Genetically-encoded phase separation sensors for intracellular probing of biomolecular condensates.

Biomolecular condensates are dynamic membraneless compartments with enigmatic roles across intracellular phenomena. Intrinsically-disordered proteins (IDPs) often function as condensate scaffolds, fueled by their liquid-liquid phase separation (LLPS) dynamics. Intracellular probing of these condensates relies on live-cell imaging of IDP-scaffolds tagged with fluorescent proteins. Conformational heterogeneity in IDPs, however, renders them uniquely sensitive to molecular-level fusions, risking distortion of the native biophysical properties of IDP-scaffolds and their assemblies. Probing epidermal condensates in mouse skin, we recently introduced genetically encoded LLPS-sensors that circumvent the need for molecular-level tagging of skin IDPs. The concept of LLPS-sensors involves a shift in focus from subcellular tracking of IDP-scaffolds to higher-level observations that report on the assembly and liquid-dynamics of their condensates. Towards advancing the repertoire of intracellular LLPS-sensors, here we demonstrate biomolecular approaches for the evolution and tunability of epidermal LLPS-sensors and assess their impact in early and late stages of intracellular LLPS dynamics. Benchmarking against scaffold-bound fluorescent reporters, we found that tunable ultraweak scaffold-sensor interactions are key to the sensitive and innocuous probing of nascent and established biomolecular condensates. Our LLPS-sensitive tools pave the way for the high-fidelity intracellular probing of IDP-governed biomolecular condensates across biological systems.

Rethinking students' psychological need states: The unique role of need unfulfilment to understanding ill-being in academic settings.

Prior research has shown that students face various stressors which can affect their psychological health. The present study examines the role of students' psychological need states in explaining their burnout and dropout intentions. More precisely, relying on recent findings from Self-Determination Theory research, we examined whether students' psychological need unfulfilment could contribute to explain their ill-being over and above need satisfaction and frustration. To this end, we also tested the validity of a tripartite instrument allowing to assess these need states in academic settings (Psychological Need States in Education-Scale [PNSE-S]). A study was conducted among two samples of high school (N = 473; Sample 1) and college (N = 1143; Sample 2) students. Results supported the construct validity of the 35-item PNSE-S in both samples by showing that students' relatedness, autonomy, and competence unfulfilment can be modelled as distinct need states alongside the frustration and satisfaction of those three needs. Moreover, these different need states displayed a well-differentiated pattern of associations with various facets of student burnout and with dropout intentions. Results also showed the critical role of psychological need unfulfilment in explaining students' ill-being.

Pathological Markers of Alzheimer's Disease and Related Dementia in the Rhesus Macaque Amygdala.

Rhesus macaques develop amyloid-ß (Aß) plaques during old age, but it is unclear how extensively they express other pathological hallmarks of dementia. Here we used immunohistochemistry to examine expression of phosphorylated tau (pTau) protein and cytoplasmic inclusions of TAR DNA binding protein 43 kDa (TDP-43) within the amygdala of young and old males, and also in old surgically-menopausal females that were maintained on regular or obesogenic diets. Only one animal, a 23-year-old female, showed pTau expression and none showed TDP-43 inclusions. What genetic and/or environmental factors protect macaques from expressing more severe human neuro-pathologies remains an interesting unresolved question.

Comprehensive medication management by pharmacists via telehealth in rural primary care: is it feasible and effective?

INTRODUCTION: Patients with uncontrolled diabetes living in rural communities experience many challenges, including lack of access to needed medication management services. Telepharmacy has been identified as a promising approach for addressing this gap. This presentation describes early insights into the implementation of a Comprehensive Medication Management (CMM) service in seven rural primary care clinics in North Carolina and Arkansas (USA). The CMM service involved two pharmacists meeting remotely with patients in their homes to identify and resolve Medication Therapy Problems (MTPs). STUDY DESIGN: This exploratory mixed methods study uses a pre-post design. Data sources include surveys, qualitative interviews, administrative data, and medical records (eg MTPs, hemoglobin A1Cs) collected as part of the first 3 months of a 1-year implementation period. METHODS: Lessons learned were identified through qualitative interviews with six clinic liaisons, review of pharmacists' observations, and open-ended survey questions with clinic staff and providers. Early service effectiveness was informed by MTP resolution rates and changes in patients' A1C levels. RESULTS: Key insights centered on the perceived benefits of the service for patients and clinics, the importance of patient engagement, access to implementation strategies (eg workflows and technical assistance calls), and the need to adapt the CMM service and implementation strategies to local context. The MTP resolution rate averaged 88% across pharmacists. There was a significant decrease in A1Cs in participating patients as a result of the service. CONCLUSION: Although preliminary, these results support the value of a pharmacist-led medication optimization service through remote delivery for complex patients with uncontrolled diabetes.

