BACKGROUND: Persons with diabetes have 27% elevated risk of developing colorectal cancer (CRC) and are disproportionately from priority health disparities populations. Federally qualified health centers (FQHCs) struggle to implement CRC screening programs for average risk patients. Strategies to effectively prioritize and optimize CRC screening for patients with diabetes in the primary care safety-net are needed.
METHODS: Guided by the Exploration, Preparation, Implementation and Sustainment Framework, we conducted a stakeholder-engaged process to identify multi-level change objectives for implementing optimized CRC screening for patients with diabetes in FQHCs. To identify change objectives, an implementation planning group of stakeholders from FQHCs, safety-net screening programs, and policy implementers were assembled and met over a 7-month period. Depth interviews (n = 18-20) with key implementation actors were conducted to identify and refine the materials, methods and strategies needed to support an implementation plan across different FQHC contexts. The planning group endorsed the following multi-component implementation strategies: identifying clinic champions, development/distribution of patient educational materials, developing and implementing quality monitoring systems, and convening clinical meetings. To support clinic champions during the initial implementation phase, two learning collaboratives and bi-weekly virtual facilitation will be provided. In single group, hybrid type 2 effectiveness-implementation trial, we will implement and evaluate these strategies in a in six safety net clinics (n = 30 patients with diabetes per site). The primary clinical outcomes are: (1) clinic-level colonoscopy uptake and (2) overall CRC screening rates for patients with diabetes assessed at baseline and 12-months post-implementation. Implementation outcomes include provider and staff fidelity to the implementation plan, patient acceptability, and feasibility will be assessed at baseline and 12-months post-implementation.
CONCLUSIONS: Study findings are poised to inform development of evidence-based implementation strategies to be tested for scalability and sustainability in a future hybrid 2 effectiveness-implementation clinical trial. The research protocol can be adapted as a model to investigate the development of targeted cancer prevention strategies in additional chronically ill priority populations.
BACKGROUND: This study was registered in ClinicalTrials.gov (NCT05785780) on March 27, 2023 (last updated October 21, 2023).

BACKGROUND: Patient navigation is an individualized intervention to facilitate comprehensive care which has not yet been fully implemented in obstetric or postpartum care.
METHODS: We aimed to develop and evaluate a mechanism to incorporate feedback regarding implementation of postpartum patient navigation for low-income birthing individuals at an urban academic medical center. This study analyzed the role of an Implementation Advisory Board (IAB) in supporting an ongoing randomized trial of postpartum navigation. Over the first 24 months of the trial, the IAB included 11 rotating obstetricians, one clinic resource coordinator, one administrative leader, two obstetric nurses, one primary care physician, one social worker, and one medical assistant. Members completed serial surveys regarding program implementation, effects on patient care, and areas for improvement. Quarterly IAB meetings offered opportunities for additional feedback. Survey responses and meeting notes were analyzed using the constant comparative method and further interpreted within the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework.
RESULTS: Members of the IAB returned 37 surveys and participated in five meetings over 24 months. Survey analysis revealed four themes among the inner context: reduced clinician burden, connection of care teams, communication strategies, and clinic workflow. Bridging factors included improved patient access to care, improved follow-up, and adding social context to care. Innovation factors included availability of navigators, importance of consistent communication, and adaptation over time. Meeting notes highlighted the importance of bidirectional feedback regarding implementation, and members expressed positive opinions regarding navigators\' effects on patient care, integration into clinic workflow, and responsiveness to feedback. IAB members initially suggested changes to improve implementation; later survey responses demonstrated successful program adaptations.
CONCLUSIONS: Members of an implementation advisory board provided key insights into the implementation of postpartum patient navigation that may be useful to promote dissemination of navigation and establish avenues for the engagement of implementing partners in other innovations.
BACKGROUND: ClinicalTrials.gov, NCT03922334 . Registered April 19, 2019. The results here do not present the results of the primary trial, which is ongoing.

