Expression, purification, and biochemical characterization of micro- and macroalgal kainoid synthases.

Kainoid natural products are a series of potent ionotropic glutamate receptor agonists produced by a variety of divergent marine micro- and macro-algae. The key biosynthetic step in the construction of the pyrrolidine ring pharmacophore involves a unique branch of non-heme iron α-ketoglutarate dependent dioxygenases (Fe/αKGs) termed the kainoid synthases. These Fe/αKG homologs catalyze a stereoselective C-H abstraction followed by a radical carbon-carbon bond reaction to form the bioactive core on N-prenylated L-glutamic acid substrates. In this article, we describe the expression, purification, and biochemical characterization of four divergent kainoid synthases (DabC, RadC1, DsKabC, GfKabC). Furthermore, we compare and contrast their substrate preferences and product distributions, and provide some preliminary insight into how to repurpose these enzymes for whole cell biocatalysis.

Time Perspective and Perceived Social Isolation: The Role of Social Interaction Anxiety.

Time perspective is a theoretical construct that describes how humans perceive time, which can influence decision-making and subsequent behavior. Research has shown that an individual's dominant time perspective can be linked to increased risk of poor health. This study aimed to investigate the relationships between time perspective and perceived social isolation. Specifically, we examined the role of social interaction anxiety in the relationship between time perspective and perceived social isolation in a normative sample of college-aged individuals. Undergraduates (n = 1780) at a large midwestern university completed an online survey. Results revealed that future-oriented, past-positive, and present-hedonistic time perspectives were significantly negatively associated with perceived social isolation. In contrast, past-negative was positively associated with perceived social isolation, and these relationships were partially explained by social interaction anxiety. Understanding dominant time perspectives can help us to better assess health risk factors and may help to develop interventions to promote healthy behaviors.

Development of a Health Insurance Navigation Program for Long-Term Childhood Cancer Survivors.

Adapting interventions to new contexts requires consideration of the needs, norms, and delivery structures of the new setting. We describe how we followed the ORBIT model of intervention development to create Health Insurance Navigation Tools (HINT), a health insurance patient navigation intervention for childhood cancer survivors. By engaging stakeholders and leveraging institutional resources, we identified and preemptively addressed real-world barriers, which may improve the feasibility and efficacy of the intervention. Using evidence-based implementation science models to adapt and refine interventions enhances rigor and reproducibility, implements checks and balances, and surmounts challenges of intervention rollout to accelerate the delivery of health insurance education to childhood cancer survivors.

The relationship between treatment-related changes in total hip bone mineral density measured after 12, 18 and 24 months and fracture risk reduction in osteoporosis clinical trials: the FNIH-ASBMR-SABRE Project.

There is a strong association between total hip bone mineral density (THBMD) changes after 24 months of treatment and reduced fracture risk. We examined whether changes in THBMD after 12- and 18 months of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomised, placebo-controlled, double-blind trials of osteoporosis medications. We calculated the difference in mean percent change in THBMD (active-placebo) at 12, 18, and 24 months using data available for each trial. We determined the treatment-related fracture reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for hip, non-vertebral, "all" (combination of non-vertebral, clinical vertebral, and radiologic vertebral) fractures, and all clinical fractures (combination of non-vertebral and clinical vertebral). We performed meta-regression to estimate the study-level association (r2 and 95% confidence interval) between treatment-related differences in THBMD changes for each BMD measurement interval and fracture risk reduction. The meta-regression revealed that for vertebral fractures, the r2 (95% confidence interval) was 0.59 (0.19, 0.75), 0.69 (0.32, 0.82), and 0.73 (0.33, 0.84) for 12, 18 and 24 months, respectively. Similar patterns were observed for hip: r2 = 0.27 (0.00, 0.54), 0.39 (0.02, 0.63), and 0.41 (0.02, 0.65); non-vertebral: r2 = 0.27 (0.01, 0.52), 0.49 (0.10, 0.69), and 0.53 (0.11, 0.72); all fractures: r2 = 0.44 (0.10, 0.64), 0.63 (0.24, 0.77), and 0.66 (0.25, 0.80); and all clinical fractures: r2 = 0.46 (0.11, 0.65), 0.64 (0.26, 0.78), and 0.71 (0.32, 0.83), for 12-, 18- and 24-month changes in THBMD, respectively. These findings demonstrate that treatment-related THBMD changes at 12, 18 and 24 months are associated with fracture risk reductions across trials. We conclude that BMD measurement intervals as short as 12 months could be used to assess fracture efficacy, but the association is stronger with longer BMD measurement intervals.

