Hap2-Ino80-facilitated transcription promotes de novo establishment of CENP-A chromatin.

Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily conserved histone H3 variant, which directs kinetochore assembly and hence centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity-selected solubilized fission yeast CENP-ACnp1 chromatin. All subunits of the Ino80 complex were enriched, including the auxiliary subunit Hap2. Chromatin association of Hap2 is Ies4-dependent. In addition to a role in maintenance of CENP-ACnp1 chromatin integrity at endogenous centromeres, Hap2 is required for de novo assembly of CENP-ACnp1 chromatin on naïve centromere DNA and promotes H3 turnover on centromere regions and other loci prone to CENP-ACnp1 deposition. Prior to CENP-ACnp1 chromatin assembly, Hap2 facilitates transcription from centromere DNA. These analyses suggest that Hap2-Ino80 destabilizes H3 nucleosomes on centromere DNA through transcription-coupled histone H3 turnover, driving the replacement of resident H3 nucleosomes with CENP-ACnp1 nucleosomes. These inherent properties define centromere DNA by directing a program that mediates CENP-ACnp1 assembly on appropriate sequences.

Epigenetic gene silencing by heterochromatin primes fungal resistance.

Heterochromatin that depends on histone H3 lysine 9 methylation (H3K9me) renders embedded genes transcriptionally silent1-3. In the fission yeast Schizosaccharomyces pombe, H3K9me heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent4,5. Heterochromatin heritability might allow wild-type cells under certain conditions to acquire epimutations, which could influence phenotype through unstable gene silencing rather than DNA change6,7. Here we show that heterochromatin-dependent epimutants resistant to caffeine arise in fission yeast grown with threshold levels of caffeine. Isolates with unstable resistance have distinct heterochromatin islands with reduced expression of embedded genes, including some whose mutation confers caffeine resistance. Forced heterochromatin formation at implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, letting wild-type cells adapt to unfavourable environments without genetic alteration. In some isolates, subsequent or coincident gene-amplification events augment resistance. Caffeine affects two anti-silencing factors: Epe1 is downregulated, reducing its chromatin association, and a shortened isoform of Mst2 histone acetyltransferase is expressed. Thus, heterochromatin-dependent epimutation provides a bet-hedging strategy allowing cells to adapt transiently to insults while remaining genetically wild type. Isolates with unstable caffeine resistance show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to resistance of plant and human fungal pathogens to such agents.

Stc1: a critical link between RNAi and chromatin modification required for heterochromatin integrity.

In fission yeast, RNAi directs heterochromatin formation at centromeres, telomeres, and the mating type locus. Noncoding RNAs transcribed from repeat elements generate siRNAs that are incorporated into the Argonaute-containing RITS complex and direct it to nascent homologous transcripts. This leads to recruitment of the CLRC complex, including the histone methyltransferase Clr4, promoting H3K9 methylation and heterochromatin formation. A key question is what mediates the recruitment of Clr4/CLRC to transcript-bound RITS. We have identified a LIM domain protein, Stc1, that is required for centromeric heterochromatin integrity. Our analyses show that Stc1 is specifically required to establish H3K9 methylation via RNAi, and interacts both with the RNAi effector Ago1, and with the chromatin-modifying CLRC complex. Moreover, tethering Stc1 to a euchromatic locus is sufficient to induce silencing and heterochromatin formation independently of RNAi. We conclude that Stc1 associates with RITS on centromeric transcripts and recruits CLRC, thereby coupling RNAi to chromatin modification.

A PRO-cision medicine intervention to personalize cancer care using patient-reported outcomes: intervention development and feasibility-testing.

