Comparing, contrasting, and integrating dissemination and implementation outcomes included in the RE-AIM and Implementation Outcomes Frameworks

As the field of dissemination and implementation science matures, there are a myriad of outcomes, identified in numerous frameworks, that can be considered across individual, organizational, and population levels. This can lead to difficulty in summarizing literature, comparing across studies, and advancing translational science. This manuscript sought to (1) compare, contrast, and integrate the outcomes included in the RE-AIM and Implementation Outcomes Frameworks (IOF) and (2) expand RE-AIM indicators to include relevant IOF dissemination and implementation outcomes. Cross tabular comparisons were made between the constitutive definitions of each construct, across frameworks, to reconcile apparent discrepancies between approaches and to distinguish between implementation outcomes and implementation antecedents. A great deal of consistency was identified across approaches, including adoption (the intention, initial decision, or action to employ an evidence-based intervention), fidelity/implementation (the degree to which an intervention was delivered as intended), organizational maintenance/sustainability (extent to which a newly implemented treatment is maintained or institutionalized), and cost. The IOF construct of penetration was defined as a higher-order construct that may encompass the reach, adoption, and organizational maintenance outcomes within RE-AIM. Within the IOF approach acceptability, appropriateness, and feasibility did not match constitutive definitions of dissemination or implementation but rather reflected theoretical antecedents of implementation outcomes. Integration of the IOF approach across RE-AIM indicators was successfully achieved by expanding the operational definitions of RE-AIM to include antecedents to reach, adoption, implementation, and organizational maintenance. Additional combined metrics were also introduced including penetration, individual level utility, service provider utility, organizational utility, and systemic utility. The expanded RE-AIM indicators move beyond the current approaches described within both the REAIM framework and IOF and provides additional planning and evaluation targets that can contribute to the scientific field and increase the translation of evidence into practice

Endogenous Cholinergic Neurotransmission Contributes to Behavioral Sensitization to Morphine

Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg), a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter) in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg) dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials

A randomised controlled trial of an intervention to increase the implementation of a healthy canteen policy in Australian primary schools: study protocol

Background: The implementation of healthy school canteen policies has been recommended as a strategy to help prevent unhealthy eating and excessive weight gain. Internationally, research suggests that schools often fail to implement practices consistent with healthy school canteen policies. Without a population wide implementation, the potential benefits of these policies will not be realised. The aim of this trial is to assess the effectiveness of an implementation intervention in increasing school canteen practices consistent with a healthy canteen policy of the New South Wales (NSW), Australia, government known as the \u27Fresh Tastes @ School NSW Healthy School Canteen Strategy\u27.Methods/design: The parallel randomised trial will be conducted in 70 primary schools located in the Hunter region of New South Wales, Australia. Schools will be eligible to participate if they are not currently meeting key components of the healthy canteen policy. Schools will be randomly allocated after baseline data collection in a 1:1 ratio to either an intervention or control group using a computerised random number function in Microsoft Excel. Thirty-five schools will be selected to receive a multi-component intervention including implementation support from research staff, staff training, resources, recognition and incentives, consensus and leadership strategies, follow-up support and implementation feedback. The 35 schools allocated to the control group will not receive any intervention support as part of the research trial. The primary outcome measures will be i) the proportion of schools with a canteen menu that does not contain foods or beverages restricted from regular sale (\u27red\u27 and \u27banned\u27 items) and ii) the proportion of schools where healthy canteen items (\u27green\u27 items) represent the majority (>50%) of products listed on the menu. Outcome data will be collected via a comprehensive menu audit, conducted by dietitians blind to group allocation. Intervention effectiveness will be assessed using logistic regression models adjusting for baseline values.Discussion: The proposed trial will represent a novel contribution to the literature, being the first randomised trial internationally to examine the effectiveness of an intervention to facilitate implementation of a healthy canteen policy

Early Predictors of Objectively Measured Physical Activity and Sedentary Behaviour in 8–10 Year Old Children: The Gateshead Millennium Study

With a number of studies suggesting associations between early life influences and later chronic disease risk, it is suggested that associations between early growth and later physical activity (PA) may be a mediator. However, conflicting evidence exists for association between birth weight and childhood PA. In addition, it is important to know what other, potentially modifiable, factors may influence PA in children given its' association with childhood and later adiposity. We used the Gateshead Millennium Study (GMS) to identify predictors of childhood PA levels. The GMS is a cohort of 1029 infants born in 1999–2000 in Gateshead in northern England. Throughout infancy and early childhood, detailed information was collected. Assessments at age 9 years included body composition, objective measures of habitual PA and a range of lifestyle factors. Mean total volumes of PA (accelerometer count per minute, cpm) and moderate-vigorous intensity PA (MVPA), and the percentage of time spent in sedentary behaviour (%SB) were quantified and related to potential predictors using linear regression and path analysis. Children aged 8–10 years were included. Significant differences were seen in all three outcome variables between sexes and season of measurement (p<0.001). Restricting children’s access to television was associated with decreased MVPA. Increased paternal age was associated with significant increases in %SB (p = 0.02), but not MVPA or total PA. Increased time spent in out of school sports clubs was significantly associated with decreased %SB (p = 0.02). No significant associations were seen with birth weight. A range of factors, directly or indirectly, influenced PA and sedentary behaviour. However, associations differed between the different constructs of PA and %SB. Exploring further the sex differences in PA would appear to be useful, as would encouraging children to join out of school sports clubs