In this study, we looked at how changes in hip bone density over time relate to the risk of fractures in people taking osteoporosis medications. We analysed data from over 122 000 participants across 22 different clinical trials. We found that the increase in bone density measured after 12, 18, and 24 months of treatment was linked to the risk of fractures. Specifically, greater improvements in bone density were associated with fewer fractures in the spine, hips, and other bones. Using statistical methods, we calculated the strength of this association. We discovered that the later we measured bone mineral density in people taking the medication, the stronger the link between improved bone density and reduced fracture risk became. Our findings suggest that bone density measurements after 12 months of treatment could help predict how well a medication will prevent fractures. However, the best predictions came from bone density changes measured over longer periods.

Species distribution models predict genetic isolation of Hetaerina vulnerata Hagen in Selys, 1853 (Odonata, Calopterygidae).

Understanding how past and current environmental conditions shape the demographic and genetic distributions of organisms facilitates our predictions of how future environmental patterns may affect populations. The Canyon Rubyspot damselfly (Odonata: Zygoptera: Hetaerina vulnerata) is an insect with a range distribution from Colombia to the arid southwestern United States, where it inhabits shaded mountain streams in the arid southwestern United States. Past spatial fragmentation of habitat and limited dispersal capacity of H. vulnerata may cause population isolation and genetic differentiation, and projected climate change may exacerbate isolation by further restricting the species' distribution. We constructed species distribution models (SDMs) based on occurrences of H. vulnerata and environmental variables characterizing the species' niche. We inferred seven current potential population clusters isolated by unsuitable habitat. Paleoclimate models indicated habitat contiguity in past conditions; projected models indicated some habitat fragmentation in future scenarios. Seventy-eight H. vulnerata individuals from six of the current clusters were sequenced via ddRADseq and processed with Stacks. Principal components and phylogeographic analyses resolved three subpopulations; Structure resolved four subpopulations. F ST values were low (<0.05) for nearby populations and >0.15 for populations separated by expanses of unsuitable habitat. Isolation by distance was an existing but weak factor in determining genomic structure; isolation by environment and the intervening landscape explained a significant proportion of genetic distance. Hetaerina vulnerata populations were shown to be isolated by a lack of tree canopy coverage, an important habitat predictor for oviposition and territoriality. Thus, H. vulnerata populations are likely separated and are genetically isolated. Integrating SDMs with landscape genetics allowed us to identify populations separated by distance and unsuitable habitat, explaining population genetic patterns and probable fates for populations under future climate scenarios.

Blast-related mild TBI: LIMBIC-CENC focused review with implications commentary.

BACKGROUND: A significant factor for the high prevalence of traumatic brain injury (TBI) among U.S. service members is their exposure to explosive munitions leading to blast-related TBI. Our understanding of the specific clinical effects of mild TBI having a component of blast mechanism remains limited compared to pure blunt mechanisms. OBJECTIVE: The purpose of this review is to provide a synopsis of clinical research findings on the long-term effects of blast-related mild TBI derived to date from the Long-Term Impact of Military-Relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC). METHODS: Publications on blast-related mild TBI from LIMBIC-CENC and the LIMBIC-CENC prospective longitudinal study (PLS) cohort were reviewed and their findings summarized. Findings from the broader literature on blast-related mild TBI that evaluate similar outcomes are additionally reviewed for a perspective on the state of the literature. RESULTS: The most consistent and compelling evidence for long-term effects of blast-related TBI is for poorer psychological health, greater healthcare utilization and disability levels, neuroimaging impacts on brain structure and function, and greater headache impact on daily life. To date, evidence for chronic cognitive performance deficits from blast-related mild TBI is limited, but futher research including crucial longitudinal data is needed. CONCLUSION: Commentary is provided on: how LIMBIC-CENC findings assimilate with the broader literature; ongoing research gaps alongside future research needs and priorities; how the scientific community can utilize the LIMBIC-CENC database for independent or collaborative research; and how the evidence from the clinical research should be assimilated into clinical practice.

Factors associated with care partner identification and education among hospitalized persons living with dementia.

