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Abstract Globally, land and seascapes across the bioculturally diverse tropics are in transition. Impacted by the demands of distant consumers, the processes of global environmental change and numerous interventions seeking climate, conservation and development goals, these transitions have the potential to impact the relationships and plurality of values held between people and place. This paper is a Synthesis of seven empirical studies within the Special Feature (SF): ‘What is lost in transition? Capturing the impacts of conservation and development interventions on relational values and human wellbeing in the tropics’. Through two Open Forum workshops, and critical review, contributing authors explored emergent properties across the papers of the SF. Six core themes were identified and are subsumed within broad categories of: (i) the problem of reconciling scale and complexity, (ii) key challenges to be overcome for more plural understanding of social dimensions of landscape change and (iii) ways forward: the potential of an environmental justice framework, and a practical overview of methods available to do so. The Synthesis interprets disparate fields and complex academic work on relational values, human well‐being and de‐colonial approaches in impact appraisal. It offers a practical and actionable catalogue of methods for plural valuation in the field, and reflects on their combinations, strengths and weaknesses. The research contribution is policy relevant because it builds the case for why a more plural approach in intervention design and evaluation is essential for achieving more just and sustainable futures, and highlights some of the key actions points deemed necessary to achieve such a transition to conventional practice. Read the free Plain Language Summary for this article on the Journal blog.

The top-down approach of assigning the whole class articles by authors of historically privileged identities, and expecting students to dutifully read and reflect in writing, is an ineffective way to respect, excite, connect with, and challenge students, most especially students of identities historically marginalized in the online academy. In this article, I discuss how student-created texts can be used as an alternative to engage and affirm the humanities of students, the class, and communities beyond the classroom. Drawing upon Freirean (1970) notions of humanizing pedagogy, I explain how developing student-created texts can create space for students to center identity, values, place, and social change in their online class experience. Then, by engaging with texts created by peers, students learn from, with, and about others; therefore, fostering empathy, connection, and critically conscious inspiration among class participants. An illustrative example of student-created texts and accompanying assignments within the online higher education setting is offered. I advance the concept of student-created texts not as a universal method to simply be reproduced. Rather, Freirean humanizing necessitates radically reconstructed approaches enacted by critically conscious educators. Student-created texts may be one piece within a larger system of coursework, that when paired with critical ideology, foci, and dialog between students, professor, and community, can support online classroom communities aspiring to Freire's ideals.

TeachersPayTeachers.com (TpT) is an influential online education resource marketplace where users download, buy, and sell education content. How and why educators use platforms like TpT has received only limited scholarly attention. This research therefore addresses a gap in the literature by exploring educators' (N = 1359) self-reported uses and perceptions of TpT. Participants reported intensive and multifaceted TpT use, in particular to address curriculum gaps and time pressures. Most respondents perceived TpT content to be of high quality, but many also noted challenges with TpT. We discuss implications related to education resource production, distribution, and consumption in a digital era.

Abstract Background Germline genetic testing is recommended by the National Comprehensive Cancer Network (NCCN) for individuals including, but not limited to, those with a personal history of ovarian cancer, young-onset (

Abstract Background Audit and feedback (A&F) is a widely used implementation strategy to influence health professionals’ behavior that is often tested in implementation trials. This study examines how A&F trials describe sustainability, spread, and scale. Methods This is a theory-informed, descriptive, secondary analysis of an update of the Cochrane systematic review of A&F trials, including all trials published since 2011. Keyword searches related to sustainability, spread, and scale were conducted. Trials with at least one keyword, and those identified from a forward citation search, were extracted to examine how they described sustainability, spread, and scale. Results were qualitatively analyzed using the Integrated Sustainability Framework (ISF) and the Framework for Going to Full Scale (FGFS). Results From the larger review, n = 161 studies met eligibility criteria. Seventy-eight percent (n = 126) of trials included at least one keyword on sustainability, and 49% (n = 62) of those studies (39% overall) frequently mentioned sustainability based on inclusion of relevant text in multiple sections of the paper. For spread/scale, 62% (n = 100) of trials included at least one relevant keyword and 51% (n = 51) of those studies (31% overall) frequently mentioned spread/scale. A total of n = 38 studies from the forward citation search were included in the qualitative analysis. Although many studies mentioned the need to consider sustainability, there was limited detail on how this was planned, implemented, or assessed. The most frequent sustainability period duration was 12 months. Qualitative results mapped to the ISF, but not all determinants were represented. Strong alignment was found with the FGFS for phases of scale-up and support systems (infrastructure), but not for adoption mechanisms. New spread/scale themes included (1) aligning affordability and scalability; (2) balancing fidelity and scalability; and (3) balancing effect size and scalability. Conclusion A&F trials should plan for sustainability, spread, and scale so that if the trial is effective, the benefits can continue. A deeper empirical understanding of the factors impacting A&F sustainability is needed. Scalability planning should go beyond cost and infrastructure to consider other adoption mechanisms, such as leadership, policy, and communication, that may support further scalability. Trial registration Registered with Prospero in May 2022. CRD42022332606.

Abstract Background The opioid epidemic in the US continues to worsen. Opioid-only and polysubstance-involved opioid overdose deaths are increasing among adolescents and young adults, who have limited knowledge of opioid overdose prevention, including recognition and response. College campuses have infrastructure to support national-level implementation of evidence-based public health strategies for providing opioid overdose prevention and naloxone training programs among this priority population. However, college campuses are an underutilized, understudied setting for this programming. To address this gap, we conducted research assessing barriers and facilitators to planning and implementing this programming on college campuses. Methods We held 9 focus groups among purposively selected campus stakeholders whose perceptions were important to understand in planning for the dissemination and implementation of opioid overdose prevention and naloxone training. Focus group scripts were informed by The Consolidated Framework for Implementation Research (CFIR) to query about perceptions of opioid and other substance use, opioid and other substance use-related resources, and naloxone administration training. We used a deductive-inductive, iterative approach to thematic analysis. Results Themes about implementation barriers included (1) the perception that problematic use of other (non-opioid) substances was more prevalent than opioid use on campus and focus on those substances would be a greater priority on college campuses; (2) student schedules were overwhelmed with academic commitments and extracurricular activities, making delivery of additional training challenging; (3) barriers related to the perceived complexity and decentralization of communication on campus, preventing students from knowing how to access substance use-related resources. Themes about implementation facilitators included (1) framing naloxone training as important in becoming a responsible leader on campus and in the broader community and (2) leveraging existing infrastructure, champions within existing campus groups, and tailored messaging to facilitate participation in naloxone training. Conclusions This is the first study to provide in-depth insights into potential barriers and facilitators to widespread, routine implementation of naloxone/opioid education on undergraduate college campuses. The study captured diverse stakeholder perspectives and was theoretically grounded in CFIR, contributing to the growing literature on the application and refinement of CFIR across diverse community and school contexts.

