Leveraging systems science and design thinking to advance implementation science: moving toward a solution-oriented paradigm.

Many public health challenges are characterized by complexity that reflects the dynamic systems in which they occur. Such systems involve multiple interdependent factors, actors, and sectors that influence health, and are a primary driver of challenges of insufficient implementation, sustainment, and scale of evidence-based public health interventions. Implementation science frameworks have been developed to help embed evidence-based interventions in diverse settings and identify key factors that facilitate or hinder implementation. These frameworks are largely static in that they do not explain the nature and dynamics of interrelationships among the identified determinants, nor how those determinants might change over time. Furthermore, most implementation science frameworks are top-down, deterministic, and linear, leaving critical gaps in understanding of both how to intervene on determinants of successful implementation and how to scale evidence-based solutions. Design thinking and systems science offer methods for transforming this problem-oriented paradigm into one that is solution-oriented. This article describes these two approaches and how they can be integrated into implementation science strategies to promote implementation, sustainment, and scaling of public health innovation, ultimately resulting in transformative systems changes that improve population health.

Dietary Patterns and Health: Insights From NESR Systematic Reviews to Inform the Dietary Guidelines for Americans.

This perspective article shares unique insights from the extensive experience of the US Department of Agriculture Nutrition Evidence Systematic Review branch in conducting systematic reviews on dietary patterns and health outcomes to inform the Dietary Guidelines for Americans. Methodological approaches for reviewing dietary patterns research are described, including approaches to operationalizing definitions and analyzing labeled dietary patterns. The review also describes techniques for synthesizing dietary patterns research across life stages in systematic reviews that inform food-based, federal dietary guidance. Current research activities and recommendations for how to improve or address gaps in dietary patterns research in the future are also discussed.

USDA Nutrition Evidence Systematic Review's collaborative approach for conducting systematic reviews: Promoting diversity of expertise while managing potential conflicts of interest.

U.S. Department of Agriculture's (USDA) Nutrition Evidence Systematic Review (NESR) Branch develops food-and nutrition-related systematic reviews and other evidence synthesis products. NESR has established itself as a key resource for the Federal government when making evidence-informed decisions related to public health nutrition, such as the development of the Dietary Guidelines for Americans. NESR's systematic review methodology is rigorous, protocol-driven, and highly collaborative. NESR's systematic reviews examine the complex interplay between diet and health with input and support from various collaborators, including Federal stakeholders, expert groups, and public stakeholders. Implementing NESR's rigorous methodology ensures that the appropriate steps are taken to minimize conflict of interest, producing systematic reviews that are high-quality, trustworthy, and useful to end users who make decisions based on their findings. This article describes how NESR's systematic review process leverages a diversity of expertise and experience, while managing potential conflicts of interest. It describes the groups who collaborate to conduct NESR systematic reviews, their expertise, and why their involvement is critical for ensuring the rigor and utility of NESR's work.

Strengthening Research that Answers Nutrition Questions of Public Health Importance: Leveraging the Experience of the USDA Nutrition Evidence Systematic Review Team.

The Nutrition Evidence Systematic Review (NESR) team conducts nutrition- and public health-related systematic reviews and is within the USDA's Center for Nutrition Policy and Promotion. NESR has collaborated with scientific experts to conduct systematic reviews on nutrition and public health topics for more than a decade and is uniquely positioned to share recommendations with the research community to strengthen research quality and impact, especially the evidence base that supports public health nutrition guidance, including future editions of the Dietary Guidelines for Americans. Leveraging the expertise of NESR and its systematic review process resulted in the following recommendations for the research community: a) use the strongest study design feasible with sufficient sample size(s); b) enroll study participants who reflect the diversity of the population of interest and report participant characteristics; c) use valid and reliable dietary assessment methods; d) describe the interventions or exposures of interest and use standard definitions to promote consistency; e) use valid and reliable health outcome measures; f) account for variables that may impact the relationship between nutrition-related interventions or exposures and health outcomes; g) carry out studies for a sufficient duration and include repeated measures, as appropriate; and h) report all relevant information to inform accurate interpretation and evaluation of study results. Implementing these recommendations can strengthen nutrition and public health evidence and increase its utility in future public health nutrition systematic reviews. However, implementation will require additional support from the entire research community, including scientific journals and funding agencies.