Objective: Care partners of persons living with dementia (PLWD) often feel unprepared to care for their loved ones. Improving PLWD care partner identification and education during hospital stays can improve preparedness. This retrospective EHR study investigated PLWD characteristics that may relate to care partner identification, education, and teaching methods during hospital stays. Methods: Encounters from a Midwestern academic healthcare system were used. Patients were over 18, had a documented dementia diagnosis, were admitted to the hospital for at least 24 h, and had information documented in care partner or education data fields (N = 7982). Logistic regressions assessed patient's demographics, care partner identification and education. Chi-square tests compared education teaching methods and patient discharge location. Results: PLWD's who were unmarried, discharged to other care facilities, or received the diagnosis "degeneration of nervous system due to alcohol" were associated with lacking care partner identification. Care partners of unmarried PLWDs or those with the diagnosis "Alzheimer's disease, unspecified" received less education. Multiple teaching methods were associated with discharge location. Conclusion: Multiple characteristics were related to PLWD care partner identification and education differences during hospital stays. Innovation: Novel analyses highlight need for a protocol to systematically prepare dementia care partners.

Biomarkers of Intestinal Permeability are Associated with Inflammation in Metabolically Healthy Obesity, but not Normal-Weight Obesity.

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota) - and their relationships with measured inflammation - in NWO and MHO, healthy controls (CON) and metabolically unhealthy obesity (MUO; N=80; n=20/group). Serum indicators of intestinal permeability and inflammation were assessed using ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing (n=9-10/group). For C-reactive protein (CRP), MUO > NWO > CON (p<0.0001). In MHO, CRP was intermediate - and similar to - both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO versus CON/NWO (p's<0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample (r=0.78;ß = 0.57;p's<0.0001) and in MHO (r=0.74;p<0.01), but not NWO (r=0.37;p = 0.11). Shannon index was higher in CON compared to MUO (p<0.05) and inversely correlated with CRP in the full sample (r=-0.37;p<0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk.

Differential Drug Susceptibility Across Trichomonasvirus Species Allows for Generation of Varied Isogenic Clones of Trichomonas vaginalis.

Trichomonas vaginalis (Tvag) is a sexually transmitted human pathogen that is commonly infected with strains of one or more of five known species of Trichomonas vaginalis viruses (TVVs), members of genus Trichomonasvirus . TVVs are thought not to have an extracellular phase to their lifecycle and instead to be transmitted vertically from mother to daughter cells. As a result, generation of isogenic virus-positive and virus-negative sets of Tvag clones has been a major barrier to study interactions between TVVs and their host. Nucleoside analog 2'-C-methylcytidine (2CMC) has been recently reported to clear trichomonads of infections with TVV1, TVV2, and TVV3. We used 2CMC to treat a panel of Tvag isolates that collectively harbor at least one representative strain of each TVV species and thereby provided evidence that infections with TVV4 and TVV5 can also be cleared by 2CMC. Furthermore, our results suggest a newly identified difference in drug susceptibility between TVV species. We took advantage of these susceptibility difference to generate isogenic sets of Tvag clones harboring different combinations of the five TVV species. These results provide both new insight into differences between these species and new avenues for generating tools to study the potential roles of TVVs in Tvag biology.

Enhancing Health Literacy: Evaluating the Readability of Patient Handouts Revised by ChatGPT's Large Language Model.

OBJECTIVE: To use an artificial intelligence (AI)-powered large language model (LLM) to improve readability of patient handouts. STUDY DESIGN: Review of online material modified by AI. SETTING: Academic center. METHODS: Five handout materials obtained from the American Rhinologic Society (ARS) and the American Academy of Facial Plastic and Reconstructive Surgery websites were assessed using validated readability metrics. The handouts were inputted into OpenAI's ChatGPT-4 after prompting: "Rewrite the following at a 6th-grade reading level." The understandability and actionability of both native and LLM-revised versions were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Results were compared using Wilcoxon rank-sum tests. RESULTS: The mean readability scores of the standard (ARS, American Academy of Facial Plastic and Reconstructive Surgery) materials corresponded to "difficult," with reading categories ranging between high school and university grade levels. Conversely, the LLM-revised handouts had an average seventh-grade reading level. LLM-revised handouts had better readability in nearly all metrics tested: Flesch-Kincaid Reading Ease (70.8 vs 43.9; P < .05), Gunning Fog Score (10.2 vs 14.42; P < .05), Simple Measure of Gobbledygook (9.9 vs 13.1; P < .05), Coleman-Liau (8.8 vs 12.6; P < .05), and Automated Readability Index (8.2 vs 10.7; P = .06). PEMAT scores were significantly higher in the LLM-revised handouts for understandability (91 vs 74%; P < .05) with similar actionability (42 vs 34%; P = .15) when compared to the standard materials. CONCLUSION: Patient-facing handouts can be augmented by ChatGPT with simple prompting to tailor information with improved readability. This study demonstrates the utility of LLMs to aid in rewriting patient handouts and may serve as a tool to help optimize education materials. LEVEL OF EVIDENCE: Level VI.

