High-Intensity Functional Training: Perceived Functional and Psychosocial Health-Related Outcomes from Current Participants with Mobility-Related Disabilities.

BACKGROUND: People with mobility-related disabilities (MRDs) experience many personal and environmental barriers to engagement in community-based exercise programs. We explored the experiences of adults with MRD who currently participate in high-intensity functional training (HIFT), an inclusive and accessible community-based exercise program. METHODS: Thirty-eight participants completed online surveys with open-ended questions, with ten individuals also participating in semi-structured interviews via telephone with project PI. Surveys and interviews were designed to examine changes to perceived health, and the elements of HIFT that promote sustained participation. RESULTS: Thematic analysis revealed themes related to health changes following HIFT participation including improved physical, functional, and psychosocial health outcomes. Other themes emerged within the HIFT environment that promoted adherence for participants such as accessible spaces and equipment, and inclusive HIFT sessions and competitions. Additional themes included participants' advice for the disability and healthcare communities. The resulting themes are informed by the World Health Organization's International Classification of Functioning, Disability, and Health. CONCLUSION: The findings provide initial data on the potential effects of HIFT on multiple dimensions of health outcomes and contribute to the growing literature on community-based programs that are adaptable and inclusive for people with MRD.

Evidence-based practices in developing and maintaining clinical nurse preceptors: An integrative review.

OBJECTIVES: This integrative review of literature explores the best practice for establishing and maintaining a hospital-based nurse preceptor program. The intent is to provide nurse leadership and educators with guidance for optimizing preceptor programs in order to improve patient, staff, and organizational outcomes. DESIGN: The project team conducted an integrative review of literature to inform best practice using the Johns Hopkins Evidence-Based Practice Model and Guidelines. DATA SOURCES: Data sources included the PubMed, CINAHL, and Cochrane databases. REVIEW METHODS: Each applicable article underwent a rigorous review and appraisal by the project team. The team used the Johns Hopkins Evidence-Based Practice Model to guide the appraisal process and to synthesize results to generate a comprehensive list of recommendations. RESULTS: The search yielded 115 unique articles that answered the evidence-based practice question. What are best practices for establishing and maintaining a hospital-based nursing preceptor program? Due to the abundance of data, the practice question was divided into three separate sub questions that explored preceptor development, continuous preceptor support, and essential competencies of preceptors. Relevant evidence included one level I article, seven level II articles, and one level IV article. Most of the evidence was found in articles ranking as level III (n = 54) and level V (n = 52). CONCLUSIONS: Many preceptorship themes and recommendations resonate throughout multiple levels of evidence. Recommendations include implementing an evidence-based, standardized curriculum that features diverse teaching modalities, critical thinking, and clinical reasoning. Common themes in the literature echo that preceptors need ongoing education, training, and support to improve nursing satisfaction, retention, and the quality of nursing care.

Association of various weight-based doses of continuous albuterol on hospital length of stay.

Introduction: Continuous albuterol is a mainstay in management of pediatric status asthmaticus. While the National Heart Lung and Blood Institute Asthma Guidelines suggest 0.5 mg/kg/h as the recommended dosage, there is a paucity of evidence comparing different weight-based rates on hospital outcomes.Methods: Patients requiring continuous albuterol for asthma exacerbation from January 2015 to December 2016 were identified using ICD codes. The concentration of albuterol (5 mg/h-20 mg/h) and the duration of treatment were used to determine total albuterol administration. After dividing by patient weight, average weight-based doses were divided into equal quintiles. Unadjusted and length of stay adjusted for age, initial asthma severity score, and administration of magnesium were compared among the quintiles. The same multivariate analysis was used for duration of continuous albuterol.Results: Five hundred thirty-three hospitalizations for asthma were identified of which 289 received continuous albuterol. Weight-based dosage quintiles ranged from lowest (0.07-0.29 mg/kg/h) to the highest (>0.76-3.2 mg/kg/h). Baseline characteristics were similar aside from age, race, and magnesium administration. There was no difference in adjusted length of stay or adjusted duration of continuous albuterol therapy among the five quintiles.Conclusion: No optimal weight-based dose of continuous albuterol was found. Further investigation is needed to see if lower amounts of continuous albuterol may be as efficacious as higher doses. This could improve cost of status asthmaticus management and limit the number of adverse events associated with high exposure to continuous albuterol.

