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ABSTRACT Background The role of whole‐brain radiotherapy for patients with brain metastases is changing as immunotherapy and molecularly targeted therapies advance. However, whole‐brain radiotherapy continues to be part of the multimodal concept. Methods This retrospective study included 285 patients who received whole‐brain radiotherapy for brain metastases, using a median dose of 30 Gy. The study analyzed prognostic factors for survival using Cox regression analyses, while two landmark analyses, reflecting a minimum survival of 60 and 90 days, accounted for early deaths. Neurological symptoms were compared before and after treatment using the McNemar test. Results The median patient age was 62 years. Non‐small cell lung cancer (n = 95), breast cancer (n = 53), and small cell lung cancer (n = 48) were the most frequent cancer types. Median survival was 4.3 months (interquartile range 1.8–11.1). In the multivariable Cox regression model, patients who received additional immunotherapy/molecularly targeted therapy had a higher chance of survival than others. Overall survival was influenced by control of primary cancer, extracranial metastases, age, Karnofsky performance status, and number of brain metastases. The 90‐day landmark analysis included 181 patients who survived at least 90 days, reflecting that 104 patients (36.5%) died within the first 90 days. The 90‐day landmark analysis confirmed all predictive variables for survival. Patients who died before the 90‐day landmark endpoint had more brain metastases, lower Karnofsky performance status, higher age, and were less frequently treated with immunotherapy/molecularly targeted therapy than those surviving at least 90 days. The treatment significantly improved neurological symptoms. Conclusion These results indicate an insufficient patient selection, as one‐third of patients treated with whole‐brain radiotherapy died within 90 days. However, neurological symptoms improved, and the addition of immunotherapy and/or molecularly targeted therapy to whole‐brain radiotherapy was associated with better survival. Patients receiving whole‐brain irradiation should be more carefully selected. Trial Registration ClinicalTrials: 24‐3626‐104

ABSTRACT Background Recruitment of cancer patients into clinical trials (CTs) is a challenge. We aimed to explore how patient eligibility assessment is conducted in practice, what factors support or hinder this process, and to assess the potential usefulness of Clinical Trial Recruitment Support Systems (CTRSS) for patient‐to‐trial matching. Methods We conducted semi‐structured interviews in France with healthcare professionals involved in cancer CTs and experts on trial recruitment. We focused on the stages in‐between trial feasibility, and patient information and consent. Interviews were recorded, and the transcripts were analyzed thematically. We used the Systems Engineering Initiative for Patient Safety (SEIPS) 2.0 framework to organize our results. Results We interviewed 25 participants. We identified common steps for cancer patient eligibility assessment: prescreening under medical supervision, followed by the validation of patient‐trial matching based on manual chart review. This process built on rich interactions between clinicians, other professionals (clinical research assistants, data scientists, medical coding experts), and patients. Technological factors, mainly related to data infrastructure (both for patient data and trial data), and organizational factors (research culture, incentives, formal and informal research networks) mediated the performance of the recruitment process. Participants had mixed feelings towards CTRSSs; they welcomed automated pre‐screening but insisted on manual verification. Given the necessary collaborative nature of multisite trials, coordinated efforts to support a common data infrastructure could be helpful. Conclusions Material, organizational, and human factors affect cancer patient eligibility assessment for CTs. Patient‐to‐trial matching tools bear potential, but good understanding of the ecosystem, including stakeholders' motivations, is a prerequisite.

Abstract This scoping review aimed to determine whether the COVID‐19 pandemic influenced any modifications to patient selection methods or prioritisation and services provided by proton therapy (PT) centres. This review was conducted based on the PRISMA methodology and Joanna Briggs Institute scoping review guidelines. A literature search was performed in Medline, Embase, Web of Science and Scopus, as well as grey literature. Keywords such as “COVID‐19” and “Proton Therapy” were used. Articles published from 1 January 2020 in English were included. In total, 138 studies were identified of which 11 articles met the inclusion criteria. A scoping review design was chosen to capture the full extent of information published relating to the aim. Six of 11 articles included statements regarding treatment of COVID‐19 patients. Three publications recommended deferred or alternative treatment, two indicated to treat urgent/emergency patients and one reported continuous treatment for infectious patients. Recurring impacts on PT provision included more frequent use of unconventional therapies, reduced referrals, delayed treatment starts and CT simulation, change in treatment target volumes and staffing limitations due to pandemic restrictions. Consequently, telehealth consults, remote work, reduction in patient visitors, screening procedures and rigorous cleaning protocols were recommended. Few publications detailed changes to patient selection or workflow methods during the pandemic. Further research is needed to obtain more detailed information regarding current global patient selection methods in PT, collecting this data could aid in future planning for PT in Australia.

Abstract The aim was to explore various national and international clinical decision‐making tools and dose comparison methods used for selecting cancer patients for proton versus X‐ray radiation therapy. To address this aim, a literature search using defined scoping review methods was performed in Medline and Embase databases as well as grey literature. Articles published between 1 January 2015 and 4 August 2020 and those that clearly stated methods of proton versus X‐ray therapy patient selection and those published in English were eligible for inclusion. In total, 321 studies were identified of which 49 articles met the study’s inclusion criteria representing 13 countries. Six different clinical decision‐making tools and 14 dose comparison methods were identified, demonstrating variability within countries and internationally. Proton therapy was indicated for all paediatric patients except those with lymphoma and re‐irradiation where individualised model‐based selection was required. The most commonly reported patient selection tools included the Normal Tissue Complication Probability model, followed by cost‐effectiveness modelling and dosimetry comparison. Model‐based selection methods were most commonly applied for head and neck clinical indications in adult cohorts (48% of studies). While no ‘Gold Standard’ currently exists for proton therapy patient selection with variations evidenced globally, some of the patient selection methods identified in this review can be used to inform future practice in Australia. As literature was not identified from all countries where proton therapy centres are available, further research is needed to evaluate patient selection methods in these jurisdictions for a comprehensive overview.

