Increased hepatoprotective effects of the novel farnesoid X receptor agonist INT-787 versus obeticholic acid in a mouse model of nonalcoholic steatohepatitis.

The nuclear farnesoid X receptor (FXR), a master regulator of bile acid and metabolic homeostasis, is a key target for treatment of nonalcoholic steatohepatitis (NASH). This study compared efficacy of FXR agonists obeticholic acid (OCA) and INT-787 by liver histopathology, plasma biomarkers of liver damage, and hepatic gene expression profiles in the Amylin liver NASH (AMLN) diet-induced and biopsy-confirmed Lepob/ob mouse model of NASH. Lepob/ob mice were fed the AMLN diet for 12 weeks before liver biopsy and subsequent treatment with vehicle, OCA, or INT-787 for 8 weeks. Hepatic steatosis, inflammation, and fibrosis (liver lipids, galectin-3, and collagen 1a1 [Col1a1], respectively), as well as plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, were assessed. Hepatic gene expression was assessed in Lepob/ob mice that were fed the AMLN diet for 14 weeks then treated with vehicle, OCA, or INT-787 for 2 weeks. INT-787, which is equipotent to OCA but more hydrophilic, significantly reduced liver lipids, galectin-3, and Col1a1 compared with vehicle, and to a greater extent than OCA. INT-787 significantly reduced plasma ALT and AST levels, whereas OCA did not. INT-787 modulated a substantially greater number of genes associated with FXR signaling, lipid metabolism, and stellate cell activation relative to OCA in hepatic tissue. These findings demonstrate greater efficacy of INT-787 treatment compared with OCA in improving liver histopathology, decreasing liver enzyme levels, and enhancing gene regulation, suggesting superior clinical potential of INT-787 for the treatment of NASH and other chronic liver diseases.

Safety, pharmacokinetics and pharmacodynamics of obeticholic acid in subjects with fibrosis or cirrhosis from NASH.

BACKGROUND & AIMS: Fibrosis stage is a strong predictor of nonalcoholic steatohepatitis (NASH) outcomes. Two blinded studies evaluated the pharmacokinetics, pharmacodynamics and safety of obeticholic acid (OCA) in subjects with staged NASH fibrosis or cirrhosis. METHODS: Study 747-117 randomized 51 subjects with NASH (fibrosis stages F1-F4) to daily placebo, OCA 10 or OCA 25 mg (1:2:2) for 85 days. Study 747-118 randomized 24 subjects with NASH cirrhosis (F4; Child-Pugh [CP]-A) and normal liver control subjects matched for similar body weight to daily OCA 10 or OCA 25 mg (1:1) for 28 days. Individual and combined study data were analysed. RESULTS: No severe or serious adverse events (AEs) or AEs leading to discontinuation or death occurred. Pruritus was the most frequent AE. Plasma OCA exposure (dose-normalized area under the curve) increased with fibrosis stage but was a relatively poor predictor of hepatic OCA exposure (primary site of action), which remained constant across fibrosis stages F1-F3 and increased 1.8-fold compared with F1 in subjects with cirrhosis due to NASH. Both cohorts showed robust changes in farnesoid X receptor activation markers with OCA treatment and marked decreases in alanine transaminase, aspartate transaminase and gamma-glutamyltransferase. CONCLUSIONS: Despite higher drug exposures in subjects with NASH cirrhosis, short-term daily treatment with OCA 10 or 25 mg was generally safe and well tolerated in subjects with NASH fibrosis or NASH CP-A cirrhosis. Both cohorts experienced improvements in nonhistologic pharmacodynamic markers consistent with previously conducted OCA phase 2 and phase 3 studies in NASH fibrosis.

An integrated analysis of fecal microbiome and metabolomic features distinguish non-cirrhotic NASH from healthy control populations.