Abstract Background Sustainability is concerned with the long-term delivery and subsequent benefits of evidence-based interventions. To further this field, we require a strong understanding and thus measurement of sustainability and what impacts sustainability (i.e., sustainability determinants). This systematic review aimed to evaluate the quality and empirical application of measures of sustainability and sustainability determinants for use in clinical, public health, and community settings. Methods Seven electronic databases, reference lists of relevant reviews, online repositories of implementation measures, and the grey literature were searched. Publications were included if they reported on the development, psychometric evaluation, or empirical use of a multi-item, quantitative measure of sustainability, or sustainability determinants. Eligibility was not restricted by language or date. Eligibility screening and data extraction were conducted independently by two members of the research team. Content coverage of each measure was assessed by mapping measure items to relevant constructs of sustainability and sustainability determinants. The pragmatic and psychometric properties of included measures was assessed using the Psychometric and Pragmatic Evidence Rating Scale (PAPERS). The empirical use of each measure was descriptively analyzed. Results A total of 32,782 articles were screened from the database search, of which 37 were eligible. An additional 186 publications were identified from the grey literature search. The 223 included articles represented 28 individual measures, of which two assessed sustainability as an outcome, 25 covered sustainability determinants and one explicitly assessed both. The psychometric and pragmatic quality was variable, with PAPERS scores ranging from 14 to 35, out of a possible 56 points. The Provider Report of Sustainment Scale had the highest PAPERS score and measured sustainability as an outcome. The School-wide Universal Behaviour Sustainability Index-School Teams had the highest PAPERS score (score=29) of the measure of sustainability determinants. Conclusions This review can be used to guide selection of the most psychometrically robust, pragmatic, and relevant measure of sustainability and sustainability determinants. It also highlights that future research is needed to improve the psychometric and pragmatic quality of current measures in this field. Trial registration This review was prospectively registered with Research Registry (reviewregistry1097), March 2021.

Abstract Background Dense breast notification (DBN) legislation aims to increase a woman’s awareness of her personal breast density and the implications of having dense breasts for breast cancer detection and risk. This information may adversely affect women’s breast cancer worry, perceptions of risk, and uncertainty about screening, which may persist over time or vary by sociodemographic factors. We examined short- and long-term psychological responses to DBN and awareness of breast density (BD). Methods In a predominantly Hispanic New York City screening cohort (63% Spanish-speaking), ages 40–60 years, we assessed breast cancer worry, perceived breast cancer risk, and uncertainties about breast cancer risk and screening choices, in short (1–3 months)- and long-term (9–18 months) surveys following the enrollment screening mammogram (between 2016 and 2018). We compared psychological responses by women’s dense breast status (as a proxy for DBN receipt) and BD awareness and examined multiplicative interaction by education, health literacy, nativity, and preferred interview language. Results In multivariable models using short-term surveys, BD awareness was associated with increased perceived risk (odds ratio (OR) 2.27, 95% confidence interval (CI) 0.99, 5.20 for high, OR 2.19, 95% CI 1.34, 3.58 for moderate, vs. low risk) in the overall sample, and with increased uncertainty about risk (OR 1.97 per 1-unit increase, 95% CI 1.15, 3.39) and uncertainty about screening choices (OR 1.73 per 1-unit increase, 95% CI 1.01, 2.9) in Spanish-speaking women. DBN was associated with decreased perceived risk among women with at least some college education (OR 0.32, 95% CI 0.11, 0.89, for high, OR 0.50, 95% CI 0.29, 0.89, for moderate vs. low risk), while those with a high school education or less experienced an increase (OR 3.01, 95% CI 1.05, 8.67 high vs. low risk). There were no associations observed between DBN or BD awareness and short-term breast cancer worry, nor with any psychological outcomes at long-term surveys. Conclusions Associations of BD awareness and notification with breast cancer-related psychological outcomes were limited to short-term increases in perceived breast cancer risk dependent on educational attainment, and increases in uncertainty around breast cancer risk and screening choices among Spanish-speaking women.

Sustainability and health inequities are key challenges in public health and healthcare. Research suggests that only about half of evidence-based interventions (EBIs) are sustained over time, and settings and populations experiencing systemic and structural barriers to health (e.g., poverty, racism, stigma, and discrimination) experience even greater challenges to sustainability. In this article, we argue that an enhanced focus on sustainability in the field of implementation science is critical in order to maximize the long-term health benefits and broader societal impacts of EBIs for all populations and settings. From an equity perspective, a focus on sustainability is particularly critical to prioritize among population sub-groups that have not historically received the benefits of health-related EBIs. We discuss how a health equity framing is essential to sustaining EBIs in under-resourced communities, and requires moving away from a deficit mindset that focuses on why EBIs are challenging to sustain, to one that focuses more on identifying and nurturing existing assets within individuals and communities to increase the likelihood that EBIs are sustained. We conclude with a discussion of future directions as well as recommendations and resources (e.g., frameworks, tools) to advance and make progress toward sustainability from a health equity mindset, including: (1) Actively planning early for sustainability alongside key partners; (2) Tracking progress toward enhancing sustainability and being accountable in doing so equitably for all settings and populations; and (3) Focusing on both equity and engagement early and often throughout the research process and all implementation phases.

