brentuximab vedotin or multi-agent chemotherapy, nivolumab and pembrolizumab provide high complete remission rates and durable progression-free survival after consolidative autologous stem cell transplant. Incorporation of these agents into frontline chemotherapy regimens is feasible, and early results from a Phase III trial of nivolumab-AVD compare favorably with the existing standard for advanced stage HL, brentuximab vedotin plus AVD. As nivolumab and pembrolizumab move into earlier lines of HL therapy, open research questions include the efficacy of checkpoint inhibitor regimens in patients who relapse after frontline exposure to nivolumab or pembrolizumab; the selection of patients with relapsed HL who can achieve durable remissions without autologous stem cell transplant; and the efficacy of the PD-1 inhibitors in the frontline therapy of patients with early stage Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzes real-world outcomes for advanced, non-oncogene addicted non-small cell lung cancer patients treated with atezolizumab monotherapy following platinum-based chemotherapy, based on data from two academic institutions in Serbia. Progression-free survival did not significantly differ between patients receiving atezolizumab as a second, third, or later line of therapy, indicating consistent efficacy across treatment lines. Additionally, the number of prior chemotherapy cycles had no significant impact on progression-free survival, suggesting that a higher prior treatment burden did not compromise atezolizumab effectiveness. Importantly, a good ECOG performance status emerged as the strongest predictor of prolonged progression-free survival, highlighting the importance of patients' health status at treatment initiation. Immune checkpoint inhibitors (ICIs) like atezolizumab have improved outcomes in advanced non-small cell lung cancer (NSCLC) patients, especially in the second-line setting after progression on platinum-based chemotherapy. However, access to ICIs remains limited in many developing nations. This study evaluated the efficacy of atezolizumab as a second-line versus later-line treatment for advanced NSCLC patients in Serbia. Methods: This retrospective study involved 147 advanced NSCLC patients treated with atezolizumab following progression on prior platinum-based chemotherapy at two academic centers in Serbia. Data on demographics and clinical, pathological, and molecular characteristics were collected. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and multivariable Cox proportional hazards regression identified outcome predictors. Results: The median PFS was 7.13 months, and median OS was 38.6 months. The overall response rate (ORR) was 15%, with a disease control rate (DCR) of 57.9%. No significant PFS differences were observed between patients treated with atezolizumab in the second line versus later lines. Patients with good performance status (ECOG 0–1) had significantly better PFS compared to those with poorer status (12.03 vs. 1.63 months, p < 0.0001). Conclusions: Atezolizumab is effective in both second-line and later-line settings for advanced NSCLC, particularly in patients with good performance status. This highlights the importance of patient selection based on performance status, as well as the need for wider access to ICIs in resource-limited regions. [ABSTRACT FROM AUTHOR]

Simple Summary: The spine is the most common site of osseous metastatic involvement. Advances in diagnosing and treating spinal metastasis have improved patient survival and quality of life. There is now a strong focus on customized imaging to enhance treatment planning for tumor ablation and reduce treatment-related complications. This review discusses imaging protocols and findings in the pre- and post-SBRT setting and the imaging features differentiating expected post-SBRT treatment changes from LF. Spine metastases (SMs) are common, arising in 70% of the cases of the most prevalent malignancies in males (prostate cancer) and females (breast cancer). Stereotactic body radiotherapy, or SBRT, has been incorporated into clinical treatment algorithms over the past decade. SBRT has shown promising rates of local control for oligometastatic spinal lesions with low radiation dose to adjacent critical tissues, particularly the spinal cord. Imaging is critically important in SBRT planning, guidance, and response monitoring. This paper reviews the roles of imaging in spine SBRT, including conventional and advanced imaging approaches for SM detection, treatment planning, and post-SBRT follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer treatments traditionally focus on the type of tissue where the cancer starts, but recent research has shifted to targeting genetic changes that drive cancer growth, regardless of where the tumor originates. This approach is known as histology-agnostic therapy. In this review, we provide an update on these therapies, focusing on several newly developed drugs that are changing the way cancer is treated. Our goal was to explain how these drugs work, the benefits they offer, and the challenges that remain, such as resistance to treatment. This research may help doctors and researchers better understand how to choose the right treatments for patients with different types of cancer. By addressing the strengths and limitations of histology-agnostic therapies, we hope to support ongoing efforts in cancer treatment and encourage further studies to improve outcomes for patients. Recent advancements in oncology have led to the development of histology-agnostic therapies, which target genetic alterations irrespective of the tumor's tissue of origin. This review aimed to provide a comprehensive update on the current state of histology-agnostic drug development, focusing on key therapies, including pembrolizumab, larotrectinib, entrectinib, dostarlimab, dabrafenib plus trametinib, selpercatinib, trastuzumab deruxtecan, and reprotrectinib. We performed a detailed analysis of each therapy's mechanism of action, clinical trial outcomes, and associated biomarkers. The review further explores challenges in drug resistance, such as adaptive signaling pathways and neoantigen variability, as well as diagnostic limitations in identifying optimal patient populations. While these therapies have demonstrated efficacy in various malignancies, significant hurdles remain, including intratumoral heterogeneity and resistance mechanisms that diminish treatment effectiveness. We propose considerations for refining trial designs and emerging biomarkers, such as tumor neoantigen burden, to enhance patient selection. These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers. [ABSTRACT FROM AUTHOR]