Assessing the safety of bioactive ingredients in infant formula that affect the immune system: recommendations from an expert panel.

Bioactive ingredients for infant formula have been sought to reduce disparities in health outcomes between breastfed and formula-fed infants. Traditional food safety methodologies have limited ability to assess some bioactive ingredients. It is difficult to assess the effects of nutrition on the infant immune system because of coincident developmental adaptations to birth, establishment of the microbiome and introduction to solid foods, and perinatal environmental factors. An expert panel was convened to review information on immune system development published since the 2004 Institute of Medicine report on evaluating the safety of new infant formula ingredients and to recommend measurements that demonstrate the safety of bioactive ingredients intended for that use. Panel members participated in a 2-d virtual symposium in November 2020 and in follow-up discussions throughout early 2021. Key topics included identification of immune system endpoints from nutritional intervention studies, effects of human milk feeding and human milk substances on infant health outcomes, ontologic development of the infant immune system, and microbial influences on tolerance. The panel explored how "nonnormal" conditions such as preterm birth, allergy, and genetic disorders could help define developmental immune markers for healthy term infants. With consideration of breastfed infants as a reference, ensuring proper control groups, and attention to numerous potential confounders, the panel recommended a set of standard clinical endpoints including growth, response to vaccination, infection and other adverse effects related to inflammation, and allergy and atopic diseases. It compiled a set of candidate markers to characterize stereotypical patterns of immune system development during infancy, but absence of reference ranges, variability in methods and populations, and unreliability of individual markers to predict disease prevented the panel from including many markers as safety endpoints. The panel's findings and recommendations are applicable for industry, regulatory, and academic settings, and will inform safety assessments for immunomodulatory ingredients in foods besides infant formula.

Perspective: USDA Nutrition Evidence Systematic Review Methodology: Grading the Strength of Evidence in Nutrition- and Public Health-Related Systematic Reviews.

The USDA's Nutrition Evidence Systematic Review (NESR) team conducts food- and nutrition-related systematic reviews used to inform US Federal guidelines and programs, including the Dietary Guidelines for Americans. NESR's systematic review methodology includes a step to grade the strength of the evidence underlying conclusion statements, which is critical for ensuring that end users understand the level of certainty in conclusions when using them to make decisions. Over time, NESR has ensured its grading process not only remains state of the art but is also designed specifically for systematic reviews that inform Federal guidelines and programs on nutrition and public health. The NESR grading process used by the 2020 Dietary Guidelines Advisory Committee included 5 grading elements: risk of bias, consistency, directness, precision, and generalizability. Evidence was grouped by study design and assessed against these elements, and the grade assigned to the entire body of evidence took into consideration the strengths and limitations of each design. Based on this assessment, 1 of 4 grades was assigned: strong, moderate, limited, or grade not assignable. The grade was clearly communicated by integrating specific language into each conclusion statement (e.g., "strong evidence demonstrates" or "limited evidence suggests"), and supported by rationale documented in the review. NESR's grading process aligns with approaches used by other organizations that conduct systematic reviews, while retaining aspects unique to NESR's role in informing Federal nutrition and public health guidelines and programs. It provides a framework that promotes consistency in grading across food- and nutrition-related reviews, while offering flexibility that allows for thorough consideration of the body of evidence underlying an individual conclusion statement. NESR's rigorous and transparent methods for grading the strength of evidence in food- and nutrition-related systematic reviews ensure that decisions related to nutrition and public health are based on the strongest available evidence.

Evaluation of Dietary Patterns and All-Cause Mortality: A Systematic Review.