Abstract Background Professional guidelines in the U.S. do not recommend routine screening mammography for women ≥75 years with limited life expectancy and/or poor health. Yet, routine mammography remains widely used in older women. We examined older women's experiences, beliefs, and opinions about screening mammography in relation to aging and health. Methods We performed thematic analysis of transcribed semi‐structured interviews with 19 women who had a recent screening visit at a mammography clinic in New York City (average age: 75 years, 63% Hispanic, 53% ≤high school education). Results Three main themes emerged: (1) older women typically perceive mammograms as a positive, beneficial, and routine component of care; (2) participation in routine mammography is reinforced by factors at interpersonal, provider, and healthcare system levels; and (3) older women do not endorse discontinuation of screening mammography due to advancing age or poor health, but some may be receptive to reducing screening frequency. Only a few older women reported having discussed mammography cessation or the potential harms of screening with their providers. A few women reported they would insist on receiving mammography even without a provider recommendation. Conclusions Older women's positive experiences and views, as well as multilevel and frequently automated cues toward mammography are important drivers of routine screening in older women. These findings suggest a need for synergistic patient, provider, and system level strategies to reduce mammography overuse in older women.

Abstract Background Implementation science is at a sufficiently advanced stage that it is appropriate for the field to reflect on progress thus far in achieving its vision, with a goal of charting a path forward. In this debate, we offer such reflections and report on potential threats that might stymie progress, as well as opportunities to enhance the success and impact of the field, from the perspective of a group of US-based researchers. Main body Ten mid-career extramurally funded US-based researchers completed a “pre-mortem” or a group brainstorming exercise that leverages prospective hindsight to imagine that an event has already occurred and to generate an explanation for it — to reduce the likelihood of a poor outcome. We came to consensus on six key themes related to threats and opportunities for the field: (1) insufficient impact, (2) too much emphasis on being a “legitimate science,” (3) re-creation of the evidence-to-practice gap, (4) difficulty balancing accessibility and field coherence, (5) inability to align timelines and priorities with partners, and (6) overly complex implementation strategies and approaches. Conclusion We submit this debate piece to generate further discussion with other implementation partners as our field continues to develop and evolve. We hope the key opportunities identified will enhance the future of implementation research in the USA and spark discussion across international groups. We will continue to learn with humility about how best to implement with the goal of achieving equitable population health impact at scale.

BackgroundCardiac rehabilitation (CR) is an evidence-based intervention that improves event-free survival in patients with cardiac conditions, yet

Drug overdose is the leading cause of accidental death in the United States, with over 70% of drug related fatalities resulting from the use of opioids. Federal agencies have responded to this crisis with various recommendations including enhancing harm reduction approaches such as training laypersons to administer naloxone through Opioid Overdose Education and Naloxone Distribution (OEND) programs. Several studies have demonstrated that OEND programs effectively reduce opioid overdose mortality and are both safe and cost-effective, however, they are typically implemented in urban areas as part of large medical center research programs, needle exchanges, or drug treatment programs. Individuals living in areas without these programs or services lack access to critical and life-saving OEND. The current study examined the acceptability and feasibility of online recruitment, online opioid overdose education, and remote distribution of naloxone kits. Persons who illicitly use opioids and are at risk for overdose were recruited through online media and completed an opioid use questionnaire. If interested in receiving opioid overdose and naloxone administration training, participants completed pre- and post-intervention knowledge questionnaires, engaged in audiovisual training, and were randomized to either receive a naloxone kit or be given information on where they could obtain one. Preliminary results indicate feasibility and acceptability as evidenced by strong recruitment and retention, as well as high participant satisfaction ratings. Successful implementation of remote OEND through this project supports future employment of similar remote programs to expand this critical harm reduction strategy to high-risk individuals in areas lacking traditional OEND programs. Trial Registration #: Clinitaltrials.gov- NCT04303000.

Abstract Background We aimed to: (1) identify school-level factors associated with the sustainment of weekly physical activity (PA) scheduled in elementary schools following withdrawal of effective implementation support; and (2) determine teacher’s perceived usefulness of suggested strategies for sustaining the scheduling of weekly PA. Methods A secondary exploratory analysis was employed of data from the intervention arm (n = 31 schools) of a randomised controlled trial. Self-report survey data from 134 classroom teachers in New South Wales, Australia, collected following withdrawal of initial implementation support (follow-up T1) and six-months following completion of support (follow-up T2) were used. The outcomes of sustainment of weekly overall PA and energisers (short classroom PA breaks) scheduled were measured via teachers’ completion of a daily activity logbook, with results presented as the difference in mean minutes of PA and energisers scheduled at T1 and T2. An adapted version of the Program Sustainability Assessment Tool (PSAT) was used to measure capacity for program sustainability across seven key domains at follow-up T2. Linear mixed regressions were conducted to evaluate associations between school-level sociodemographic characteristics (e.g., school size, remoteness, and type), teacher-reported school factors (i.e., seven adapted PSAT domains) and the sustainment of PA and energisers scheduled across the school week. Perceived usefulness of 14 proposed sustainability strategies was measured via the teacher survey at follow-up T2 and reported descriptively. Results No school-level factor was statistically associated with the sustainment of overall weekly PA or energisers scheduled. Teacher-reported factors in two PSAT domains – ‘strategic planning’ and ‘program evaluation’ were statistically negatively associated with the sustainment of weekly energisers scheduled (− 6.74, 95% CI: − 13.02; − 0.47, p = 0.036 and − 6.65, 95% CI: − 12.17; − 1.12, p = 0.019 respectively). The proposed support sustainability strategy – ‘provision of PA equipment packs that enable energisers or integrated lessons’ was perceived useful by the most teachers (85%). Conclusions Further research is required to explore additional contextual-specific, and end-user appropriate factors associated with schools’ sustainment of weekly PA scheduled. This will help accurately inform the development of strategies to address these determinants and support the sustainment and long-term benefits of school-based health interventions more broadly.