PURPOSE: PRO-cision medicine refers to personalizing care using patient-reported outcomes (PROs). We developed and feasibility-tested a PRO-cision Medicine remote PRO monitoring intervention designed to identify symptoms and reduce the frequency of routine in-person visits. METHODS: We conducted focus groups and one-on-one interviews with metastatic breast (n = 15) and prostate (n = 15) cancer patients and clinicians (n = 10) to elicit their perspectives on a PRO-cision Medicine intervention's design, value, and concerns. We then feasibility-tested the intervention in 24 patients with metastatic breast cancer over 6-months. We obtained feedback via end-of-study surveys (patients) and interviews (clinicians). RESULTS: Focus group and interview participants reported that remote PRO symptom reporting could alert clinicians to issues and avoid unneeded/unwanted visits. However, some patients did not perceive avoiding visits as beneficial. Clinicians were concerned about workflow. In the feasibility-test, 24/236 screened patients (10%) enrolled. Many patients were already being seen less frequently than monthly (n = 97) or clinicians did not feel comfortable seeing them less frequently than monthly (n = 31). Over the 6-month study, there were 75 total alerts from 392 PRO symptom assessments (average 0.19 alert/assessment). Patients had an average of 4 in-person visits (vs. expected 6.5 without the intervention). Patients (n = 19/24) reported high support on the end-of-study survey, with more than 80% agreeing with positive statements about the intervention. Clinician end-of-study interviews (n = 11/14) suggested that PRO symptom monitoring be added to clinic visits, rather than replacing them, and noted the increasing role of telemedicine. CONCLUSIONS: Future research should explore combining remote PRO symptom monitoring with telemedicine and in-person visits.

Comparison of machine learning algorithms for the prediction of five-year survival in oral squamous cell carcinoma.

BACKGROUND/AIM: Machine learning analyses of cancer outcomes for oral cancer remain sparse compared to other types of cancer like breast or lung. The purpose of the present study was to compare the performance of machine learning algorithms in the prediction of global, recurrence-free five-year survival in oral cancer patients based on clinical and histopathological data. METHODS: Data were gathered retrospectively from 416 patients with oral squamous cell carcinoma. The data set was divided into training and test data set (75:25 split). Training performance of five machine learning algorithms (Logistic regression, K-nearest neighbours, Naïve Bayes, Decision tree and Random forest classifiers) for prediction was assessed by k-fold cross-validation. Variables used in the machine learning models were age, sex, pain symptoms, grade of lesion, lymphovascular invasion, extracapsular extension, perineural invasion, bone invasion and type of treatment. Variable importance was assessed and model performance on the testing data was assessed using receiver operating characteristic curves, accuracy, sensitivity, specificity and F1 score. RESULTS: The best performing model was the Decision tree classifier, followed by the Logistic Regression model (accuracy 76% and 60%, respectively). The Naïve Bayes model did not display any predictive value with 0% specificity. CONCLUSIONS: Machine learning presents a promising and accessible toolset for improving prediction of oral cancer outcomes. Our findings add to a growing body of evidence that Decision tree models are useful in models in predicting OSCC outcomes. We would advise that future similar studies explore a variety of machine learning models including Logistic regression to help evaluate model performance.

Breast cancer survivorship care plans: what are they covering and how well do they align with national guidelines?

PURPOSE: Survivorship care plans (SCPs) provide key information about cancer treatment history and follow-up recommendations. We describe the completeness of breast cancer SCPs and evaluate guideline concordance of follow-up recommendations. METHODS: We analyzed 149 breast cancer SCPs from two sites, abstracting demographics, cancer/treatment details, surveillance plans, and health promotion advice. SCP recommendations and provided information were compared to American Cancer Society/American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. RESULTS: SCP information provided in > 90% of the plans included patient age; relevant providers; cancer stage; treatment details; and physical exam, mammogram, and health promotion recommendations. SCP components completed less frequently included post-treatment symptoms/side effects (67%). All SCPs at the community site were uniform but had the potential for oversurveillance if visits occurred every 3 months in years 1-2 or every 6 months in years 3-5 with multiple cancer providers. The academic site recommended three predominant patterns of follow-up: (1) primary care provider every 6-12 months; (2) cancer team every 3-6 months (year 1), every 6-12 months (years 4-5); and (3) alternating oncology providers every 3-6 months (years 1-2) then every 6 months. Compared to guidelines, these patterns recommend under- and oversurveillance at various times. Mammography recommendations showed guideline concordance (annual) for 84%, oversurveillance for 10%, and were incomplete for 6%. SCPs of only 12/79 (15%) women on aromatase inhibitors recommended guideline-concordant bone density testing. CONCLUSIONS: SCP content is more complete for demographic and treatment summary information but has follow-up recommendation gaps. Efforts to improve follow-up recommendations are needed.