Purpose: For unicompartmental knee arthroplasty (UKA), patient selection using correct indications can optimise postsurgical outcomes. The current gold standard for assessing eligibility is with radiographs; however, magnetic resonance imaging (MRI) may allow for more accurate assessments of cartilage damage. This study aimed to evaluate the utility of MRI for preoperative assessment of medial UKA patients by (1) comparing osteoarthritis severity of the medial, lateral and patellofemoral (PF) compartments when assessed using MRI compared with standard radiographs, and (2) investigating associations of these two assessments with postoperative clinical outcomes., Methods: This study had ethical approval. A retrospective review was performed for 88 primary medial UKA between 1 January 2017 and 31 December 2021. The main outcome measures were preoperative cartilage loss and patient-reported clinical outcomes. Preoperative cartilage loss was recorded using the International Cartilage Repair Society (ICRS) classification using MRI, and Kellgren-Lawrence (K-L) scores from radiographs. Patient-reported clinical outcomes were measured using preop, early (6-week) and late (1- or 2-year) Oxford Knee Score (OKS) change scores., Results: The use of MRI has improved accuracy over radiographs. In the medial compartment, 37 (44%) patients had less severe radiographic K-L scores (1-3); however, all patients had the most severe MRI ICRS scores (4). For patients with mild K-L scores (0 and 1), 20 (43%) and 7 (78%) patients had more severe ICRS scores (3 and 4) within their lateral and PF compartments, respectively. No associations were found between ICRS or K-L scores and OKS for any compartments., Conclusions: Assessment of medial cartilage thickness loss using MRI provides additional utility over standard radiographs in preoperative assessments of medial UKA patients. However, evidence of disease in the PF compartment assessed using MRI should not be considered a contraindication for UKA., Level of Evidence: Level III, retrospective cohort study., (© 2025 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: Some patients with anterior cruciate ligament (ACL) injury initially treated with rehabilitation need ACL reconstruction (ACLR); yet, it is unclear what characterizes these patients. This review aimed to describe predictors for ACLR in patients initially treated with rehabilitation., Methods: A systematic literature search was performed in the Cochrane, Embase, Medline, SportsDiscus and Web of Science databases from inception to 21 February 2023. Articles describing characteristics in adult patients with ACL injury undergoing ACLR after a minimum of 5 weeks rehabilitation were included. It was a priori chosen that characteristics described in at least three articles were considered more certain and could be defined as a predictor for ACLR, and those described in less than three articles were considered less certain and therefore defined as possible predictors. Articles were screened by two independent reviewers. The study was originally intended as a systematic review with meta-analysis, but in case of limited data, we would convert it to a scoping review, as was the case for this review., Results: There were 22,836 studies identified, and 181 full texts were screened, of which 10 papers were finally included. Only lower age and higher preinjury activity level were identified as predictors for ACLR. Another 12 possible predictors were identified in single studies. Through an iterative process, potential predictors were categorized into four groups: patient demographics, knee function, patient-reported outcome measures and anatomical structures., Conclusion: Lower age and higher preinjury activity level were the only predictors for ACLR after initial treatment with rehabilitation. While younger and highly active patients show a higher need for ACLR, more studies focussing on predictors and reasons for delayed ACLR are warranted., Level of Evidence: Level II., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Health care inequities have partially contributed to the existing racial gaps in health. Despite having lower incidence rates of breast cancer, Black women have a 41% higher mortality rate than White women. Black individuals remain underrepresented in research. Diversity in research is paramount to the improvement of clinical care practices and subgroup-specific guidelines., Methods: Black women from various community venues across geographic regions of the United States were invited via email, online fliers, social media platforms, and word of mouth to participate in focus groups. Six online focus groups of six to 10 Black women aged 25-65 years (N = 38) with and without a history of cancer were conducted with an in-depth semistructured discussion guide., Results: Most participants were college educated (32 of 38; 84.2%), aged 50 years or older (31 of 38; 81.6%), and had an annual income of $50,000 or more (26 of 38; 68.4%). Several barriers to research participation were identified. They included a lack of empathy and respect in health care settings, apprehension regarding the sharing of personal information, mistrust of medical research, and logistical/technical barriers. Alternatively, building individual and community trust and communicating the value of conducting research beneficial to the Black community were viewed as facilitators to research participation., Conclusions: Successful engagement of Black women in research requires the acknowledgment and consideration of the numerous barriers that affect their ability to participate. Black women are more inclined to participate in research when the research team is knowledgeable, has experience within their communities, and engages trusted community partners. Additionally, the research must be meaningful and impactful to future generations of Black women., (© 2024 American Cancer Society.)

Objective: Assess the impact of tracheostomy on postoperative morbidity and mortality and examine factors that predicted tracheostomy in head and neck flap patients., Study Design: Retrospective cohort January 2017 to December 2021., Setting: Single tertiary center., Methods: Adult patients undergoing head and neck flap reconstruction were included, excluding cutaneous reconstruction, laryngectomy, or with tracheostomy present at surgery. Patients were routinely extubated immediately following surgery. Univariate and multivariable analyses examined associations between tracheostomy and postoperative outcomes and identified predictors of tracheostomy., Results: We included 193 patients, 69 (35.8%) with tracheostomy and 124 (64.2%) without. Tracheostomy avoidance was associated with no difference in 30-day mortality (P = .531) and with decreased likelihood of 30-day complications (0.019), unplanned return to the operating room (0.021), and discharge to a facility (<0.001) and with 2.2 decrease in length of stay on multivariable analysis (confidence interval [CI]: 0.62-3.82, P = .007). Four patients (2.1%) required reactive tracheostomy with no resulting mortalities. Significant associations with tracheostomy on multivariable analysis included bilateral neck dissections (odds ratio [OR]: 3.13, CI 1.12-9.06, P = .030), number of resected mandibular subsites (OR: 2.65, CI: 1.50-5.67, P = .0023), specimen volume (OR: 1.87, CI: 1.29-2.71, P = .001), body mass index < 20 (OR: 3.80, CI: 1.24-11.64, P = .019), mandibulectomy (OR: 0.04, CI: 0.01-0.22, P < .001), forearm flap (OR: 0.15, CI: 0.05-0.41, P < .001), oral cavity site (OR: 0.21, CI: 0.06-0.73, P = .014), and age > 70 (OR: 0.33, CI: 0.14-0.81, P = .016)., Conclusion: Tracheostomy avoidance is safe in properly selected patients undergoing head and neck flap reconstruction. Multiple factors predicted tracheostomy, which may guide patient selection at other centers., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: The growth of patient and public involvement in clinical research highlights the paucity of literature on operational practices that ensure the success of large, patient-centered outcomes trials. The authors' objective was to identify tools launched by the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study team to determine their effectiveness in maximizing patient enrollment in this observational, pragmatic trial., Methods: The primary outcomes for this study were patient screening and enrollment across 36 CISTO study sites. The operational strategies included CISTOquestion email correspondence and All Sites Meetings, specifically poll performance data from meetings, and a nonanonymized feedback survey about the CISTO study's management practices. Effectiveness was measured using correlation analysis with patient cohort data, including screenings, enrollments, post-hoc exclusions, and the post-hoc exclusion rate., Results: Average screenings and enrollment rose after the implementation of CISTOquestion in April 2021, with the average number of screenings rising from 7.42 to 26.8 patients per month and enrollment rising from 3.76 to 16 patients per month. Use of CISTOquestion was correlated strongly with increased patient screenings and enrollment across all study sites. Eighty-three percent of sites with above-average post-hoc exclusion rates (≥0.092) sent below the average number of CISTOquestion inquiries. Poll performance and survey data revealed that all survey respondents who used CISTOquestion found that it was a valuable and accessible resource., Conclusions: Of the several operational tools implemented within the CISTO study that aimed to improve patient enrollment, CISTOquestion, a centralized email for addressing eligibility questions, was most beneficial to overall patient accrual., (© 2024 American Cancer Society.)

Broadening eligibility criteria in cancer trials has been advocated to represent the intended patient population more accurately. The advantages are clear in terms of generalizability and recruitment, however there are some important considerations in terms of design for efficiency and patient safety. While toxicity may be expected to be homogeneous across these subpopulations, designs should be able to recommend safe and precise doses if subpopulations with different toxicity profiles exist. Dose-finding designs accounting for patient heterogeneity have been proposed, but existing methods assume that the source of heterogeneity is known. We propose a broadened eligibility dose-finding design to address the situation of unknown patient heterogeneity in phase I cancer clinical trials where eligibility is expanded, and multiple eligibility criteria could potentially lead to different optimal doses for patient subgroups. The design offers a two-in-one approach to dose-finding by simultaneously selecting patient criteria that differentiate the maximum tolerated dose (MTD), using stochastic search variable selection, and recommending the subpopulation-specific MTD if needed. Our simulation study compares the proposed design to the naive approach of assuming patient homogeneity and demonstrates favorable operating characteristics across a wide range of scenarios, allocating patients more often to their true MTD during the trial, recommending more than one MTD when needed, and identifying criteria that differentiate the patient population. The proposed design highlights the advantages of adding more variability at an early stage and demonstrates how assuming patient homogeneity can lead to unsafe or sub-therapeutic dose recommendations., (© 2024 John Wiley & Sons Ltd.)