BACKGROUND AND AIMS: There is great interest in identifying microbiome features as reliable noninvasive diagnostic and/or prognostic biomarkers for non-cirrhotic NASH fibrosis. Several cross-sectional studies have reported gut microbiome features associated with advanced NASH fibrosis and cirrhosis, where the most prominent features are associated with cirrhosis. However, no large, prospectively collected data exist establishing microbiome features that discern non-cirrhotic NASH fibrosis, integrate the fecal metabolome as disease biomarkers, and are unconfounded by BMI and age. APPROACH AND RESULTS: Results from shotgun metagenomic sequencing performed on fecal samples prospectively collected from 279 US patients with biopsy-proven NASH (F1-F3 fibrosis) enrolled in the REGENERATE I303 study were compared to those from 3 healthy control cohorts and integrated with the absolute quantification of fecal bile acids. Microbiota beta-diversity was different, and BMI- and age-adjusted logistic regression identified 12 NASH-associated species. Random forest prediction models resulted in an AUC of 0.75-0.81 in a receiver operator characteristic analysis. In addition, specific fecal bile acids were significantly lower in NASH and correlated with plasma C4 levels. Microbial gene abundance analysis revealed 127 genes increased in controls, many involving protein synthesis, whereas 362 genes were increased in NASH many involving bacterial environmental responses (false discovery rate < 0.01). Finally, we provide evidence that fecal bile acid levels may be a better discriminator of non-cirrhotic NASH versus health than either plasma bile acids or gut microbiome features. CONCLUSIONS: These results may have value as a set of baseline characteristics of non-cirrhotic NASH against which therapeutic interventions to prevent cirrhosis can be compared and microbiome-based diagnostic biomarkers identified.

Maternal immune activation accelerates puberty initiation and alters mechanical allodynia in male and female C57BL6/J mice.

The mechanisms that link maternal immune activation (MIA) with the onset of neurodevelopmental disorders remain largely unclear. Accelerated puberty is also associated with a heightened risk for psychopathology in later life, but there is a dearth of evidence on the impacts of maternal infection on pubertal timing. We examined the effects of MIA on reproductive development, mechanical allodynia, and sensorimotor gating in juvenile, adolescent, and adult male and female mice. Moreover, we investigated hypothalamic neural markers associated with the reproductive and stress axes. Finally, we tested the mitigating effects of environmental enrichment (EE), which has clinical relevancy in human rehabilitation settings. Our results show that administration of polyinosinic-polycytidylic acid (poly(I:C)) on gestational day 12.5 led to early preputial separation, vaginal openings, and age of first estrus in offspring. MIA exposure altered pain sensitivity across development and modestly altered prepulse inhibition. The downregulation of Nr3c1 and Oprk mRNA in the hypothalamus of juvenile mice suggests that MIA's effects may be mediated through disruption of hypothalamic-pituitary-adrenal axis activity. In contrast, life-long housing with EE rescued many of these MIA-induced consequences. Overall, our findings suggest that accelerated puberty may be associated with the deleterious effects of infection during pregnancy and the onset of psychopathology.

Poly (I:C)-induced maternal immune activation modifies ventral hippocampal regulation of stress reactivity: prevention by environmental enrichment.

Environmental enrichment (EE) has been successfully implemented in human rehabilitation settings. However, the mechanisms underlying its success are not understood. Incorporating components of EE protocols into our animal models allows for the exploration of these mechanisms and their role in mitigation. Using a mouse model of maternal immune activation (MIA), the present study explored disruptions in social behavior and associated hypothalamic pituitary adrenal (HPA) axis functioning, and whether a supportive environment could prevent these effects. We show that prenatal immune activation of toll-like receptor 3, by the viral mimetic polyinosinic-polycytidylic acid (poly(I:C)), led to disrupted maternal care in that dams built poorer quality nests, an effect corrected by EE housing. Standard housed male and female MIA mice engaged in higher rates of repetitive rearing and had lower levels of social interaction, alongside sex-specific expression of several ventral hippocampal neural stress markers. Moreover, MIA males had delayed recovery of plasma corticosterone in response to a novel social encounter. Enrichment housing, likely mediated by improved maternal care, protected against these MIA-induced effects. We also evaluated c-Fos immunoreactivity associated with the novel social experience and found MIA to decrease neural activation in the dentate gyrus. Activation in the hypothalamus was blunted in EE housed animals, suggesting that the putative circuits modulating social behaviors may be different between standard and complex housing environments. These data demonstrate that augmentation of the environment supports parental care and offspring safety/security, which can offset effects of early health adversity by buffering HPA axis dysregulation. Our findings provide further evidence for the viability of EE interventions in maternal and pediatric settings.