A recent article in Perspectives on Psychological Science (Webb & Tangney, 2022) reported a study in which just 2.6% of participants recruited on Amazon's Mechanical Turk (MTurk) were deemed "valid." The authors highlighted some well-established limitations of MTurk, but their central claims—that MTurk is "too good to be true" and that it captured "only 14 human beings... [out of] N = 529"—are radically misleading, yet have been repeated widely. This commentary aims to (a) correct the record (i.e., by showing that Webb and Tangney's approach to data collection led to unusually low data quality) and (b) offer a shift in perspective for running high-quality studies online. Negative attitudes toward MTurk sometimes reflect a fundamental misunderstanding of what the platform offers and how it should be used in research. Beyond pointing to research that details strategies for effective design and recruitment on MTurk, we stress that MTurk is not suitable for every study. Effective use requires specific expertise and design considerations. Like all tools used in research—from advanced hardware to specialist software—the tool itself places constraints on what one should use it for. Ultimately, high-quality data is the responsibility of the researcher, not the crowdsourcing platform. [ABSTRACT FROM AUTHOR]

Background Medial branch blocks are used to select patients for cervical facet joint radiofrequency neurotomy (CRFN). Blocks are typically performed under fluoroscopic guidance (ie, fluoroscopy-guided blocks [FLBs]). The validity of ultrasound-guided blocks (USBs) is not well established. No prior research has compared cervical USB validity and FLB validity with CRFN outcome used as the criterion standard. Objective To evaluate cervical USB versus FLB validity with CRFN outcome used as the criterion standard. Methods Demographic and outcome data were extracted from the electronic medical records of 2 affiliated musculoskeletal pain management clinics for all patients between 2015 and 2023 inclusive who had cervical USB leading to CRFN. CRFN outcomes of each USB patient were compared with those of a matched FLB patient from the radiofrequency neurotomy (RFN) outcome database of the same clinics. Matching variables included patient age, sex, pain duration, diagnostic/prognostic block paradigm, and CRFN number. Each patient completed a numeric rating scale (NRS) pain score and Pain Disability Quality-of-Life Questionnaire (PDQQ) just before and 3 months after CRFN. At repeat CRFN, patients provided a retrospective estimate of the duration and average magnitude (percentage) of relief after the CRFN. Results USB and FLB groups were comprised of 27 patients (58 RFNs) and 38 patients (58 RFNs), respectively. Post-RFN NRS pain severity and PDQQ-Spine scores demonstrated comparable (P  > .05) absolute improvements, proportion of patients achieving ≥50% improvement, and attainment of the minimum clinically important difference. Retrospective estimates of pain relief magnitude and duration were also comparable. Conclusions This study finds cervical USB and FLB to be comparably valid as defined by their ability to predict CRFN outcome. Within the limitations of operator competence, USB can be used to select patients for CRFN. [ABSTRACT FROM AUTHOR]