Importance: The 2020 Dietary Guidelines Advisory Committee conducted a systematic review of existing research on diet and health to inform the current Dietary Guidelines for Americans. The committee answered this public health question: what is the association between dietary patterns consumed and all-cause mortality (ACM)? Objective: To ascertain the association between dietary patterns consumed and ACM. Evidence Review: Guided by an analytical framework and predefined inclusion and exclusion criteria developed by the committee, the US Department of Agriculture's Nutrition Evidence Systematic Review (NESR) team searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase and dual-screened the results to identify articles that were published between January 1, 2000, and October 4, 2019. These studies evaluated dietary patterns and ACM in participants aged 2 years and older. The NESR team extracted data from and assessed risk of bias in included studies. Committee members synthesized the evidence, developed conclusion statements, and graded the strength of the evidence supporting the conclusion statements. Findings: A total of 1 randomized clinical trial and 152 observational studies were included in the review. Studies enrolled adults and older adults (aged 17-84 years at baseline) from 28 countries with high or very high Human Development Index; 53 studies originated from the US. Most studies were well designed, used rigorous methods, and had low or moderate risks of bias. Precision, directness, and generalizability were demonstrated across the body of evidence. Results across studies were highly consistent. Evidence suggested that dietary patterns in adults and older adults that involved higher consumption of vegetables, fruits, legumes, nuts, whole grains, unsaturated vegetable oils, fish, and lean meat or poultry (when meat was included) were associated with a decreased risk of ACM. These healthy patterns were also relatively low in red and processed meat, high-fat dairy, and refined carbohydrates or sweets. Some of these dietary patterns also included intake of alcoholic beverages in moderation. Results based on additional analyses with confounding factors generally confirmed the robustness of main findings. Conclusions and Relevance: In this systematic review, consuming a nutrient-dense dietary pattern was associated with reduced risk of death from all causes.

Hypertrophic cardiomyopathy genetic test reports: A qualitative study of patient understanding of uninformative genetic test results.

Studies have shown that patients with hypertrophic cardiomyopathy (HCM) may misinterpret the meaning of uninformative genetic testing results to mean that a genetic etiology and family members' risk is ruled out. We hypothesized that poor comprehension of the laboratory genetic test report may contribute to this misunderstanding. We conducted a qualitative study to examine patient understanding of uninformative laboratory results and reports and elicit suggestions for an improved report. Fifteen participants with HCM were interviewed after undergoing genetic testing and receiving their report. While all patients read the report, most participants reported only partially reading it. Most reported not understanding the report at all or only partially understanding it because a provider explained it to them. Some participants said that the report was helpful for understanding their result, but there was evidence of misunderstanding; most participants stated that specific aspects of the report were unhelpful. While most of our participants communicated risk with relatives, none said that the report helped with the communication. Most participants did not recall or find the accompanying physician-directed result letter useful for their understanding or familial communication. Many participants expressed need for a supplemental report that illustrates a personalized clinical 'action plan' that could summarize clinical and familial implications of the result for the patient and their family. We conclude that laboratory reports and physician-directed result letters did not help participants understand their results or their familial implications. Our results suggest opportunities for research to explore the utility of a patient-directed result supplement to improve patient comprehension of genetic test results and outline clinical recommendations via a patient action plan.

Caregiver feeding practices and child weight outcomes: a systematic review.

BACKGROUND: As part of the USDA-Department of Health and Human Services Pregnancy and Birth to 24 Months Project, we conducted systematic reviews (SRs) on topics important for health and nutrition of young children. OBJECTIVES: The purpose of the present SR was to examine the relation between caregiver feeding practices in children from birth to 24 mo and child weight gain, size, and body composition. METHODS: A search of articles published from January 1980 to January 2017 in 4 databases identified 8739 references. Nutrition Evidence Systematic Review (NESR) analysts used the Nutrition Evidence Library Risk of Bias Assessment Tool to assess potential bias in the studies, and a Technical Expert Collaborative graded the body of evidence using the NESR grading rubric. RESULTS: Twenty-seven articles were included in this review (8 controlled trials, 19 longitudinal cohort studies). Moderate evidence from randomized controlled trials suggests that providing responsive feeding guidance to teach mothers to recognize and respond appropriately to children's hunger and satiety cues can lead to "normal" weight gain and/or "normal" weight status in children aged ≤2 y compared with children whose mothers did not receive responsive feeding guidance. Moderate evidence from longitudinal cohort studies indicates an association between maternal feeding practices and the child's weight status and/or weight gain, but the direction of effect has not been adequately studied. Restrictive feeding practices are associated with increased weight gain and higher weight status, and pressuring feeding practices are associated with decreased weight gain and lower weight status. Evidence suggests that a mother's feeding practices are related to concerns about her child's body weight. CONCLUSIONS: This review highlights the importance of the interaction between caregivers and infants and toddlers related to child feeding practices on children's weight outcomes. Research is needed on more diverse populations with consistent methodological app-roaches and objective measures.