Background: Patient Engagement in Research (PER) has demonstrated benefits for patients, researchers and research outcomes. However, China lacks substantial experience in implementing PER. The implementation of PER in China faces unique challenges due to social-cultural differences. This study explores the perspectives of Chinese researchers to identify barriers and facilitators, aiming to guide future PER initiatives and enhance the role of patients in research., Method: Purposive sampling was employed to recruit clinical researchers with diverse healthcare backgrounds in China. Semi-structured interviews, conducted by a qualified researcher, followed interview guidelines derived from a literature review and pilot study modifications. Thematic analysis was applied using QSR Nvivo 8.0., Results: A total of 13 participants were included. Five main themes were identified from interview: (1) selection of patients for research engagement, (2) strategies to alleviate the patient burden in implementing PER, (3) strategies to encourage patients for active expression, (4) benefits to attract patient engagement and (5) researcher's preparation., Conclusion: The cultural trait of 'reservedness' in Chinese culture hinders active expression by patients in the research engagement process. Researchers tend to recruit patients with specific characteristics and emphasize the importance of aligning benefits with patient values to motivate engagement. Addressing patient burden is crucial, and researchers should be well-prepared before PER. These findings underscore the necessity of adopting culturally adapted strategies in PER to effectively address specific challenges., Patient or Public Contribution: The public participated in the interpretation of the interview results, enriching our understanding of the results., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Background: Current guidelines recommend adrenal venous sampling (AVS) for subtyping primary aldosteronism (PA). However, bilateral adrenal cannulation failure is common especially at low-volume centers. The role of unilateral-cannulating AVS in selecting patients for unilateral adrenalectomy is unclear., Methods: Fifty consecutive patients underwent AVS between 2009 and 2023 and thirty-three (66%) underwent unilateral adrenalectomy. We defined unilateral PA (uPA) by the normalized plasma aldosterone and the aldosterone-renin ratio following unilateral adrenalectomy. We examined the effectiveness of unilateral-cannulating AVS in identifying uPA., Results: 88%, 50%, and 48% of patients had the left, right, and bilateral adrenal veins successfully cannulated, respectively. Among patients with bilateral successful cannulation, a lateralization index (LI) > 4 provided a sensitivity of 100% and a positive predictive value (PPV) of 86.7% for uPA. Thresholds for the contralateral suppression index (CSI) and relative aldosterone secretion index (RASI) were derived from this subgroup and applied to the entire cohort. CSI <0.5 demonstrated a sensitivity of 76.5% and PPV of 92.9% for uPA, whereas RASI >2.4 showed a sensitivity of 85.0% and PPV of 94.4% for uPA. With CSI <0.5 or RASI >2.4 combined, a higher PPV (95.5%) was achieved when compared to computed tomography and iodocholesterol scintigraphy (86.2% and 62.5%, respectively)., Conclusion: Despite unsuccessful bilateral cannulation, our study confirms that unilateral-cannulating AVS can effectively select patients for unilateral adrenalectomy based on a combination of CSI or RASI criteria., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Introduction: In the Netherlands, since 1996, there is a national cervical cancer (CC) screening programme in place for women aged 30-60 years. The participation of Turkish- and Moroccan-Dutch women is very low. To facilitate their informed decision-making, we developed a culturally sensitive educational video, and evaluated it through a questionnaire study. Since we used multiple strategies for the recruitment of respondents, we aimed (1) to explore which sampling strategy resulted in which type of respondents, (2) to investigate which sampling strategy and individual characteristics were associated with successful recruitment of other respondents, and (3) to examine similarity between those recruited via respondent-driven sampling (RDS)., Methods: Six sampling strategies were used and compared to explore their recruitment success: (1) RDS (i.e. peer-to-peer recruitment), (2) public and private women's Facebook groups, (3) Instagram, (4) researchers' network, (5) offline organizations (e.g., community centres and mosques), and (6) other channels (e.g. flyers, infographics, and information meetings). To do this, χ 2 tests, a multivariate logistic regression, and intra class correlations (ICCs) were performed., Results: Overall, 782 Moroccan- and 696 Turkish-Dutch respondents were included in the analysis. Almost 40% filled out the questionnaire via RDS. RDS yields more often older, lower educated, and first-generation immigrant women than average. Respondents recruited via RDS have more often low CC screening knowledge and make more often uninformed CC screening decisions than average. Social media channels, however, yielded more younger, highly educated, and second-generation immigrant women than average. Sociodemographic characteristics and attitudes towards CC screening varied more strongly within than between network trees. The probability that paired respondents within a network tree had similar characteristics varied strongly depending on the characteristic., Conclusions: By using RDS and asking respondents to recruit peers, the more hard-to-reach individuals (i.e. older, lower educated, and first-generation immigrants) were reached. By using social media channels, younger, highly educated, and second-generation individuals can be recruited. RDS yielded more often women with low CC screening knowledge and women making uninformed CC screening decisions. To reach the individuals in need of tailored information or an intervention conform their needs, we recommend to use RDS as an intervention delivery strategy., Patient or Public Contribution: Following RDS, we involved Moroccan- and Turkish-Dutch women in recruiting other Moroccan- and Turkish-Dutch women. Through this recruitment, women were able to fill out our questionnaire, and watch our culturally sensitive educational video to improve their informed decision-making in regard to the CC screening programme., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Abstract Background Patients with metastatic cancer referred to radiation oncology have diverse prognoses and there is significant interest in personalizing treatment. We hypothesized that patients selected for higher biologically equivalent doses have improved overall survival. Methods The study population consists of 355 consecutive adult patients with distant metastases treated by a single radiation oncologist from 2014 to 2018. The validated NEAT model was used to prospectively stratify patients into four distinct cohorts. Radiation dose intensity was standardized using the equivalent dose in 2 Gy fractions (EQD2) model with an α/β of 10. Radiation dose intensity on survival was assessed via Cox regression models and propensity score match pairing with Kaplan–Meier analysis. Results The median survival was 9.3 months and the median follow‐up for surviving patients was 18.3 months. The NEAT model cohorts indicated median survivals of 29.5, 11.8, 4.9, and 1.8 months. Patients receiving an EQD2 of ≥40 Gy had a median survival of 16.0 months versus 3.8 months for patients receiving an EQD2 of

Abstract Two‐stage hepatectomy (TSH) is one of the specific surgical techniques that can expand the pool of resectable patients with initially unresectable colorectal liver metastases (CRLM). The indication of TSH for CRLM is only bilateral, multinodular disease, which cannot be resected by a single hepatectomy. TSH is nowadays considered an effective treatment for selected patients, with acceptable morbidity/mortality rates and promising long‐term outcomes. However, not all eligible patients can benefit from the TSH strategy. One of the most important issues is dropout from the strategy (failure to complete both of the two sequential procedures), because the survival of such patients is drastically worse compared with patients who can complete both stages. Another important issue is the early recurrence rate and subsequent poor survival even after completion of TSH. Thus, the selection of appropriate patients who can really benefit from the TSH strategy is crucial. This review discusses the optimal patient selection for TSH, which should be helpful for the development of treatment strategies for patients with extensive CRLM.