Perineural invasion in oral squamous cell carcinoma: Incidence, prognostic impact and molecular insight.

BACKGROUND: The objective of this study was to characterise the incidence and prognostic correlation of perineural invasion (PNI) in oral squamous cell carcinoma and determine whether nerve growth factor and its receptor tyrosine Kinase A expression could be used as biological markers for PNI. METHODS: A retrospective review of pathology reports of 430 patients with oral squamous cell carcinoma who were treated from 1992 to 2014 in Tayside, Scotland, was carried out. The expression of nerve growth factor and tyrosine kinase A was assessed with immunohistochemistry in 132 tissue sections of oral squamous cell carcinoma. RESULTS: Perineural invasion was identified in 17.4% of oral squamous cell carcinomas. High expression of nerve growth factor and tyrosine kinase A was seen in 84% and 92% of oral squamous cell carcinoma, respectively. Tumours with PNI expressed nerve growth factor and tyrosine kinase A with a greater frequency than tumours without PNI. PNI and high expression of nerve growth factor were significantly associated with pain. PNI was significantly associated with stage IV tumours and poor disease-specific survival. CONCLUSIONS: A higher level of expression of nerve growth factor and tyrosine kinase A may predict PNI and therefore may be considered as biological markers for PNI in oral squamous cell carcinoma. PNI and nerve growth factor overexpression may contribute to the pain generation in oral cancer patients. PNI and nerve growth factor expression can predict the aggressiveness and prognosis of oral squamous cell carcinoma patients.

Nerve growth factor-induced migration in oral and salivary gland tumour cells utilises the PI3K/Akt signalling pathway: Is there a link to perineural invasion?

OBJECTIVES: The aims of this study were to investigate the role of nerve growth factor on perineural invasion in oral and salivary gland tumour cell lines and whether there is an involvement of PI3K/Akt pathway. MATERIALS AND METHODS: Four cell lines were investigated: HSG and TYS (salivary gland tumours), SAS-H1 (oral squamous cell carcinoma) and HaCaT (human skin keratinocyte). Initially, Boyden chamber assay was done to examine the effect of different concentration of nerve growth factor on cell migration. Western blot/ immunofluorescence techniques were used to investigate the phosphorylation status of the Akt pathway within the cells in response to nerve growth factor. The effect of this growth factor and the addition of an Akt inhibitor on cell morphology and migration were also examined using scatter/scratch assays. RESULTS: Nerve growth factor triggered the PI3K/Akt pathway in oral and salivary tumour cells and induced oral and salivary tumour cell scattering and migration. Inhibitor assays confirmed that oral and salivary gland tumour cell scattering and migration is Akt dependent. CONCLUSIONS: Nerve growth factor can stimulate scattering and migration in cells derived from oral and salivary gland tumours, thereby potentially enhancing perineural invasion. Phosphorylated Akt controls cancer cell migration and scattering. Blocking the Akt pathway may inhibit cell migration and therefore perineural invasion and metastasis.

The SmoCar Study: A Caribbean-Based Multicenter Study on the Prevalence and Disparities Linked to Smoking and Gingival Health.