Abstract Background A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants’ perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research. Methods We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the survey queried respondents about different aspects of engaging in and conducting equity-oriented D&I research. All analyses were conducted in SPSS Version 27.0. Results A total of 180 participants responded to the survey. Most participants were women (81.7%), white (66.1%), academics (78.9%), and faculty members (53.9%). Many reported they were advanced (36.7%) or advanced beginners (27.8%) in the D&I field, and a substantial proportion (37.8%) reported being novice in D&I research that focused on health equity. Participants reported high motivation (e.g., 62.8% were motivated to apply theories, models, frameworks for promoting health equity in D&I research), but low capability to conduct equity-oriented D&I research (e.g., 5% had the information needed for promoting health equity in D&I research). Most participants (62.2%) reported not having used measures to examine equity in their D&I projects, and for those who did use measures, they mainly used individual-level measures (vs. organizational- or structural-level measures). When asked about factors that could influence their ability to conduct equity-oriented D&I research, 44.4% reported not having the skills necessary, and 32.2% stated difficulties in receiving funding for equity-oriented D&I research. Conclusions Study findings provide empirical insight into the perspectives of researchers from different backgrounds on what is needed to conduct equity-oriented D&I research. These data suggest the need for a multi-pronged approach to enhance the capability and opportunities for conducting equity-oriented D&I work, such as: training specifically in equity-oriented D&I, collaboration between D&I researchers with individuals with expertise and lived experience with health equity research, funding for equity-oriented D&I research, and recognition of the value of community engaged research in promotion packages.

Abstract Background The past decade of research has seen theoretical and methodological advances in both implementation science and health equity research, opening a window of opportunity for facilitating and accelerating cross-disciplinary exchanges across these fields that have largely operated in siloes. In 2019 and 2020, the National Cancer Institute’s Consortium for Cancer Implementation Science convened an action group focused on ‘health equity and context’ to identify opportunities to advance implementation science. In this paper, we present a narrative review and synthesis of the relevant literature at the intersection of health equity and implementation science, highlight identified opportunities (i.e., public goods) by the action group for advancing implementation science in cancer prevention and control, and integrate the two by providing key recommendations for future directions. Discussion In the review and synthesis of the literature, we highlight recent advances in implementation science, relevant to promoting health equity (e.g., theories/models/frameworks, adaptations, implementation strategies, study designs, implementation determinants, and outcomes). We acknowledge the contributions from the broader field of health equity research and discuss opportunities for integration and synergy with implementation science, which include (1) articulating an explicit focus on health equity for conducting and reviewing implementation science; (2) promoting an explicit focus on health equity in the theories, models, and frameworks guiding implementation science; and (3) identifying methods for understanding and documenting influences on the context of implementation that incorporate a focus on equity. Summary To advance the science of implementation with a focus on health equity, we reflect on the essential groundwork needed to promote bi-directional learning between the fields of implementation science and health equity research and recommend (1) building capacity among researchers and research institutions for health equity-focused and community-engaged implementation science; (2) incorporating health equity considerations across all key implementation focus areas (e.g., adaptations, implementation strategies, study design, determinants, and outcomes); and (3) continuing a focus on transdisciplinary opportunities in health equity research and implementation science. We believe that these recommendations can help advance implementation science by incorporating an explicit focus on health equity in the context of cancer prevention and control and beyond.

Abstract Background Evidence, in multiple forms, is a foundation of implementation science. For public health and clinical practice, evidence includes the following: type 1 evidence on etiology and burden; type 2 evidence on effectiveness of interventions; and type 3: evidence on dissemination and implementation (D&I) within context. To support a vision for development and use of evidence in D&I science that is more comprehensive and equitable (particularly for type 3 evidence), this article aims to clarify concepts of evidence, summarize ongoing debates about evidence, and provide a set of recommendations and tools/resources for addressing the “how-to” in filling evidence gaps most critical to advancing implementation science. Main text Because current conceptualizations of evidence have been relatively narrow and insufficiently characterized in our opinion, we identify and discuss challenges and debates about the uses, usefulness, and gaps in evidence for implementation science. A set of questions is proposed to assist in determining when evidence is sufficient for dissemination and implementation. Intersecting gaps include the need to (1) reconsider how the evidence base is determined, (2) improve understanding of contextual effects on implementation, (3) sharpen the focus on health equity in how we approach and build the evidence-base, (4) conduct more policy implementation research and evaluation, and (5) learn from audience and stakeholder perspectives. We offer 15 recommendations to assist in filling these gaps and describe a set of tools for enhancing the evidence most needed in implementation science. Conclusions To address our recommendations, we see capacity as a necessary ingredient to shift the field’s approach to evidence. Capacity includes the “push” for implementation science where researchers are trained to develop and evaluate evidence which should be useful and feasible for implementers and reflect community or stakeholder priorities. Equally important, there has been inadequate training and too little emphasis on the “pull” for implementation science (e.g., training implementers, practice-based research). We suggest that funders and reviewers of research should adopt and support a more robust definition of evidence. By critically examining the evolving nature of evidence, implementation science can better fulfill its vision of facilitating widespread and equitable adoption, delivery, and sustainment of scientific advances.