Abstract Background The CD47‐signal regulatory protein alpha (SIRPα) ‘don't eat me’ signalling axis is perhaps the most prominent innate immune checkpoint to date. However, from initial clinical trials, it is evident that monotherapy with CD47‐SIRPα blocking has a limited therapeutic effect at the maximum tolerated dose. Furthermore, treatment is associated with severe side effects, most notably anaemia, that are attributable to the ubiquitous expression of CD47. Nevertheless, promising clinical responses have been reported upon combination with the tumour‐targeting antibody rituximab or azacytidine, although toxicity issues still hamper clinical application. Main body Here, we discuss the current state of CD47‐SIRPα blocking therapy with a focus on limitations of current strategies, such as depletion of red blood cells. Subsequently, we focus on innovations designed to overcome these limitations. These include novel antibody formats designed to selectively target CD47 on tumour cells as well as tumour‐targeted bispecific antibodies with improved selectivity. In addition, the rationale and outcome of combinatorial approaches to improve the therapeutic effect of CD47 blockade are discussed. Such combinations include those with tumour‐targeted opsonizing antibodies, systemic therapy, epigenetic drugs, other immunomodulatory T‐cell‐targeted therapeutics or dual immunomodulatory CD47 bispecific antibodies. Conclusion With these advances in the design of CD47‐SIRPα‐targeting therapeutic strategies and increasing insight into the mechanism of action of this innate checkpoint, including the role of adaptive immunity, further advances in the clinical application of this checkpoint can be anticipated.

Abstract The reported results of trimodal treatment (TMT) in muscle‐invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2‐4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre‐TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow‐up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease‐specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p 5 cm TMT renders unacceptably poor treatment outcomes.

Background This study reports the outcomes of a single institutional experience treating non‐small cell lung cancer (NSCLC) involving the pulmonary hilum with low‐dose stereotactic body radiation therapy (SBRT). The authors also present a series of repeat hilar SBRT. Methods Inclusion criteria required treatment with SBRT for NSCLC involving regional lymph nodes of the: (i) hilum, (ii) mediastinum, (iii) aortopulmonary window (station 5), or (iv) mainstem bronchus. At least one clinical follow‐up with imaging was required, unless the patient had a prior documented death from cancer. Results A total of 32 patients with 44 treatments were included, and 37 treatments targeted the hilum directly, with seven concerning the mediastinum, AP window, or mainstem bronchus. Median dose was 28 Gy in four fractions with once‐weekly fractionation. At a median clinical follow‐up of 23 months, local control was 64%. Median overall survival was 24 months, and median progression‐free survival was 15 months. A total of 48% of treatments resulted in complete radiographic response on last imaging follow‐up, and no cases of grade ≥ 3 toxicity were reported. For repeat SBRT (after prior hilar SBRT), local control was 92%. Median overall survival was 20 months, and median progression‐free survival was 19 months. Complete radiographic response was noted after 58% of treatments, with 0 instances of progressive response and no reported side effects. Conclusions Low‐dose hilar SBRT was efficacious and well‐tolerated, with impressive overall survival and no grade ≥ 3 toxicity. Repeat treatments with SBRT were feasible and effective, demonstrating overall survival, local control, and toxicity comparable to primary treatments. Key points Significant findings of the study Low‐dose hilar SBRT was efficacious and well‐tolerated Repeated treatments with SBRT demonstrated encouraging results, comparable to primary treatments What this study adds This study contributes to the small body of literature concerning hilar SBRT Repeat hilar SBRT was safe and feasible Toxicity was minimal with low‐dose SBRT Once‐weekly fractionation may have contributed to low rate of side effects.

Background Given that percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is indicated primarily for symptom relief, identifying patients most likely to benefit is critically important for patient selection and shared decision‐making. Therefore, we identified factors associated with residual angina frequency after CTO PCI and developed a model to predict postprocedure anginal burden. Methods and Results Among patients in the OPEN‐CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry, we evaluated the association between patient characteristics and residual angina frequency at 6 months, as assessed by the Seattle Angina Questionnaire Angina Frequency Scale. We then constructed a prediction model for angina status after CTO PCI using ordinal regression. Among 901 patients undergoing CTO PCI, 28% had no angina, 31% had monthly angina, 30% had weekly angina, and 12% had daily angina at baseline. Six months later, 53% of patients had a ≥20‐point increase in Seattle Angina Questionnaire Angina Frequency Scale score. The final model to predict residual angina after CTO PCI included baseline angina frequency, baseline nitroglycerin use frequency, dyspnea symptoms, depressive symptoms, number of antianginal medications, PCI indication, and presence of multiple CTO lesions and had a C index of 0.78. Baseline angina frequency and nitroglycerin use frequency explained 71% of the predictive power of the model, and the relationship between model components and angina improvement at 6 months varied by baseline angina status. Conclusions A 7‐component OPEN‐AP (OPEN‐CTO Angina Prediction) score can predict angina improvement and residual angina after CTO PCI using variables commonly available before intervention. These findings have implications for appropriate patient selection and counseling for CTO PCI.

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., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Adolescent health research with biomarker data collection is limited due to difficulties in recruiting and engaging this age group. Thus, successful recruitment, engagement, and retention of adolescents in translational research are necessary to elucidate factors influencing mental and physical health conditions, uncover novel biomarkers, and expand prevention and treatment options. This paper describes strategies for effective recruitment and retention of adolescents in a research study, using a project examining depressive symptoms and the microbiome to illustrate these approaches. This cross-sectional study collected electronic self-reported survey data and self-collected biospecimens (stool and salivary samples) from adolescents 13-19 years old. All but two participants completed the questionnaires, with few missing responses. 94% provided at least one salivary sample and 89% supplied a stool sample. Participants were able to adhere to the study instructions. Using a participant-centered approach, our study successfully recruited and engaged the targeted 90 participants in self-collection of electronic survey data and biospecimens. Successful strategies of recruitment and retention included: 1) on-site clinic recruitment by research team, 2) active involvement of parents as appropriate, 3) use of electronic surveys and self-collection of biospecimens to foster control and ease of participation while addressing privacy concerns, 4) noninvasive collection of data on biospecimen, 5) frequent texting to communicate with participants, 6) flexibility in the pickup and transferring of biospecimens to accommodate adolescent schedules, 7) developmentally appropriate research, 8) participant reimbursement, and 9) sensitivity toward discussing stool sample materials. As a result of these strategies, adolescent participation in the research proved feasible., (© 2024 The Author(s). Research in Nursing & Health published by Wiley Periodicals LLC.)