Sustainable biocatalytic synthesis of substituted muconic acids.

The development of sustainable routes to organic building blocks is a critical endeavor for reducing the environmental impact of chemical synthesis. Biocatalysts are poised to play an important role in sustainable synthesis, as they perform highly selective reactions under mild conditions. The application of enzymes to organic synthesis requires an approach which is operationally simple, inexpensive to prepare, and reasonably scalable. In this work, we demonstrated the utility of a Type I ring-cleaving dioxygenase CatA (P. putida KT2440) for preparative-scale synthesis of muconic acid derivatives. Muconic acids are important precursors in the synthesis of polymers and commodity chemicals. In this work, we optimized the performance of CatA under millimolar substrate concentrations and characterized the activity of the enzyme with an array of catechol substrates. Furthermore, we developed a scalable platform using cellular lysates to produce diverse muconic acids, generating up to a gram of the desired product. A simple trituration procedure was utilized for the purification of these muconic acids that obviated the need for chromatographic purification and reduced overall solvent waste.

Pembrolizumab-induced vasculitis demonstrated by FDG-PET/CT.

A 76-year-old man with a history of malignant pleural mesothelioma treated with pembrolizumab underwent FDG-PET/CT for restaging. The images demonstrated FDG uptake overlying the right hepatic and splenic artery, which were new from the previous FDG-PET/CT 2.5 years prior before the patient started pembrolizumab, suspicious for vasculitis. A follow-up MRI supported the diagnosis with evidence of celiac, splenic, common hepatic, and right hepatic artery involvement. Pembrolizumab was discontinued and the patient received a short course of oral glucocorticoids. Subsequent FDG-PET/CT performed 14 months after initiation of treatment for vasculitis demonstrated resolution of vasculitis. Immune checkpoint inhibitors can cause vasculitis, which can be recognized on FDG-PET/CT and lead to appropriate treatment.

Material, Psychological, and Behavioral Financial Hardship Among Lesbian, Gay, and Bisexual Cancer Survivors in the United States.

PURPOSE: Driven by anti-LGBTQ+ stigma, emerging literature suggests that lesbian, gay, and bisexual (LGB) cancer survivors experience financial hardship (FH) more frequently than heterosexual survivors. However, few studies have used nationally representative samples to estimate this inequity. METHODS: National Health Interview Survey data from 2019 to 2022 were pooled and weighted. Outcomes included material, psychological, and behavioral FH. The behavioral domain was further broken down into subdomains including medical care, prescription medications, and mental health care. Multivariable logit models controlling for a variety of factors were used to generate LGB and heterosexual predicted probabilities and differential effects for each FH outcome. Stratified estimates were generated by sex and age groups. RESULTS: A total of N = 374 LGB and N = 12,757 heterosexual cancer survivors were included in this analysis. In adjusted analyses, LGB cancer survivors had significantly higher material (19%, 95% CI, 15 to 24 v 12%, 95% CI, 11 to 13; P = .004), psychological (44%, 95% CI, 38 to 51 v 37%, 95% CI, 36 to 38; P = .035), and behavioral (23%, 95% CI, 18 to 28 v 13%, 95% CI, 13 to 14; P < .0001) FH than heterosexual survivors. LGB cancer survivors also had higher medical behavioral (11%, 95% CI, 7 to 15 v 7%, 95% CI, 6 to 7; P = .030), prescription medication behavioral (14%, 95% CI, 10 to 19 v 10%, 95% CI, 9 to 10; P = .032), and mental health behavioral (9%, 95% CI, 6 to 13 v 3%, 95% CI, 3 to 4; P < .0001) FH than heterosexual survivors. Stratified estimates revealed young LGB cancer survivors had the highest probability of each outcome (material: 31%, 95% CI, 23 to 40; psychological: 58%, 95% CI, 50 to 66; behavioral: 45%, 95% CI, 36 to 53). CONCLUSION: In this nationally representative analysis, LGB cancer survivors experience substantial inequities in all FH outcomes. It is crucial that future FH interventional work should prioritize populations at the highest risk of FH, such as LGB cancer survivors.

