A scoping review examining patient experience and what matters to people experiencing homelessness when seeking healthcare.

BACKGROUND: Homelessness is associated with significant health disparities. Conventional health services often fail to address the unique needs and lived experience of homeless individuals and fail to include participatory design when planning health services. This scoping review aimed to examine areas of patient experience that are most frequently reported by people experiencing homelessness when seeking and receiving healthcare, and to identify existing surveys used to measure patient experience for this cohort. METHODS: A scoping review was undertaken reported according to the PRISMA-ScR 2020 Statement. Databases were searched on 1 December 2022: MEDLINE, EMBASE, APA PsychINFO and CINAHL. Included studies focused on people experiencing homelessness, healthcare services and patient experience, primary research, published in English from 2010. Qualitative papers and findings were extracted and synthesized against a modified framework based on the National Institute for Health and Care Excellence guidelines for care for people experiencing homelessness, the Institute of Medicine Framework and Lachman's multidimensional quality model. People with lived experience of homelessness were employed as part of the research team. RESULTS: Thirty-two studies were included. Of these, 22 were qualitative, seven quantitative and three mixed methods, from the United States of America (n = 17), United Kingdom (n = 5), Australia (n = 5) and Canada (n = 4). Health services ranged from primary healthcare to outpatient management, acute care, emergency care and hospital based healthcare. In qualitative papers, the domains of 'accessible and timely', 'person-centred', and values of 'dignity and respect' and 'kindness with compassion' were most prevalent. Among the three patient experience surveys identified, 'accessible and timely' and 'person-centred' were the most frequent domains. The least frequently highlighted domains and values were 'equitable' and 'holistic'. No questions addressed the 'safety' domain. CONCLUSIONS: The Primary Care Quality-Homeless questionnaire best reflected the priorities for healthcare provision that were highlighted in the qualitative studies of people experiencing homelessness. The most frequently cited domains and values that people experiencing homelessness expressed as important when seeking healthcare were reflected in each of the three survey tools to varying degrees. Findings suggest that the principles of 'Kindness and compassion' require further emphasis when seeking feedback on healthcare experiences and the domains of 'safety', 'equitable', and 'efficiency' are not adequately represented in existing patient experience surveys.

Red Blood Cell Membrane Fatty Acid Composition, Dietary Fatty Acid Intake and Diet Quality as Predictors of Inflammation in a Group of Australian Adults.

Evidence suggests that diet can play a role in modulating systemic inflammation. This study aims to examine the relationship between fatty acids (FAs) (self-reported dietary intake and red blood cell (RBC) membrane fatty acid concentrations), three diet quality scores, and the plasma concentrations of inflammatory markers (interleukin-6, IL-6; tumour necrosis factor alpha, TNF-α; and C-reactive protein, CRP) in a group of Australian adults (n = 92). Data were collected on their demographic characteristics, health status, supplement intake, dietary intake, RBC-FAs and plasma inflammatory markers over a nine-month period. Mixed-effects models were used to determine the relationship between RBC-FAs, dietary intake of FAs, diet quality scores and inflammatory markers to determine which variable most strongly predicted systemic inflammation. A significant association was identified between dietary saturated fat intake and TNF-α (ß = 0.01, p < 0.05). An association was also identified between RBC membrane saturated fatty acids (SFA) and CRP (ß = 0.55, p < 0.05). Inverse associations were identified between RBC membrane monounsaturated fatty acids (MUFAs) (ß = -0.88, p < 0.01), dietary polyunsaturated fatty acids (PUFAs) (ß = -0.21, p < 0.05) and CRP, and the Australian Eating Survey Modified Mediterranean Diet (AES-MED) score and IL-6 (ß = -0.21, p < 0.05). In summary, using both objective and subjective measures of fat intake and diet quality, our study has confirmed a positive association between saturated fat and inflammation, while inverse associations were observed between MUFAs, PUFAs, the Mediterranean diet, and inflammation. Our results provide further evidence that manipulating diet quality, in particular fatty acid intake, may be useful for reducing chronic systemic inflammation.