Introduction: Catheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. Background: Studies on catheter ablation of AF may benefit from well‐described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost‐effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects. Methods: A panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials. Results: A comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm‐related and other endpoints. Conclusion: This expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology. Recent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies. [ABSTRACT FROM AUTHOR]

Randomized trials estimate the average treatment effect within individuals who are eligible, invited, and agree to enroll. However, decision-makers often require evidence that extends beyond the trial's enrolled population to inform policy or actions for their specific target population. Each decision-maker has distinct target populations, the composition of which may not often align with that of the trial population. As researchers, we should identify a decision-maker for whom we aim to generate evidence early in the research process. We can then specify a target population of their interest and determine if a policy or action can be informed using results from a trial alone, or if additional complementary real-world data and analysis are required. In this commentary, we outline 5 key groupings of decision-makers: policymakers, payers, purchasers, providers, and patients. We then specify relevant target populations for decision-makers interested in the effectiveness of beta-blockers after a myocardial infarction with preserved ejection fraction. Finally, we summarize the scenarios in which results from a randomized trial may or may not apply to these target populations and suggest relevant analytic approaches that can generate evidence to better align with a decision-maker's needs. This article is part of a Special Collection on Pharmacoepidemiology. [ABSTRACT FROM AUTHOR]

Background: Minority populations are utilizing mobile health applications more frequently to access health information. One group that may benefit from using mHealth technology is underserved women, specifically those on community supervision. Objective: Discuss methodological approaches for navigating digital health strategies to address underserved women's health disparities. Description of the innovative method: Using an intersectional lens, we identified strategies for conducting research using digital health technology and artificial intelligence amongst the underserved, particularly those with community supervision. Description of its effectiveness: We explore (1) methodological approaches that combine traditional research methods with precision medicine, digital phenotyping, and ecological momentary assessment; (2) implications for artificial intelligence; and (3) ethical considerations with data collection, storage, and engagement. Discussion: Researchers must address gendered differences related to health, social, and economic disparities concurrently with an unwavering focus on the protection of human subjects when addressing the unique needs of underserved women while utilizing digital health methodologies. Public contribution: Women on community supervision in South Central Texas helped inform the design of JUN, the mHealth app we reported in the case exemplar. JUN is named after the Junonia shell, a native shell to South Texas, which means strength, power, and self‐sufficiency, like the participants in our preliminary studies. [ABSTRACT FROM AUTHOR]

Selecting the right individuals for a sports team, organization, or military unit has a large influence on the achievements of the organization. However, the approaches commonly used for selection are either not reporting predictive performance or not explainable (i.e., black box models). In the present study, we introduce a novel approach to selection research, using various machine learning models. We examined 274 special forces recruits, of whom 196 dropped out, who performed a set of physical and psychological tests. On this data, we compared four machine learning models on their predictive performance, explainability, and stability. We found that a stable rule‐based (SIRUS) model was most suitable for classifying dropouts from the special forces selection program. With an averaged area under the curve score of 0.70, this model had good predictive performance, while remaining explainable and stable. Furthermore, we found that both physical and psychological variables were related to dropout. More specifically, a higher score on the 2800 m time, need for connectedness, and skin folds was most strongly associated with dropping out. We discuss how researchers and practitioners can benefit from these insights in sport and performance contexts. Highlights: In high‐stakes contexts such as elite sports and the military, selecting the right individuals has a large influence on individual and organizational achievements.We compare four machine learning models, with various levels of explainability, on a dataset of 274 Dutch special forces recruits.A fully explainable SIRUS model could achieve an average area under the curve score of 0.70 for predicting dropouts from the program.Both physical and psychological variables were related to dropout, especially the 2800 m time, need for connectedness, and skin folds. [ABSTRACT FROM AUTHOR]

Purpose: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB. Methods: [68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept. Results: [225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment. Conclusion: [225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands. [ABSTRACT FROM AUTHOR]