The aim of the SmoCar (Smoking in the Caribbean) study was to estimate the prevalence of smoking and the disparities in the smoking practices of three regions in the Caribbean: Jamaica, Dominican Republic, and Puerto Rico. The secondary objective was to assess the prevalence and severity of gingivitis in relation to the smoking practices. The study population comprised 1,847 (weighted N = 1,830) individuals (18 years and older) who were volunteer participants from the capitals of Jamaica, Dominican Republic, and Puerto Rico. A structured interview was used to assess the participants' smoking behaviors. The gingival index was used to determine the extent of gingival inflammation. Polytomous regression was used to estimate the adjusted odds ratios (aORs) for smoking status (current, past, or never), according to risk factors (sex, age-group, education, marital status, tooth-brushing frequency, and city of residence). Logistic regression models were used to assess the associations between different smoking status variables and mild to moderate/severe gingivitis. The majority of the participants were never-smokers, with current smokers being found most commonly in Kingston (33.22%), followed by San Juan (12.76%) and Santo Domingo (8.8%). Both current (aOR = 2.22, 95% confidence interval [1.45, 3.40]) and past (aOR = 1.87, 95% confidence interval [1.19, 2.93]) smoking (vs. never smoking) was strongly associated with severe gingivitis. Smoking was the most prevalent in Jamaicans and the least prevalent in Dominicans. The study population of current smokers was found to have a fourfold increased risk of severe gingivitis and a twofold increased risk of moderate gingivitis.

Primary carcinoid tumor of the bladder.

Transitional cell carcinoma is the most common type of bladder cancer in the United States. This case report discusses the finding of primary bladder carcinoid tumor (also called well-differentiated neuroendocrine tumor) in a woman with gross hematuria. With only 15-20 reported cases, primary bladder carcinoid is rare and the approach to treatment is unclear. There have been two muscle-invasive cases reported which required more extensive treatment plans. The patient presented in this case underwent complete transurethral resection of the tumor with the recommendation of surveillance cystoscopy every 3 months.

All You Need to Know as an Authorized User.

OBJECTIVE: The purpose of this article is to review the training requirements for practicing nuclear radiology, the scope of licensing, how to start a new practice, and the key concepts an authorized user needs to know for responsible use of radiopharmaceuticals. CONCLUSION: Physicians responsible for the daily operations of nuclear medicine clinics often find the regulations concerning the safe handling and administration of radiopharmaceuticals daunting. Even experienced authorized users have concerns about handling many new therapeutic agents. Those studying for certifying and subspecialty examinations or for maintenance of certification for the American Board of Nuclear Medicine and the American Board of Radiology must clearly understand the overall process for becoming an authorized user.

Raf1 Is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification.

Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demonstrate that Raf1 promotes H3K9 methylation and siRNA amplification via two distinct, separable functions. The association of the DCAF Raf1 with Cul4-Rik1 is critical for H3K9 methylation, but dispensable for processing of centromeric transcripts into siRNAs. Thus the association of a DCAF, Raf1, with its adaptor, Rik1, is required for histone methylation and to allow RNAi to signal to chromatin.

Essentials and guidelines for clinical medical physics residency training programs: executive summary of AAPM Report Number 249.

There is a clear need for established standards for medical physics residency training. The complexity of techniques in imaging, nuclear medicine, and radiation oncology continues to increase with each passing year. It is therefore imperative that training requirements and competencies are routinely reviewed and updated to reflect the changing environment in hospitals and clinics across the country. In 2010, the AAPM Work Group on Periodic Review of Medical Physics Residency Training was formed and charged with updating AAPM Report Number 90. This work group includes AAPM members with extensive experience in clinical, professional, and educational aspects of medical physics. The resulting report, AAPM Report Number 249, concentrates on the clinical and professional knowledge needed to function independently as a practicing medical physicist in the areas of radiation oncology, imaging, and nuclear medicine, and constitutes a revision to AAPM Report Number 90. This manuscript presents an executive summary of AAPM Report Number 249.

Blood Glucose Levels of Patients With Diabetes in the Immediate Post-Acute Hemodialysis Period: An Exploratory Study.

UNLABELLED: PROBLEM/PURPOSE: To establish the evidence on which to base a protocol for monitoring capillary blood glucose in hospitalized patients with diabetes mellitus in the immediate post-acute hemodialysis period. SAMPLE: Hospitalized, non-critically ill, adult patients (n = 68) with diabetes undergoing acute hemodialysis treatments. METHODS: Capillary blood glucose was tested 30 minutes prior to the end of the hemodialysis treatment, at the end of the treatment, and 30 minutes and 60 minutes post-treatment. Data were analyzed to determine both within and between patient variability. RESULTS: Glucose levels varied widely before, during, and after hemodialysis, with greatest variability at 60 minutes post-hemodialysis. Levels did not vary based on diabetes type or admitting diagnosis. Possible relationships were identified with length of treatment, insulin administration prior to treatment, and food consumed within an hour after treatment. CONCLUSIONS/NURSING IMPLICATIONS: Testing post-dialysis glucose levels earlier than 60 minutes post-treatment may miss the need for additional medication.