Omega-3 Fatty Acids during Pregnancy in Indigenous Australian Women of the Gomeroi Gaaynggal Cohort.

Higher dietary intakes of Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have been linked to lower rates of preterm birth and preeclampsia. The aim of this analysis was to describe dietary intake and fractions of red blood cell (RBC) membrane LC-PUFAs during pregnancy in a cohort of Indigenous Australian women. Maternal dietary intake was assessed using two validated dietary assessment tools and quantified using the AUSNUT (Australian Food and Nutrient) 2011-2013 database. Analysis from a 3-month food frequency questionnaire indicated that 83% of this cohort met national n-3 LC-PUFA recommendations, with 59% meeting alpha-linolenic acid (ALA) recommendations. No nutritional supplements used by the women contained n-3 LC-PUFAs. Over 90% of women had no detectable level of ALA in their RBC membranes, and the median Omega-3 Index was 5.5%. This analysis appears to illustrate a decline in concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) across gestation in women who had preterm birth. However, there was no visible trend in LC-PUFA fractions in women who experienced hypertension during pregnancy. Further research is needed to better understand the link between dietary intake of n-3 LC-PUFA-rich foods and the role of fatty acids in preterm birth and preeclampsia.

Preliminary Evidence that Memantine Enhances Prepulse Effects on Startle Magnitude and Latency in Patients with Alzheimer's Disease.

BACKGROUND: The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer's disease (AD); conceivably, its acute impact on PPI might be used to predict a patient's sensitivity to MEM's therapeutic effects. OBJECTIVE: To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients. METHODS: 18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency. RESULTS: Fifteen out of 18 participants exhibited reliable startle responses. MEM did not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p < 0.04; d = 0.40); this comparison reached a large effect size for the 60 ms interval (d = 0.62), where maximal MEM effects on PPI were previously detected. Prepulses reduced peak startle latency ("latency facilitation") and this effect was amplified after MEM (p = 0.03; d = 0.41; for 60 ms intervals, d = 0.69). No effects of MEM were detected on cognition, nor were MEM effects on startle associated with cognitive or clinical measures. CONCLUSION: MEM enhances prepulse effects on startle magnitude and latency in AD; these changes in PPI and latency facilitation with MEM suggest that these measures can be used to detect an AD patient's neural sensitivity to acute MEM challenge. Studies in progress will determine whether such a "biomarker" measured at the outset on treatment can predict sensitivity to MEM's therapeutic effects.

Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis.

Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with antimicrobial and immune-modulating properties. This review aimed to examine the evidence for the effect of Lf supplementation on inflammation, immune function, and respiratory tract infections (RTIs) in humans. Online databases were searched up to December 2020 to identify relevant, English-language articles that examined the effect of Lf supplementation in human subjects of all ages, on either inflammation, immune cell populations or activity, or the incidence, duration, or severity of respiratory illness or RTIs. Twenty-five studies (n = 20 studies in adults) were included, of which 8 of 13 studies (61%) in adults reported a decrease in at least 1 systemic inflammatory biomarker. Immune function improved in 6 of 8 studies (75%) in adults, with changes in immune cell populations in 2 of 6 studies (33%), and changes in immune cell activity in 2 of 5 studies (40%). RTI outcomes were reduced in 6 of 10 studies (60%) (n = 5 in adults, n = 5 in children), with decreased incidence in 3 of 9 studies (33%), and either decreased frequency (2/4, 50%) or duration (3/6, 50%) in 50% of studies. In adults, Lf reduced IL-6 [mean difference (MD): -24.9 pg/mL; 95% CI: -41.64, -8.08 pg/mL], but not C-reactive protein (CRP) [standardized mean difference: -0.09; 95% CI: -0.82, 0.65], or NK cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children (OR: 0.78; 95% CI: 0.61, 0.98) but not in adults (OR: 1.00; 95% CI: 0.76, 1.32). Clinical studies on Lf supplementation are limited, although findings show 200 mg Lf/d reduces systemic inflammation, while formulas containing 35-833 mg Lf/d may reduce RTI incidence in infants and children, suggesting improved immune function. Future research is required to determine optimal supplementation strategies and populations most likely to benefit from Lf supplementation. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232186) as CRD42021232186.