Background. To explore preferred and actual involvement in chemotherapy decision making among stage II and III colon cancer (CC) patients by sociodemographic, interpersonal, and intrapersonal communication factors. Methods. Cross-sectional exploratory study collecting self-reported survey data from stage II and III CC patients from 2 cancer centers located in northern Manhattan. Results. Of 88 patients approached, 56 completed the survey. Only 19.3% reported shared involvement in their chemotherapy decisions. We observed significant differences in preferred involvement by gender, with women preferring more physician-controlled decisions. CC patients with higher levels of decisional self-efficacy significantly preferred shared decisions ( F = 4.4 [2], P = 0.02). Actual involvement in decisions differed by race (physician controlled 33% for White v. 67% for Other, P < 0.01), age (shared control 18% for ≤55 y, 55% for 55–64 y, and 27% for 65+ y, P = 0.04), and perception of choice (shared control 73% “yes” v. 27% “no,” P = 0.02). Actual or preferred involvement did not differ by stage. Significantly higher levels of medical mistrust (discrimination t = 2.8 [50], P = 0 .01; lack of support t = 3.6 [49], P < 0.01), and lower levels of decisional self-efficacy ( t = 2.5 [49], P = 0 .01) were reported among women. Discussion. Reports of shared involvement around chemotherapy decisions is limited among CC patients. Factors influencing preferred versus actual chemotherapy decision making are complex and may differ; hence, more research is needed to understand and address factors contributing to discordance between preferred and actual involvement in chemotherapy decision making for CC patients. Highlights Shared involvement around chemotherapy decisions remains limited for patients diagnosed with colon cancer. Sociodemographic (age, race, gender), interpersonal (medical mistrust), and intrapersonal (decisional self-efficacy, perception of choice) factors that influence preferred involvement in chemotherapy decision making may differ from those influencing actual involvement in chemotherapy decision making. Shared involvement in chemotherapy decisions may look different than currently conceptualized, notably when uncertainty around the benefits exists.

Abstract Background: A Health Equity Task Force (HETF) of members from seven Centers funded by the National Cancer Institute’s (NCI) Implementation Science in Cancer Control Centers (ISC3) network sought to identify case examples of how Centers were applying a focus on health equity in implementation science to inform future research and capacity-building efforts. Methods: HETF members at each ISC3 collected information on how health equity was conceptualized, operationalized, and addressed in initial research and capacity-building efforts across the seven ISC3 Centers funded in 2019–2020. Each Center completed a questionnaire assessing five health equity domains central to implementation science (e.g., community engagement; implementation science theories, models, and frameworks (TMFs); and engaging underrepresented scholars). Data generated illustrative examples from these five domains. Results: Centers reported a range of approaches focusing on health equity in implementation research and capacity-building efforts, including (1) engaging diverse community partners/settings in making decisions about research priorities and projects; (2) applying health equity within a single TMF applied across projects or various TMFs used in specific projects; (3) evaluating health equity in operationalizing and measuring health and implementation outcomes; (4) building capacity for health equity-focused implementation science among trainees, early career scholars, and partnering organizations; and (5) leveraging varying levels of institutional resources and efforts to engage, include, and support underrepresented scholars. Conclusions: Examples of approaches to integrating health equity across the ISC3 network can inform other investigators and centers’ efforts to build capacity and infrastructure to support growth and expansion of health equity-focused implementation science.

Abstract Background Serious illness conversations (SICs) are an evidence-based approach to eliciting patients’ values, goals, and care preferences that improve patient outcomes. However, most patients with cancer die without a documented SIC. Clinician-directed implementation strategies informed by behavioral economics (“nudges”) that identify high-risk patients have shown promise in increasing SIC documentation among clinicians. It is unknown whether patient-directed nudges that normalize and prime patients towards SIC completion—either alone or in combination with clinician nudges that additionally compare performance relative to peers—may improve on this approach. Our objective is to test the effect of clinician- and patient-directed nudges as implementation strategies for increasing SIC completion among patients with cancer. Methods We will conduct a 2 × 2 factorial, cluster randomized pragmatic trial to test the effect of nudges to clinicians, patients, or both, compared to usual care, on SIC completion. Participants will include 166 medical and gynecologic oncology clinicians practicing at ten sites within a large academic health system and their approximately 5500 patients at high risk of predicted 6-month mortality based on a validated machine-learning prognostic algorithm. Data will be obtained via the electronic medical record, clinician survey, and semi-structured interviews with clinicians and patients. The primary outcome will be time to SIC documentation among high-risk patients. Secondary outcomes will include time to SIC documentation among all patients (assessing spillover effects), palliative care referral among high-risk patients, and aggressive end-of-life care utilization (composite of chemotherapy within 14 days before death, hospitalization within 30 days before death, or admission to hospice within 3 days before death) among high-risk decedents. We will assess moderators of the effect of implementation strategies and conduct semi-structured interviews with a subset of clinicians and patients to assess contextual factors that shape the effectiveness of nudges with an eye towards health equity. Discussion This will be the first pragmatic trial to evaluate clinician- and patient-directed nudges to promote SIC completion for patients with cancer. We expect the study to yield insights into the effectiveness of clinician and patient nudges as implementation strategies to improve SIC rates, and to uncover multilevel contextual factors that drive response to these strategies. Trial registration ClinicalTrials.gov , NCT04867850 . Registered on April 30, 2021. Funding National Cancer Institute P50CA244690

Abstract Background There is growing concern that routine mammography screening is overused among older women. Successful and equitable de-implementation of mammography will require a multi-level understanding of the factors contributing to mammography overuse. Methods This explanatory, sequential, mixed-methods study collected survey data (n= 52, 73.1% Hispanic, 73.1% Spanish-speaking) from women ≥70 years of age at the time of screening mammography, followed by semi-structured interviews with a subset of older women completing the survey (n=19, 63.2% Hispanic, 63.2% Spanish-speaking) and providers (n=5, 4 primary care, 1 obstetrics and gynecology) to better understand multi-level factors influencing mammography overuse and inform potential de-implementation strategies. We conducted a descriptive analysis of survey data and content analysis of qualitative interview data. Survey and interview data were examined separately, compared, integrated, and organized according to Norton and Chambers Continuum of Factors Influencing De-Implementation Process. Results Survey findings show that 87.2% of older women believe it is important to plan for an annual mammogram, 80.8% received a provider recommendation, and 78.9% received a reminder in the last 12 months to schedule a mammogram. Per interviews with older women, the majority were unaware of or did not perceive to have experienced overuse and intended to continue mammography screening. Findings from interviews with older women and providers suggest that there are multiple opportunities for older women to obtain a mammogram. Per provider interviews, almost all reported that reducing overuse was not viewed as a priority by the system or other providers. Providers also discussed that variation in mammography screening practices across providers, fear of malpractice, and monetary incentives may contribute to overscreening. Providers identified potential strategies to reduce overscreening including patient and provider education around harms of screening, leveraging the electronic health record to identify women who may receive less health benefit from screening, customizing system-generated reminder letters, and organizing workgroups to develop standard processes of care around mammography screening. Conclusions Multi-level factors contributing to mammography overuse are dynamic, interconnected, and reinforced. To ensure equitable de-implementation, there is a need for more refined and empirical testing of theories, models, and frameworks for de-implementation with a strong patient-level component that considers the interplay between multilevel factors and the larger care delivery process.