Schools are a critical setting to promote healthy youth development through the provision of evidence-based programs (EBPs), yet preventive EBPs in schools are underutilized. The Exploration, Preparation, Implementation, Sustainment (EPIS) framework highlights numerous factors that may influence program adoption during the Exploration phase and progress monitoring during the Implementation phase. However, no research has systematically and simultaneously identified the factors that influence school administrators\' decision-making during these important processes. We conducted semi-structured interviews with 24 school administrators in the Midwestern region of the U.S. to understand how they weigh various considerations that inform their adoption and progress monitoring of prevention programs. Results indicated that school administrators consider five separate factors during the adoption decision, prioritized in the following order: need for the program, school community buy-in, contextual fit, resources, and program characteristics (including the evidence-base). Further, administrators consider five indicators to monitor program performance, prioritized as follows: intervention fidelity, quantitative and qualitative data that determine if the identified need was met, school community buy-in, resource consumption, and program characteristics. Implications for prevention scientists and suggestions for future research are discussed.

Spatial and temporal distributions and influencing factors of extreme precipitation are important bases for coping with future climate change. The spatiotemporal variability and affecting factors of extreme precipitation indices (EPIs) in east of northwest China (ENW) during 1961-2015 were investigated using a series of approaches such as modified Mann-Kendall trend test, Hurst exponent, ensemble empirical mode decomposition (EEMD), and geodetector model. The results showed that CDD and CWD decreased significantly (P < 0.01), with rates of 1.4 days/decade and 0.07 days/decade, respectively. EPIs in ENW exhibited an obvious heterogeneity. CDD gradually increased from the southeast to the northwest. The remaining EPIs generally showed the opposite trend. Geodetector results demonstrated that large-scale circulation factors had a significant impact on EPIs in ENW. The influence of large-scale climate factors on EPIs was concentrated in nonlinear enhancement, and Nino3.4 and SO were the dominant driving factors that played a major role in the variability of EPIs. The results of this study provided a reference for ENW and other arid and semi-arid regions to cope with extreme climates and develop corresponding strategies.

BACKGROUND: Norwegian school health services received a national best-practice guideline in 2017. To promote healthy life skills and identify adolescents needing support, the guideline includes strong recommendations for individual consultations with all 8th graders and increased collaboration with schools. To help implement the recommendations, a blended implementation strategy (SchoolHealth) was co-created with school nurses, students, and stakeholders. SchoolHealth consists of three implementation elements: Digital dialog and administration tool (audit and feedback +), Dialog support (external consultation), and Collaboration materials (targeted dissemination). This hybrid study will test the main and combined effects of the elements on guideline fidelity and effectiveness.
METHODS: The GuideMe study is a factorial cluster randomized controlled trial examining SchoolHealth\'s effectiveness on guideline fidelity and guideline effectiveness goals. Forty Norwegian secondary schools will be randomized to eight different combinations of the elements in SchoolHealth. Participants will include school nurses and school personnel from these schools, and 8th grade students (n = 1200). Primary outcomes are school nurses\' fidelity to the guidelines and student\'s ability to cope with their life (i.e., health literacy, positive health behaviors and self-efficacy). Quantitative methods will be used to test effects and mechanisms, while mixed- and qualitative methods will be used to explore mechanisms, experiences, and other phenomena in depth. Participants will complete digital questionnaires at the start and end of the schoolyear, and after the consultation during the schoolyear. The study will run in two waves, each lasting for one school year. The multifactorial design allows testing of interactions and main effects due to equal distribution of all factors within each main effect. Sustainment and scale-up of optimized SchoolHealth elements using national infrastructure are simultaneously prepared.
CONCLUSIONS: The study will investigate possible effects of the implementation elements in isolation and in combination, and hypothesized implementation mechanisms. In-depth study of user experiences will inform improvements to elements in SchoolHealth. The results will yield causal knowledge about implementation strategies and the mechanisms through which they assert effects. Mixed-methods will provide insights into how and when the elements work. Optimizing guideline implementation elements can support adolescents in a crucial life phase.
BACKGROUND: ISRCTN24173836. Registration date 8 August 2022.