Contemplative pedagogy as a framework for education about ageism.

Current education in gerontology focuses on sharing knowledge and promoting intergenerational contact in order to shift students' attitudes about aging and elders. Existing interventions, however, may be less effective in modifying students' emotional reactions and implicit ageism. Contemplative pedagogy includes practices that help students notice cognitive and emotional patterns and that may serve to reduce bias. Suggestions are made for ways to incorporate contemplative pedagogy in the gerontology classroom.

Obeticholic acid improves hepatic bile acid excretion in patients with primary biliary cholangitis.

BACKGROUND & AIMS: Obeticholic acid (OCA) is an agonist of the nuclear bile acid receptor farnesoid X receptor, which regulates hepatic bile acid metabolism. We tested whether OCA treatment would influence hepatic transport of conjugated bile acids in patients with primary biliary cholangitis (PBC) who responded inadequately to treatment with ursodeoxycholic acid (UDCA). METHODS: Eight UDCA-treated patients with PBC with alkaline phosphatase ≥1.5 times the upper limit of normal range participated in a double-blind, placebo-controlled study. While continuing on UDCA, the patients were randomised to two 3-month crossover treatment periods with placebo and OCA, in random order, separated by a 1-month washout period without study treatment. After each of the two treatment periods, we determined rate constants for transport of conjugated bile acids between blood, hepatocytes, biliary canaliculi, and bile ducts by positron emission tomography of the liver using the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar). The hepatic blood perfusion was measured using infusion of indocyanine green and Fick's principle. RESULTS: Compared with placebo, OCA increased hepatic blood perfusion by a median of 11% (p = 0.045), the unidirectional uptake clearance of 11C-CSar from blood into hepatocytes by a median of 11% (p = 0.01), and the rate constant for secretion of 11C-CSar from hepatocytes into biliary canaliculi by a median of 73% (p = 0.03). This resulted in an OCA-induced decrease in the hepatocyte residence time of 11C-CSar by a median of 30% (p = 0.01), from group median 11 min to 8 min. CONCLUSIONS: This study of UDCA-treated patients with PBC showed that, compared with placebo, OCA increased the hepatic transport of the conjugated bile acid tracer 11C-CSar, and thus endogenous conjugated bile acids, from hepatocytes into biliary canaliculi. As a result, OCA reduced the time hepatocytes are exposed to potentially cytotoxic bile acids. LAY SUMMARY: Primary biliary cholangitis is a chronic liver disease in which the small bile ducts are progressively destroyed. We tested whether the treatment with obeticholic acid (OCA) would improve liver excretion of bile acids compared with placebo in 8 patients with primary biliary cholangitis. A special scanning technique (PET scan) showed that OCA increased the transport of bile acids from blood to bile. OCA thereby reduced the time that potentially toxic bile acids reside in the liver by approximately one-third.

Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsy-confirmed NASH.