The relationship between interactive-imagery instructions and association memory.

Interactive imagery, one of the most effective strategies for remembering pairs of words, involves asking participants to form mental images during study. We tested the hypothesis that the visual image is, in fact, responsible for its memory benefit. Neither subjectively reported vividness (all experiments) nor objective imagery skill (experiments 1 and 3) could explain the benefit of interactive imagery for cued recall. Aphantasic participants, who self-identified little to no mental imagery, benefited from interactive-imagery instructions as much as controls (experiment 3). Imagery instructions did not improve memory for the constituent order of associations (AB versus BA), even when participants were told how to incorporate order within their images (experiments 1 and 2). Taken together, our results suggest that the visual format of images may not be responsible for the effectiveness of the interactive-imagery instruction and moreover, interactive imagery may not result in qualitatively different associative memories.

Effect of hormone replacement therapy on amyloid beta (Aß) plaque density in the rhesus macaque amygdala.

Background: Amyloid beta (Aß) plaque density was examined in the amygdala of rhesus macaques, to elucidate the influence of age, diet and hormonal environment. Methods: Luminex technology was used to measure cerebrospinal fluid (CSF) concentrations of Aß40 and Aß42 across three decades, while immunohistochemistry was used to examine Aß plaque density in the amygdala. Results: Aß40 was found to be the predominant isoform of Aß in the CSF, but neither Aß40 or Aß42 concentrations showed an age-related change, and the ratio of Aß42 to Aß40 showed only a marginal increase. Significantly fewer Aß plaques were detected in the amygdala of old ovariectomized animals if they received estradiol HRT (p < 0.001); similar results were obtained regardless of whether they had been maintained on a regular monkey chow for ∼48 months or on a high-fat, high-sugar, Western-style diet for ∼30 months. Conclusion: The results demonstrate that HRT involving estrogen can reduce Aß plaque load in a cognitive brain region of aged non-human primates. The results from this translational animal model may therefore have clinical relevance to the treatment of AD in post-menopausal women, whether used alone, or as a supplement to current pharmacological and monoclonal antibody-based interventions.

Environmental, human health and socioeconomic impacts of Ostreopsis spp. Blooms in the NW Mediterranean.

This paper summarizes the research conducted by the partners of the EU co-funded CoCliME project to ascertain the ecological, human health and economic impacts of Ostreopsis (mainly O. cf. ovata) blooms in the NW Mediterranean coasts of France, Monaco and Spain. This knowledge is necessary to design strategies to prevent, mitigate and, if necessary, adapt to the impacts of these events in the future and in other regions. Ostreopsis proliferations in the Mediterranean have been related to massive mortalities of benthic organisms and to symptoms of respiratory and cutaneous irritation in humans. A six-year epidemiologic study in a Ostreopsis hot spot in Catalonia and the accumulated experience of the French Mediterranean National Ostreopsis Surveillance Network confirm the main effects of these blooms on human health in the NW Mediterranean. The impacts are associated to direct exposure to seawater with high Ostreopsis cell concentrations and to inhalation of aerosols containing unknown irritative chemicals produced under certain circumstances during the blooms. A series of mild acute symptoms, affecting the entire body as well as the ophthalmic, digestive, respiratory and dermatologic systems have been identified. A main remaining challenge is to ascertain the effects of the chronic exposure to toxic Ostreopsis blooms. Still, the mechanisms involved in the deletereous effects of Ostreopsis blooms are poorly understood. Characterizing the chemical nature of the harmful compounds synthesized by Ostreopsis as well as the role of the mucus by which cells attach to benthic surfaces, requires new technical approaches (e.g., metabolomics) and realistic and standardized ecotoxicology tests. It is also necessary to investigate how palytoxin analogues produced by O. cf. ovata could be transferred through the marine food webs, and to evaluate the real risk of seafood poisonings in the area. On the other hand, the implementation of beach monitoring and surveillance systems in the summer constitutes an effective strategy to prevent the impacts of Ostreopsis on human health. In spite of the confirmed noxious effects, a survey of tourists and residents in Nice and Monaco to ascertain the socioeconomic costs of Ostreopsis blooms indicated that the occurrence of these events and their impacts are poorly known by the general public. In relationship with a plausible near future increase of Ostreopsis blooms in the NW Mediterranean coast, this survey showed that a substantial part of the population might continue to go to the beaches during Ostreopsis proliferations and thus could be exposed to health risks. In contrast, some people would not visit the affected areas, with the potential subsequent negative impacts on coastal recreational and touristic activities. However, at this stage, it is too early to accurately assess all the economic impacts that a potentially increasing frequency and biogeographic expansion of the events might cause in the future.