Abstract Background Public health emergencies—such as the 2020 COVID-19 pandemic—accelerate the need for both evidence generation and rapid dissemination and implementation (D&I) of evidence where it is most needed. In this paper, we reflect on how D&I frameworks and methods can be pragmatic (i.e., relevant to real-world context) tools for rapid and iterative planning, implementation, evaluation, and dissemination of evidence to address public health emergencies. The pragmatic, rapid, and iterative D&I (PRIDI) cycle The PRIDI cycle is based on a “double-loop” learning process that recognizes the need for responsiveness and iterative adaptation of implementation cycle (inner loop) to the moving landscapes, presented by the outer loops of emerging goals and desired outcomes, emerging interventions and D&I strategies, evolving evidence, and emerging characteristics and needs of individuals and contexts. Stakeholders iteratively evaluate these surrounding landscapes of implementation, and reconsider implementation plans and activities. Conclusion Even when the health system priority is provision of the best care to the individuals in need, and scientists are focused on development of effective diagnostic and therapeutic technologies, planning for D&I is critical. Without a flexible and adaptive process of D&I, which is responsive to emerging evidence generation cycles, and closely connected to the needs and priorities of stakeholders and target users through engagement and feedback, the interventions to mitigate public health emergencies (e.g., COVID-19 pandemic), and other emerging issues, will have limited reach and impact on populations that would most benefit. The PRIDI cycle is intended to provide a pragmatic approach to support planning for D&I throughout the evidence generation and usage processes.

Abstract Background Sustainment has been defined as the sustained use or delivery of an intervention in practice following cessation of external implementation support. This review aimed to identify and synthesise factors (barriers and facilitators) that influence the sustainment of interventions (policies, practices, or programmes) in schools and childcare services that address the leading risk factors of chronic disease. Methods Seven electronic databases and relevant reference lists were searched for articles, of any design, published in English, from inception to March 2020. Articles were included if they qualitatively and/or quantitatively reported on school or childcare stakeholders’ (including teachers, principals, administrators, or managers) perceived barriers or facilitators to the sustainment of interventions addressing poor diet/nutrition, physical inactivity, obesity, tobacco smoking, or harmful alcohol use. Two independent reviewers screened texts, and extracted and coded data guided by the Integrated Sustainability Framework, an existing multi-level sustainability-specific framework that assesses factors of sustainment. Results Of the 13,158 articles identified, 31 articles met the inclusion criteria (8 quantitative, 12 qualitative, 10 mixed-methods, and 1 summary article). Overall, 29 articles were undertaken in schools (elementary n=17, middle n=3, secondary n=4, or a combination n=5) and two in childcare settings. The main health behaviours targeted included physical activity (n=9), diet (n=3), both diet and physical activity (n=15), and smoking (n=4), either independently (n=1) or combined with other health behaviours (n=3). Findings suggest that the majority of the 59 barriers and 74 facilitators identified to impact on intervention sustainment were similar across school and childcare settings. Factors predominantly relating to the ‘inner contextual factors’ of the organisation including: availability of facilities or equipment, continued executive or leadership support present, and team cohesion, support, or teamwork were perceived by stakeholders as influential to intervention sustainment. Conclusions Identifying strategies to improve the sustainment of health behaviour interventions in these settings requires a comprehensive understanding of factors that may impede or promote their ongoing delivery. This review identified multi-level factors that can be addressed by strategies to improve the sustainment of such interventions, and suggests how future research might address gaps in the evidence base. Trial registration This review was prospectively registered on PROSPERO: CRD42020127869 , Jan. 2020.

Abstract Background The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. Results Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45–55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. Conclusion Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs.

This paper analyses seven inter-connected William Hogarth prints in the context of medical history. Hogarth is noted for his eighteenth-century prints featuring perceptive depictions of London life. The most famous series is Four Stages of Cruelty, generally accepted as a Sermon intended to influence public opinion by drawing attention to animal cruelty. That opinion is founded on the cruel and sadistic treatment of a dog in First Stage of Cruelty; and relies on an assumption the dog is male. But, what if that dog is female? In considering that option, this paper presents evidence showing Hogarth did intend the dog as female. In so doing, the paper reaches a radically new perspective. Four Stages of Cruelty is a dark Satire, intended by Hogarth to force the cessation of murders-for-dissection, then being undertaken by man-midwives William Smellie and William Hunter; in conducting Caesaraean experiments on pregnant women. In analysing events, the paper reveals Hogarth included within each print, recognisable likenesses of selected contemporaries, with scores of artistic puns. Realisation of the dog as female, and the series as a Satire, allows explanation of the many cryptic puns, and presents Four Stages of Cruelty as a Hogarth masterpiece.