Intratumoral IL12 mRNA Therapy Promotes TH1 Transformation of the Tumor Microenvironment.

PURPOSE: While immune checkpoint inhibitors such as anti-PD-L1 are rapidly becoming the standard of care in the treatment of many cancers, only a subset of treated patients have long-term responses. IL12 promotes antitumor immunity in mouse models; however, systemic recombinant IL12 had significant toxicity and limited efficacy in early clinical trials. EXPERIMENTAL DESIGN: We therefore designed a novel intratumoral IL12 mRNA therapy to promote local IL12 tumor production while mitigating systemic effects. RESULTS: A single intratumoral dose of mouse (m)IL12 mRNA induced IFNγ and CD8+ T-cell-dependent tumor regression in multiple syngeneic mouse models, and animals with a complete response demonstrated immunity to rechallenge. Antitumor activity of mIL12 mRNA did not require NK and NKT cells. mIL12 mRNA antitumor activity correlated with TH1 tumor microenvironment (TME) transformation. In a PD-L1 blockade monotherapy-resistant model, antitumor immunity induced by mIL12 mRNA was enhanced by anti-PD-L1. mIL12 mRNA also drove regression of uninjected distal lesions, and anti-PD-L1 potentiated this response. Importantly, intratumoral delivery of mRNA encoding membrane-tethered mIL12 also drove rejection of uninjected lesions with very limited circulating IL12p70, supporting the hypothesis that local IL12 could induce a systemic antitumor immune response against distal lesions. Furthermore, in ex vivo patient tumor slice cultures, human IL12 mRNA (MEDI1191) induced dose-dependent IL12 production, downstream IFNγ expression and TH1 gene expression. CONCLUSIONS: These data demonstrate the potential for intratumorally delivered IL12 mRNA to promote TH1 TME transformation and robust antitumor immunity.See related commentary by Cirella et al., p. 6080.

Associations of Erythrocyte Polyunsaturated Fatty Acids with Inflammation and Quality of Life in Post-Menopausal Women with Obesity Completing a Pilot Dietary Intervention.

Study objectives were to determine if erythrocyte omega-3 polyunsaturated fatty acids (n-3 PUFAs) increased in women participating in a dietary intervention that reduced inflammation and body weight and examine PUFA associations with markers of inflammation and quality of life (QOL). An experimental pre-post test, single group design was used. Fifteen post-menopausal women with obesity were enrolled in a 12-week pilot intervention focusing on lowering added sugars and increasing fiber and fish rich in n-3 PUFAs. Measurements included fasting blood samples, anthropometric, lifestyle and dietary data collected at baseline, end of intervention (Week 12) and follow-up (Week 24). Primary outcomes were change in erythrocyte PUFAs and associations between erythrocyte PUFAs, QOL (Short Form 12), and inflammatory markers (interleukin-6, tumor necrosis factor-α-receptor 2, and high sensitivity C-reactive protein (CRP)). Fourteen women completed all intervention visits. Mean erythrocyte docosahexaenoic acid and arachidonic acid (AA) increased at Week 12 and Week 24 (p < 0.001 for both), while eicosapentaenoic acid increased at Week 24 (p < 0.01). After adjustment for percent weight change, week 12 QOL related to physical function was significantly associated with erythrocyte linoleic acid (p < 0.05) and trended toward significant association with EPA (p = 0.051); week 24 CRP was directly associated with erythrocyte AA (p < 0.05). Erythrocyte n-3 PUFAs were not associated with inflammation.

Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs.