Due to the recent advances in the systemic treatment of non-small cell lung cancer, the management of locoregional recurrences, especially after initial radiotherapy (with or without concurrent chemotherapy), is of increasing significance. The potential alternatives in this setting include: a salvage local strategy (based on surgery, radiotherapy or thermoablative treatment), promising approach, but sometimes difficult to implement in often frail patients, and whose modalities remain under-researched; or alternatively, the initiation of systemic treatment, where the prognosis aligns with that of de novo metastatic patients. This comprehensive literature review focused on salvage radiotherapy treatment of recurrent non-small cell lung carcinomas, after initial radiotherapy, with or without associated systemic treatment. It aims to present the main findings on this area, from patient selection and preparation, to key characteristics, including dosimetric aspects, and the main limitations and uncertainties associated with this therapeutic modality. [ABSTRACT FROM AUTHOR]

Environ 10 à 15 % des patientes atteintes d'un cancer du sein seront atteintes d'une récidive locale après un traitement conservateur initial ou une mastectomie. La mastectomie totale est historiquement le traitement de référence en cas de récidive locale. Cependant, la réirradiation peut être une option en cas de second traitement conservateur en association à une segmentectomie ou en cas de récidive sur la paroi thoracique afin d'améliorer le taux de contrôle local. Différentes modalités sont disponibles : la curiethérapie, la radiothérapie externe avec ou sans hyperthermie. Bien que les résultats carcinologiques soient encourageants, cette situation complexe nécessite une sélection rigoureuse des patientes et une maîtrise technique afin d'obtenir le meilleur taux de contrôle local et de limiter la toxicité. Cet article présente une revue des données de la littérature sur les indications et différentes techniques de réirradiation des récidives homolatérales des carcinomes mammaires afin d'apporter une aide à la prise de décision en pratique clinique. Approximately 10 to 15% of patients with breast cancer will have a local recurrence after initial conservative treatment or mastectomy. Total mastectomy has historically been the standard treatment for local recurrence. However, the question of reirradiation may arise as part of a second conservative treatment in conjunction with segmentectomy or in the case of chest wall recurrence to improve local control. Different modalities are available: brachytherapy, external beam radiotherapy with or without hyperthermia. Although the carcinologic results are encouraging, this complex situation requires rigorous patient selection and technical requirements to achieve the best local control and limit toxicity events. This article presents a review of the literature on the different indications and techniques for reirradiation of ipsilateral recurrent breast cancer, with the aim of providing decision support in clinical practice. [ABSTRACT FROM AUTHOR]

The modalities of management by reirradiation for recurrence or a second localization of head and neck squamous cell carcinoma (HNSCC) in previously irradiated terrain is challenging due to the great heterogeneity of data in the literature, mainly retrospective data reporting non-negligible risks of serious late toxicity events. With the recent development of more precise and conformal radiotherapy techniques such as intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic radiotherapy (SBRT), the benefit-to-risk ratio of reirradiation has evolved in recent years with encouraging results, but patient selection is crucial. The aim of this review is to discuss the role of HNSCC reirradiation in terms of patient selection and external photon radiotherapy techniques for definitive tumor reirradiation and postoperative reirradiation. [ABSTRACT FROM AUTHOR]