Primary Care Evaluation of a Hepatitis C Virus (HCV) Screening Education Intervention.

INTRODUCTION: Increased screening efforts and the development of effective antiviral treatments have led to marked improvement in Hepatitis C (HCV) patient outcomes. However, many people in the US are believed to have undiagnosed HCV. Successful screening strategies and access to a coordinated system of care are critical for HCV affected adults. The objective of this study was to evaluate a primary care HCV screening education intervention that took place 2018 to 2019 to improve primary care training and management of patients after the implementation of the electronic medical record (EMR) screening alert. METHODS: Using 15 primary care practices located in vicinity of neighborhoods at-risk for higher rates of HCV infections, a stepped wedge randomized control study design was utilized to deliver an educational screening intervention. The education intervention was implemented sequentially with 5 practices being presented to every 3 months. Number of patients within the Baby Boomer cohort (birth years 1945-1965) were collected 3 months before the first practice receiving the intervention to 3 months after the last practice receiving the education intervention. The main outcome collected was the HCV screening. Generalized linear mixed models were used to test the hypothesis of improved screening rates after intervention implementation. RESULTS: There were a total of 85,697 patients within the Baby Boomer cohort seen at the 15 practices. Practices receiving the intervention had patients who were more likely to be screened for HCV (ß = 0.259, P < .001; Odds Ratio [OR] [95%CI] 1.296 [1.098-1.529]).In terms of demographics, results showed that females are less likely to be screened than males (ß = -0.141, P < .001; OR [95%CI] 0.868[0.813 to 0.927]), Baby Boomer patients aged less than 65 were more likely to be screened than Baby Boomer patients aged 65 and older (ß = 0.293, P < .001; OR [95%CI] 1.340[1.251 to 1.436]). DISCUSSION: This study looked at screening rates before and after an educational intervention which happened subsequent to the activation of an EMR alert. Whereas HCV EMR alerts showed an increase in HCV screenings before the education intervention, the addition of the education showed a modest increase in HCV screening rates for Baby Boomer patients.

Designing Cost-Effective Open-Source Multihead 3D Bioprinters.

For the past decade, additive manufacturing has resulted in significant advances toward fabricating anatomic-size patient-specific scaffolds for tissue models and regenerative medicine. This can be attributed to the development of advanced bioinks capable of precise deposition of cells and biomaterials. The combination of additive manufacturing with advanced bioinks is enabling researchers to fabricate intricate tissue scaffolds that recreate the complex spatial distributions of cells and bioactive cues found in the human body. However, the expansion of this promising technique has been hampered by the high cost of commercially available bioprinters and proprietary software. In contrast, conventional three-dimensional (3D) printing has become increasingly popular with home hobbyists and caused an explosion of both low-cost thermoplastic 3D printers and open-source software to control the printer. In this study, we bring these benefits into the field of bioprinting by converting widely available and cost-effective 3D printers into fully functional, open-source, and customizable multihead bioprinters. These bioprinters utilize computer controlled volumetric extrusion, allowing bioinks with a wide range of flow properties to be bioprinted, including non-Newtonian bioinks. We demonstrate the practicality of this approach by designing bioprinters customized with multiple extruders, automatic bed leveling, and temperature controls for ∼$400 USD. These bioprinters were then used for in vitro and ex vivo bioprinting to demonstrate their utility for tissue engineering.

Application of Counter-wound Multi-arm Spirals in HTS Resonator Design.

Significant sensitivity improvements have been achieved by utilizing high temperature superconducting (HTS) resonators in nuclear magnetic resonance (NMR) probes. Many nuclei such as 13C benefit from strong excitation fields which cannot be produced by traditional HTS resonator designs. We investigate the use of double-sided, counter-wound multi-arm spiral HTS resonators with the aim of increasing the excitation field at the required nuclear Larmor frequency for 13C. When compared to double-sided, counter-wound spiral resonators with similar geometry, simulations indicate that the multi-arm spiral version develops a more uniform current distribution. Preliminary tests of a two-arm resonator indicate that it may produce a stronger excitation field.