Dual-agent treatment has become more and more popular in clinical trials. We have developed an approach called rapid enrollment dual-agent design (REDD) for dose-finding in Phase I clinical trials. This approach aims to administer treatment to patients using a dose combination that is highly probable to be the target dose combination. Unlike other non-model-based designs, rapid enrollment designs (RED and REDD) do not require waiting for all patients to complete an assessment before the assignment of the next participant. Simulations showed that across several scenarios, the average performance of REDD is comparable to that of the Bayesian optimal interval (BOIN) design and the partial order continual reassessment method (POCRM). The simulation results of REDD for late-onset toxicity assessments demonstrated that assigning patients to a dose combination as they are being enrolled, without waiting for the most recent cohort of patients to complete their follow-up, does not significantly compromise the quality of the maximum tolerated dose (MTD) estimation. Instead, it saves a considerable amount of time in clinical trial enrollment. User-friendly online applications have also been created to further facilitate the adoption of rapid enrollment designs in Phase I trials. In summary, being similar to BOIN and POCRM in performance, REDD is an approach that is easily comprehensible, straightforward to implement and offers an advantage of enrolling patients without having to wait for all current patients to complete their follow-ups for toxicity., (© 2024 John Wiley & Sons Ltd.)

Purpose: Subacromial balloon spacer implantation (SBSI) efficacy for massive rotator cuff tear treatment was evaluated based on perceived shoulder function, active shoulder mobility, pain, complications and research study methodological quality. The purpose was to better discern the efficacy of this device from both surgical and rehabilitative perspectives to improve patient outcomes., Methods: PubMed, EMBASE and Cochrane Library databases were searched (1 January 2010 to 1 June 2024) using 'balloon spacer', 'subacromial spacer', 'subacromial balloon spacer', 'shoulder spacer' and 'inspace' terms. Pre-surgery (baseline), 12-month (12-m) and 24-month (24-m) post-SBSI mean changes were compared using one-way ANOVA and Scheffe post hoc tests, and comparative study effect sizes were calculated (p ≤ 0.05)., Results: This review consists of 27 studies with 894 patients (67.8 ± 5 years of age) and 29.4 ± 17-month follow-up. Modified Coleman Methodology Scores (MCMS) revealed fair overall quality (mean = 61.4 ± 11). Constant-Murley scores improved from 34.8 ± 6 (baseline), to 64.2 ± 9 (12-m) and 67.9 ± 8 (24-m) (12-m, 24-m > baseline, p < 0.001). ASES scores improved from 35.1 ± 14 (baseline), to 83.3 ± 7 (12-m) and 81.8 ± 5 (24-m)(12-m, 24-m > baseline, p < 0.001). VAS pain scores improved from 6.6 ± 1 (baseline), to 2.6 ± 1 (12-m) and 2.0 ± 1 (24-m) (12-m, 24-m < baseline, p < 0.001). Flexion increased from 108.5 ± 25° (baseline), to 128.5 ± 30° (12-m) and 151.2 ± 14° (24-m) (24-m > 12-m, baseline, p = 0.01). Abduction increased from 97.7 ± 24° (baseline) to 116.3 ± 23° (12-m) and 142.3 ± 15° (24-m) (24-m > 12-m, baseline, p = 0.02). External rotation (ER) in adduction changed from 33.1 ± 7° (baseline) to 32.5 ± 4° (12-m) and 53.9 ± 9° (24-m)(24-m > 12-m, baseline, p = 0.01). ER at 90° abduction increased from 56.3 ± 3° (baseline) to 83.5 ± 5° (12-m) and 77.1 ± 4° (24-m) (24-m, 12-m > baseline, p = 0.01). Comparison studies, however, displayed insignificant results with small effect sizes., Conclusion: Despite overall fair MCMS scores, at 24-m post-SBSI, shoulder function improved and pain decreased. More rigorous comparative studies, however, revealed insignificant findings. Patients with the potential to re-establish the essential glenohumeral joint force couple that depresses the humeral head on the glenoid fossa and who comply with physical therapy may be more likely to achieve success following SBSI., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Introduction: Disparities in clinical trials (CTs) enrollment perpetuate inequities in treatment access and outcomes, but there is a paucity of Canadian data. The objective of this study was to examine disparities in cancer CT enrollment at a large Canadian comprehensive cancer center., Methods: Retrospective study of CT enrollment among new patient consultations from 2006 to 2019, with follow-up to 2021 (N = 154,880), with the primary outcome of enrollment as a binary variable. Factors associated with CT enrollment were evaluated using multivariable Bayesian hierarchical logistic regression with random effects for most responsible physician (MRP) and geography, adjusted for patient characteristics (sex, age, language, geography, and primary care provider [PCP]), area-level marginalization (residential instability, material deprivation, dependency, and ethnic concentration), disease (cancer site and stage), and MRP (department, sex, language, and training). A sensitivity analysis of the cumulative incidence of enrollment was conducted to account for differences in disease type and follow-up length., Results: CT enrollment was 11.2% overall, with a 15-year cumulative incidence of 18%. Lower odds of enrollment were observed in patients who were female (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.78-0.86), ≥65 years (AOR vs. <40, 0.61; 95% CI, 0.56-0.66), non-English speakers (0.72; 95% CI, 0.67-0.77), living ≥250 km away (AOR vs. <15 km, 0.71; 95% CI, 0.62-0.80), and without a PCP. Disease characteristics accounted for the largest proportion of observed variation (20.8%), with significantly greater odds of enrollment in patients with genitourinary cancers and late-stage disease., Conclusion: Significant sociodemographic disparities were observed, suggesting the need for targeted strategies to increase diversity in access to cancer CTs in Canada., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: Preoperative prudent patient selection plays a crucial role in knee osteoarthritis management but faces challenges in appropriate referrals such as total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA) and nonoperative intervention. Deep learning (DL) techniques can build prediction models for treatment decision-making. The aim is to develop and evaluate a knee arthroplasty prediction pipeline using three-view X-rays to determine the suitable candidates for TKA, UKA or are not arthroplasty candidates., Methods: A study was conducted using three-view (anterior-posterior, lateral and patellar) X-rays and surgical data of patients undergoing TKA, UKA or nonarthroplasty interventions from sites A and B. Data from site A were used to derive and validate models. Data from site B were used as external test set. A DL pipeline combining YOLOv3 and ResNet-18 with confident learning (CL) was developed. Multiview Convolutional Neural Network, EfficientNet-b4, ResNet-101 and the proposed model without CL were also trained and tested. The models were evaluated using metrics such as area under the receiver operating characteristic curve (AUC), accuracy, precision, specificity, sensitivity and F1 score., Results: The data set comprised a total of 1779 knees. Of which 1645 knees were from site A as a derivation set and an internal validation cohort. The external validation cohort consisted of 134 knees. The internal validation cohort demonstrated superior performance for the proposed model augmented with CL, achieving an AUC of 0.94 and an accuracy of 85.9%. External validation further confirmed the model's generalisation, with an AUC of 0.93 and an accuracy of 82.1%. Comparative analysis with other neural network models showed the proposed model's superiority., Conclusions: The proposed DL pipeline, integrating YOLOv3, ResNet-18 and CL, provides accurate predictions for knee arthroplasty candidates based on three-view X-rays. This prediction model could be useful in performing decision making for the type of arthroplasty procedure in an automated fashion., Level of Evidence: Level III, diagnostic study., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Objective: The study objective was to determine the event-free survival (EFS) of Australian patients with diffuse cutaneous systemic sclerosis (dcSSc) who met eligibility criteria for autologous stem cell transplant (ASCT) in previously published randomized controlled trials but were not treated with ASCT., Methods: Patients who met inclusion criteria for the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) and Scleroderma: Cyclophosphamide Or Transplantation (SCOT) trials were identified from the multicenter Australian Scleroderma Cohort Study (ASCS). EFS (survival without cardiac, renal, or pulmonary failure or death) at 4 years was assessed. ASCS patients who had already undergone transplantation were excluded from analysis., Results: Of the 492 patients with dcSSc in the ASCS, 56 met ASTIS inclusion criteria for ASCT (56 of 492 [11.4%]) and 30 met SCOT inclusion criteria (30 of 492 [6.1%]). An additional 11 patients met ASTIS or SCOT inclusion criteria, but they were excluded due to severe organ manifestations. EFS at 4 years in ASCS patients meeting ASTIS inclusion criteria was 83.3% and in ASCS patients meeting SCOT inclusion criteria was 81.2%. EFS at 4 years in ASCS patients who met ASTIS and SCOT inclusion but also exclusion criteria was 46.7% and 45.7%, respectively., Conclusion: ASCS patients meeting ASTIS and/or SCOT inclusion criteria who were not treated with ASCT have similar EFS at 4 years as patients receiving ASCT and better EFS than those receiving cyclophosphamide in the ASTIS and SCOT trials. This may reflect confounders unable to be controlled for, including survivor bias, but may also reflect improved standard of care for dcSSc over time., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Young adults with type 1 diabetes (T1D) face complex health challenges, including a heightened risk for distress. To counter this distress, there is a need to develop accessible, acceptable comprehensive care solutions that integrate diabetes and mental health care to enhance self-efficacy and counter mental health challenges in this population., Objective: To describe the engagement of individuals with lived experience of T1D and mental health challenges in the development of a recruitment strategy to support the co-design of an innovative integrated care programme., Results: Seven individuals with lived experience formed a Partner Advisory Council (PAC) to recruit young adults (18-29 years old) living with T1D, their friends or family and health researchers and professionals in co-design interviews (n = 19) and co-design events (n = 12). The PAC played a key role in developing a comprehensive recruitment strategy, overcoming traditional barriers and stigmas in the design of an integrated model of care., Conclusion: Assuming the presence of mental health challenges in young adults living with T1D during recruitment had far-reaching impacts on the development of a whole-person and integrated diabetes and mental health care solution. The efficient recruitment of this sample provided invaluable insights into the nuanced challenges experienced by young adults with T1D, the individual skills developed in response to their mental health challenges and the ways that this understanding can shape future programming to support mental health, quality of life and well-being. The ongoing involvement of the PAC as co-researchers underscores the enduring impact of patient engagement in developing integrated care solutions., Patient or Public Contribution: The co-design of the TECC-T1D3 model was enriched by the invaluable contributions of individuals with lived experience. This included the engagement of a diverse PAC in the recruitment of participants in co-design interviews and co-design events. PAC members actively participated in research decision-making with their insights informing a robust recruitment strategy. Beyond recruitment, PAC members continue to serve as co-researchers, shaping ongoing research and actively contributing to the TECC-T1D3 project. Six PAC members are co-authors on this manuscript., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