Objective: To review the technique and outcomes of using dermal filler to camouflage forehead osteoma, providing a minimally invasive alternative to surgical excision. Background: Forehead osteoma, commonly known as a forehead bump or bone spur, can be a cosmetic concern. Surgical excision, while effective, carries risks of scarring and postoperative complications. An innovative approach using dermal filler offers a potential solution. Methods: A hyaluronic acid‐based filler is injected into the deep subcutaneous plane over the bony prominence using a cannula. The fanning technique ensures even distribution of the filler. The procedure's safety, patient selection, and communication between the injector and patient are emphasized to achieve optimal results. Results: The technique provides immediate aesthetic improvement with results that can last up to 12 months, depending on the filler used. While generally safe, potential complications include infections, swelling, asymmetry, and lumpiness. Proper technique, patient selection, and good communication between the injector and patient are critical to achieving optimal outcomes. Conclusion: Using dermal filler to camouflage forehead osteoma is a minimally invasive alternative to surgical excision, offering immediate and long‐lasting results with minimal downtime and fewer risks. Further studies are needed to refine the technique and optimize outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Tracheal resection anastomosis has been established as the definitive surgery for high grade postintubation subglottic stenosis. To achieve a relaxed tension-free anastomosis, various laryngeal release techniques were discussed in literature with potential effect on postoperative swallowing dysfunction. This study aims to compare the difference in swallowing outcomes following two methods of infrahyoid laryngeal release: with and without fracture of the superior thyroid horns. Methods: A retrospective cohort study was carried out at our tertiary referral hospitals including cases with grade III and IV subglottic stenosis treated by partial crico-tracheal resection with thyro-tracheal anastomosis. The patients were divided into two groups according to the method used in laryngeal release; mini infrahyoid release (group A) or infrahyoid full release (group B) where full means with fracture of the superior thyroid horn bilaterally while mini means their preservation. Swallowing assessment preoperatively and postoperatively was done by comparing swallowing dysfunction symptoms, Gugging swallowing screen (GUSS) score and fiberoptic endoscopic evaluation of swallowing (FEES) according to penetration aspiration scale (PAS). Results: A total of 71 patients were included; 46 in Group A and 25 in Group B. Clinical swallowing evaluation one week postoperatively showed statistically significant difference between the two groups being affected in 80.04% and 100% of patients in group A and B, respectively. The mean postoperative GUSS were 18 ± 1.32 in group A patients in comparison to 8.84 ± 5.18 in group B (p-value < 0.001). With FEES assessment, group A had full improvement of their swallowing abilities one month after the surgery while patients in group B had significantly lower PAS scores. Unfavourable scores for both the GUSS test and PAS were associated with increasing patients' age in group B. Conclusion: In this retrospective cohort study, cases with mini infrahyoid laryngeal release had significantly better swallowing outcomes and full resolution of dysphagia in comparison to full laryngeal release. Also, full laryngeal release is associated with delayed resolution of swallowing difficulty in older patients. This point should be considered during preoperative patient selection and counselling. [ABSTRACT FROM AUTHOR]

Acute right ventricular failure (RVF) is prevalent in multiple disease states and is associated with poor clinical outcomes. Right-sided temporary mechanical circulatory support (tMCS) devices are used to unload RV congestion and increase cardiac output in cardiogenic shock (CS) with hemodynamically significant RVF. Several RV-tMCS device platforms are available; however consensus is lacking on patient selection, timing of escalation to RV-tMCS, device management, and device weaning. The purposes of this review are to 1) describe the current state of tMCS device therapies for acute RVF with CS, 2) discuss principles of escalation to RV-tMCS device therapy, 3) examine important aspects of clinical management for patients supported by RV-tMCS devices including volume management, anticoagulation, and positive pressure ventilation, and 4) provide a framework for RV-tMCS weaning. [ABSTRACT FROM AUTHOR]