Multi-omic machine learning predictor of breast cancer therapy response.

Breast cancers are complex ecosystems of malignant cells and the tumour microenvironment1. The composition of these tumour ecosystems and interactions within them contribute to responses to cytotoxic therapy2. Efforts to build response predictors have not incorporated this knowledge. We collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumours from 168 patients treated with chemotherapy with or without HER2 (encoded by ERBB2)-targeted therapy before surgery. Pathology end points (complete response or residual disease) at surgery3 were then correlated with multi-omic features in these diagnostic biopsies. Here we show that response to treatment is modulated by the pre-treated tumour ecosystem, and its multi-omics landscape can be integrated in predictive models using machine learning. The degree of residual disease following therapy is monotonically associated with pre-therapy features, including tumour mutational and copy number landscapes, tumour proliferation, immune infiltration and T cell dysfunction and exclusion. Combining these features into a multi-omic machine learning model predicted a pathological complete response in an external validation cohort (75 patients) with an area under the curve of 0.87. In conclusion, response to therapy is determined by the baseline characteristics of the totality of the tumour ecosystem captured through data integration and machine learning. This approach could be used to develop predictors for other cancers.

Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients.

BACKGROUND: Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings. METHODS: In this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I-III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for between-study heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype. FINDINGS: We analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20-80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0-186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1·55 (95% CI 1·41-1·71) for hormone receptor-positive, HER2-negative patients to 2·16 (1·79-2·61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p<0·0001 for all subtypes). RCB score remained prognostic for event-free survival in multivariable models adjusted for age, grade, T category, and nodal status at baseline: the adjusted HR ranged from 1·52 (1·36-1·69) in the hormone receptor-positive, HER2-negative group to 2·09 (1·73-2·53) in the hormone receptor-negative, HER2-positive group (p<0·0001 for all subtypes). INTERPRETATION: RCB score and class were independently prognostic in all subtypes of breast cancer, and generalisable to multiple practice settings. Although variability in hormone receptor subtype definitions and treatment across patients are likely to affect prognostic performance, the association we observed between RCB and a patient's residual risk suggests that prospective evaluation of RCB could be considered to become part of standard pathology reporting after neoadjuvant therapy. FUNDING: National Cancer Institute at the US National Institutes of Health.

Comparing race and ethnicity across safety-net and non-safety net practices pre- and post-an HIV screening alert.

CONTEXT: Societal and economic burdens of human immunodeficiency virus (HIV) continue to grow, even as treatments and prevention for this disease becomes more readily available and efficacious. HIV screening is more likely to be performed in minority (including Black) patient populations compared to whites. The likelihood of getting screened also depends on primary care practice attributes. OBJECTIVE: Evaluate HIV screening demographics by safety-net and non-safety net practices. STUDY DESIGN and ANALYSIS: Pre-post analysis. SETTING: Atrium Health is a non-profit, vertically integrated healthcare system with approximately 16 million patient encounters per year across the Southeast US. POPULATION STUDIED: Twelve primary care practices, including four safety-net practices serving predominantly Medicaid and uninsured patients, with over 115,00 patients between the ages of 18 and 64 were selected for the educational intervention. INTERVENTION/INSTRUMENT: A system-wide electronic medical record alert prompting HIV screening was implemented in October 2017 targeting adults between 18-64 years old. In addition to the system alert, a provider peer-to-peer educational program detailing HIV disease epidemiology, screening recommendations, and algorithms to guide screening efforts was developed. OUTCOME MEASURES: HIV screenings. RESULTS: From October 2016- April 2017, 3,413 patients were screened for HIV at the twelve participating primary care practices. Immediately after the HIV alert activation, from October 2017 - April 2018, 6,256 patients were screened, resulting in an 83% increase in screening. However, increases were different based on practice type, race and ethnicity. Black patients in safety net clinics had higher screening rates prior to the alert and showed less of an increase in screening (37%) compared to whites (102%) after the alert was activated. Hispanic/Latino patients showed similar increases at both safety net (99%) and non-safety net (108%) practices. Both Black and white patients showed larger increases of 99% and 139% in non-safety net clinics. Chi-squared analysis comparing the percentage of patients screened during these time periods was significantly different (p=0.001). CONCLUSION: While race and practice characteristics influence the likelihood of HIV screening, EMR modifications and provider education can significantly enhance screening and care for patients with HIV regardless of race and practice type.

Progress Towards a Higher Sensitivity 13C-Optimized 1.5 mm HTS NMR Probe.