Abstract Background Faith-based organizations (FBOs) can be effective partners in the implementation of health interventions to reach underserved audiences. However, little is known about the capacity they have or need to engage in these efforts. We examined inner-setting organizational characteristics hypothesized to be important for program implementation by the Consolidated Framework for Implementation Research (CFIR). Methods This cross-sectional study involved 34 churches with predominantly Latino congregations in Massachusetts. FBO leaders completed a survey assessing inner-setting CFIR organizational characteristics, including organizational readiness, implementation climate, organizational culture, and innovation “fit” with organizational mission. Results There was limited variability in CFIR organizational characteristics, with scores on a scale from 1 to 5 skewed toward higher values, ranging from 3.27 (SD 0.94) for implementation climate to 4.58 (SD 0.54). Twenty-one percent of the FBOs had offered health programs in the prior year. Conclusions FBOs had high scores on most of the organizational factors hypothesized to be important for the implementation of health programs, although relatively few FBOs offered them. While this suggests that FBOs have favorable characteristics for health programming, prospective studies are needed to understand relative salience of inner-setting organizational characteristics versus factors external to the organization (e.g., policies, incentives), as well as the potential direction of relationships between internal organizational characteristics and health program offerings. Trial registration Clinical trials identifier number NCT01740219 ( clinicaltrials.gov )

Dissemination and implementation (D&I) science is dedicated to studying how to effectively translate and apply research in real-world contexts. There has been increasing interest in health equity within the D&I field to ensure the equitable implementation of evidence-based programs/practices across a range of diverse populations and settings. At the same time, health equity researchers recognize the potential of D&I science to promote the more widespread dissemination, implementation, and sustainment of evidence-based interventions to address health inequities. The National Center for Accelerating Clinical and Translational Science Clinical and Translational Science Award (CTSA) Program has been a champion for community engagement and translational scholarship in its mission to improve individual and population health. The overall CTSA infrastructure and resources within and among CTSA hubs are well-equipped to facilitate a health equity focus to D&I across the phases of translational research. This paper proposes a framework that demonstrates the interaction and opportunities between health equity and D&I science and highlights how CTSAs can support and facilitate wider efforts in translational research with a focus on equitable D&I.

Background Despite the promise of implementation science (IS) to reduce health inequities, critical gaps and opportunities remain in the field to promote health equity. Prioritizing racial equity and antiracism approaches is critical in these efforts, so that IS does not inadvertently exacerbate disparities based on the selection of frameworks, methods, interventions, and strategies that do not reflect consideration of structural racism and its impacts. Methods Grounded in extant research on structural racism and antiracism, we discuss the importance of advancing understanding of how structural racism as a system shapes racial health inequities and inequitable implementation of evidence-based interventions among racially and ethnically diverse communities. We outline recommendations for explicitly applying an antiracism lens to address structural racism and its manifests through IS. An anti-racism lens provides a framework to guide efforts to confront, address, and eradicate racism and racial privilege by helping people identify racism as a root cause of health inequities and critically examine how it is embedded in policies, structures, and systems that differentially affect racially and ethnically diverse populations. Results We provide guidance for the application of an antiracism lens in the field of IS, focusing on select core elements in implementation research, including: (1) stakeholder engagement; (2) conceptual frameworks and models; (3) development, selection, adaptation of EBIs; (4) evaluation approaches; and (5) implementation strategies. We highlight the need for foundational grounding in antiracism frameworks among implementation scientists to facilitate ongoing self-reflection, accountability, and attention to racial equity, and provide questions to guide such reflection and consideration. Conclusion We conclude with a reflection on how this is a critical time for IS to prioritize focus on justice, racial equity, and real-world equitable impact. Moving IS towards making consideration of health equity and an antiracism lens foundational is central to strengthening the field and enhancing its impact. Plain language abstract There are important gaps and opportunities that exist in promoting health equity through implementation science. Historically, the commonly used frameworks, measures, interventions, strategies, and approaches in the field have not been explicitly focused on equity, nor do they consider the role of structural racism in shaping health and inequitable delivery of evidence-based practices/programs. This work seeks to build off of the long history of research on structural racism and health, and seeks to provide guidance on how to apply an antiracism lens to select core elements of implementation research. We highlight important opportunities for the field to reflect and consider applying an antiracism approach in: 1) stakeholder/community engagement; 2) use of conceptual frameworks; 3) development, selection and adaptation of evidence-based interventions; 4) evaluation approaches; 5) implementation strategies (e.g., how to deliver evidence-based practices, programs, policies); and 6) how researchers conduct their research, with a focus on racial equity. This is an important time for the field of implementation science to prioritize a foundational focus on justice, equity, and real-world impact through the application of an anti-racism lens in their work.

Abstract Background Patients with depression who are treated with esketamine nasal spray may commonly experience dysgeusia (bad/metallic/bitter taste) and related side effects such as nausea and vomiting. While pretreatment with antiemetics can mitigate or prevent nausea and vomiting, it may not address dysgeusia as a contributing factor. Alternative interventions could help to manage vomiting due to dysgeusia following administration of esketamine nasal spray in those patients who are affected. Case presentation A 40-year-old man presented to the emergency department with depression and started treatment with an oral antidepressant. After providing informed consent to participate in a clinical trial evaluating the efficacy and safety of esketamine for major depressive disorder with active suicidal ideation with intent, he received 84 mg of esketamine nasal spray twice per week for 4 weeks. On the first 2 days of esketamine administration, the patient reported dysgeusia lasting several hours and intermittent retching lasting approximately 20 min. The patient was then given a fruit punch–flavored powdered drink (Crystal Light Fruit Punch™) approximately 25 min after nasal spray administration during the study period. The use of a fruit punch drink resulted in notable improvement of dysgeusia and associated vomiting, with time to resolution occurring within 30 min of the report of the adverse event. Conclusions A fruit punch–flavored powdered drink mix taken shortly after administration of esketamine nasal spray may rapidly manage and prevent vomiting due to dysgeusia.

Abstract Background Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. Methods This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. Results At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. Conclusions The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. Trial registration Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.