Many solid cancers contain dysfunctional immune microenvironments. Immune system modulators that initiate responses to foreign pathogens could be promising candidates for reigniting productive responses toward tumors. Interleukin-1 (IL-1) and IL-12 cytokine family members cooperate at barrier tissues after microbial invasion, in human inflammatory diseases, and in antitumoral immunity. IL-36γ, in classic alarmin fashion, acts in damaged tissues, whereas IL-23 centrally coordinates immune responses to danger signals. In this study, direct intratumoral delivery of messenger RNAs (mRNAs) encoding these cytokines produced robust anticancer responses in a broad range of tumor microenvironments. The addition of mRNA encoding the T cell costimulator OX40L increased complete response rates in treated and untreated distal tumors compared to the cytokine mRNAs alone. Mice exhibiting complete responses were subsequently protected from tumor rechallenge. Treatments with these mRNA mixtures induced downstream cytokine and chemokine expression, and also activated multiple dendritic cell (DC) and T cell types. Consistent with this, efficacy was dependent on Batf3-dependent cross-presenting DCs and cytotoxic CD8+ T cells. IL-23/IL-36γ/OX40L triplet mRNA mixture triggered substantial immune cell recruitment into tumors, enabling effective tumor destruction irrespective of previous tumoral immune infiltrates. Last, combining triplet mRNA with checkpoint blockade led to efficacy in models otherwise resistant to systemic immune checkpoint inhibition. Human cell studies showed similar cytokine responses to the individual components of this mRNA mixture, suggesting translatability of immunomodulatory activity to human patients.

Improving Diet Quality Is Associated with Decreased Inflammation: Findings from a Pilot Intervention in Postmenopausal Women with Obesity.

BACKGROUND: Chronic inflammation is associated with obesity, morbidity, and mortality in postmenopausal women. OBJECTIVE: The objective of this pilot study was to determine preliminary feasibility and efficacy of a dietary intervention to improve diet quality and lower inflammation. DESIGN: The study had a single-arm, pre- and posttest design. PARTICIPANTS/SETTING: Fourteen postmenopausal women (body mass index >30 [calculated as kg/m2]) from the greater Columbus, OH, area participated between August 2015 and April 2016. INTERVENTION: This was a 12-week individualized dietary intervention targeting lower consumption of added sugars and increased fiber and fatty fish. MAIN OUTCOME MEASURES: Primary outcomes of this analysis were serum tumor necrosis factor α receptor-2 (TNFαR-2), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP); other outcomes included intake of targeted food components and Healthy Eating Index-2010 (HEI-2010) scores calculated from food frequency questionnaires at baseline, end of intervention (week 12 [WK12]), and 24-week (WK24) follow-up. STATISTICAL ANALYSES PERFORMED: Repeated measures analysis of variance and partial Pearson correlations, respectively, were used to assess changes in outcomes and associations between dietary variables and inflammatory markers, controlling for percent weight change. RESULTS: Mean levels of TNFαR-2 decreased pre- to postintervention (P<0.01) and remained reduced at WK24 (P<0.001). Mean intake of added sugars and n-3-rich fish improved from baseline to WK12 and remained better at WK24 (all P<0.001); mean fiber intake did not change significantly (P=0.66; baseline to WK24). Mean HEI-2010 score increased (P<0.001; baseline to WK12). Change in HEI-2010 score inversely correlated with change in TNFαR-2 (P<0.05; baseline to WK24). Change in added sugars directly correlated with change in TNFαR-2 (P<0.05; baseline to WK24), but inversely correlated with change in hsCRP (P<0.05; baseline to WK12, and WK12 to WK24). All participants lost weight by WK12 (P<0.001). CONCLUSIONS: These pilot intervention findings suggest that improving diet quality is associated with decreases in TNFαR-2.

RESHAPES: Increasing AAST EGS grade is associated with anastomosis type.

INTRODUCTION: Threatened, perforated, and infarcted bowel is managed with conventional resection and anastomosis (hand sewn [HS] or stapled [ST]). The SHAPES analysis demonstrated equivalence between HS and ST techniques, yet surgeons appeared to prefer HS for the critically ill. We hypothesized that HS is more frequent in patients with higher disease severity as measured by the American Association for the Surgery of Trauma Emergency General Surgery (AAST EGS) grading system. METHODS: We performed a post hoc analysis of the SHAPES database. Operative reports were submitted by volunteering SHAPES centers. Final AAST grade was compared with various outcomes including duration of stay, physiologic/laboratory data, anastomosis type, anastomosis failure (dehiscence, abscess, or fistula), and mortality. RESULTS: A total of 391 patients were reviewed, with a mean age (±SD) of 61.2 ± 16.8 years, 47% women. Disease severity distribution was as follows: grade I (n = 0, 0%), grade II (n = 106, 27%), grade III (n = 113, 29%), grade IV (n = 123, 31%), and grade V (n = 49, 13%). Increasing AAST grade was associated with acidosis and hypothermia. There was an association between higher AAST grade and likelihood of HS anastomosis. On regression, factors associated with mortality included development of anastomosis complication and vasopressor use but not increasing AAST EGS grade or anastomotic technique. CONCLUSION: This is the first study to use standardized anatomic injury grades for patients undergoing urgent/emergent bowel resection in EGS. Higher AAST severity scores are associated with key clinical outcomes in EGS diseases requiring bowel resection and anastomosis. Anastomotic-specific complications were not associated with higher AAST grade; however, mortality was influenced by anastomosis complication and vasopressor use. Future EGS studies should routinely include AAST grading as a method for reliable comparison of injury between groups. LEVEL OF EVIDENCE: Prognostic, level III.