During the period of 2011-2023, the US Food and Drug Administration (US FDA) granted 139 accelerated and 329 regular approvals for 86 and 152 cancer therapeutic products, respectively. The percentage of approvals for a biomarker-defined population was numerically higher in accelerated approvals in comparison to regular approvals, that is, 48% vs. 40%. From 2011-2016 to 2017-2023, there was an increasing number of approvals with biomarker-defined populations in lung and breast cancers, serving as the primary driver for the overall increase in the percentage of approvals for biomarker-defined populations in solid tumors relative to hematological malignancies. Over the years, approvals were incorporating a more diverse collection of distinct biomarkers, from 3 in 2011 to 16 in 2022. Overall, HER2, hormone receptor (HR), EGFR, ALK, BRAF, and PD-L1-defined populations received the highest numbers of approvals. The FDA decision on approving a biomarker-defined or an all-comers population may depend on a number of factors and may evolve over time based on emerging evidence. The review discusses selected FDA approvals where a pivotal trial enrolled an all-comers population but the approved indication was restricted to a biomarker-defined population, as well as challenges in clinical trial design in the context of precision medicine. The prominent role of biomarkers in optimizing trial design and identifying a population most likely to benefit from treatment underlines the significance of a comprehensive understanding of disease biology and drug mechanisms. Our review illustrates that biomarker-driven approaches enhance the likelihood of identifying optimal patient populations, potentially streamlining trials through accelerated approval pathways for cancer drug development., (© 2024 Astrazeneca. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

In a multi-center randomized controlled trial (RCT) with competitive recruitment, eligible patients are enrolled sequentially by different study centers and are randomized to treatment groups using the chosen randomization method. Given the stochastic nature of the recruitment process, some centers may enroll more patients than others, and in some instances, a center may enroll multiple patients in a row, for example, on a given day. If the study is open-label, the investigators might be able to make intelligent guesses on upcoming treatment assignments in the randomization sequence, even if the trial is centrally randomized and not stratified by center. In this paper, we use enrollment data inspired by a real multi-center RCT to quantify the susceptibility of two restricted randomization procedures, the permuted block design and the big stick design, to selection bias under the convergence strategy of Blackwell and Hodges (1957) applied at the center level. We provide simulation evidence that the expected proportion of correct guesses may be greater than 50% (i.e., an increased risk of selection bias) and depends on the chosen randomization method and the number of study patients recruited by a given center that takes consecutive positions on the central allocation schedule. We propose some strategies for ensuring stronger encryption of the randomization sequence to mitigate the risk of selection bias., (© 2024 John Wiley & Sons Ltd.)

Introduction: It is crucial to identify and evaluate feasible, proactive ways to reach teens with eating disorders (EDs) who may not otherwise have access to screening or treatment. This study aimed to explore the feasibility of recruiting teens with EDs to a digital intervention study via social media and a publicly available online ED screen, and to compare the characteristics of teens recruited by each approach in an exploratory fashion., Method: Teens aged 14-17 years old who screened positive for a clinical/subclinical ED or at risk for an ED and who were not currently in ED treatment completed a baseline survey to assess current ED symptoms, mental health comorbidities, and barriers to treatment. Bivariate analyses were conducted to examine differences between participants recruited via social media and those recruited after completion of a widely available online EDs screen (i.e., National Eating Disorders Association [NEDA] screen)., Results: Recruitment of teens with EDs using the two online approaches was found to be feasible, with 934 screens completed and a total of 134 teens enrolled over 6 months: 77% (n = 103) via social media 23% (n = 31) via the NEDA screen. Mean age of participants (N = 134) was 16 years old, with 49% (n = 66) identifying as non-White, and 70% (n = 94) identifying as a gender and/or sexual minority. Teens from NEDA reported higher ED psychopathology scores (medium effect size) and more frequent self-induced vomiting and driven exercise (small effect sizes). Teens from NEDA also endorsed more barriers to treatment, including not feeling ready for treatment and not knowing where to find a counselor or other resources (small effect sizes)., Discussion: Online recruitment approaches in this study reached a large number of teens with an interest in a digital intervention to support ED recovery, demonstrating the feasibility of these outreach methods. Both approaches reached teens with similar demographic characteristics; however, teens recruited from NEDA reported higher ED symptom severity and barriers to treatment. Findings suggest that proactive assessment and intervention methods should be developed and tailored to meet the needs of each of these groups., Public Significance: This study examined the feasibility of recruiting teens with EDs to a digital intervention research study via social media and NEDA's online screen, and demonstrated differences in ED symptoms among participants by recruitment approach., (© 2024 Wiley Periodicals LLC.)