BACKGROUND: Compounds in clinical development for nonalcoholic steatohepatitis (NASH) improve liver histopathology in diet-induced obese mouse models of biopsy-confirmed NASH. Since the biopsy section used for histopathological evaluation represents only < 1% of the whole mouse liver, we evaluated how well biopsy-based quantitative image analyses correlate to stereology-based whole-liver quantitative changes upon drug treatment. METHODS: Male leptin-deficient Lepob/Lepob mice were fed the Amylin liver NASH (AMLN) diet for 16 weeks before stratification into treatment groups using a biopsy-based evaluation of type I collagen αI (col1a1) levels. Mice were treated for 8 weeks with either vehicle (PO, QD), liraglutide (0.4 mg/kg, SC, QD), elafibranor (30 mg/kg, PO, QD) or INT-767 (10 mg/kg, PO, QD). Terminal quantitative histological assessment of liver lipid (hematoxylin-eosin staining), inflammation (galectin-3 immunohistochemistry (IHC); gal-3), and fibrosis (col1a1 IHC) was performed on terminal liver biopsies and compared with stereologically sampled serial sections spanning the medial, left and right lateral lobe of the liver. RESULTS: The distribution of liver lipid and fibrosis was markedly consistent across lobes, whereas inflammation showed some variability. While INT-767 and liraglutide significantly reduced total liver weight by 20 and 48%, respectively, elafibranor tended to exacerbate hepatomegaly in Lepob/Lepob-NASH mice. All three compounds markedly reduced biopsy-based relative liver lipid content. Elafibranor and INT-767 significantly reduced biopsy-based relative gal-3 levels (P < 0.001), whereas INT-767 and liraglutide tended to reduce relative col1a1 levels. When changes in liver weight was accounted for, both INT-767 and liraglutide significantly reduced biopsy-based total col1a1 content. Although minor differences in absolute and relative liver lipid, inflammation and fibrosis levels were observed across lobes, the interpretation of drug-induced effects were consistent with biopsy-based conclusions. Notably, the incorporation of changes in total liver mass revealed that liraglutide's efficacy reached statistical significances for all analyzed parameters. CONCLUSIONS: In conclusion, in-depth analyses of liver homogeneity demonstrated that drug-induced improvement in liver biopsy-assessed histopathology is representative for overall liver effects assessed using stereology. Importantly, these findings reveal how changes in whole-liver mass should be considered to provide a deeper understanding of apparent drug treatment efficacy in preclinical NASH studies.

Poultry in the classroom: effectiveness of an online poultry-science-based education program for high school STEM instruction.

Public knowledge of the poultry industry is limited, yet attitudes towards the industry shape consumer behavior and influence the attractiveness of poultry careers and future study. This study assessed an online learning program contextualizing STEM learning within poultry science which was designed to increase poultry knowledge and interest. High school student participants (n = 169) across 16 classes (n = 12 teachers) in Indiana completed seven 30-min online modules during the fall 2018 semester. This case study used a mixed-methods, sequential explanatory design. Student knowledge and interest in poultry and teacher perceptions of the program were examined using quantitative measures. The study's qualitative portion assessed perceptions of the learning experience and comprised open-ended student and teacher survey questions and a teacher focus group. Qualitative data suggested that students' poultry knowledge, including awareness of the industry and related careers, was improved following the modules. Paired t-tests showed moderate to large effect sizes regarding increases in content quiz scores following each module (P < 0.001, Cohen's d = 0.45 to 0.80). Students' mean interest in poultry was initially low and remained statistically similar upon completion of the program (M = 1.84, 1.87; p = 0.67). Student and teacher statements indicated that design features of the program enhanced interest for some students. Other students did not perceive the program and its poultry science topics to be interesting or relevant to their lives. Results from this study can be used to inform the creation of effective poultry learning resources to contribute to workforce development and enhance the industry's public image.

Meeting the needs of children with medical complexity using a telehealth advanced practice registered nurse care coordination model.

Effective care coordination is a key quality and safety strategy for populations with chronic conditions, including children with medical complexity (CMC). However, gaps remain in parent report of the need for care coordination help and receipt of care coordination help. New models must close this gap while maintaining family-centered focus. A three-armed randomized controlled trial conducted in an established medical home utilized an advanced practice registered nurse intervention based on Presler's model of clinic-based care coordination. The model supported families of CMC across settings using telephone only or telephone and video telehealth care coordination. Effectiveness was evaluated from many perspectives and this paper reports on a subset of outcomes that includes family-centered care (FCC), need for care coordination help and adequacy of care coordination help received. FCC at baseline and end of study showed no significant difference between groups. Median FCC scores of 18.0-20.0 across all groups indicated high FCC within the medical home. No significant differences were found in the need for care coordination help within or between groups and over time. No significant difference was found in the adequacy of help received between groups at baseline. However, this indicator increased significantly over time for both intervention groups. These findings suggest that in an established medical home with high levels of FCC, families of CMC have unmet needs for care coordination help that are addressed by the APRN telehealth care coordination model.