Nuclear magnetic resonance (NMR) probes using thin-film high temperature superconducting (HTS) resonators offer high sensitivity and are particularly suitable for small-sample applications. We are developing an improved 1.5 mm HTS NMR probe designed for operation at 14.1 T and optimized for 13C detection. The total sample volume is about 35 µL and the active sample volume is 20 µL. The probe employs HTS resonators for 13C and 1H transmission and detection and the 2H lock. We examine the interactions of multiple superconducting resonators and normal metal tuning loops on coil resonance frequency and probe sensitivity. We test a recently introduced 13C resonator design, engineered to significantly increase 13C detection sensitivity over previous all-HTS probes. At zero field, we observe a 13C quality factor of 6000 which is several times higher than previous resonators. In this work the coil design considerations and probe build-out procedure are discussed.

Variability in grading of ductal carcinoma in situ among an international group of pathologists.

The prognostic value of cytonuclear grade in ductal carcinoma in situ (DCIS) is debated, partly due to high interobserver variability and the use of multiple guidelines. The aim of this study was to evaluate interobserver agreement in grading DCIS between Dutch, British, and American pathologists. Haematoxylin and eosin-stained slides of 425 women with primary DCIS were independently reviewed by nine breast pathologists based in the Netherlands, the UK, and the USA. Chance-corrected kappa (κma ) for association between pathologists was calculated based on a generalised linear mixed model using the ordinal package in R. Overall κma for grade of DCIS (low, intermediate, or high) was estimated to be 0.50 (95% confidence interval [CI] 0.44-0.56), indicating a moderate association between pathologists. When the model was adjusted for national guidelines, the association for grade did not change (κma = 0.53; 95% CI 0.48-0.57); subgroup analysis for pathologists using the UK pathology guidelines only had significantly higher association (κma = 0.58; 95% CI 0.56-0.61). To assess if concordance of grading relates to the expression of the oestrogen receptor (ER) and HER2, archived immunohistochemistry was analysed on a subgroup (n = 106). This showed that non-high grade according to the majority opinion was associated with ER positivity and HER2 negativity (100 and 89% of non-high grade cases, respectively). In conclusion, DCIS grade showed only moderate association using whole slide images scored by nine breast pathologists. As therapeutic decisions and inclusion in ongoing clinical trials are guided by DCIS grade, there is a pressing need to reduce interobserver variability in grading. ER and HER2 might be supportive to prevent the accidental and unwanted inclusion of high-grade DCIS in such trials.

Perceptions of HPV vaccination and pharmacist-physician collaboration models to improve HPV vaccination rates.

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted disease in the United States (US), with 12 cancer causing strains. Vaccination rates in the southern US fall below the national average. Pharmacists provide an opportunity to improve vaccination rates. OBJECTIVES: The objectives of this study were to 1) identify barriers and facilitators to providing the HPV vaccine and Vaccines for Children (VFC) program participation in pharmacies and clinics, and 2) assess pharmacy staff, clinic staff, and parent perceptions of 3 collaboration models to improve HPV vaccination. METHODS: A developmental formative evaluation was conducted with pharmacy staff, primary care clinic staff, and parents of adolescent children. Interview guides were informed by the Consolidated Framework for Implementation Research (CFIR). Barriers and facilitators to HPV vaccination and VFC participation were explored. Additionally, acceptability of 3 collaboration models were explored: 1) a shared-responsibility model in which a physician provides the first dose of HPV vaccine with the second provided in the pharmacy, 2) a pharmacy-based model in which a clinic refers patients to the pharmacy to receive both doses, and 3) an insourced model in which pharmacists schedule days to provide the vaccine in the collaborating clinic. RESULTS: Twenty-nine interviews were conducted between August 2019 and June 2020. Both pharmacy and clinic staff had positive views toward the HPV vaccine and vaccinations in general. Pharmacists and physicians reported parental awareness and education as a barrier to HPV vaccination. Counseling about HPV vaccine was reported as being more time-consuming because of the stigma associated with the vaccine. Parents were willing to have their children vaccinated for HPV in the pharmacy but desired their child's physician be involved in the immunization process. The shared-responsibility model was the most favored of the 3 collaboration models. CONCLUSION: Perceptions of the HPV vaccine and vaccination in pharmacies were positive. Collaboration between clinics and pharmacies to improve HPV vaccination rates is viewed positively by pharmacy staff, clinic staff, and parents. This study will guide implementation of pharmacist-physician collaborative models to improve vaccination through pharmacy participation in the VFC program and HPV vaccination.

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project.

BACKGROUND: The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. METHODS: This was a national, prospective cohort study of DCIS diagnosed during 2003-2012. RESULTS: Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of high-grade disease increased (from 60 to 65%), low-grade DCIS decreased (from 10 to 6%) and mean size increased (from 21.4 to 24.1 mm). Mastectomy was more common for high-grade (36%) than for low-grade DCIS (15%). Few (6%) patients treated with breast-conserving surgery (BCS) had a surgical margin <1 mm. Of the 9191 women diagnosed in England (median follow-up 9.4 years), 7% developed DCIS or invasive malignancy in the ipsilateral and 5% in the contralateral breast. The commonest ipsilateral event was invasive carcinoma (n = 413), median time 62 months, followed by DCIS (n = 225), at median 37 months. Radiotherapy (RT) was most protective against recurrence for high-grade DCIS (3.2% for high-grade DCIS with RT compared to 6.9% without, compared with 2.3 and 3.0%, respectively, for low/intermediate-grade DCIS). Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years. CONCLUSION: DCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.

Classifying intervention modifications in the community pharmacy context: A demonstration study.

OBJECTIVES: The objectives of this study were to apply the Stirman and colleagues' framework to identify modifications made to a motivational interviewing (MI)-based intervention for medication nonadherence and to determine whether the locally modified intervention affected expected patient medication adherence outcomes in community pharmacies. METHODS: Pharmacists at 4 pharmacies were trained to provide a brief MI intervention to 50 patients per pharmacy who were nonadherent to antihypertensive medications. The training included a 3-hour online course in MI and in-pharmacy training on patient identification and documentation. Semistructured interviews were conducted to determine modifications to the patient identification processes, MI interventions, and documentation of interventions. Directed content analysis was guided by the Stirman and colleagues' framework. Preintervention and 6 months postintervention adherence rates for the patients who received the intervention were calculated. Paired samples t tests were used to assess the impact of the intervention on adherence rates. RESULTS: Modifications were made to the context of the intervention (e.g., via telephone instead of in-pharmacy). Additionally, content modifications included "loosening the structure" (e.g., reordering intervention steps), "drifting or departing" (e.g., too busy to attempt), "adding elements" (e.g., reminder cards), and "repeating elements" (e.g., patient identification). There were statistically significant improvements in adherence from preintervention to 6 months postintervention (74.1% to 84.5%; P < 0.05) at each pharmacy regardless of the modifications applied. CONCLUSION: Modifications made during intervention implementation were classified using Stirman and colleagues' framework. Despite the modifications, adherence rates improved and were consistent with expectations based on prior studies of similar interventions. These findings support previous implementation research on adaptability and suggest that the ability to tailor, modify, or refine an intervention to meet the needs of the provider or setting may allow for intervention success. Future research on the impact of specific modifications will help determine which are detrimental or beneficial to patient outcomes and sustainability of services.

Novel Models to Identify Census Tracts for Hepatitis C Screening Interventions.

BACKGROUND: Increased screening efforts and the development of effective antiviral treatments have led to marked improvement in hepatitis C (HCV) patient outcomes. However, many people in the United States are still believed to have undiagnosed HCV. Geospatial modeling using variables representing at-risk populations in need of screening for HCV and social determinants of health (SDOH) provide opportunities to identify populations at risk of HCV. METHODS: A literature review was conducted to identify variables associated with patients at risk for HCV infection. Two sets of variables were collected: HCV Transmission Risk and SDOH Level of Need. The variables were combined into indices for each group and then mapped at the census tract level (n = 233). Multiple linear regression analysis and the Pearson correlation coefficient were used to validate the models. RESULTS: A total of 4 HCV Transmission Risk variables and 12 SDOH Level of Need variables were identified. Between the 2 indexes, 21 high-risk census tracts were identified that scored at least 2 standard deviations above the mean. The regression analysis showed a significant relationship with HCV infection rate and prevalence of drug use (B = 0.78, P < .001). A significant relationship also existed with the HCV infection rate for households with no/limited English use (B = -0.24, P = .001), no car use (B = 0.036, P < .001), living below the poverty line (B = 0.014, P = .009), and median household income (B = -0.00, P = .009). CONCLUSIONS: Geospatial models identified high-priority census tracts that can be used to map high-risk HCV populations that may otherwise be unrecognized. This will allow future targeted screening and linkage-to-care interventions for patients at high risk of HCV.