Advances in detection and treatment for breast cancer have led to an increase in the number of individuals managing significant late and long-term treatment effects. Primary care has a role in caring for patients with a history of cancer, yet there is little guidance on how to effectively implement survivorship care evidence into primary care delivery.
This protocol describes a multi-phase, mixed methods, stakeholder-driven research process that prioritizes actionable, evidence-based primary care improvements to enhance breast cancer survivorship care by integrating implementation and primary care transformation frameworks: the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework and the Practice Change Model (PCM). Informed by depth interviews and a four round Delphi panel with diverse stakeholders from primary care and oncology, we will implement and evaluate an iterative clinical intervention in a hybrid type 1 effectiveness-implementation cluster randomized design in twenty-six primary care practices. Multi-component implementation strategies will include facilitation, audit and feedback, and learning collaboratives. Ongoing data collection and analysis will be performed to optimize adoption of the intervention. The primary clinical outcome to test effectiveness is comprehensive breast cancer follow-up care. Implementation will be assessed using mixed methods to explore how organizational and contextual variables affect adoption, implementation, and early sustainability for provision of follow-up care, symptom, and risk management activities at six- and 12-months post implementation.
Study findings are poised to inform development of scalable, high impact intervention processes to enhance long-term follow-up care for patients with a history of breast cancer in primary care. If successful, next steps would include working with a national primary care practice-based research network to implement a national dissemination study. Actionable activities and processes identified could also be applied to development of organizational and care delivery interventions for follow-up care for other cancer sites.
Registered with ClinicalTrials.gov on June 2, 2022: NCT05400941.

UNASSIGNED: Adherence to intervention training implementation strategies is at the foundation of fidelity; however, few studies have linked training adherence to trainee attitudes and leadership behaviors to identify what practically matters for the adoption and dissemination of evidence-based practices. Through the conduct of this hybrid type 3 effectiveness-implementation cluster randomized controlled trial, we collected Exploration, Preparation, Implementation, and Sustainment (EPIS) data and merged it with tailored motivational interviewing training adherence data, to elucidate the relationship between provider attitudes toward evidence-based practices, leadership behaviors, and training implementation strategy (e.g., workshop attendance and participation in one-on-one coaching) adherence.
UNASSIGNED: Our sample included data from providers who completed baseline (pre-intervention) surveys that captured inner and outer contexts affecting implementation and participated in tailored motivational interviewing training, producing a dataset that included training implementation strategies adherence and barriers and facilitators to implementation (N = 77). Leadership was assessed by two scales: the director leadership scale and implementation leadership scale. Attitudes were measured with the evidence-based practice attitude scale (EBPAS-50). Adherence to training implementation strategies was modeled as a continuous outcome with a Gaussian distribution. Analyses were conducted in SPSS.
UNASSIGNED: Of the nine general attitudes toward evidence-based practice, openness was associated with training adherence (estimate [EST] = 0.096, p < .001; 95% CI = [0.040, 0.151]). Provider general (EST = 0.054, 95% CI = [0.007, 0.102]) and motivational interviewing-specific (EST = 0.044, 95% CI = [0.002, 0.086]) leadership behaviors were positively associated with training adherence (p < .05). Of the four motivational interviewing-specific leadership domains, knowledge and perseverant were associated with training adherence (p < .05). As these leadership behaviors increased, knowledge (EST = 0.042, 95% CI = [0.001, 0.083]) and perseverant (EST = 0.039, 95% CI = [0.004, 0.075]), so did provider adherence to training implementation strategies.
UNASSIGNED: As implementation science places more emphasis on assessing readiness prior to delivering evidence-based practices by evaluating organizational climate, funding streams, and change culture, consideration should also be given to metrics of leadership. A potential mechanism to overcome resistance is via the implementation of training strategies focused on addressing leadership prior to conducting training for the evidence-based practice of interest.
Researchers and practitioners, who aim to improve the uptake of evidence-based practices, continue to seek ways in which to improve provider participation in training implementation strategies. The persistent challenge in addressing provider disengagement, while linking this disinterest to poor patient outcomes, has been ascertaining how to quantify relevant delivery considerations, for example, provider attitudes and leadership behaviors that may influence commitment to learning or apathy to behavior change, concurrently with training adherence. Through the conduct of this study, we collected both types of data: (1) provider attitudes and leadership behaviors and (2) training adherence outcomes. We found that provider openness, general leadership behaviors, and motivational interviewing-specific leadership behaviors were associated with adherence to training implementation strategies. As more emphasis is placed on assessing clinic readiness prior to adopting new evidence-based practices, a discussion on including metrics of provider attitudes to evidence-based practice, innovation, and the specific intervention is warranted, alongside consideration for how implementation training strategies focused on addressing leadership can bolster change-supportive behaviors prior to delivery of innovations.