Care coordination for children with complex special health care needs: the value of the advanced practice nurse's enhanced scope of knowledge and practice.

Efficiency and effectiveness of care coordination depends on a match between the needs of the population and the skills, scope of practice, and intensity of services provided by the care coordinator. Existing literature that addresses the relevance of the advanced practice nurse (APN) role as a fit for coordination of care for children with special health care needs (SHCN) is limited. The objective of this article is to describe the value of the APN's enhanced scope of knowledge and practice for relationship-based care coordination in health care homes that serve children with complex SHCN. The TeleFamilies project is provided as an example of the integration of an APN care coordinator in a health care home for children with SHCN.

Meaningful use of data in care coordination by the advanced practice RN: the TeleFamilies project.

Meaningful use of electronic health records to coordinate care requires skillful synthesis and integration of subjective and objective data by practitioners to provide context for information. This is particularly relevant in the coordination of care for children with complex special healthcare needs. The purpose of this article is to present a conceptual framework and example of meaningful use within an innovative telenursing intervention to coordinate care for children with complex special healthcare needs. The TeleFamilies intervention engages an advanced practice nurse in a full-time care coordinator role within an existing hospital-based medical home for children with complex special healthcare needs. Care coordination is facilitated by the synthesis and integration of internal and external data using an enhanced electronic health record and telehealth encounters via telephone and videoconferencing between the advanced practice nurse and the family at home. The advanced practice nurse's ability to maintain an updated plan of care that is shared across providers and systems and build a relationship over time with the patient and family supports meaningful use of these data.

Rehabilitation programs for musculoskeletal injuries in military personnel.

PURPOSE OF REVIEW: The purpose of this review is to summarize current trends and rehabilitation programs for musculoskeletal injuries in military personnel returning from deployment. RECENT FINDINGS: Musculoskeletal injuries (MSIs) are the leading healthcare problem for military members. Risk factors include participation in sports, carrying heavy loads, older age, female sex, standing for long periods of time, and walking long distances. MSIs may lead to medical discharge from the military. Physical and occupational therapists work at the Combat Support Hospitals to provide rehabilitation care to injured personnel and reduce recovery time by 60% and costs by 123%. The Army Medical Department has developed initiatives to decrease the burden of MSI: musculoskeletal screening and referral tools to assist military medical providers in managing patients with MSI; Pain Management Task Force to optimize care for wounded soldiers; Musculoskeletal Action Plan for injury prevention, early diagnosis and management, and rehabilitation/reintegration following injury; and Musculoskeletal Action Teams to work with military recruits who make up the largest subgroup in the Army with the highest incidence of MSIs. SUMMARY: The US Military is aware of the inherent risks for MSI associated with military training and repeated combat deployments. Rehabilitation efforts have been developed to address the problem.

Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice.

These preclinical studies aimed to 1) increase our understanding the dietary induction of nonalcoholic steatohepatitis (NASH), and, 2) further explore the utility and mechanisms of glucagon-like peptide-1 receptor (GLP-1R) agonism in NASH. We compared the effects of a high trans-fat (HTF) or high lard fat (HLF) diet on key facets of nonalcoholic fatty liver disease (NAFLD)/NASH in Lep(ob)/Lep(ob) and C57BL6J (B6) mice. Although HLF-fed mice experienced overall greater gains in weight and adiposity, the addition of trans-fat better mirrored pathophysiological features of NASH (e.g., hepatomegaly, hepatic lipid, and fibrosis). Administration of AC3174, an exenatide analog, and GLP-1R agonist to Lep(ob)/Lep(ob) and B6 ameliorated hepatic endpoints in both dietary models. Next, we assessed whether AC3174-mediated improvements in diet-induced NASH were solely due to weight loss in HTF-fed mice. AC3174-treatment significantly reduced body weight (8.3%), liver mass (14.2%), liver lipid (12.9%), plasma alanine aminotransferase, and triglycerides, whereas a calorie-restricted, weight-matched group demonstrated only modest nonsignificant reductions in liver mass (9%) and liver lipid (5.1%) relative to controls. Treatment of GLP-1R-deficient (GLP-1RKO) mice with AC3174 had no effect on body weight, adiposity, liver or plasma indices pointing to the GLP-1R-dependence of AC3174's effects. Interestingly, the role of endogenous GLP-1Rs in NASH merits further exploration as the GLP-1RKO model was protected from the deleterious hepatic effects of HTF. Our pharmacological data further support the clinical evaluation of the utility of GLP-1R agonists for treatment of NASH.