Co-occurring Fatigue and Lymphatic Pain Incrementally Aggravate Their Negative Effects on Activities of Daily Living, Emotional Distress, and Overall Health of Breast Cancer Patients.

BACKGROUND: Fatigue and lymphatic pain are the most common and debilitating long-term adverse effects of breast cancer treatment. Fatigue and pain independently have negative effects on quality of life, physical functions, and cancer recurrence-free survival. The interactions between fatigue and pain may aggravate their negative effects. OBJECTIVES: Examine the effects of co-occurring fatigue and lymphatic pain on activities of daily living (ADLs), emotional distress, and overall health of breast cancer patients. METHODS: A cross-sectional and observational design was used to enroll 354 breast cancer patients. Valid and reliable instruments were used to assess fatigue, lymphatic pain, ADLs, emotional distress, and overall health. Descriptive statistics and multivariable regression models were used for data analysis. RESULTS: After controlling for demographic and clinical factors, patients with co-occurring fatigue and lymphatic pain had higher odds of having impaired ADLs (OR = 24.43, CI = [5.44-109.67], P < .001) and emotional distress (OR = 26.52, CI = [9.64-72.90], P < .001) compared to patients with only fatigue and only lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had 179% increase in impaired ADL scores (B = 8.06, CI = [5.54-10.59]) and 211% increase in emotional distress scores (B = 9.17, CI = [5.52-12.83]) compared to those without co-occurring fatigue and lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had a 34% decrease (B = -26.29, CI = [-31.90 to -20.69]) and patients with only fatigue had a 33% decrease in overall health scores (B = -25.74, 95% CI = [-34.14 to -17.33]), indicating poor overall health. CONCLUSIONS: Fatigue and lymphatic pain affected 66.4% of breast cancer patients. Findings from this study suggest that co-occurring fatigue and lymphatic pain have negative effects on breast cancer patients' ADLs, emotional distress, and overall health. The synergistic interactions between fatigue and lymphatic pain incrementally aggravated their negative effects on ADLs and emotional distress. Findings of the study highlight the need to evaluate the underlying mechanisms for co-occurring fatigue and lymphatic pain and develop interventions that target both fatigue and lymphatic pain to improve breast cancer patients' the quality of life.

Nutrition in Asthma.

An emerging body of evidence suggests that diet plays an important role in both the development and management of asthma. The relationship between dietary intake and asthma risk has been explored in epidemiological studies, though intervention trials examining the effects of nutrient intake and dietary patterns on asthma management are scarce. Evidence for diets high in fruits and vegetables, antioxidants, omega-3 fatty acids and soluble fiber such as the Mediterranean diet is conflicting. However, some studies suggest that these diets may reduce the risk of asthma, particularly in young children, and could have positive effects on disease management. In contrast, a Westernized dietary pattern, high in saturated fatty acids, refined grains, and sugars may promote an inflammatory environment resulting in the onset of disease and worsening of asthma outcomes. This review will summarize the state of the evidence for the impact of whole dietary patterns, as well as individual nutrients, on the prevalence and management of asthma.

Pharmacological and Nonpharmacological Management of Chemotherapy-Induced Peripheral Neuropathy: A Scoping Review of Randomized Controlled Trials.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment with no effective preventative strategy or definitive treatment. Purpose: To synthesize empiric literature from randomized controlled trials (RCTs) of pharmacological and nonpharmacological management of CIPN. Data Sources: Articles published between January 1, 2010, and February 28, 2021, were identified using keywords searching Medline, PubMed, CINAHL, Web of Science, Cochrane Library, and Embase. Study Selection: RCTs that recruited individuals who were post-chemotherapy and experienced persistent CIPN symptoms. Data Extraction and Synthesis: Three independent reviewers screened a total of 2023 abstracts. After screening, full-text review, and quality appraisal, 22 articles were included in this review. Data related to study design, participant characteristics, interventions, controls, outcome measures, and relevant findings were extracted from full texts. Descriptive quantitative summaries were calculated and narrative analysis was performed. Results: Of the 22 studies, 4 investigated pharmacologic treatments, 2 compared acupuncture to pharmacologic treatments, and 16 studies examined nonpharmacologic treatments. Pharmacologic studies reported mixed results with evidence of participant response varying by history of chemotherapeutic agent. Acupuncture, exercise/physical therapy, and neurofeedback appear to be effective treatments for CIPN. Evidence regarding biophysical agents and cognitive-behavioral therapy is equivocal. Scrambler therapy is not supported. Limitations: Studies included in this review share several limitations, including widely variable outcome measures, small and demographically homogenous samples, and nonstandardized treatment protocols. Conclusion: This scoping review summarized the current body of high-quality RCTs investigating treatment for CIPN. The majority of studies in this review reports benefits of pharmacologic and nonpharmacologic interventions, although management may require a multipronged approach and should be tailored to the individual. Clinical implications are proposed and suggestions made for future research include implementation of standardized intervention protocols, use of outcome measures representative of the spectrum of CIPN symptoms, and stratification by the chemotherapeutic agent.

The Effects of Prebiotics, Synbiotics, and Short-Chain Fatty Acids on Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.

Prebiotics, synbiotics, and SCFAs have been shown to decrease systemic inflammation and play a protective role in chronic respiratory conditions. However, their effects on infection and immune function are unclear. The objective of this systematic review was to summarize the current evidence for prebiotic, synbiotic, and SCFA supplementation on respiratory tract infections (RTIs) and immune function. The protocol for this systematic review was registered with PROSPERO (National Institute for Health Research, University of York, UK), accessed online at https://www.crd.york.ac.uk/prospero (CRD42019118786). Relevant English-language articles up to May 2021 were identified via online databases: MEDLINE, EMBASE, CINAHL, and Cochrane Library. Included studies (n = 58) examined the effect of prebiotics, synbiotics, or SCFA, delivered orally, on the incidence, severity, or duration of RTIs and/or markers of immune function (e.g., peripheral blood immunophenotyping, NK cell activity). The majority of studies were randomized controlled trials reporting on RTIs in infants and children. The meta-analysis indicated that the numbers of subjects with ≥1 RTI were reduced with prebiotic (OR, 0.73; 95% CI: 0.62-0.86; P = 0.0002; n = 17) and synbiotic (OR, 0.75; 95% CI: 0.65-0.87; P = 0.0001; n = 9) supplementation compared to placebo. Further, NK cell activity was increased with synbiotic (standardized mean difference, 0.74; 95% CI: 0.42-1.06; P < 0.0001, n = 3) supplementation. This review provides evidence that prebiotic, specifically oligosaccharide, supplementation may play a protective role in RTIs in infants and children. There is less evidence for this effect in adults. Supplementation with prebiotic and synbiotic treatment may alter immune function by increasing NK cell activity, though effects on immunophenotype were less clear.

Short-chain fatty acids as anti-inflammatory agents in overweight and obesity: a systematic review and meta-analysis.

CONTEXT: Short-chain fatty acids (SCFAs) derived from microbial fermentation of prebiotic soluble fibers are noted for their anti-inflammatory benefits against obese systemic inflammation. OBJECTIVE: A systematic review and meta-analysis were undertaken to investigate the effect of SCFAs and prebiotic interventions on systemic inflammation in obesity. DATA SOURCES: Relevant studies from 1947 to August 2019 were collected from the Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. STUDY SELECTION: Of 61 included studies, 29 were of humans and 32 of animals. DATA EXTRACTION: Methodological quality of studies was assessed using the critical appraisal checklist of the Academy of Nutrition and Dietetics. Data pertaining to population, intervention type and duration, and markers of systemic inflammation were extracted from included studies. RESULTS: Of 29 included human studies, 3 of 4 SCFA interventions and 11 of 25 prebiotic interventions resulted in a significant decrease in ≥1 biomarker of systemic inflammation. Of 32 included animal studies, 10 of 11 SCFA interventions and 18 of 21 prebiotic interventions resulted in a significant reduction of ≥1 biomarker of systemic inflammation. Meta-analysis revealed that prebiotics in humans reduced levels of plasma high-sensitivity C-reactive protein (standard mean difference [SMD], -0.83; 95%CI: -1.56 to -0.11; I2: 86%; P = 0.02) and plasma lipopolysaccharide (SMD, -1.20; 95%CI: -1.89 to -0.51; I2: 87%; P = 0.0006), and reduced TNF-α levels in animals (SMD, -0.63; 95%CI: -1.19 to -0.07; P = 0.03). Heterogeneity among supplement types, duration, and dose across studies was significant. CONCLUSION: Evidence from this review and meta-analysis supports the use of SCFAs and prebiotics as novel aids in treatment of obese systemic inflammation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020148529.

Exploring Factors Associated With Long-Term Opioid Therapy in Cancer Survivors: An Integrative Review.

CONTEXT: The prevalence of chronic pain in cancer survivors is double that of the general U.S. POPULATION: Opioids have been the foundation of cancer pain management for decades; however, there is a paucity of literature on long-term opioid therapy (LTOT) in cancer survivors. An understanding of factors related to LTOT use in cancer survivors is needed to address chronic pain and balance opioid harms in the expanding population of cancer survivors. OBJECTIVES: To analyze the research of LTOT utilization and factors associated with persistent opioid use in cancer survivors. METHODS: A five-stage integrative review process was adapted from Whittemore and Knafl. Data sources searched included Web of Science, PubMed, Embase, Cochrane, and Google Scholar. Quantitative research studies from 2010 to present related to cancer survivors managed on LTOT were included. Editorials, reviews, or abstracts were excluded. RESULTS: After reviewing 315 articles, 21 articles were included. We found that there were several definitions of LTOT in the reviewed studies, but the duration of opioid use (i.e., more than three months after completion of curative treatment) was the most common. The reviewed literature describes a relationship between LTOT and important biopsychosocial factors (cancer type, socioeconomic factors, and comorbidities). CONCLUSION: The studies in this review shed light on the factors associated with LTOT in cancer survivors. LTOT was common in certain populations of cancer survivors and those with a collection of patient-specific characteristics. This review suggests that there is a critical need for specialized research on chronic cancer pain and opioid safety in cancer survivors.

Effects of fish oil and curcumin supplementation on cerebrovascular function in older adults: A randomized controlled trial.

BACKGROUND AND AIMS: Chronic conditions such as obesity, which contribute to endothelial dysfunction in older adults, can cause impairments in cerebrovascular perfusion, which is associated with accelerated cognitive decline. Supplementing the diet with bioactive nutrients that can enhance endothelial function, such as fish oil or curcumin, may help to counteract cerebrovascular dysfunction. METHODS AND RESULTS: A 16-week double-blind, randomized placebo-controlled trial was undertaken in 152 older sedentary overweight/obese adults (50-80 years, body mass index: 25-40 kg/m2) to investigate effects of fish oil (2000 mg docosahexaenoic acid + 400 mg eicosapentaenoic acid/day), curcumin (160 mg/day) or a combination of both on cerebrovascular function (measured by Transcranial Doppler ultrasound), systemic vascular function (blood pressure, heart rate and arterial compliance) and cardiometabolic (fasting glucose and blood lipids) and inflammatory (C-reactive protein) biomarkers. The primary outcome, cerebrovascular responsiveness to hypercapnia, was not affected by the interventions. However, cerebral artery stiffness was significantly reduced in males following fish oil supplementation (P = 0.007). Furthermore, fish oil reduced heart rate (P = 0.038) and serum triglycerides (P = 0.006) and increased HDL cholesterol (P = 0.002). Curcumin did not significantly affect these outcomes either alone or in combination with fish oil. CONCLUSION: Regular supplementation with fish oil but not curcumin improved biomarkers of cardiovascular and cerebrovascular function. The combined supplementation did not result in additional benefits. Further studies are warranted to identify an efficacious curcumin dose and to characterize (in terms of sex, BMI, cardiovascular and metabolic risk factors) populations whose cerebrovascular and cognitive functions might benefit from either intervention. CLINICAL TRIAL REGISTRATION: ACTRN12616000732482p.

An exploratory randomized sub-study of light-to-moderate intensity exercise on cognitive function, depression symptoms and inflammation in older adults with heart failure.

OBJECTIVE: Almost half of patients with heart failure (HF) have cognitive impairment. While exercise relates to better cognitive health, a hallmark of HF is exercise intolerance. The study objective was to explore whether light-to-moderate exercise improves cognitive function in patients with HF. METHODS: This was an exploratory parallel design study of 69 patients with symptomatic HF (mean age = 65, SD = 10), recruited from VA and University of California, San Diego Healthcare Systems. Participants were randomized to Tai Chi (TC) (n = 24), resistance band (RB) exercise (n = 22) or treatment as usual (TAU) (n = 23). The primary outcome was change in Montreal Cognitive Assessment (MoCA) scores. We further explored if changes in Beck Depression Inventory - IA (BDI-IA) scores or inflammation biomarkers, CRP, TNFα and IL-6 related to altered cognitive function. RESULTS: There was a fixed effect of group for MoCA scores changes (F = 8.07, p = .001). TC and RB groups had greater MoCA score increases versus TAU, but no differences were found between TC and RB. Depression symptom changes predicted altered MoCA scores (ΔR2 = 0.15, Β = -0.413, p = .001). However, group did not interact with depression symptom levels for MoCA alterations (p = .392). Changes in CRP levels predicted MoCA scores (ΔR2 = 0.078, Β = -0.283, p = .01), but group did not interact with CRP levels for MoCA alterations (p = .689). CONCLUSIONS: Light-to-moderate exercises, TC and RB may improve cognitive function. However, the mechanisms remain unclear. ClinicalTrials.gov: NCT01625819.

Soluble fibre supplementation with and without a probiotic in adults with asthma: A 7-day randomised, double blind, three way cross-over trial.

BACKGROUND: Soluble fibre modulates airway inflammation in animal models. The aim of this study was to investigate the effects of soluble fibre supplementation, with and without a probiotic, on plasma short chain fatty acids (SCFA), airway inflammation, asthma control and gut microbiome in adults with asthma. METHODS: A randomised, double-blinded, placebo controlled 3-way cross-over trial in 17 subjects with stable asthma at the Hunter Medical Research Institute, Newcastle, Australia. Subjects received 3 × 7 day oral interventions in random order; soluble fibre (inulin 12 g/day), soluble fibre + probiotic (inulin 12 g/day + multi-strain probiotic >25 billion CFU) and placebo. Plasma SCFA, sputum cell counts and inflammatory gene expression, asthma control gut microbiota, adverse events including gastrointestinal symptoms were measured. FINDINGS: There was no difference in change in total plasma SCFA levels (µmol/L) in the placebo versus soluble fibre (Δmedian [95% CI] 16·3 [-16·9, 49·5], p = 0·335) or soluble fibre+probiotic (18·7 [-14·5, 51·9], p = 0·325) group. Following the soluble fibre intervention there was an improvement in the asthma control questionnaire (ACQ6) (∆median (IQR) -0·35 (-0·5, -0·13), p = 0·006), sputum %eosinophils decreased (-1.0 (-2·5, 0), p = 0·006) and sputum histone deacetylase 9 (HDAC9) gene expression decreased (-0.49 (-0.83, -0.27) 2-ΔCt, p = .008). Individual bacterial operational taxonomic units changed following both inulin and inulin+probiotic arms. INTERPRETATION: Soluble fibre supplementation for 7 days in adults with asthma did not change SCFA levels. Within group analysis showed improvements in airway inflammation, asthma control and gut microbiome composition following inulin supplementation and these changes warrant further investigation, in order to evaluate the potential of soluble fibre as a non-pharmacological addition to asthma management. FUND: John Hunter Hospital Charitable Trust.

Higher Omega-3 Index Is Associated with Better Asthma Control and Lower Medication Dose: A Cross-Sectional Study.

Asthma is a chronic inflammatory airway disease, associated with systemic inflammation. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have established anti-inflammatory effects, thus having potential as an adjunct therapy in asthma. This study aimed to compare erythrocyte n-3 PUFA in adults with (n = 255) and without (n = 137) asthma and determine the relationship between erythrocyte n-3 PUFA and clinical asthma outcomes. Subjects had blood collected, lung function measured and Juniper Asthma Control Questionnaire (ACQ) score calculated. Fatty acids were measured in erythrocyte membranes by gas chromatography, and the omega-3 index (O3I) was calculated (% eicosapentaenoic acid + % docosahexaenoic acid). O3I was similar in subjects with and without asthma (p = 0.089). A higher O3I was observed in subjects with controlled or partially controlled asthma (ACQ < 1.5) compared to subjects with uncontrolled asthma (ACQ ≥ 1.5) (6.0% (5.4-7.2) versus 5.6% (4.6-6.4) p = 0.033). Subjects with a high O3I (≥8%) had a lower maintenance dose of inhaled corticosteroids (ICS) compared to those with a low O3I (<8%) (1000 µg (400-1000) versus 1000 µg (500-2000) p = 0.019). This study demonstrates that a higher O3I is associated with better asthma control and with lower ICS dose, suggesting that a higher erythrocyte n-3 PUFA level may have a role in asthma management.

"In Their Own Voice"-Incorporating Underlying Social Determinants into Aboriginal Health Promotion Programs.

Despite growing acknowledgement of the socially determined nature of health disparities among Aboriginal people, how to respond to this within health promotion programs can be challenging. The legacy of Australia's assimilation policies have left profound consequences, including social marginalisation, limited educational opportunities, normalisation of premature death, and entrenched trauma. These social determinants, in conjunction with a reluctance to trust authorities, create barriers to accessing healthcare services for the prevention, treatment, and rehabilitation of chronic disease. The Heart Health program is a culturally sensitive cardiac rehabilitation program run at the local Aboriginal Medical Service in Perth, Western Australia that has since moved beyond cardiac education to provide a holistic approach to chronic disease management. A participatory action research framework was used to explore Heart Health participant and service provider perspectives on the barriers, enablers, and critical success factors to program participation and behaviour change. Thematic analysis of interview transcripts was undertaken, and through yarning (Aboriginal storytelling) sessions, many participants made unprompted reference to the impacts of white settlement, discrimination, and the forced fracturing of Aboriginal families, which have been explored in this paper reiterating the need for a social determinants lens to be taken when planning and implementing Aboriginal health promotion programs.

Fatigue Is Associated With Global and Regional Thalamic Morphometry in Veterans With a History of Mild Traumatic Brain Injury.

OBJECTIVE: Fatigue is a complex, multidimensional phenomenon that commonly occurs following traumatic brain injury (TBI). The thalamus-a structure vulnerable to both primary and secondary injuries in TBI-is thought to play a pivotal role in the manifestation of fatigue. We explored how neuroimaging markers of local and global thalamic morphometry relate to the subjective experience of fatigue post-TBI. METHODS: Sixty-three Veterans with a history of mild TBI underwent structural magnetic resonance imaging and completed questionnaires related to fatigue and psychiatric symptoms. FMRIB's Software (FSL) was utilized to obtain whole brain and thalamic volume estimates, as well as to perform regional thalamic morphometry analyses. RESULTS: Independent of age, sex, intracranial volume, posttraumatic stress disorder, and depressive symptoms, greater levels of self-reported fatigue were significantly associated with decreased right (P = .026) and left (P = .046) thalamic volumes. Regional morphometry analyses revealed that fatigue was significantly associated with reductions in the anterior and dorsomedial aspects of the right thalamic body (P < .05). Similar trends were observed for the left thalamic body (P < .10). CONCLUSIONS: Both global and regional thalamic morphometric changes are associated with the subjective experience of fatigue in Veterans with a history of mild TBI. These findings support a theory in which disruption of thalamocorticostriatal circuitry may result in the manifestation of fatigue in individuals with a history of neurotrauma.

Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells.

Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [ω-6 polyunsaturated fatty acids (PUFAs) and ω-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-α, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-α challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-α alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-α challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-κB) nor by hyperactivation of NF-κB or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ω-6 PUFAs might promote airway inflammation via multiple pathways, including COX-dependent and -independent pathways, and in an obese person, may lead to more severe airway inflammation.

Dexamethasone exacerbates cytotoxic chemotherapy induced lethargy and weight loss in female tumor free mice.

Cytotoxic chemotherapy can induce a systemic inflammatory response which has been proposed to be an underlying mechanism of cancer treatment related fatigue. Dexamethasone, a synthetic glucocorticoid that has potent anti-inflammatory effects, is incorporated into chemotherapy regimens to prevent chemotherapy-induced nausea and vomiting (CINV). The purpose of this study was to determine whether by suppressing cytotoxic chemotherapy-induced inflammation, dexamethasone could ameliorate chemotherapy induced fatigue/lethargy in tumor free mice. The effect of dexamethasone (DEX) on Cytoxan-Adriamycin (CA)-induced inflammation was assessed by measuring circulating levels of IL-1ß, TNF-α, IL-6, GCSF, KC, and MCP-1 twenty-four-hours post CA injection. Decline in voluntary wheel running activity (VWRA) from baseline (used as a proxy for fatigue/lethargy), body weight and composition, and food intake were monitored in mice administered four cycles of CA every two weeks with or without DEX. CA increased circulating levels of IL-6, GCSF, KC, and MCP-1 and caused a rapid decline in VWRA and body weight immediately following CA-injection. Although the acute CA-induced decline in VWRA and body weight was not evident in mice administered CA + DEX, DEX alone had a suppressive effect on VWRA, and body weight continued to decline in mice administered both CA and DEX while it returned to baseline in CA-treated mice. CA or DEX alone had no long term impact on VWRA but DEX exacerbated lethargy and weight loss in CA-treated mice. Despite dampening the systemic inflammatory response to chemotherapy, dexamethasone failed to ameliorate acute or long term chemotherapy related fatigue/lethargy. Our pre-clinical findings suggest that supportive therapies like dexamethasone used to acutely control nausea and vomiting in cancer patients may actually contribute to overall symptom burden in cancer patients.

Short-chain fatty acids, prebiotics, synbiotics, and systemic inflammation: a systematic review and meta-analysis.

BACKGROUND: Prebiotic soluble fibers are fermented by beneficial bacteria in the colon to produce short-chain fatty acids (SCFAs), which are proposed to have systemic anti-inflammatory effects. OBJECTIVE: This review examines the effect of SCFAs, prebiotics, and pre- and probiotic combinations (synbiotics) on systemic inflammation. DESIGN: Relevant English language studies from 1947 to May 2017 were identified with the use of online databases. Studies were considered eligible if they examined the effects of SCFAs, prebiotics, or synbiotics; were delivered orally, intravenously, or per rectum; were on biomarkers of systemic inflammation in humans; and performed meta-analysis where possible. RESULTS: Sixty-eight studies were included. Fourteen of 29 prebiotic studies and 13 of 26 synbiotic studies reported a significant decrease in ≥1 marker of systemic inflammation. Eight studies compared prebiotic and synbiotic supplementation, 2 of which reported a decrease in inflammation with synbiotics only, with 1 reporting a greater anti-inflammatory effect with synbiotics than with prebiotics alone. Meta-analyses indicated that prebiotics reduce C-reactive protein (CRP) [standardized mean difference (SMD): -0.60; 95% CI: -0.98, -0.23], and synbiotics reduce CRP (SMD: -0.40; 95% CI: -0.73, -0.06) and tumor necrosis factor-α (SMD -0.90; 95% CI: -1.50, -0.30). CONCLUSIONS: There is significant heterogeneity of outcomes in studies examining the effect of prebiotics and synbiotics on systemic inflammation. Approximately 50% of included studies reported a decrease in ≥1 inflammatory biomarker. The inconsistency in reported outcomes may be due to heterogeneity in study design, supplement formulation, dosage, duration, and subject population. Nonetheless, meta-analyses provide evidence to support the systemic anti-inflammatory effects of prebiotic and synbiotic supplementation.