Perioperative use of nonsteroidal anti-inflammatory drugs and the risk of anastomotic failure in emergency general surgery.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesic and anti-inflammatory adjuncts. Nonsteroidal anti-inflammatory drug administration may potentially increase the risk of postoperative gastrointestinal anastomotic failure (AF). We aim to determine if perioperative NSAID utilization influences gastrointestinal AF in emergency general surgery (EGS) patients undergoing gastrointestinal resection and anastomosis. METHODS: Post hoc analysis of a multi-institutional prospectively collected database was performed. Anastomotic failure was defined as the occurrence of a dehiscence/leak, fistula, or abscess. Patients using NSAIDs were compared with those without. Summary, univariate, and multivariable analyses were performed. RESULTS: Five hundred thirty-three patients met inclusion criteria with a mean (±SD) age of 60 ± 17.5 years, 53% men. Forty-six percent (n = 244) of the patients were using perioperative NSAIDs. Gastrointestinal AF rate between NSAID and no NSAID was 13.9% versus 10.7% (p = 0.26). No differences existed between groups with respect to perioperative steroid use (16.8% vs. 13.8%; p = 0.34) or mortality (7.39% vs. 6.92%, p = 0.84). Multivariable analysis demonstrated that perioperative corticosteroid (odds ratio, 2.28; 95% confidence interval, 1.04-4.81) use and the presence of a colocolonic or colorectal anastomoses were independently associated with AF. A subset analysis of the NSAIDs cohort demonstrated an increased AF rate in colocolonic or colorectal anastomosis compared with enteroenteric or enterocolonic anastomoses (30.0% vs. 13.0%; p = 0.03). CONCLUSION: Perioperative NSAID utilization appears to be safe in EGS patients undergoing small-bowel resection and anastomosis. Nonsteroidal anti-inflammatory drug administration should be used cautiously in EGS patients with colon or rectal anastomoses. Future randomized trials should validate the effects of perioperative NSAIDs use on AF. LEVEL OF EVIDENCE: Therapeutic study, level III.

Stapled versus hand-sewn: A prospective emergency surgery study. An American Association for the Surgery of Trauma multi-institutional study.

BACKGROUND: Data from the trauma patient population suggests handsewn (HS) anastomoses are superior to stapled (ST). A recent retrospective study in emergency general surgery (EGS) patients had similar findings. The aim of the current study was to evaluate HS and ST anastomoses in EGS patients undergoing urgent/emergent operations. METHODS: The study was sponsored by the American Association for the Surgery of Trauma Multi-Institutional Studies Committee. Patients undergoing urgent/emergent bowel resection for EGS pathology were prospectively enrolled from July 22, 2013 to December 31, 2015. Patients were grouped by HS/ST anastomoses, and variables were collected. The primary outcome was anastomotic failure. Similar to other studies, anastomotic failure was evaluated at the anastomosis level. Multivariable logistic regression was performed controlling for age and risk factors for anastomotic failure. RESULTS: Fifteen institutions enrolled a total of 595 patients with 649 anastomoses (253 HS and 396 ST). Mean age was 61 years, 51% were men, 7% overall mortality. Age and sex were the same between groups. The overall anastomotic failure rate was 12.5%. The HS group had higher lactate, lower albumin, and were more likely to be on vasopressors. Hospital and intensive care unit days, as well as mortality, were greater in the HS group. Anastomotic failure rates and operative time were equivalent for HS and ST. On multivariate regression, the presence of contamination at initial resection (odds ratio, 1.965; 95% confidence interval, 1.183-3.264) and the patient being managed with open abdomen (odds ratio, 2.529; 95% confidence interval, 1.492-4.286) were independently associated with anastomotic failure, while the type of anastomosis was not. CONCLUSION: EGS patients requiring bowel resection and anastomosis are at high risk for anastomotic failure. The current study illustrates an apparent bias among acute care surgeons to perform HS techniques in higher-risk patients. Despite the individualized application of technique for differing patient populations, the risk of anastomotic failure was equivalent when comparing HS and ST anastomoses. LEVEL OF EVIDENCE: Therapeutic study, level II.