Comparison of Superior versus Inferior Canaloplasty and Trabeculotomy Using the OMNI Surgical System.

Purpose: To compare outcomes of ab-interno canaloplasty and trabeculotomy of the superior versus inferior angle. Patients and methods: This was a prospective, non-randomized, interventional comparison study done at the Veteran Affairs Hospital in Long Beach, California. All patients underwent cataract surgery with intraocular lens implantation combined with ab-interno canaloplasty and trabeculotomy with the OMNI Surgical System (SightSciences, Menlo Park, CA, USA), either superiorly or inferiorly. Pre- and post-operative intraocular pressure using Goldmann applanation tonometry and best corrected visual acuity were obtained and compared using paired t-tests. Patients were excluded if they had any prior intraocular surgery or prior laser trabeculoplasty procedures. Results: 38 eyes from 29 patients were analyzed. 19 eyes were included in the superior group and 19 eyes in the inferior group. Mean pre-operative IOP in the superior group was 17.6 ± 5.2 mmHg and in the inferior group was 17.6 ± 4.6 mmHg (p > 0.99). At 12 months, mean postoperative IOP for the superior group decreased 24% to 13.3 ± 2.8 mmHg while the inferior group decreased 26% to 13.1 ± 2.2 mmHg (p = 0.92). Mean preoperative medications in the superior group were 2.2 ± 1.3 and in the inferior group was 2.4 ± 1.3 (p = 0.88). At 12 months, this decreased to 1.3 ± 1.5 post-operatively in the superior group and 2.2 ± 1.6 post-operatively in the inferior group (p = 0.64). Conclusion: There was no statistical difference in efficacy between superior versus inferior canaloplasty/trabeculotomy with OMNI. Therefore, surgeons can perform the procedure in the direction that is most comfortable for them without affecting outcomes.

Chronic Health Conditions, Disability, and Physical and Cognitive Limitations Among LGBTQ+ Cancer Survivors.

BACKGROUND: Cancer survivors are at high risk for chronic health conditions and physical and cognitive limitations. However, few studies have explored these outcomes among LGBTQ+ survivors. METHODS: We used pooled, weighted Behavioral Risk Factor Surveillance System data from 23 states that completed two specific modules from 2020-2022. We calculated age-adjusted prevalence for heart disease, asthma, COPD, depressive disorders, myocardial infarction, kidney disease, stroke, diabetes, hearing disability, vision disability, cognitive limitations, and difficulty walking, dressing, and running errands in LGBTQ+, lesbian, gay, or bisexual (LGB), transgender or gender non-conforming (TGNC), and non-LGBTQ+ cancer survivors. Four multivariable logistic regression models controlling for different factors were run for each outcome. RESULTS: Of 40,990 cancer survivors, 1,715 were LGBTQ+. LGBTQ+ survivors had significantly higher age-adjusted prevalence of all outcomes. The prevalence of all outcomes was highest among TGNC survivors except for depressive disorders and cognitive limitations. LGBTQ+ survivors had higher odds of reporting asthma (aOR: 1.5, 95%CI:1.2-1.9), depressive disorders (aOR: 1.9, 95%CI:1.6-2.4), kidney disease (aOR: 1.5, 95%CI:1.1-2.1), stroke (aOR: 1.7, 95%CI:1.3-2.3), diabetes (aOR: 1.3, 95%CI:1.0-1.6), vision disability (aOR: 1.6, 95%CI:1.2-2.2), cognitive limitations (aOR: 2.3, 95%CI:1.8-2.9), difficulty walking (aOR: 1.7, 95%CI:1.3-2.0), dressing (aOR: 2.0, 95%CI:1.5-2.7), and running errands (aOR: 1.6, 95%CI:1.3-2.1). In TGNC models, TGNC cancer survivors had increased odds of most outcomes. CONCLUSIONS: LGBTQ+ cancer survivors have an elevated burden of all chronic health conditions, disabilities, and limitations assessed. TGNC cancer survivors experience even higher burden of the same outcomes. IMPACT: Findings highlight substantial disparities regarding the health of LGBTQ+ cancer survivors.

Correction to "Intra- and Inter-Molecular Charge Transfer Dynamics of Carbene-Metal-Amide Photosensitizers".

[This corrects the article DOI: 10.1021/acs.jpcc.4c01994.].

