Actus Santé

Background: Polysomnography (PSG) is the gold standard for sleep monitoring and diagnosis, yet it is difficult to use in home environments. This study evaluated the performance of a wearable electroencephalographic(EEG) device, LANMAO Sleep Recorder in EEG recording and sleep staging algorithm by comparing with PSG. Method: Sleep of 7 Chinese adults were recorded concurrently with PSG and LANMAO devices. First, we validated the consistency of the raw signals with relative spectral power and Pearson correlation coefficient. Second, we evaluated the performance of the automated sleep staging algorithm integrated in the LANMAO device by comparing with the staging by experts. Results: The Pearson correlation coefficient between the relative spectral power of multiple frequency bands during the sleep stages ranged from 0.7613 to 0.8816, with the strongest correlation observed for delta waves (r=0.8816). The overall F1-Score of the automated sleep staging algorithm was 84.03%, with individual F1-Scores for each class as follows: Wake: 93.67%, REM: 87.23%, Light Sleep: 72.10%, and Deep Sleep: 82.82%. Conclusion: The results suggest that the EEG recorded by the LANMAO Sleep Recorder is precise and valid, and its automated sleep staging algorithm can accurately perform sleep staging with high accuracy. Therefore, in specific scenarios such as the home environment, LANMAO devices can work as a promising PSG alternative for sleep monitoring. Keywords: automatic sleep staging; PSG; forehead; EEG; wearable; machine learning

Abstract: Purpose: Providing specialised training to community-based physical activity instructors (such as circus coaches) has been identified as a potential strategy to increase participation for preschool-aged children born preterm. The objective of this study was to determine the feasibility of a novel co-designed training program CirqAll: professional development for circus coaches (CirqAll:PD), which aimed to increase coaches knowledge, skills, and confidence in working with children born preterm. Materials and methods: CirqAll:PD consisted of 10-hours of online self-directed content and four 90-minute online workshops completed over four weeks. Recruitment capability, acceptability, implementation fidelity and limited efficacy testing were evaluated using a case series design. Results: Fifty-one circus coaches were enrolled, and 27 completed CirqAll:PD. Reasons for attrition were primarily related to the Theoretical Framework of Acceptability s (TFA) concept of burden. All 27 coaches indicated that CirqAll:PD was acceptable (TFA questionnaire). Overall intervention fidelity was high (high adherence to planned delivery, moderate adherence to dosage, and excellent participant responsiveness). Limited efficacy testing revealed positive trends regarding coaches knowledge, skills, and confidence (Determinants of Implementation Behaviour Questionnaire). Conclusions: These results support the feasibility of CirqAll:PD. Adaptations to reduce attrition and burden on participants are required prior to further testing.

Background The Ethiopian government implemented a national community health program, the Health Extension Program (HEP), to provide community-based health services to address persisting access-related barriers to care using health extension workers (HEWs). We used implementation research to understand how Ethiopia leveraged the HEP to widely implement evidence-based interventions (EBIs) known to reduce under-5 mortality (U5M) and address health inequities. Methods This study was part of a six-country case study series using implementation research to understand how countries implemented EBIs between 2000-2015. Our mixed-methods research was informed by a hybrid implementation science framework using desk review of published and gray literature, analysis of existing data sources, and 11 key informant interviews. We used implementation of pneumococcal conjugate vaccine (PCV-10) and integrated community case management (iCCM) to illustrate Ethiopia ability to rapidly integrate interventions into existing systems at a national level through leveraging the HEP and other implementation strategies and contextual factors which influenced implementation outcomes. Results Ethiopia implemented numerous EBIs known to address leading causes of U5M, leveraging the HEP as a platform for delivery to successfully introduce and scale new EBIs nationally. By 2014/15, estimated coverage of three doses of PCV-10 was at 76%, with high acceptability (nearly 100%) of vaccines in the community. Between 2000 and 2015, we found evidence of improved care-seeking; coverage of oral rehydration solution for treatment of diarrhea, a service included in iCCM, doubled over this period. HEWs made health services more accessible to rural and pastoralist communities, which account for over 80% of the population, with previously low access, a contextual factor that had been a barrier to high coverage of interventions. Conclusions Leveraging the HEP as a platform for service delivery allowed Ethiopia to successfully introduce and scale existing and new EBIs nationally, improving feasibility and reach of introduction and scale-up of interventions. Additional efforts are required to reduce the equity gap in coverage of EBIs including PCV-10 and iCCM among pastoralist and rural communities. As other countries continue to work towards reducing U5M, Ethiopia experience provides important lessons in effectively delivering key EBIs in the presence of challenging contextual factors.