To investigate how clinicians correct patient misconceptions, we analyzed 23 video recordings of primary care visits. Analysis focused on operationalizing, identifying, and characterizing clinician corrections, integrating two inductive approaches: microanalysis of clinical interaction and conversation analysis. According to our definition, patient misconception-clinician correction episodes met three essential criteria: (1) the clinician refuted something the patient had said, (2) which the patient had presented without uncertainty, and (3) which contained a proposition that was factually incorrect. We identified 59 such episodes; the patient misconceptions most commonly related to medication issues; fewer than half had foreseeable implications for patients' future actions. We identified seven clinician correction practices: Three direct practices (displaying surprise, marking disagreement, contradicting the patient) and four indirect practices (presenting the correct proposition, providing explanations, invoking an outside authority, demonstrating with evidence). We found an almost equal distribution of these direct and indirect practices. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder in patient demographics over 65 years old causing debilitating cognitive impairment. Most commonly, AD is diagnosed clinically as "probable AD", and definitive diagnosis is confirmed through postmortem brain autopsies to detect extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau tangles. The exact mechanism causing AD is still unknown, but treatments for AD have been actively investigated. Currently, immunotherapies have shown substantial promise in reducing the pathologic and clinical signs of AD. Objective: This review aims to evaluate passive immunotherapies deemed to have promise for further development and use in the treatment of AD. Methods: Immunotherapies were selected via a narrative review of medications that have potential clinical effectiveness with a status of FDA accepted, FDA fast-track, FDA status pending, or emerging therapies poised to pursue FDA approval. Results: This review has yielded two anti-Aβ monoclonal antibodies (mAb) that are currently fully FDA approved, one mAb granted FDA fast-track status, two therapies on hold, three discontinued medications, and three promising emerging therapies. Conclusions: We conclude that, in the near future, passive immunotherapies will be the preferred and evidence-based method of treatment for AD with the presence of brain Aβ deposits for both symptom management and potential slowing of disease progression. Specifically, lecanemab and donanemab will require further clinical studies to optimize patient selection based on safety profiles. Despite some key limitations, these two drugs are paving the way for disease-modifying treatments in patients displaying early signs of amyloid pathology. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to explore how incorporating shared decision‐making (SDM) can address recruitment challenges in clinical trials. Specifically, it examines how SDM can align the trial process with patient preferences, enhance patient autonomy and increase active patient participation. Additionally, it identifies potential conflicts between SDM and certain clinical trial aspects, such as randomization or blinding, and proposes solutions to mitigate these issues. Materials and Methods: We conducted a comprehensive review of existing literature on patient recruitment challenges in clinical trials and the role of SDM in addressing these challenges. We analysed case studies and trial reports to identify common obstacles and assess the effectiveness of SDM in improving patient accrual. Additionally, we evaluated three proposed solutions: adequate trial design, communication skill training and patient decision aids. Results: Our review indicates that incorporating SDM can significantly enhance patient recruitment by promoting patient autonomy and engagement. SDM encourages physicians to adopt a more open and informative approach, which aligns the trial process with patient preferences and reduces psychological barriers such as fear and mental stress. However, implementing SDM can conflict with elements such as randomization and blinding, potentially complicating trial design and execution. Discussion: The desire for patient autonomy and active engagement through SDM may clash with traditional clinical trial methodologies. To address these conflicts, we propose three solutions: redesigning trials to better accommodate SDM principles, providing communication skill training for physicians and developing patient decision aids. By focussing on patient wishes and emotions, these solutions can integrate SDM into clinical trials effectively. Conclusion: Shared decision‐making provides a framework that can promote patient recruitment and trial participation by enhancing patient autonomy and engagement. With proper implementation of trial design modifications, communication skill training and patient decision aids, SDM can support rather than hinder clinical trial execution, ultimately contributing to the advancement of evidence‐based medicine. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to establish the feasibility of delivering a structured post‐diagnosis information and support program to dyads (persons living with dementia or mild cognitive impairment and family carers) in two primary care settings. Design: A two‐phase explanatory mixed‐method approach guided by the Bowen Feasibility Framework focused on acceptability, implementation, adaptation, integration and efficacy of a five‐part programme. In phase 1, the quantitative impact of the programme on the dyadic programme recipients' self‐efficacy, quality of life, dyadic relationship and volume of care was measured. In phase 2, inductive content analysis focused on nurse and dyad participant experiences of the programme. Quantitative and qualitative data were reviewed to conclude each element of feasibility. Methods: Four registered nurses working within the participating sites were recruited, trained as programme facilitators and supported to deliver the programme. Eligible dyads attending the respective primary health clinics were invited to participate in the programme and complete surveys at three time points: recruitment, post‐programme and 3‐month follow‐up. Post‐programme semi‐structured interviews were conducted with dyads and programme facilitators. Results: Twenty‐nine dyads completed the program; the majority were spousal dyads. The programme proved acceptable to the dyads with high retention and completion rates. Implementation and integration of the programme into usual practice were attributed to the motivation and capacity of the nurses as programme facilitators. Regarding programme efficacy, most dyads reported they were better prepared for the future and shared the plans they developed during the programme with family members. Conclusion: Implementing a structured information and support programme is feasible, but sustainability requires further adaptation or increased staff resources to maintain programme fidelity. Future research should consider selecting efficacy measures sensitive to the unique needs of people living with dementia and increasing follow‐up time to 6 months. Impact: This study established the feasibility of registered nurses delivering a post‐diagnosis information and support programme for people living with early‐stage dementia or mild cognitive impairment and their informal carers in primary care settings.The motivation and capacity of nurses working as programme facilitators ensured the integration of the programme into usual work, but this was not considered sustainable over time.Family carer dyads reported tangible outcomes and gained confidence in sharing their diagnosis with family and friends and asking for assistance.Findings from this study can be used to provide direction for a clinical trial investigating the effectiveness of the structured information and support programme in the primary care setting. Reporting Method: The authors have adhered to the EQUATOR STROBE Statement. Patient or Public Contribution: A public hospital memory clinic and general medical practice participated in project design, study protocol development and supported implementation. [ABSTRACT FROM AUTHOR]