UNASSIGNED: Effective teams are essential to high-quality healthcare. However, teams, team-level constructs, and team effectiveness strategies are poorly delineated in implementation science theories, models, and frameworks (TMFs), hindering our understanding of how teams may influence implementation. The Exploration, Preparation, Implementation, Sustainment (EPIS) framework is a flexible and accommodating framework that can facilitate the application of team effectiveness approaches in implementation science.
UNASSIGNED: We define teams and provide an overview of key constructs in team effectiveness research. We describe ways to conceptualize different types of teams and team constructs relevant to implementation within the EPIS framework. Three case examples illustrate the application of EPIS to implementation studies involving teams. Within each study, we describe the structure of the team and how team constructs influenced implementation processes and outcomes.
UNASSIGNED: Integrating teams and team constructs into the EPIS framework demonstrates how TMFs can be applied to advance our understanding of teams and implementation. Implementation strategies that target team effectiveness may improve implementation outcomes in team-based settings. Incorporation of teams into implementation TMFs is necessary to facilitate application of team effectiveness research in implementation science.
Teams and team-level constructs are neglected in implementation theories, models, and frameworks (TMFs). This paper calls attention to the importance of teams in implementation research and practice and provides an overview of team effectiveness research for implementation science. We illustrate how the EPIS framework can be applied to advance our understanding of how teams influence implementation processes and outcomes. We identify future directions for research on teams and implementation, including developing and testing implementation strategies that focus on team effectiveness.

BACKGROUND: The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity.
OBJECTIVE: In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3\'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties.
METHODS: The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of β-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100.
RESULTS: The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 μg/mL, or on the enzymatic mechanism of β-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 μg/mL.
CONCLUSIONS: We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.

Bacterial resistance to antibiotics has been long recognized as a priority to address for human health. Among all micro-organisms, the so-called multi-drug resistant (MDR) bacteria, which are resistant to most, if not all drugs in our current arsenal, are particularly worrisome. The World Health Organization has prioritized the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) pathogens, which include four Gram-negative bacterial species. In these bacteria, active extrusion of antimicrobial compounds out of the cell by means of \'molecular guns\' known as efflux pumps is a main determinant of MDR phenotypes. The resistance-nodulation-cell division (RND) superfamily of efflux pumps connecting the inner and outer membrane in Gram-negative bacteria is crucial to the onset of MDR and virulence, as well as biofilm formation. Thus, understanding the molecular basis of the interaction of antibiotics and inhibitors with these pumps is key to the design of more effective therapeutics. With the aim to contribute to this challenge, and complement and inspire experimental research, in silico studies on RND efflux pumps have flourished in recent decades. Here, we review a selection of such investigations addressing the main determinants behind the polyspecificity of these pumps, the mechanisms of substrate recognition, transport and inhibition, as well as the relevance of their assembly for proper functioning, and the role of protein-lipid interactions. The journey will end with a perspective on the role of computer simulations in addressing the challenges posed by these beautifully complex machineries and in supporting the fight against the spread of MDR bacteria.