GLP-1R and amylin agonism in metabolic disease: complementary mechanisms and future opportunities.

The discoveries of the incretin hormone glucagon-like peptide-1 (GLP-1) and the ß-cell hormone amylin have translated into hormone-based therapies for diabetes. Both classes of molecules also exhibit weight-lowering effects and have been investigated for their anti-obesity potential. In the present review, we explore the mechanisms underlying the physiological and pharmacological actions of GLP-1 and amylin agonism. Despite their similarities (e.g. both molecular classes slow gastric emptying, decrease glucagon and inhibit food intake), there are important distinctions between the central and/or peripheral pathways that mediate their effects on glycaemia and energy balance. We suggest that understanding the similarities and differences between these molecules holds important implications for the development of novel, combination-based therapies, which are increasingly the norm for diabetes/metabolic disease. Finally, the future of GLP-1- and amylin agonist-based therapeutics is discussed.

Risk factors for dating violence among adolescent females presenting to the pediatric emergency department.

BACKGROUND: Intimate partner violence (IPV) among the adolescent population is an increasing concern. This study was designed to assess the prevalence, associated risk factors, and best ways to identify IPV among teens presenting to a pediatric emergency room. METHODS: This prospective, convenience study was conducted in a busy, pediatric emergency department. Young women, aged 15 years to 21 years, presenting with any chief complaint were enrolled. Adolescents completed a verbally assisted survey, and responses were recorded. Surveys consisted of three sections: demographic information, an eight-item date violence screening tool, and a risk factor assessment tool. Teens who screened positive for IPV were offered immediate social services assistance. Analysis was performed to compare youth risk factors between young women who were screened positive and negative for IPV. All eight of the date violence screening questions were reviewed to analyze whether a set of questions were consistently positive in all the teens who were screened. RESULTS: A total of 246 of 270 (91%) approached were enrolled. The prevalence of IPV was 36.6%. Many of the risk-taking behaviors assessed correlated with dating violence. The most significant included having tried alcohol (odds ratio [OR], 2.4; confidence interval [CI], 1.3-4.4), having ridden in a car with a partner who was doing drugs (OR, 2.4; CI, 1.1-5.0) or alcohol (OR, 2.5; CI, 1.0-6.3), fighting with peers (OR, 3.5; CI, 1.6-7.8), and history of sexually transmitted disease (OR, 2.2; CI, 1.2-4.2). Four questions were identified that detected 99% of positive screens for adolescent dating violence. CONCLUSIONS: IPV among female adolescents presenting to a pediatric emergency department is high. Certain risk-taking behaviors are correlated with adolescent dating violence. Four specific questions, if asked in this setting, can capture teens at risk.

Intergenerational service learning with elders: multidisciplinary activities and outcomes.

This article provides an overview of the activities included in a 3-year, multidisciplinary, intergenerational service-learning project conducted as part of a Foundation for Long-Term Care Service Learning: Linking Three Generations grant. Courses from four departments (gerontology, psychology, occupational therapy, and health promotion and physical education) and one interdisciplinary clinical intervention for stroke patients (speech pathology, occupational therapy, and therapeutic recreation) were involved. Service-learning activities were embedded in course curricula and varied from semester-long activities in group settings to activities involving one-on-one contact for several hours. In total, eight faculty and 225 students worked with 148 elders and 12 different community organizations to plan and implement activities for 357 older adults. Students and elders reported a high degree of satisfaction with the intergenerational activities and indicated that they learned from them and found them of value personally.

Sensitivity of the pediatric early warning score to identify patient deterioration.