Background: Despite several decades of treatment research for anorexia nervosa (AN), many of the same questions remain: how to boost enrollment, engage participants, prevent attrition, and meet the needs of a diverse patient population within the rigorous framework of a randomized controlled trial (RCT)., Methods: In this research forum, we highlight some of the challenges and opportunities observed over the course of TRIANGLE, the largest RCT for severe AN treatment in the UK to date. We discuss strategies for addressing common challenges and avoiding common pitfalls and propose solutions to future researchers seeking to conduct treatment research in AN., Results: Our experience underscores the value of involving people with lived experience at every stage of intervention research. We offer additional recommendations for treatment researchers, including, (1) early qualitative research to identify patient barriers and obstacles, (2) clear, systematic collaboration with clinical sites for patient recruitment and passive data collection, (3) careful consideration of assessment metrics, including repeated measurement of quality of life, (4) adopting a flexible, patient-centered approach to clinical trial research, and (5) considering the unique needs and obstacles that might impact carer participation in research and their ability to provide support to their loved ones., Discussion: We hope that these lessons learned will prove fruitful for the next generation of researchers embarking on treatment research for AN., Public Significance: Using the TRIANGLE trial as an illustrative case study, we highlight the value of lived experience and codesign for developing and testing interventions for AN. We offer several lessons learned over the course of the trial, pertaining to trial enrollment, retention and engagement, measurement of outcomes, and research adaptations for real-world settings, and hope that these recommendations facilitate future treatment research for AN., (© 2024 Wiley Periodicals LLC.)

Introduction: Recruitment and long-term retention of adolescent participants in longitudinal research are challenging and may be especially so in studies involving remote measurement and biosampling components. The ability to effectively recruit and retain participants can be supported by the use of specific evidence-based engagement strategies that are built in from the earliest stages., Methods: Informed by a review of the evidence on effective engagement strategies and consultations with adolescents (via two Young Person Advisory Groups [YPAGs]; ages 11-13 and 14-17), the current protocol describes the planned participant engagement strategy for the Mental Health in the Moment Study: a multimodal measurement burst study of adolescent mental health across ages 11-19., Results: The protocol incorporates engagement strategies in four key domains: consultations/co-design with the target population, incentives, relationship-building and burden/barrier reduction. In addition to describing general engagement strategies in longitudinal studies, we also discuss specific concerns regarding engagement in data collection methods such as biosampling and ecological momentary assessment where a paucity of evidence exists., Conclusion: Engagement strategies for adolescent mental health studies should be based on existing evidence and consultations with adolescents. We present our approach in developing the planned engagement strategies and also discuss limitations and future directions in engaging adolescents in longitudinal research., Patient or Public Contribution: The study design for this project places a strong emphasis on the active engagement of adolescents throughout its development. Specifically, the feedback and suggestions provided by the YPAGs have been instrumental in refining our strategies for maximising the recruitment and retention of participants., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Caused by duplications of the gene encoding peripheral myelin protein 22 (PMP22), Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common hereditary neuropathy. Despite this shared genetic origin, there is considerable variability in clinical severity. It is hypothesized that genetic modifiers contribute to this heterogeneity, the identification of which may reveal novel therapeutic targets. In this study, we present a comprehensive analysis of clinical examination results from 1564 CMT1A patients sourced from a prospective natural history study conducted by the RDCRN-INC (Inherited Neuropathy Consortium). Our primary objective is to delineate extreme phenotype profiles (mild and severe) within this patient cohort, thereby enhancing our ability to detect genetic modifiers with large effects., Methods: We have conducted large-scale statistical analyses of the RDCRN-INC database to characterize CMT1A severity across multiple metrics., Results: We defined patients below the 10th (mild) and above the 90th (severe) percentiles of age-normalized disease severity based on the CMT Examination Score V2 and foot dorsiflexion strength (MRC scale). Based on extreme phenotype categories, we defined a statistically justified recruitment strategy, which we propose to use in future modifier studies., Interpretation: Leveraging whole genome sequencing with base pair resolution, a future genetic modifier evaluation will include single nucleotide association, gene burden tests, and structural variant analysis. The present work not only provides insight into the severity and course of CMT1A, but also elucidates the statistical foundation and practical considerations for a cost-efficient and straightforward patient enrollment strategy that we intend to conduct on additional patients recruited globally., (© 2024 Peripheral Nerve Society.)