Development of a tool to assess adherence to a model of the division of responsibility in feeding young children: using response mapping to capacitate validation measures.

BACKGROUND: Accurate early assessment and targeted intervention with problematic parent/child feeding dynamics is critical for the prevention and treatment of child obesity. The division of responsibility in feeding (sDOR), articulated by the Satter Feeding Dynamics Model (fdSatter), has been demonstrated clinically as an effective approach to reduce child feeding problems, including those leading to obesity. Lack of a tested instrument to examine adherence to fdSatter stimulated initial construction of the Satter Feeding Dynamics Inventory (fdSI). The aim of this project was to refine the item pool to establish translational validity, making the fdSI suitable for advanced psychometric analysis. METHODS: Cognitive interviews (n = 80) with caregivers of varied socioeconomic strata informed revisions that demonstrated face and content validity. fdSI responses were mapped to interviews using an iterative, multi-phase thematic approach to provide an instrument ready for construct validation. RESULTS: fdSI development required five interview phases over 32 months: Foundational; Refinement; Transitional; Assurance; and Launching. Each phase was associated with item reduction and revision. Thirteen items were removed from the 38-item Foundational phase and seven were revised in the Refinement phase. Revisions, deletions, and additions prompted by Transitional and Assurance phase interviews resulted in the 15-item Launching phase fdSI. Only one Foundational phase item was carried through all development phases, emphasizing the need to test for item comprehension and interpretation before psychometric analyses. CONCLUSIONS: Psychometric studies of item pools without encrypted meanings will facilitate progress toward a tool that accurately detects adherence to sDOR. Ability to measure sDOR will facilitate focus on feeding behaviors associated with reduced risk of childhood obesity.

Evaluation of About Being Active, an online lesson about physical activity shows that perception of being physically active is higher in eating competent low-income women.

BACKGROUND: Eating competence (EC) has been associated with positive health outcomes such as reduced cardiovascular risk and higher diet quality. This study compared reported physical activity and EC in 512 low-income women participating in an online program that included a physical activity lesson and assessed response to this lesson. METHODS: Educational intervention and surveys were completed online. EC was assessed with the Satter Eating Competence Inventory for Low-Income (ecSI/LI). RESULTS: Participants were mostly white, <31 years, overweight/obese (60%), and food insecure (58%). EC was higher for those who self-reported being physically active (30.1 ± 8.3 vs. 24.9 ± 8.1; P<0.001) and were active for ≥ 30 minutes/day (29.9 ± 8.3 vs. 26.3 ± 8.6), even with age, weight satisfaction, and BMI controlled. EC of obese physically active persons was higher than normal weight, but physically inactive women. The physical activity module was well received with responses unrelated to time involved or physical activity level. CONCLUSIONS: Low-income women were interested in learning about physical activity and responded positively to online delivery. Overall EC levels were low, but higher for physically active women, supporting efforts to enhance EC. Additional research is needed to determine if EC is associated with responses to physical activity education.

A digital program informs low-income caregivers of preschool-age children about family meals.

OBJECTIVE: To evaluate the digital program, Mealtime is Family Time, as a means of educating caregivers of preschoolers on the importance of family meals within the division of feeding responsibility framework. METHODS: Descriptive design using 2 approaches: focus group program review and discussion or self-report survey after independent program review in low-income venues. All participants completed an inventory of child feeding practices. RESULTS: About 75% of feedback survey respondents (n = 147) found the program understandable, easy to read, and helpful and expressed interest in child cues of hunger and satiety. Focus group findings corroborated program utility and were congruent with need for division of feeding responsibility implementation. For example, 39% of respondents reported that children must always or often taste mealtime food. CONCLUSIONS AND IMPLICATIONS: Education about family meals and child feeding is critical; Mealtime is Family Time was well received by this low-income audience. Further development to measure practice of the division of feeding responsibility is warranted.