Genetic Testing for Early Detection of Individuals at Risk of Coronary Heart Disease and Monitoring Response to Therapy: Challenges and Promises

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient’s lifetime, can help guide therapy selection, and may be of utility in family counseling

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. FUNDING: US National Institutes of Health and Operation Warp Speed

Selected abstracts from the Breastfeeding and Feminism International Conference 2016

Table of contents A1. Infant feeding and poverty: a public health perspective in a global context Lisa H. Amir A2. Mothers’ experiences with galactagogues for lactation: an exploratory cross sectional study Alessandra Bazzano, Shelley Thibeau, Katherine P. Theall A3. The motherhood journey and breastfeeding: from self-efficacy to resilience and social stigma Anna Blair, Karin Cadwell A4. Breastfeeding as an evolutionary adaptive behavior Emily A. Bronson A5. Conflict-of-interest in public health policy: as real as that logo on your website Elizabeth C. Brooks A6. Co-opting sisterhood and motherhood: behind the scenes of Similac’s aggressive social media campaigns Jodine Chase A7. The exclusion of women from the definition of exclusive breastfeeding Ellen Chetwynd, Rebecca Costello, Kathryn Wouk A8. Healthy maternity policies in the workplace: a state health department’s experience with the “Bring Your Infant to Work” program Lindsey Dermid-Gray A9. Implications for a paradigm shift: factors related to breastfeeding among African American women Stephanie Devane-Johnson, Cheryl Woods Giscombe, Miriam Labbok A10. Social experiences of breastfeeding: building bridges between research and policy: an ESRC-funded seminar series in the UK Sally Dowling A11. Manager’s perspectives of lactation breaks Melanie Fraser A12. The challenging second night: a dialogue from two perspectives Jane Grassley, Deborah McCarter-Spaulding, Becky Spencer A13. The role of lactation consultants in two council breastfeeding services in Melbourne, Australia – some preliminary impressions Jennifer Hocking, Pranee Liamputtong A14. Integrating social marketing and community engagement concepts in community breastfeeding programs Sheree H. Keitt, Harumi Reis-Reilly A15. What happens before and after the maternity stay? Creating a community-wide Ten Steps approach Miriam Labbok A16. #RVABREASTFEEDS: cultivating a breastfeeding-friendly community Leslie Lytle A17. Public health vs. free trade: a longitudinal analysis of a global policy to protect breastfeeding Mary Ann Merz A18. Legislative advocacy and grassroots organizing for improved breastfeeding laws in Virginia Kate Noon A19. Breastfeeding and the rights of incarcerated women Krista M Olson A20. Barriers and support for Puerto Rican breastfeeding working mothers Ana M. Parrilla-Rodríguez, José J. Gorrín-Peralta Melissa Pellicier, Zeleida M. Vázquez-Rivera A21. Pumping at work: a daily struggle for Puerto Rican breastfeeding mothers in spite of the law Melissa Pellicier A22. “I saw a wrong and I wanted to stand up for what I thought was right:” a narrative study on becoming a breastfeeding activist Jennifer L. Pemberton A23. Peer breastfeeding support: advocacy and action Catherine McEvilly Pestl A24. Good intentions: a study of breastfeeding intention and postpartum realities among first-time Central Brooklyn mothers Jennifer Pierre, Philip Noyes, Khushbu Srivastava, Sharon Marshall-Taylor A25. Women describing the infant feeding choice: the impact of the WIC breastfeeding classes on infant feeding practices in Ionia, Michigan Jennifer Proto, Sarah Hyland Laurie Brinks A26. Local and state programs and national partnership to reduce disparities through community breastfeeding support Harumi Reis-Reilly, Martelle Esposito, Megan Phillippi A27. Beyond black breastfeeding week: instagram image content analysis for #blackwomendobreastfeed/#bwdbf Cynthia L. Sears, Delores James, Cedric Harville, Kristina Carswell A28. Stakeholder views of breastfeeding education in the K-12 environment: a review of the literature Nicola Singletary, L. Suzanne Goodell, April Fogleman A29. “The Breastfeeding Transition”: a framework for explaining changes in global breastfeeding rates as related to large-scale forces shaping the status of women Paige Hall Smith A30. Breastfeeding, contraception, and ethics, oh my! Advocacy and informed decision-making in the post-partum period Alison M. Stuebe, Amy G. Bryant, Anne Drapkin Lyerly A31. A hard day’s night: juggling nighttime breastfeeding, sleep, and work Cecilia Tomori A32. Empowering change in Indian country through breastfeeding education Amanda L. Watkins, Joan E. Dodgson A33. Servants and “Little Mothers” take charge: work, class, and breastfeeding rates in the early 20th-century U.S. Jacqueline H. Wol