OBJECTIVE: We evaluated the Pediatric Early Warning Score (PEWS) sensitivity as an early indicator of patients deterioration leading to a Rapid Response Team (RRT)/code event. We hypothesized that at least 80% of patients had a critical PEWS preceding the event. We determined staff awareness of deterioration in patient status prior to the event as evidenced by consults, addition of monitoring equipment or increased frequency of assessment. The timing of these events was compared to critical PEWS times. METHODS: One hundred and seventy non-ICU RRT and 16 code events were identified between October 2006 and February 2008. We completed retrospective PEWS at four-hour intervals or less for twenty-four hours preceding the event. The PEWS algorithm, guiding staff to consult at a critical score > or =4 or a single domain score equal to 3, was applied. RESULTS: For 85.5% of patients the earliest indicator of deterioration, evidenced by a critical PEWS, was a median of 11 hours 36 minutes and the earliest preceding the event was 30 minutes. For 97.1% of patients the earliest median time to a consult was 80 minutes. Oximetry was added 6.9 hours for 43.5% of patients. 7% of patients had increased nursing assessment. A sub-group of patients had 1) critical PEWS, 2) consult and 3) addition of a monitor. The median time for earliest critical PEWS for these was significant (P < 0.001). CONCLUSION: PEWS can potentially provide a forewarning time >11 hours, alerting the team to adapt the care plan and possibly averting an RRT or code.

Occupational therapy for service members with mild traumatic brain injury.

More occupational therapists are needed to provide client-centered, evidence-based rehabilitation to the large numbers of service members who sustained mild traumatic brain injury (mTBI) while deployed in Afghanistan and Iraq. The Proponency for Rehabilitation and Reintegration tasked a team of occupational and physical therapists to assemble evidence-based best practices specific to mTBI. Despite the fact that evidence-based reviews, guidelines, and research regarding occupational therapy for mTBI are sparse, the team developed the Clinical Practice Guidance: Occupational Therapy and Physical Therapy for Mild Traumatic Brain Injury. Occupational therapy practice recommendations specific to client education, vision, cognition, resumption of roles, and emotional well-being are summarized for civilians and characterized as practice standards or practice options. By using evidence-informed and holistic services, occupational therapists have the potential to lead rehabilitation and reintegration efforts for service members with mTBI and advance changes in the profession itself.

Dose-response relationship between moderate-intensity exercise duration and coronary heart disease risk factors in postmenopausal women.

PURPOSE: This study was designed to investigate whether, in a dose-response manner, there would be greater health benefits in a group of postmenopausal women completing 45 minute- vs. 30 minutes of moderate intensity (50% maximal oxygen uptake reserve, VO2R) exercise 5 days . wk(-1). METHODS: Apparently healthy but sedentary postmenopausal women (n = 33) were randomized to a nonexercise control group, a 30-minute exercise duration group, or a 45-minute exercise duration group. Exercise training was performed 5 days . wk(-1) for 12 weeks at 50% VO2R. Participants were instructed to not change their usual diet throughout the study. RESULTS: Twenty-six women completed the study. After 12 weeks, VO2max increased significantly (p < 0.05) in both 30-minute (0.20 +/- 0.21 L . min(-1)) and 45-minute (0.41 +/- 0.10 L . min(-1)) groups. Repeated measures ANOVA identified a significant interaction between exercise duration and VO2max values (F = 4.72, p < 0.05), indicating that VO2max responded differently to 30-minute and 45-minute exercise durations. Trend analysis showed that body mass, body composition, waist circumference, and high-density lipoprotein cholesterol (HDL-C) changed favorably (p < 0.05) across control, 30-minute, and 45-minute groups. CONCLUSIONS: Although most health organizations agree that 150 min . wk(-1) of physical activity will reduce the risk of all-cause and cardiovascular mortality, few randomized, controlled studies have examined whether completing more physical activity than the recommended amount will yield additional benefits. Findings from the present study suggest that there is a dose-response relationship between exercise duration and numerous health outcomes in postmenopausal women, including cardiorespiratory fitness, body mass, body composition, waist circumference, and HDL-C.