The US Food and Drug Administration (FDA) encourages the use of enrollment practices that will lead to clinical trials that reflect the population most likely to use the therapeutic product (drug or biologic), if approved. In doing so, the benefit-risk profile of the product may be assessed more completely and offer patients and their health care providers a better understanding of the drug profile and greater confidence in clinical trial results. The objective of this systematic review was to assess recent literature on the demographic diversity of clinical trial participants, describe the methods used in defining clinical trial diversity, and address knowledge gaps to enhance clinical trial diversity. Our literature search initially yielded 246 articles. After applying our eligibility criteria, we conducted a full-text review and analyzed the contents of the 28 remaining articles in our systematic review. Eleven (39%) of the 28 articles used a reference standard to compare the participation of populations in clinical trials to assess diversity. The majority of the 28 articles reported on adult participants; only 5 included pediatric populations. Most articles found that women and minority populations were underrepresented in clinical trials. Some articles proposed solutions to improve clinical trial diversity; however, several did not comment on clinical trial diversity. Despite a growing emphasis on demographic diversity in research, certain populations continue to be underrepresented in clinical trials. There is a need to standardize the definition of diversity in clinical trials. Future research into effective enrollment approaches and appropriate reference standards could improve demographic diversity., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Objective: The Food and Drug Administration recently approved upper airway stimulation (UAS) for children with Down Syndrome and persistent obstructive sleep apnea who meet certain inclusion and exclusion criteria. Although there is a robust experience with this therapy in the adult population, established protocols used in adults are not directly transferrable to a complex pediatric population. This review aims to combine the protocols from several institutions for patient selection and postimplantation optimization, including a protocol for Drug-Induced Sleep Endoscopy in children with Down Syndrome, preactivation threshold measurements, device titration, and follow-up sleep studies., Study Design: Expert panel development of best Practice algorithm., Setting: Multi-institutional investigator review., Methods: An expert panel was assembled of pediatric otolaryngologists with extensive experience in hypoglossal nerve stimulation in children with Down Syndrome. Thirty statements were created during an initial drafting session. A modified Delphi method was used assess consensus among the panel., Results: After 2 rounds of Delphi surveys, 29 statements met criteria for consensus. One statement did not meet consensus. The statements were grouped into several categories to facilitate presentation., Conclusions: A standardized approach to UAS for children with Down Syndrome must take into account the unique challenges inherent to treating a complex pediatric population with a high rate of sensory processing disorders. This expert panel has met consensus on several statements that will guide clinicians as this novel therapy is adopted., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Introduction: Treatment of pregnancy-associated breast cancer is complex, as providers try to balance risks to the pregnant person and the developing fetus. Given increased case fatality and increasing incidence, there is a pressing need understand the efficacy and safety of different treatment regimens in this population; however, pregnant and lactating people have traditionally been excluded from participating in randomized controlled trials (RCTs). Given recent efforts to expand the inclusion criteria for oncology RCTs, this study aimed to review the inclusion/exclusion criteria of current breast cancer RCTs to assess what proportion of trials permitted enrollment of pregnant and lactating persons., Material and Methods: We conducted a comprehensive search of ClinicalTrials.gov in January 2022 to identify interventional studies of breast cancer in adults that were actively recruiting. The primary outcomes were the exclusion of pregnant and lactating people., Results: The search identified 1706 studies, of which 1451 met eligibility criteria. Overall, 69.4% and 54.8% of studies excluded pregnant and lactating people, respectively. The exclusion of pregnant and lactating persons differed by study characteristics but extended across all trial designs, locations, phases and interventions. Exclusion of pregnant and lactating persons was most common in trials where the intervention was biological (86.3%), drug (83.5%) or radiation (81.5%)., Conclusions: The exclusion of pregnant and lactating people from clinical trials contributes to evidence gaps in how to treat this population. A paradigm shift is needed that focuses on how research can be used to protect pregnant people from future harms, instead of protecting pregnant people from research-related risks., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC., Methods: We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts., Results: Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy., Conclusions: Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Objective: To assess the feasibility and relevancy of a systematic data collection process in characterizing factors influencing research acceptability through women during pregnancy and early postpartum., Methods: A pilot prospective observational crossover unicentric study was conducted in Est France. All the women (except language barrier and intensive care transfer) were called upon to complete a survey (33 questions). The primary endpoints were the participation rate and the completeness of the information. The secondary endpoint was the participants' sociodemographic background and preferences regarding research (bivariate analysis, P value <0.20)., Results: Within the research period (February 23-March 8, 114 childbirths), 105 women fitting the criteria were called upon for the survey. The participation rate and completeness were high. The participation rate was 93% with six lost to follow-up, and one refusal. The global filling rate was 95%. We highlighted two plausible variables of interests for research participation: women age older (P value 0.119) and level of education (P value 0.176). A sufficient cooling-off period, the commitment of women's health providers, and the possibility to accede research results might favor women's involvement. Acceptability would appear to be decreasing when the protocol implied fetal or neonatal data collection (compared to maternal data), unless research led to a better therapeutic option., Conclusion: The data collection process is highly feasible and provide consistent data. Larger-scale output obtention should enhance the conception and rollout of projects, first by calculating sample size based on potentials for recruitments adjusted to populations, characteristics and second by fitting the experimental design to women's expectations., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Recruitment of cancer clinical trial (CCT) participants, especially participants representing the diversity of the US population, is necessary to create successful medications and a continual challenge. These challenges are amplified in Phase I cancer trials that focus on evaluating the safety of new treatments and are the gateway to treatment development. In preparation for recruitment to a Phase I recurrent head and neck cancer (HNC) trial, we assessed perceived barriers to participation or referral and suggestions for recruitment among people with HNC and community physicians (oncologist, otolaryngologist or surgeon)., Methods: Between December 2020 and February 2022, we conducted a qualitative needs assessment via semistructured interviews with a race and ethnicity-stratified sample of people with HNC (n = 30: 12 non-Hispanic White, 9 non-Hispanic African American, 8 Hispanic and 1 non-Hispanic Pacific Islander) and community physicians (n = 16) within the University of Florida Health Cancer Center catchment area. Interviews were analyzed using a qualitative content analysis approach to describe perspectives and identify relevant themes., Results: People with HNC reported thematic barriers included: concerns about side effects, safety and efficacy; lack of knowledge and systemic and environmental obstacles. Physicians identified thematic barriers of limited physician knowledge; clinic and physician barriers and structural barriers. People with HNC and physicians recommended themes included: improved patient education, dissemination of trial information and interpersonal communication between community physicians and CCT staff., Conclusions: The themes identified by people with HNC and community physicians are consistent with research efforts and recommendations on how to increase the participation of people from minoritized populations in CCTs. This community needs assessment provides direction on the selection of strategies to increase CCT participation and referral., Patient or Public Contribution: This study focused on people with HNC and community physicians' lived experience and their interpretations of how they would consider a future Phase I clinical trial. In addition to our qualitative data reflecting community voices, a community member reviewed the draft interview guide before data collection and both people with HNC and physicians aided interpretation of the findings., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Recruitment of residents for research from long-term care settings is known to be difficult. The purpose of this study was to summarize the effectiveness and cost in terms of time and dollars of recruitment methods for a cluster-randomized controlled clinical trial conducted in long-term care settings. This study was a retrospective, exploratory, descriptive analysis of recruitment data. After recruitment of 15 independent and assisted living communities, residents at each site were recruited to participate in the study using combinations of 12 different recruitment methods. Recruitment methods, time spent screening, and enrollment data were collected. Recruitment data were analyzed at the levels of site, research staff member, and participant. Over the study period, 279 older adults were screened and 172 enrolled from the 15 sites. Many participants were cognitively impaired. Research staff spent 39-89 h recruiting at each site and utilized an average of four different recruitment methods per site. Introductions of participants by site contacts yielded the most consented participants compared to other recruitment methods. Sites that had a dedicated recruiter utilized more recruiting methods and enrolled more participants than those without a dedicated recruiter. The cost of recruiting averaged $1490 per site and $93-$258 per enrollee (mean $144, standard deviation $58), but was more costly in larger facilities. Recruitment of older adults from long-term care communities requires multiple methods of recruitment, skilled recruitment staff, and trust with the staff and potential participants., (© 2023 Wiley Periodicals LLC.)

Background: A lack of onsite clinical trials is the largest barrier to participation of cancer patients in trials. Development of an automated process for regional trial eligibility screening first requires identification of patient electronic health record data that allows effective trial screening, and evidence that searching for trials regionally has a positive impact compared with site-specific searching., Methods: To assess a screening framework that would support an automated regional search tool, a set of patient clinical variables was analyzed for prescreening clinical trials. The variables were used to assess regional compared with site-specific screening throughout the United States., Results: Eight core variables from patient electronic health records were identified that yielded likely matches in a prescreen process. Assessment of the screening framework was performed using these variables to search for trials locally and regionally for an 84-patient cohort. The likelihood that a trial returned in this prescreen was a provisional trial match was 45.7%. Expanding the search radius to 20 miles led to a net 91% increase in matches across cancers within the tested cohort. In a U.S. regional analysis, for sparsely populated areas, searching a 100-mile radius using the prescreening framework was needed, whereas for urban areas a 20-mile radius was sufficient., Conclusion: A clinical trial screening framework was assessed that uses limited patient data to efficiently and effectively identify prescreen matches for clinical trials. This framework improves trial matching rates when searching regionally compared with locally, although the applicability of this framework may vary geographically depending on oncology practice density., Plain Language Summary: Clinical trials provide cancer patients the opportunity to participate in research and development of new drugs and treatment approaches. It can be difficult to find available clinical trials for which a patient is eligible. This article describes an approach to clinical trial matching using limited patient data to search for trials regionally, beyond just the patient's local care site. Feasibility testing shows that this process can lead to a net 91% increase in the number of potential clinical trial matches available within 20 miles of a patient. Based on these findings, a software tool based on this model is being developed that will automatically send limited, deidentified information from patient medical records to services that can identify possible clinical trials within a given region., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)