CREB activation drives acinar to ductal reprogramming and promote pancreatic cancer progression in animal models of alcoholic chronic pancreatitis.

BACKGROUND AND AIMS: In vivo induction of alcoholic chronic pancreatitis (ACP) causes significant acinar damage, increased fibroinflammatory response, and heightened activation of cyclic response element binding protein 1 (CREB) when compared with alcohol (A) or chronic pancreatitis (CP) mediated pancreatic damage. However, the study elucidating the cooperative interaction between CREB and the oncogenic Kras G12D/+ (Kras*) in promoting pancreatic cancer progression with ACP remains unexplored. METHODS: Experimental ACP induction was established in multiple mouse models, followed by euthanization of the animals at various time intervals during the recovery periods. Tumor latency was determined in these mice cohorts. Here, we established CREB deletion (Creb fl/fl ) in Ptf1a CreERTM/+ ;LSL-Kras G12D+/-(KC) genetic mouse models (KCC-/-). Western blot, phosphokinase array, and qPCR were used to analyze the pancreata of Ptf1a CreERTM+/-, KC and KCC -/- mice. The pancreata of ACP-induced KC mice were subjected to single-cell RNA sequencing (scRNAseq). Further studies involved conducting lineage tracing and acinar cell explant cultures. RESULTS: ACP induction in KC mice had detrimental effects on the pancreatic damage repair mechanism. The persistent existence of acinar cell-derived ductal lesions demonstrated a prolonged state of hyperactivated CREB. Persistent CREB activation leads to acinar cell reprogramming and increased pro-fibrotic inflammation in KC mice. Acinar-specific Creb ablation reduced advanced PanINs lesions, hindered tumor progression, and restored acinar cell function in ACP-induced mouse models. CONCLUSIONS: Our findings demonstrate that CREB cooperates with Kras* to perpetuate an irreversible ADM and PanIN formation. Moreover, CREB sustains oncogenic activity to promote the progression of premalignant lesions toward cancer in the presence of ACP.

How pharmacists would design and implement a community pharmacy-based colorectal cancer screening program.

Background: Distributing CRC screening through pharmacies, a highly accessible health service, may create opportunities for more equitable access to CRC screening. However, providing CRC screening in a new context introduces a substantial implementation challenge. Methods: We conducted 23 semi-structured interviews with community pharmacists practicing in Washington state and North Carolina about distributing fecal immunochemical tests (FIT) to patients in the pharmacy. The Consolidated Framework for Implementation Research (CFIR) was used to guide analysis. Results: Pharmacists believed that delivering FITs was highly compatible with their environment, workflow, and scope of practice. While knowledge about FIT eligibility criteria varied, pharmacists felt comfortable screening patients. They identified standardized eligibility criteria, patient-facing educational materials, and continuing education as essential design features. Pharmacists proposed adapting existing pharmacy electronic health record systems for patient reminders/prompts to facilitate FIT completion. While pharmacists felt confident that they could discuss test results with patients, they also expressed a need for stronger communication and care coordination with primary care providers. Discussion: When designing a pharmacy-based CRC screening program, pharmacists desired programmatic procedures to fit their current knowledge and context. Findings indicate that if proper attention is given to multi-level factors, FIT delivery can be extended to pharmacies.

Sticking to the script: Breast cancer patients' decision making regarding oral endocrine therapy.

OBJECTIVES: We sought to understand why some women with early-stage breast cancer decide to forgo or discontinue endocrine therapy (ET), and to identify factors that might lead to greater acceptance of, and long-term adherence to, this treatment. METHODS: We conducted in-depth interviews with N = 53 stage I-III HR+ women who were either non-initiators of ET, initiators who discontinued or initiators who continued with variable daily patterns of adherence. An inductive content analysis was performed to explore the decision-making process of women prescribed ET. RESULTS: Qualitative analyses revealed 55 themes that drove complex decision making. The initiators generally trusted their physicians and did little research before starting the medication. Non-initiators were more suspicious of the medical system, believing that ET presented more risks than benefits. Most discontinuers stopped ET because of side effects. Both non-initiators and discontinuers indicated that push-back from their physicians could have changed their decision. Stories and social support were important in decision making. CONCLUSIONS: Although ET can significantly reduce the risk of breast cancer recurrence, substantial barriers prevent many women from initiating or continuing it. PRACTICE IMPLICATIONS: Physicians have powerful influence over patients' decisions to initiate ET and can be important levers for motivating patients to persist.