Influence of maternal diet on flavor transfer to amniotic fluid and breast milk and children's responses: a systematic review.

BACKGROUND: Maternal diet during pregnancy and lactation may provide the earliest opportunity to positively influence child food acceptance. OBJECTIVE: Systematic reviews were completed to examine the relation among maternal diet during pregnancy and lactation, amniotic fluid flavor, breast-milk flavor, and children's food acceptability and overall dietary intake. DESIGN: A literature search was conducted in 10 databases (e.g., PubMed, Embase, Cochrane, and CINAHL) to identify articles published from January 1980 to June 2017. Data from each included study were extracted, risk of bias assessed, evidence synthesized qualitatively, conclusion statements developed, and strength of the evidence graded. RESULTS: Eleven and 15 articles met a priori criteria for inclusion to answer questions related to maternal diet during pregnancy and lactation, respectively. CONCLUSIONS: Limited but consistent evidence indicates that flavors (alcohol, anise, carrot, garlic) originating from the maternal diet during pregnancy can transfer to and flavor amniotic fluid, and fetal flavor exposure increases acceptance of similarly flavored foods when re-exposed during infancy and potentially childhood. Moderate evidence indicates that flavors originating from the maternal diet during lactation (alcohol, anise/caraway, carrot, eucalyptus, garlic, mint) transmit to and flavor breast milk in a time-dependent manner. Moderate evidence indicates that infants can detect diet-transmitted flavors in breast milk within hours of a single maternal ingestion (alcohol, garlic, vanilla, carrot), within days after repeated maternal ingestion (garlic, carrot juice), and within 1-4 mo postpartum after repeated maternal ingestion (variety of vegetables including carrot) during lactation. Findings may not generalize to all foods and beverages. Conclusions cannot be drawn to describe the relationship between mothers' diet during either pregnancy or lactation and children's overall dietary intake.

Repeated exposure to food and food acceptability in infants and toddlers: a systematic review.

BACKGROUND: Repeated exposure has been found to be an effective strategy to increase acceptability of foods in older children and adults, but little is known about its effectiveness in the birth to 24-mo population. OBJECTIVES: This systematic review was conducted to examine the effects of repeated exposure to a single or multiple foods on acceptance of those or other foods among infants and toddlers. METHODS: A search was conducted for peer-reviewed articles related to food acceptability, flavor, taste, and infants and toddlers in 12 databases (e.g., PubMed, Embase, Cochrane, and CINAHL) with a date range of January 1980 to July 2017. The Nutrition Evidence Library (NEL) Bias Assessment Tool was used to assess potential bias in the included studies, and the NESR grading rubric was used to grade evidence supporting the conclusion statement. RESULTS: From the 10,844 references obtained, 21 studies (19 controlled trials and 2 longitudinal cohort studies) published from 1980 to 2015 were included in this review. Moderate evidence indicates that tasting a single vegetable or fruit or multiple vegetable(s) or fruit(s) 1 food per day for 8-10 or more days is likely to increase acceptability of an exposed food (indicated by an increase in intake or faster rate of feeding after comparison with before the exposure period) in infants and toddlers 4-24 mo old. The effect of repeated exposure on acceptability is likely to generalize to other foods within the same food category but not foods from a different food category. Findings are based on the effects of repeated exposure to mostly vegetables with some findings on repeated exposure to fruits. CONCLUSION: This review advances the understanding of early food experiences and the development of food acceptability. Additional research is needed using diverse foods and textures with a focus on the transition to table foods.

Systematic review methods for the Pregnancy and Birth to 24 Months Project.