We present a patient with the initial misdiagnosis of a metallic foreign body in the abdominal aorta. Computed tomographic angiography utilizing microanatomical reconstruction technique revealed the structure to instead be a partially calcified abdominal aortic congenital fibrous band. Most congenital fibrous bands spanning the aortic lumen are proximal within the aorta and are thought to be supportive structures of the aortic valve leaflets. Congenital fibrous bands distal to the sinotubular junction are quite rare. Keywords: Aorta, Band, CT angiography, Intravascular foreign body, Postprocessing, Reconstruction

Abstract Introduction: Understanding, categorizing, and using implementation science theories, models, and frameworks is a complex undertaking. The issues involved are even more challenging given the large number of frameworks and that some of them evolve significantly over time. As a consequence, researchers and practitioners may be unintentionally mischaracterizing frameworks or basing actions and conclusions on outdated versions of a framework. Methods: This paper addresses how the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework has been described, summarizes how the model has evolved over time, and identifies and corrects several misconceptions. Results: We address 13 specific areas where misconceptions have been noted concerning the use of RE-AIM and summarize current guidance on these issues. We also discuss key changes to RE-AIM over the past 20 years, including the evolution to Pragmatic Robust Implementation and Sustainability Model, and provide resources for potential users to guide application of the framework. Conclusions: RE-AIM and many other theories and frameworks have evolved, been misunderstood, and sometimes been misapplied. To some degree, this is inevitable, but we conclude by suggesting some actions that reviewers, framework developers, and those selecting or applying frameworks can do to prevent or alleviate these problems.

Implementation science offers a compelling value proposition to translational science. As such, many translational science stakeholders are seeking to recruit, teach, and train an implementation science workforce. The type of workforce that will make implementation happen consists of both implementation researchers and practitioners, yet little guidance exists on how to train such a workforce. We—members of the Advancing Dissemination and Implementation Sciences in CTSAs Working Group—present the Teaching For Implementation Framework to address this gap. We describe the differences between implementation researchers and practitioners and demonstrate what and how to teach them individually and in co-learning opportunities. We briefly comment on educational infrastructures and resources that will be helpful in furthering this type of approach.

RE-AIM is a widely adopted, robust implementation science (IS) framework used to inform intervention and implementation design, planning, and evaluation, as well as to address short-term maintenance. In recent years, there has been growing focus on the longer-term sustainability of evidence-based programs, policies and practices (EBIs). In particular, investigators have conceptualized sustainability as the continued health impact and delivery of EBIs over a longer period of time (e.g., years after initial implementation) and incorporated the complex and evolving nature of context. We propose a reconsideration of RE-AIM to integrate recent conceptualizations of sustainability with a focus on addressing dynamic context and promoting health equity. In this Perspective, we present an extension of the RE-AIM framework to guide planning, measurement/evaluation, and adaptations focused on enhancing sustainability. We recommend consideration of: (1) extension of “maintenance” within RE-AIM to include recent conceptualizations of dynamic, longer-term intervention sustainability and “evolvability” across the life cycle of EBIs, including adaptation and potential de-implementation in light of changing and evolving evidence, contexts, and population needs; (2) iterative application of RE-AIM assessments to guide adaptations and enhance long-term sustainability; (3) explicit consideration of equity and cost as fundamental, driving forces that need to be addressed across RE-AIM dimensions to enhance sustainability; and (4) use or integration of RE-AIM with other existing frameworks that address key contextual factors and examine multi-level determinants of sustainability. Finally, we provide testable hypotheses and detailed research questions to inform future research in these areas.

Abstract Background The South African National Mental Health Policy Framework and Strategic Plan 2013–2020 was adopted to address the country’s substantial burden and inadequate treatment of mental illness. It outlines measures toward the goal of full integration of mental health services into primary care by 2020. To evaluate progress and challenges in implementation, we conducted a mixed-methods assessment of mental health service provision in tuberculosis and maternal-child healthcare services of four districts in South Africa. Methods Forty clinics (ten per district) were purposively selected to represent both urban and rural locations. District-level program managers (DPMs) for mental health, tuberculosis, and maternal-child healthcare were qualitatively interviewed about district policy and procedures for management of mental illness and challenges in integrating mental health services into primary care. Clinic nurses and mental health practitioners (MHPs) completed a quantitative questionnaire to assess their engagement with stepped care for patients with mental illness. Qualitative and quantitative data were collected concurrently and compared to triangulate progress in implementation of integrated services. Results A total of 59 nurses and 17 MHPs completed questionnaires, and nine DPMs were interviewed (total n = 85). DPMs indicated that nurses should screen for mental illness at every patient visit, although only 43 (73%) nurses reported conducting universal screening and 26 (44%) reported using a specific screening tool. For patients who screen positive for mental illness, DPMs described a stepped-care approach in which MHPs diagnose patients and then treat or refer them to specialized care. However, only 7 (41%) MHPs indicated that they diagnose mental illness and 14 (82%) offer any treatment for mental illness. Addressing challenges to current integration efforts, DPMs highlighted 1) insufficient funding and material resources, 2) poor coordination at the district administrative level, and 3) low mental health awareness in district administration and the general population. Conclusions Though some progress has been made toward integration of mental health services into primary care settings, there is a substantial lack of training and clarity of roles for nurses and MHPs. To enhance implementation, increased efforts must be directed toward improving district-level administrative coordination, mental health awareness, and financial and material resources.

Abstract Background This study explores the association of demographic and clinical features with quality of life and functioning in individuals with bipolar disorder. Methods Adult participants (N = 482) with bipolar I or II disorder were enrolled in a comparative effectiveness study across eleven study sites and completed baseline measures of medical and psychiatric history, current mood, quality of life, and functioning. Participants with at least mildly depressive or manic/hypomanic symptomatic severity were randomized to receive lithium or quetiapine in addition to adjunctive personalized treatment for 6 months. Results Participants with more severe depressive and irritability symptoms had lower quality of life and higher functional impairment. All psychiatric comorbid conditions except substance use disorder were associated with worse quality of life. On average, females had lower quality of life than males. Patients who were married, living as married, divorced, or separated had worse functional impairment compared with patients who were single or never married. A composite score of social disadvantage was associated with worse functioning and marginally associated with worse quality of life. Symptom severity did not moderate the effect of social disadvantage on quality of life or functioning. Conclusions Our findings highlight that depression, irritability, and psychiatric comorbid conditions negatively impact quality of life and functioning in bipolar disorder. The study suggests that individuals with social disadvantage are at risk for functional impairment. Trial Registration This study is registered with ClinicalTrials.gov. Identification number: NCT01331304

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients.