Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation.

Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.

The emergence of inflammatory microglia during gut inflammation is not affected by FFAR2 expression in intestinal epithelial cells or peripheral myeloid cells.

Gut inflammation can trigger neuroinflammation and is linked to mood disorders. Microbiota-derived short-chain fatty acids (SCFAs) can modulate microglia, yet the mechanism remains elusive. Since microglia do not express free-fatty acid receptor (FFAR)2, but intestinal epithelial cells (IEC) and peripheral myeloid cells do, we hypothesized that SCFA-mediated FFAR2 activation within the gut or peripheral myeloid cells may impact microglia inflammation. To test this hypothesis, we developed a tamoxifen-inducible conditional knockout mouse model targeting FFAR2 exclusively on IEC and induced intestinal inflammation with dextran sodium sulfate (DSS), a well-established colitis model. Given FFAR2's high expression in myeloid cells, we also investigated its role by selectively deleting it in these populations of cells. In an initial study, male and female wild-type mice received 0 or 2% DSS for 5d and microglia were isolated 3d later to assess inflammatory status. DSS induced intestinal inflammation and upregulated inflammatory gene expression in microglia, indicating inflammatory signaling via the gut-brain axis. Despite the lack of significant effects of sex in the intestinal phenotype, male mice showed higher microglial inflammatory response than females. Subsequent studies using FFAR2 knockout models revealed that FFAR2 expression in IECs or immune myeloid cells did not affect DSS-induced colonic pathology (i.e. clinical and histological scores and colon length), or colonic expression of inflammatory genes. However, FFAR2 knockout led to an upregulation of several microglial inflammatory genes in control mice and downregulation in DSS-treated mice, suggesting that FFAR2 may constrain neuroinflammatory gene expression under healthy homeostatic conditions but may permit it during intestinal inflammation. No interactions with sex were observed, suggesting sex does not play a role on FFAR2 potential function in gut-brain communication in the context of colitis. To evaluate the role of FFAR2 activated by microbiota-derived SCFAs, we employed the same knockout and DSS models adding fermentable dietary fiber (0 or 2.5% inulin for 8 wks). Despite no genotype or fiber main effects, contrary to our hypothesis, inulin feeding augmented DSS-induced inflammation and signs of colitis, suggesting context-dependent effects of fiber. These findings highlight microglial involvement in colitis-associated neuroinflammation and advance our understanding of FFAR2's role in the gut-brain axis. Although not integral, we observed that the role of FFAR2 differs between homeostatic and inflammatory conditions, underscoring the need to consider different inflammatory conditions and disease contexts when investigating the role of FFAR2 and SCFAs in the gut-brain axis.

Clinical Utility and Impact of Phosphatidylethanol Testing in Liver Transplantation Evaluations.

BACKGROUND: Phosphatidylethanol (PEth) is a serum biomarker that can detect alcohol use within the last 28 days with excellent sensitivity and specificity. Urinary ethyl glucuronide (uEtG) is commonly used in transplant settings to screen for alcohol use; however, it has several limitations relevant to liver transplantation. Transplant centers are beginning to regularly utilize PEth as part of the screening process for high-risk liver transplantation candidates although the clinical utility of uniform pre-transplant PEth testing is unclear. METHODS: This was a retrospective chart review of all patients evaluated for liver transplantation from December 1, 2019, through May 31, 2022, at a large academic tertiary referral center utilizing uniform serum PEth and uEtG screening. Information regarding the patients' transplantation status, age, sex, race, Model for End-Stage Liver Disease score, and PEth levels was obtained. In those with a positive PEth, we examined if the result would have been detected with uEtG, identified a discrepancy from the documented patient report of last use, led to a change in the Psychosocial Assessment of Candidate for Transplantation score, or influenced the transplant selection committee's decision. RESULTS: Our sample included 865 individuals (mean age = 55.20, 61.27% male and 82.54% white) with calculated Model for End-Stage Liver Disease-Sodium scores ranging from 6.43 to 50.65 (mean: 18.09; median: 16.46). Forty-eight patients were found to have a positive PEth (PEth range 20-1833); 75% of the sample had alcohol-associated liver disease. In 23 of 48 (47.91%) cases, the positive PEth identified alcohol use missed by a concomitant uEtG screen. A positive PEth test identified a discrepancy from patients' self-report in 29 (60.42%) cases and influenced the selection committee's decision in 28 cases (58.33%). CONCLUSION: Uniform pretransplant PEth screening of liver transplant candidates at the time of initial evaluation identified alcohol use that would have been missed by uEtG testing, identified discrepancies from the patient's self-report, and influenced clinical decision-making in a significant number of cases. These findings support the use of uniform PEth screening in liver transplantation evaluations.

Complementary and alternative medicine for long COVID: a systematic review of randomized controlled trials.

Background: Complementary and alternative medicine (CAM) interventions are growing in popularity as possible treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking. Objective: This study aims to review existing published studies on the use of CAM interventions for patients experiencing long COVID through a systematic review. Design: Systematic review of randomized controlled trials (RCTs). Methods: A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of CAM for long COVID were included. Methodological quality of each included trial was appraised with the Cochrane 'risk of bias' tool. A qualitative analysis was conducted due to heterogeneity of included studies. Results: A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that CAM interventions could benefit patients with long COVID, especially those suffering from neuropsychiatric disorders, olfactory dysfunction, cognitive impairment, fatigue, breathlessness, and mild-to-moderate lung fibrosis. The main interventions reported were self-administered transcutaneous auricular vagus nerve stimulation, neuro-meditation, dietary supplements, olfactory training, aromatherapy, inspiratory muscle training, concurrent training, and an online breathing and well-being program. Conclusion: CAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.

Applying Kern's Model to the Development and Evaluation of Medical Student Well-Being Programs.

The Liaison Committee on Medical Education (LCME) requires that well-being programs must be "effective." Yet most medical schools do not robustly assess their well-being programs. Most evaluate their programs using one question on the Association of American Medical College's annual Graduation Questionnaire (AAMC GQ) survey for fourth-year students on their satisfaction with well-being programs, which is inadequate and nonspecific and only assesses a specific time in training. In this perspective, we, as members of the AAMC Group on Student Affairs (GSA) - Committee on Student Affairs (COSA) Working Group on Medical Student Well-being, suggest adapting Kern's 6-step approach to curriculum development as an effective framework to guide the development and evaluation of well-being programs. We suggest strategies for applying Kern's steps to well-being programs, with attention to conducting needs assessments, identifying goals, implementation, and evaluation and feedback. While each institution will have unique goals emerging from their needs assessment, we put forth five common medical student well-being goals as examples. Applying a rigorous and structured approach to developing and evaluating undergraduate medical education well-being programs will involve defining a guiding philosophy and clear goals and implementing a strong assessment strategy. This Kern-based framework can help schools meaningfully assess the impact of their initiatives on student well-being.

Effects of an inulin fiber diet on the gut microbiome, colon, and inflammatory biomarkers in aged mice.

Due to the increasing human life expectancy and limited supply of healthcare resources, strategies to promote healthy aging and reduce associated functional deficits are of public health importance. The gut microbiota, which remodels with age, has been identified as a significant contributor to the aging process that is modifiable by diet. Since prebiotic dietary components such as inulin have been shown to impart positive benefits with regards to aging, this study used C57Bl6 mice to investigate whether 8 weeks on a 2.5 % inulin enhanced AIN-93M 1 % cellulose diet could offset age-associated changes in gut microbiome composition and markers of colon health and systemic inflammation in comparison to a AIN 93M 1 % cellulose diet with 0 % inulin. Our results demonstrated that, in both age groups, dietary inulin significantly increased production of butyrate in the cecum and induced changes in the community structure of the gut microbiome but did not significantly affect systemic inflammation or other markers of gastrointestinal health. Aged mice had different and less diverse microbiomes when compared to adult mice and were less sensitive to inulin-induced microbiome community shifts, evidenced by longitudinal differences in differentially abundant taxa and beta diversity. In aged mice, inulin restored potentially beneficial taxa including Bifidobacterium and key butyrate producing genera (e.g. Faecalibaculum). Despite inducing notable taxonomic changes, however, the 2.5 % inulin diet reduced alpha diversity in both age groups and failed to reduce overall community compositional differences between age groups. In conclusion, a 2.5 % inulin enhanced diet altered gut microbiome α and ß diversity, composition, and butyrate production in both adult and aged mice, with more potent effects on ß diversity and greater number of taxa significantly altered in adult mice. However, significant benefits in age-associated changes in systemic inflammation or intestinal outcomes were not detected.

Efficacy and safety of Tuina for chronic nonspecific low back pain: A PRISMA-compliant systematic review and meta-analysis.

OBJECTIVE: Chronic nonspecific low back pain (CNLBP) is a serious medical and social problem resulting in functional decline and decreased work ability. Tuina, a form of manual therapy, has been sparsely used to treat patients with CNLBP. To systematically assess the efficacy and safety of Tuina for patients with CNLBP. METHODS: Multiple English and Chinese literature databases were searched until September 2022 for randomized controlled trials (RCTs) of Tuina in the treatment of CNLBP. The methodological quality was assessed using the Cochrane Collaboration's tool, and certainty of the evidence was determined with the online Grading of Recommendations, Assessment, Development and Evaluation tool. RESULTS: Fifteen RCTs with 1390 patients were included. Tuina demonstrated a significant effect on pain (SMD: -0.82; 95% CI -1.12 to -0.53; P < .001; I2 = 81%) and physical function (SMD: -0.91; 95% CI -1.55 to -0.27; P = .005; I2 = 90%) when compared to control. However, Tuina resulted in no significant improvement for quality of life (QoL) (SMD: 0.58; 95% CI -0.04 to 1.21; P = .07; I2 = 73%;) compared to control. The Grading of Recommendations, Assessment, Development and Evaluation evidence quality was determined to be low level for pain relief, physical function, and QoL measurements. Only six studies reported adverse events; none were serious. CONCLUSION: Tuina might be an effective and safe strategy for treating CNLBP in terms of pain and physical function, but not for QoL. The study results should be interpreted with caution for their low-level evidence. More multicenter, large-scale RCTs with a rigorous design are required to further confirm our findings.

Exercise training modifies xenometabolites in gut and circulation of lean and obese adults.

Regular, moderate exercise modifies the gut microbiome and contributes to human metabolic and immune health. The microbiome may exert influence on host physiology through the microbial production and modification of metabolites (xenometabolites); however, this has not been extensively explored. We hypothesized that 6 weeks of supervised, aerobic exercise 3×/week (60%-75% heart rate reserve [HRR], 30-60 min) in previously sedentary, lean (n = 14) and obese (n = 10) adults would modify both the fecal and serum xenometabolome. Serum and fecal samples were collected pre- and post-6 week intervention and analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Linear mixed models (LMMs) identified multiple fecal and serum xenometabolites responsive to exercise training. Further cluster and pathway analysis revealed that the most prominent xenometabolic shifts occurred within aromatic amino acid (ArAA) metabolic pathways. Fecal and serum ArAA derivatives correlated with body composition (lean mass), markers of insulin sensitivity (insulin, HOMA-IR) and cardiorespiratory fitness ( V ̇ O 2 max $$ \dot{\mathrm{V}}{\mathrm{O}}_{2\max } $$ ), both at baseline and in response to exercise training. Two serum aromatic microbial-derived amino acid metabolites that were upregulated following the exercise intervention, indole-3-lactic acid (ILA: fold change: 1.2, FDR p < 0.05) and 4-hydroxyphenyllactic acid (4-HPLA: fold change: 1.3, FDR p < 0.05), share metabolic pathways within the microbiota and were associated with body composition and markers of insulin sensitivity at baseline and in response to training. These data provide evidence of physiologically relevant shifts in microbial metabolism that occur in response to exercise training, and reinforce the view that host metabolic health influences gut microbiota population and function. Future studies should consider the microbiome and xenometabolome when investigating the health benefits of exercise.

Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids.

Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly by signaling through the gut-brain axis or directly by reaching the brain. The present work evaluated the anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated microglia from mice fed inulin, a soluble fiber that is fermented by intestinal microbiota to produce SCFAs in vivo, and SCFAs applied to primary microglia in vitro. Feeding mice inulin increased SCFAs in the cecum and in plasma collected from the hepatic portal vein. Microglia isolated from mice fed inulin and stimulated with LPS in vitro secreted less tumor necrosis factor α (TNF-α) compared to microglia from mice not given inulin. Additionally, when mice were fed inulin and injected i.p with LPS, the ex vivo secretion of TNF-α by isolated microglia was lower than that secreted by microglia from mice not fed inulin and injected with LPS. Similarly, in vitro treatment of primary microglia with acetate and butyrate either alone or in combination downregulated microglia cytokine production with the effects being additive. SCFAs reduced histone deacetylase activity and nuclear factor-κB nuclear translocation after LPS treatment in vitro. Whereas microglia expression of SCFA receptors Ffar2 or Ffar3 was not detected by single-cell RNA sequencing analysis, the SCFA transporters Mct1 and Mct4 were. Nevertheless, inhibiting monocarboxylate transporters on primary microglia did not interfere with the anti-inflammatory effects of SCFAs, suggesting that if SCFAs produced in the gut regulate microglia directly it is likely through an epigenetic mechanism following diffusion.

Improving stroke clinical guideline adherence in an Australian hospital using a clinician-led implementation process.

BACKGROUND: Private hospitals in Australia manage 11% of acute and 48% of rehabilitation stroke admissions, yet little is known about implementation of stroke clinical guidelines in this setting. Clinical guidelines recommend that acute stroke patients be co-located in a stroke unit in a geographically defined area, rather than dispersed across the hospital. OBJECTIVE: To investigate post-intervention adherence to clinical guidelines for stroke management, and to explore staff barriers and facilitators to guideline implementation. METHODS: Observational study before-and-after local implementation of Australian stroke clinical guidelines. The primary outcome was a change in the proportion of patients who were physically co-located in an acute stroke unit. Secondary outcomes included changes in adherence to additional acute and rehabilitation guideline criteria, and staff identification of barriers and facilitators to guide implementation. Data were collected from medical record audits, health service information and staff surveys. RESULTS: Co-location in an acute stroke unit did not change significantly after guideline implementation (49% adherence pre-intervention and 54% post-intervention). Across acute and rehabilitation wards, 15% (11/72) of guideline criteria improved (p < .05). These related to assessments of swallowing and neglect, presence of a stroke care co-ordinator and occupational therapist, post-discharge care plan, provision of patient education and return to driving. Facilitators to guideline implementation included staff education, collaboration, and dissemination of user-friendly stroke policies. CONCLUSION: Stroke clinical guideline implementation led to a favorable uptake of some criteria, yet not all. Implementation was assisted by staff education, user-friendly stroke policies and multidisciplinary team collaboration. TRIAL REGISTRATION: ANZCTR: registration number ACTRN12616000646448 (http://www.ANZCTR.org.au/ACTRN12616000646448.aspx).

Effects of Broad-Spectrum Antibiotic Treatment or Germ-Free Status on Endurance Performance and Exercise Adaptations in Mice.

PURPOSE: Endurance exercise alters the gut microbiome independently of diet. The extent to which gut microbes are responsible for physiologic adaptations to exercise training is unknown. The purpose of these experiments was to determine the role of gut microbes in performance and muscle adaptation to 6 wk of voluntary wheel running (VWR) in mice. METHODS: We depleted microbes with broad-spectrum antibiotic (ABX) treatment and used germ-free (GF) mice to determine effects on adaptations to VWR. Male and female C57Bl/6 mice ( n = 56) were assigned to daily VWR or sedentary conditions. After the intervention, treadmill endurance and glucose tolerance were assessed, and gastrocnemius and soleus tissues were harvested and analyzed for citrate synthase (CS) enzyme activity and expression of exercise training-sensitive genes. RESULTS: ABX treatment and GF status resulted in VWR volumes ~22% and 26% lower than controls, respectively. Analysis of variance revealed that, although VWR increased treadmill endurance, ABX had no effect. GF status significantly reduced treadmill performance in trained GF mice after training. VWR increased gastrocnemius CS enzyme activity in all groups, and ABX and GF status did not reduce the VWR effect. VWR also increased muscle expression of PGC1a, but this was not affected by ABX treatment. CONCLUSIONS: ABX treatment and GF status reduced VWR behavior but did not affect VWR-induced adaptations in endurance capacity, CS activity, or expression of muscle metabolic genes. However, GF status reduced endurance capacity. These data indicated that reducing microbes in adulthood does not inhibit endurance training adaptations in C57Bl/6 mice, but that GF mice possess a reduced responsiveness to endurance exercise training, perhaps because of a developmental defect associated with lack of microbes from birth.

Patient experiences of codesigned rehabilitation interventions in hospitals: a rapid review.

BACKGROUND: Codesign strengthens partnerships between healthcare workers and patients. It also facilitates collaborations supporting the development, design and delivery of healthcare services. Prior rehabilitation reviews have focused mainly on the clinical and organisational outcomes of codesign with less focus on the lived experience of rehabilitation patients. OBJECTIVE: To explore patient experiences of codesigned hospital rehabilitation interventions. DESIGN: Rapid review and evidence synthesis of the literature. DATA SOURCES: CINAHL, MEDLINE, Embase and Cochrane were searched from 1 January 2000 to 25 April 2022. STUDY SELECTION: Studies reporting patient experiences of codesigned rehabilitation interventions in hospitals. RESULTS: 4156 studies were screened, and 38 full-text studies were assessed for eligibility. Seven studies were included in the final rapid review. Five out of the seven studies involved neurological rehabilitation. All eligible studies used qualitative research methods. The main barriers to codesign were related to staffing and dedicated time allocated to face-to-face patient-therapist interactions. High-quality relationships between patients and their therapists were a facilitator of codesign. Thematic synthesis revealed that codesigned rehabilitation interventions can enable a meaningful experience for patients and facilitate tailoring of treatments to align with individual needs. Personalised rehabilitation increases patient involvement in rehabilitation planning, delivery and decision-making. It also promotes positive feelings of empowerment and hope. CONCLUSION: This rapid review supports the implementation of codesigned rehabilitation interventions to improve patient experiences in hospitals. PROSPERO REGISTRATION NUMBER: CRD42021264547.

Implementing PROMS for elective surgery patients: feasibility, response rate, degree of recovery and patient acceptability.

BACKGROUND: Patient reported outcome measures (PROMs) engage patients in co-evaluation of their health and wellbeing outcomes. This study aimed to determine the feasibility, response rate, degree of recovery and patient acceptability of a PROM survey for elective surgery. METHODS: We sampled patients with a broad range of elective surgeries from four major Australian hospitals to evaluate (1) feasibility of the technology used to implement the PROMs across geographically dispersed sites, (2) response rates for automated short message service (SMS) versus email survey delivery formats, (3) the degree of recovery at one and four weeks post-surgery as measured by the Quality of Recovery 15 Item PROM (QoR-15), and (4) patient acceptability of PROMS based on survey and focus group results. Feasibility and acceptability recommendations were then co-designed with stakeholders, based on the data. RESULTS: Over three months there were 5985 surveys responses from 20,052 surveys (30% response rate). Feasibility testing revealed minor and infrequent technical difficulties in automated email and SMS administration of PROMs prior to surgery. The response rate for the QoR-15 was 34.8% (n = 3108/8919) for SMS and 25.8% (n = 2877/11,133) for email. Mean QoR-15 scores were 122.1 (SD 25.2; n = 1021); 113.1 (SD 27.7; n = 1906) and 123.4 (SD 26.84; n = 1051) for pre-surgery and one and four weeks post-surgery, respectively. One week after surgery, 825 of the 1906 responses (43%) exceeded 122.6 (pre-surgery average), and at four weeks post-surgery, 676 of the 1051 responses (64%) exceeded 122.6 (pre-surgery average). The PROM survey was highly acceptable with 76% (n = 2830/3739) of patients rating 8/10 or above for acceptability. Fourteen patient driven recommendations were then co-developed. CONCLUSION: Administering PROMS electronically for elective surgery hospital patients was feasible, acceptable and discriminated changes in surgical recovery over time. Patient co-design and involvement provided innovative and practical solutions to implementation and new recommendations for implementation. Trial Registration and Ethical Approval ACTRN12621000298819 (Phase I and II) and ACTRN12621000969864 (Phase III). Ethics approval has been obtained from La Trobe University (Australia) Human Research Ethics Committee (HEC20479). KEY POINTS: Patient reported outcome measures (PROMs) help to engage patients in understanding their health and wellbeing outcomes. This study aimed to determine how patients feel about completing a PROM survey before and after elective surgery, and to develop a set of recommendations on how to roll out the survey, based on patient feedback. We found that implementing an electronic PROM survey before and after elective surgery was relatively easy to do and was well accepted by patients. Consumer feedback throughout the project enabled co-design of innovative and practical solutions to PROM survey administration.

Development of the ‘AusPROM’ recommendations for elective surgery patients.

Objective Implementing the routine collection of patient reported outcome measures (PROMs) is key to improving healthcare quality and patient satisfaction. The implementation process can be strengthened through staff and patient co-design. The aim of this project was to develop a set of Australian PROM implementation recommendations ('AusPROM') to guide rapid translation into practice. Methods Staff working across 29 Australian private hospitals participated in the project. The hospitals provided elective surgery and spanned each state and territory of Australia. Staff engaged in a Delphi technique to develop the AusPROM, which involved three iterative focus groups. To ensure full disclosure, staff were also provided with additional project-related data sources throughout the Delphi technique. This included data from a patient focus group (patient co-design), patient survey, technical feasibility testing, 3 months of pilot testing (four sites), 3 months of national implementation (29 sites) and global evidence. This process ensured that staff and patient feedback was used to co-design the three iterations of the AusPROM recommendations until the final agreed version was established. Results A total of 22 AusPROM recommendations were included in the final iteration. The recommendations covered the domains of PROM characteristics, healthcare organisation characteristics, external influences, staff and patient characteristics, and facilitators to implementing AusPROMS in routine practice. Conclusion The AusPROM recommendations offer practical considerations for the implementation of PROMs in hospitals. The iterative nature of the Delphi technique ensured that staff and patient co-design were central to the development of the AusPROM recommendations.

Patient Judgement of Change with Elective Surgery Correlates with Patient Reported Outcomes and Quality of Life.

Obtaining pre-surgery PROM measures is not always feasible. The aim of this study was to examine if self-reports of change following elective surgery correlate with change scores from a validated PROM (15-item Quality of Recovery (QoR-15)). This cross-sectional study across 29 hospitals enrolled elective surgery patients. PROMs were collected one-week pre-surgery, as well as one- and four-weeks post-surgery via an electronic survey. We examined associations between patient "judgement of change" at one and four-weeks after surgery and the actual pre-to post-surgery PROM change scores. A total of 4177 surveys were received. The correlation between patient judgement of change, and the actual change score was moderately strong at one-week (n = 247, rs = 0.512, p < 0.001), yet low at four-weeks (n = 241, rs = 0.340, p < 0.001). Patient judgement was aligned to the direction of the PROM change score from pre- to post-surgery. We also examined the correlation between the QoR-15 (quality of recovery) and the EQ-5D-5L (QOL). There was a moderately strong positive correlation between the two PROMs (n = 356, rs = 0.666, p < 0.001), indicating that change in quality of recovery was related to change in QOL. These findings support the use of a single "judgement of change" recall question post-surgery.

Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction.

With increasing age, microglia shift toward a pro-inflammatory phenotype that may predispose individuals to neurodegenerative disease. Because fiber fermentation in the colon produces bioactive short-chain fatty acids (SCFAs; e.g., acetate, butyrate, and propionate) that signal through the gut-brain axis, increasing dietary fiber may prevent or reverse age-related dysregulation of microglia. Adult (3-4 months old) and aged (23-24 months old) male and female mice were given ad libitum access to a modified AIN-93M diet with 1% cellulose or the same diet with 2.5 or 5.0% inulin for 8 weeks. Several adult and aged male mice fed 0 or 5% inulin were randomly selected for whole brain single-cell RNA sequencing (scRNA-seq) and differential gene expression analysis to classify brain microglia according to gene expression profile; and identify additional genetic markers of aging as possible targets for dietary interventions. Microglia were isolated from remaining mice and expression of selected aging-, inflammatory-, and sensome-related genes was assessed by Fluidigm as was the ex vivo secretion of tumor necrosis factor-alpha (TNF-α). SCFAs were measured in samples collected from the cecum. Microglia from adult and aged mice segregated into distinct phenotypes according to their gene expression profile. In aged mice, a considerably greater proportion of the population of microglia was identified being "activated" and a considerably smaller proportion was identified being "quiescent." These findings using whole brain scRNA-seq were largely corroborated using highly purified microglia and Fluidigm analysis to assess a selected panel of genes. Aged mice compared to adults had lower levels of SCFA's in cecum. Dietary inulin increased SCFAs in cecum and mostly restored microglial cell gene expression and TNF-α secretion to that seen in adults. Sex differences were observed with females having lower levels of SCFAs in cecum and increased neuroinflammation. Overall, these data support the use of fiber supplementation as a strategy to counterbalance the age-related microglial dysregulation.

Patient experiences of co-designed rehabilitation interventions: protocol for a rapid review.

INTRODUCTION: Patient-centred care can be facilitated by co-design, which refers to collaboration between healthcare professionals and consumers in producing and implementing healthcare. Systematic reviews on co-design have mainly focused on the effectiveness of co-produced healthcare interventions. Less attention has been directed towards the experiences of patients in co-designed interventions. This rapid review aims to explore patient experiences of co-designed rehabilitation interventions and inform rehabilitation decision-making. METHODS AND ANALYSIS: A rapid review will expedite timely information on co-design experiences for stakeholders. Four electronic databases, including Cochrane CENTRAL, MEDLINE, Embase and CINAHL, will be searched for papers published from 1 January 2000 to 1 January 2022. The Cochrane Risk of Bias tool will be used for randomised trials. Critical appraisal checklists from The Joanna Briggs Institute shall evaluate the risk of bias of non-randomised trials and qualitative studies. A narrative synthesis will be provided for the quantitative studies. Thematic synthesis will be conducted on qualitative findings. The overall strength of the evidence will be measured using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for quantitative investigations and the GRADE-Confidence in Evidence from Reviews of Qualitative Research for qualitative studies. The results will be presented using narrative summaries, identified themes, summary tables, flow charts and quantitative statistical analyses. ETHICS AND DISSEMINATION: Ethics approval is not required for the review. The protocol and rapid review will be submitted to an online, open access and peer-reviewed journal for publication. The review findings will be rapidly translated to consumers, clinicians, healthcare leaders, organisations, researchers and policy makers via publications, evidence summaries, conferences, workshops, websites, social media and online events. PROSPERO REGISTRATION NUMBER: CRD42021264547.

The Effect of Deployment on Pulmonary Function in Military Personnel With Asthma.

INTRODUCTION: Military personnel with a diagnosis of asthma report increased respiratory symptoms in the deployment and post-deployment periods. The long-term effect of deployment on pulmonary function in this population is unknown. This study sought to determine the effect of deployment on post-deployment pulmonary function in active duty military personnel with asthma. MATERIALS AND METHODS: A retrospective chart review of active duty military personnel with deployment to southwest Asia and an ICD-9 diagnosis of asthma with documented pre- and post-deployment spirometry was performed. RESULTS: A total of 642 active duty individuals with a diagnosis of asthma and documented spirometry with deployment to southwest Asia between 2006 and 2015 were identified. Of these, 76 individuals were identified with pre- and post-deployment spirometry. There was no significant change in the post-deployment forced expiratory volume at 1 second (% predicted), from 86.0 ± 14.8 to 87.6 ± 14.4 (P = .30). There was no significant change in post-deployment forced vital capacity (% predicted), from 93.8 ± 12.4 to 94.9 ± 12.1 (P = .42). The absolute change in forced expiratory volume at 1 second (L) after bronchodilator administration was decreased from pre-deployment to post-deployment (+0.31 ± 0.26 to +0.16 ± 0.23; P = .02). CONCLUSIONS: There was no significant post-deployment change in spirometry in this military population with asthma deployed to southwest Asia. These findings suggest that deployment itself is not associated with any short-term deleterious effect on post-deployment spirometric measures of lung function in many military personnel with asthma.

Sources of Resilience in Frontline Health Professionals during COVID-19.

BACKGROUND: While the challenges for psychological well-being for Australian healthcare workers have been documented, there has been a dearth of qualitative research on the sources of resilience that sustained workers during the COVID-19 pandemic. This study identified sources of resilience that clinicians used to cope with frontline challenges during the COVID-19 pandemic. METHODS: Semi-structured interviews were conducted with 20 frontline health professionals, across five Australian hospitals, between October 2020 and April 2021. The interviews were recorded and transcribed, and the results were analysed using thematic analysis based on a phenomenological approach. RESULTS: Three sources of resilience were identified by respondents: personal, relational, and organisational. A positive mindset, sense of purpose, and self-care behaviours emerged as key sources of personal resilience. Teamwork, altruism, and social support from family and friends contributed to relational resilience. Leadership, effective communication, and effective implementation of COVID-19 policies were associated with resilience at the organisational level. Frontline healthcare workers also voiced the need for the implementation of further strategies to support personal resilience whilst nurturing resilience within clinical teams and across entire healthcare organisations. CONCLUSIONS: Trust in healthcare systems, organisation leaders, colleagues, and personal support teams was an overarching theme supporting resilience.

Protocol for implementation of the 'AusPROM' recommendations for elective surgery patients: a mixed-methods cohort study.

INTRODUCTION: Incorporating patient-reported outcome measures (PROMs) into usual care in hospitals can improve safety and quality. Gaps exist in electronic PROM (ePROM) implementation recommendations, including for elective surgery. The aims are to: (1) understand barriers and enablers to ePROM implementation in hospitals and develop Australian ePROM implementation recommendations (AusPROM); (2) test the feasibility and acceptability of the Quality of Recovery 15 item short-form (QoR-15) PROM for elective surgery patients applying the AusPROM and (3) establish if the QoR-15 PROM has concurrent validity with the EQ-5D-5L. METHODS AND ANALYSIS: Phase I will identify staff barriers and facilitators for the implementation of the AusPROM recommendations using a Delphi technique. Phase II will determine QoR-15 acceptability for elective surgery patients across four pilot hospitals, using the AusPROM recommendations. For phase II, in addition to a consumer focus group, patients will complete brief acceptability surveys, incorporating the QoR-15, in the week prior to surgery, in the week following surgery and 4 weeks postsurgery. The primary endpoint will be 4 weeks postsurgery. Phase III will be the national implementation of the AusPROM (29 hospitals) and the concurrent validity of the QoR-15 and generic EQ-5D-5L. This protocol adopts the Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trials Protocols guidelines. ETHICS AND DISSEMINATION: The results will be disseminated via public forums, conferences and peer-reviewed journals. Ethics approval: La Trobe University (HEC20479). TRIAL REGISTRATION NUMBER: ACTRN12621000298819 (Phase I and II) and ACTRN12621000969864 (Phase III).