5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

[89Zr]-Atezolizumab-PET Imaging Reveals Longitudinal Alterations in PDL1 during Therapy in TNBC Preclinical Models.

Triple-negative breast cancers (TNBCs) currently have limited treatment options; however, PD-L1 is an indicator of susceptibility to immunotherapy. Currently, assessment of PD-L1 is limited to biopsy samples. These limitations may be overcome with molecular imaging. In this work, we describe chemistry development and optimization, in vitro, in vivo, and dosimetry of [89Zr]-Atezolizumab for PD-L1 imaging. Atezolizumab was conjugated to DFO and radiolabeled with 89Zr. Tumor uptake and heterogeneity in TNBC xenograft and patient-derived xenograft (PDX) mouse models were quantified following [89Zr]-Atezolizumab-PET imaging. PD-L1 expression in TNBC PDX models undergoing therapy and immunohistochemistry (IHC) was used to validate imaging. SUV from PET imaging was quantified and used to identify heterogeneity. PET/CT imaging using [89Zr]-Atezolizumab identified a significant increase in tumor:muscle SUVmean 1 and 4 days after niraparib therapy and revealed an increased trend in PD-L1 expression following other cytotoxic therapies. A preliminary dosimetry study indicated the organs that will receive a higher dose are the spleen, adrenals, kidneys, and liver. [89Zr]-Atezolizumab PET/CT imaging reveals potential for the noninvasive detection of PD-L1-positive TNBC tumors and allows for quantitative and longitudinal assessment. This has potential significance for understanding tumor heterogeneity and monitoring early expression changes in PD-L1 induced by therapy.

Evaluating potential overuse of surveillance care in cancer survivors.

BACKGROUND: Survivorship care plans (SCPs) communicate cancer-related information from oncology providers to patients and primary care providers. SCPs may limit overuse testing by specifying necessary follow-up care. From a randomized, controlled trial of SCP delivery, we examined whether cancer-related tests not specified in SCPs, but conducted after SCP receipt, were appropriate or consistent with overuse. METHODS: Survivors of breast, colorectal, or prostate cancer treated at urban-academic or rural-community health systems were randomized to one of three SCP delivery arms. Tests during 18 months after SCP receipt were classified as consistent with overuse if they were (1) not included in SCPs and (2) on a guideline-based predetermined list of "not recommended surveillance." After chart abstraction, physicians performed review and adjudication of potential overuse. Descriptive analyses were conducted of tests consistent with overuse. Negative binomial regression models determined if testing consistent with overuse differed across study arms. RESULTS: Among 316 patients (137 breast, 67 colorectal, 112 prostate), 140 individual tests were identified as potential overuse. Upon review, 98 were deemed to be consistent with overuse: 78 tumor markers and 20 imaging tests. The majority of overuse testing was breast cancer-related (95%). Across sites, 27 patients (9%) received ≥1 test consistent with overuse; most were breast cancer patients (22/27). Exploratory analyses of overuse test frequency by study arm showed no significant difference. CONCLUSIONS: This analysis identified practice patterns consistent with overuse of surveillance testing and can inform efforts to improve guideline-concordant care. Future interventions may include individual practice patterns and provider education.

Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance.

Epe1 histone demethylase restricts H3K9-methylation-dependent heterochromatin, preventing it from spreading over, and silencing, gene-containing regions in fission yeast. External stress induces an adaptive response allowing heterochromatin island formation that confers resistance on surviving wild-type lineages. Here we investigate the mechanism by which Epe1 is regulated in response to stress. Exposure to caffeine or antifungals results in Epe1 ubiquitylation and proteasome-dependent removal of the N-terminal 150 residues from Epe1, generating truncated Epe1 (tEpe1) which accumulates in the cytoplasm. Constitutive tEpe1 expression increases H3K9 methylation over several chromosomal regions, reducing expression of underlying genes and enhancing resistance. Reciprocally, constitutive non-cleavable Epe1 expression decreases resistance. tEpe1-mediated resistance requires a functional JmjC demethylase domain. Moreover, caffeine-induced Epe1-to-tEpe1 cleavage is dependent on an intact cell integrity MAP kinase stress signaling pathway, mutations in which alter resistance. Thus, environmental changes elicit a mechanism that curtails the function of this key epigenetic modifier, allowing heterochromatin to reprogram gene expression, thereby bestowing resistance to some cells within a population. H3K9me-heterochromatin components are conserved in human and crop-plant fungal pathogens for which a limited number of antifungals exist. Our findings reveal how transient heterochromatin-dependent antifungal resistant epimutations develop and thus inform on how they might be countered.

Implementing survivorship care planning in two contrasting health systems: lessons learned from a randomized controlled trial.

OBJECTIVE: Survivorship care plans (SCPs) are recommended to promote appropriate follow-up care, but implementation has been limited. We conducted a randomized controlled trial comparing three SCP delivery models in two health systems. We utilize mixed methods to compare the feasibility and participants' perceived value of the three models. METHODS: Patients completing treatment for stage I-III breast, prostate, or colorectal cancer from one urban-academic and one rural community cancer center were randomized to (1) mailed SCP, (2) SCP delivered during an in-person survivorship visit, or (3) SCP delivered during an in-person survivorship visit plus 6-month follow-up. Clinics had flexibility in intervention implementation. Quantitative data summarize intervention fidelity and protocol deviations. Qualitative interview data provide patients' perspectives on feasibility and intervention value. RESULTS: Of 475 eligible participants approached, 378 (79%) were randomized. Of 345 SCPs delivered, 265 (76.8%) were by protocol. Protocol deviations were more common at the urban-academic center. In post-study qualitative interviews, participants recalled little about the SCP document or visit(s). SCPs were valued for information and care coordination, although their static nature was limiting, and sometimes SCP information differed from that provided elsewhere. Visits were opportunities for care and reassurance, but time and distance to the clinic were barriers. CONCLUSIONS: SCP provision was challenging. Patients were interested in SCP, but not necessarily additional survivorship visits, particularly at the urban-academic hospital. IMPLICATIONS FOR CANCER SURVIVORS: These findings suggest that patients value careful consideration of health care needs during the transition out of treatment; SCP documents are one element of this. For many patients, models without additional visits and dynamic SCPs may be preferred.

Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed-Methods Study.

OBJECTIVE: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) can be elevated prior to inflammatory arthritis (IA). The potential to intervene in people with ACPA positivity underpins the development of prevention trials in RA. The Research Participation Influences Study examined factors influencing the decisions of individuals who are ACPA(+) to participate in a prevention trial using qualitative and quantitative methods. METHODS: Individuals with ACPA positivity without IA were provided information regarding their risk for future RA, were provided a description of a clinical prevention trial using hydroxychloroquine, and were asked if they would participate in the trial. After agreeing to or declining participation, they were surveyed on what influenced their decision using Likert scales and open-response questions. RESULTS: Thirty-nine individuals who agreed to trial participation (enrollees) and 31 individuals who declined (nonenrollees) completed surveys. Enrollees expressed greater perceived risk for RA and greater perception of benefit to themselves or others than nonenrollees. Nonenrollees expressed greater concern about medication effects and less personal or family experience with RA than enrollees. There was a higher proportion of first-degree relatives (FDRs) of people with RA in enrollees versus nonenrollees (54% vs. 23%, P = 0.01). CONCLUSION: Enrollees were more likely than nonenrollees to be FDRs, exhibit stronger concern for personal risk for RA, and have less concern about adverse effects. Further exploration is needed to determine why these differences were present, including exploration of symptoms and the role of family history. Understanding these issues will better inform researchers and individuals who are candidates for prevention.