The USDA's Nutrition Evidence Systematic Review (NESR) team specializes in conducting systematic reviews (SRs) to inform federal nutrition policy and programs. The NESR's dedicated staff collaborate with leading scientists to answer important food- and nutrition-related public health questions by objectively reviewing, evaluating, and synthesizing research using state-of-the-art methodology. NESR uses a rigorous, protocol-driven methodology that is designed to minimize bias; to ensure availability of SRs that are relevant, timely, and high quality; and to ensure transparency and reproducibility of findings. This article describes the methods used by NESR to conduct a series of SRs on diet and health in infants, toddlers, and women who are pregnant as part of the Pregnancy and Birth to 24 Months Project.

The association of lifetime physical inactivity with head and neck cancer: a hospital-based case-control analysis.

Despite mounting epidemiological evidence suggesting an inverse association between recreational physical activity and cancer risk, evidence associated with head and neck cancer is scant. We conducted a case-control analysis to examine the associations of lifetime physical inactivity with the risk of head and neck squamous cell carcinoma (HNSCC). We utilized data from the Patient Epidemiology Data System at Roswell Park Cancer Institute (RPCI). Participants included 246 patients with HNSCC and 504 cancer-free controls who received medical services at RPCI between 1990 and 1998. Participants were considered physically inactive if they did not participate in any regular, weekly recreational physical activity throughout their lifetime, prior to diagnosis. Multivariate logistic regression models were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) representing the association between lifetime physical inactivity and HNSCC risk. We observed a significant positive association between recreational physical inactivity and HNSCC risk (OR = 2.73, 95% CI 1.87-3.99, p < 0.001). In subgroup analyses by body mass index (BMI) (underweight/normal-weight: OR = 3.40, 95% CI 1.89-6.12, p < 0.001; overweight/obese: OR = 2.40, 95% CI 1.43-4.02, p < 0.001) and smoking status (former smoker: OR = 3.12, 95% CI 1.89-5.14, p < 0.001; never smoker: OR = 2.71, 95% CI 1.21-6.05, p = 0.020; current smoker: OR = 1.61, 95% CI 0.66-3.95, p = 0.300), significant positive associations were also observed. Results of the current analyses suggest that lifetime physical inactivity associates with HNSCC independent of BMI. In addition, physical inactivity may be a modifiable risk factor among never smokers. These data add to the growing body of evidence suggesting that physical inactivity may be an independent risk factor for cancer.

Reducing Sodium Intake in Children: A Public Health Investment.

The antecedents of elevated blood pressure (BP) and its major consequences (cardiovascular disease and stroke) begin in childhood. Higher levels of BP early in life track into adulthood and are associated with subclinical target organ damage in children and adults. Diet behaviors, including the choice of high sodium containing foods, are established during childhood. On average, children, ages 2-19, consume more than 3,100 mg of sodium per day, with substantially greater sodium intakes in boys than girls. Importantly, studies show that lowering sodium intake in children lowers blood pressure. In view of this evidence, U.S. Dietary Guidelines recommend a reduced sodium intake in children. Current federal nutrition standards include a step-wise reduction in the sodium levels of school meals. The ultimate goal is to help children achieve daily sodium intakes that do not exceed upper levels recommended by the Institute of Medicine and the Dietary Guidelines for Americans. In summary, available data are sufficiently strong to recommend a lower sodium intake beginning in early in life as an effective and well-tolerated approach to reducing BP in children. Current efforts to weaken nutrition standards for school meals undermine an effective strategy aimed at improving the health of our children and our nation.

An investigation of quantity discrimination in Clark's nutcrackers (Nucifraga columbiana).

We examined quantity discrimination in the Clark's nutcracker (Nucifraga columbiana), a corvid bird with a strong dependence upon caching and recovering nuts. We presented 2 sets of nuts simultaneously, in 21 different conditions, to see if the nutcrackers could choose the larger of the 2 quantities. The nutcrackers displayed a strong ability to discriminate quantities of nuts. Like other animals tested previously, the nutcrackers' performance decreased as the ratio of the 2 quantities approached 1. Interestingly, at constant distances, the nutcrackers did not have more difficulty with contrasts containing larger quantities. Thus, nutcrackers have a fine sensitivity for discriminating between 2 quantities. We review the relevant literature and explore the possibility that nutcrackers, like some other birds, may have developed a keen ability to discriminate quantities. This ability may have developed as an adaptive specialization to cope with their scatter-hoarding ecology, though the evidence for such a conclusion is mixed.