Aim: To explore the feasibility of development and implementation of an educational intervention addressing sexual and gender minority healthcare issues; examine recruitment processes and instrument appropriateness. Design: Non‐randomized feasibility study. Methods: The educational intervention was developed and implemented in family nurse practitioner courses with data collection from August through December 2022. Clinical preparedness, attitudinal awareness and basic knowledge were measured using the lesbian, gay, bisexual and transgender Development of Clinical Skills Scale. Results: Development and implementation of the intervention was feasible but will require amendment before progressing to the pilot study. Clinical preparedness and basic knowledge increased post‐intervention, but attitudinal awareness did not improve. Recruitment did not achieve the desired sample size. Instrument internal consistency reliability was confirmed. Conclusion: Feasibility was established but will require amendment prior to the pilot study. Implications for the Profession and/or Patient Care: To prepare nurses and nurse practitioners to care for sexual and gender minority patients. Impact: This study addressed the feasibility of developing and implementing a sexual and gender minority healthcare education using an e‐Learning platform. Findings confirm that the intervention was feasible but will require amendment. The intervention increased knowledge and clinical preparedness in caring for this population, but recruitment was challenging. This research will impact nurses, nurse practitioners and nurse educators. Reporting Method: The authors adhered to the relevant EQUATOR guidelines. The Consolidated Standards of Reporting Trials guideline extension for reporting randomized and feasibility guidelines were used. Public Contribution: Sexual and gender minority community members contributed to the intervention development. What Does this Paper Contribute to the Wider Global Clinical Community?: The feasibility of using interactive e‐learning educational resources to provide sexual and gender minority healthcare curriculum.Evidence to support the use of the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale to measure learning outcomes. Trial Registration: This study was not prospectively registered because it was an educational intervention involving graduate student nurses and did not assess clinical outcomes of patients. [ABSTRACT FROM AUTHOR]

The rational use of medicinal products is of fundamental importance for a successful and efficiently conducted therapy of the patient. Biomarkers have a crucial role in the rational use of medicines. They provide valuable information and help guide treatment decisions, optimize drug therapies, and improve patient outcomes. Aim: To analyse the role of biomarkers in the rational use of medicinal products. Methods and materials: The literature review was made through a documentary analysis of scientific statistics in the PubMed and Google Scholar platforms. Results: Biomarkers facilitate a personalized approach to drug therapy, improving rational use by providing guidance for accurate patient selection, making a more accurate diagnosis, choosing the appropriate drug according to the patient's condition, accurate dosing for a specific patient, reducing contraindications and risk from the occurrence of ADRs. Their use leads to savings for the health system created by unnecessary use of the wrong drugs, in the wrong quantities, for the wrong patient, and at the wrong time. As well as benefits, biomarkers also have their imperfections, so their application must be strictly monitored and controlled, and they must undergo serious study and validation. Conclusion: Biomarkers contribute significantly to increasing rational use, guiding healthcare professionals in making well-informed decisions about treatments tailored to individual patients, as long as they are wellstudied and their clinical relevance is demonstrated. [ABSTRACT FROM AUTHOR]

As cancer has become better understood on the molecular level with the evolution of gene sequencing techniques, considerations for individualized therapy using predictive biomarkers (those associated with a treatment's effect) have shifted to a new level. In the last decade or so, randomized "adaptive enrichment" clinical trials have become increasingly utilized to strike a balance between enrolling all patients with a given tumor type, versus enrolling only a subpopulation whose tumors are defined by a potential predictive biomarker related to the mechanism of action of the experimental therapy. In this review article, we review recent innovative design extensions and adaptations to adaptive enrichment designs proposed during the last few years in the clinical trial methodology literature, both from Bayesian and frequentist perspectives. [ABSTRACT FROM AUTHOR]