Interoceptive mismatch is a perceptual discrepancy between ascending bodily signals and higher-order representation of anticipated physiological state. This mismatch is implicated in emotion inference within predictive coding models. We present autonomic perceptual mismatch as a novel in vivo measure of the discrepancy between actual and perceived autonomic signals, for clinical application to brain-body interactions, specifically in the expression of anxiety. Joint hypermobility is disproportionately found in individuals with anxiety disorders, revealing an underexplored link between the mind and body. Atypical autonomic reactivity represents a likely mediating mechanism consequent of altered connective tissue within the vasculature and nervous system. The present fMRI study determined neural substrates of autonomic perceptual mismatch on affective processing in the hypermobility-anxiety interaction. We compared regional brain activity during emotional face processing in participants with and without hypermobility and generalized anxiety disorder diagnosis, then tested association with perceptual mismatch. In the brain, autonomic perceptual mismatch correlated with enhanced activation in emotion processing and autonomic control regions, notably anterior cingulate cortex. Anxious individuals exhibited increased mid-insula cortex activity in relation to perceptual mismatch. Activity was decreased within the inferior frontal gyrus, a region implicated in cognitive control. Dysautonomia mediated the link between hypermobility and anxiety. Together, these findings support a neural basis of an autonomic perceptual mismatch model in a clinical sample. This is supported by the engagement of neural systems for emotion-cognition and interoception. This work highlights convergent aspects of neurodiversity, mental health, connective tissue disorders and brain-body interactions relevant to precision healthcare.

Early-life gut microbiome-metabolome crosstalk has a pivotal role in the maintenance of host physiology. However, our understanding on early-life gut microbiome-metabolome maturation trajectories in humans remains limited. This study aims to explore the longitudinal patterns of gut metabolites during early life, and how they are related to gut microbiota composition in birth cohort samples of n = 670 children collected at 2.5 (n=272), 6 (n=232), 14 (n=289), and 30 months (n=157) of age. Factor analysis showed that breastfeeding has an effect on several metabolites including secondary bile acids. We found that the prevalent gut microbial abundances were associated with metabolite levels, especially in the 2.5 months-olds. We also demonstrated that the prevalent early colonizers Bacteroides, Escherichia and Bifidobacterium abundances associated with microbial metabolites bile acids especially in the breastfed infants. Taken together, our results suggests that as the microbiome matures during the early-life there is an association with the metabolome composition in an analogous fashion to how the genome information mature during early life.

Inflammatory breast cancer (IBC) is the most aggressive and lethal breast cancer subtype, but lags in biomarker identification. Here, we used an improved Thermostable Group II Intron Reverse Transcriptase RNA sequencing (TGIRT-seq) method to simultaneously profile coding and non-coding RNAs from tumors, PBMCs, and plasma of IBC and non-IBC patients and healthy donors. Besides RNAs from known IBC-relevant genes, we identified hundreds of other overexpressed coding and non-coding RNAs (p[≤]0.001) in IBC tumors and PBMCs, including higher proportions with elevated intron-exon depth ratios (IDRs), likely reflecting enhanced transcription resulting in accumulation of intronic RNAs. As a consequence, differentially represented protein-coding gene RNAs in IBC plasma were largely intron RNA fragments, whereas those in healthy donor and non-IBC plasma were largely fragmented mRNAs. Potential IBC biomarkers in plasma included T-cell receptor pre-mRNA fragments traced to IBC tumors and PBMCs; intron RNA fragments correlated with high IDR genes; and LINE-1 and other retroelement RNAs that we found globally up-regulated in IBC and preferentially enriched in plasma. Our findings provide new insights into IBC and demonstrate advantages of broadly analyzing transcriptomes for biomarker identification. The RNA-seq and data analysis methods developed for this study may be broadly applicable to other diseases.

We investigated the lifestyle factors influencing weight gain in university students during restrictions (mild lockdown) imposed owing to the novel coronavirus disease pandemic in Japan. In this cross-sectional study, a questionnaire survey of Nagasaki University students undergoing health examinations was conducted in 2021. Students reporting >=3 kg weight gain were included in the weight gain group; the remaining students were in the non-weight gain group. Fishers exact test and binary logistic regression were performed to detect the associations between weight gain and each lifestyle factor. We included 3,059 respondents (response rate: 45.7%), and 9.5% respondents reported >=;3 kg weight gain. The following factors were associated with weight gain (odds ratio, 95% confidence interval, p value from Fishers exact test): dining out for >=4 times/week (2.16 [1.40, 3.32], p = 8.7 x 10-4), gaming time of >=4 h/day (2.26 [1.45, 3.47], p = 2.4 x 10-4). Binary logistic regression among the four highest odds ratios showed that after adjusting for other factors frequently dining out and prolonged gaming time were significantly associated with weight gain. Prolonged gaming and frequently dining out were associated with weight gain in students during the mild lockdown.

Background People with severe and multiple disadvantage (SMD- combinations of homelessness, substance misuse, violence, abuse and poor mental health) have high health needs and poor access to primary care. Aim To explore perceptions and experiences of improving access to general practice for people with SMD in healthcare staff and people with lived experience. Design and Setting Bridging Gaps is a collaboration between healthcare staff, researchers, women with lived experience of SMD and a charity that supports them in a UK city. We co-produced a project to improve access to general practice for marginalised patients, that was further developed with 3 inner city general practices. Method We observed six collaborative service improvement meetings at three general practices and conducted documentary analysis of minutes of a further three meetings. We interviewed nine practice staff and four participants with lived experience. Three participants with lived experience and one staff member who supports them participated in a focus group. Data was analysed inductively and deductively using thematic analysis. Results Enabling motivated general practice staff with time and funding opportunities, galvanised by lived experience involvement, resulted in sustained service changes. These included: care coordinators and patient lists to support access to patients in greater need and an information sharing tool. The process and outcomes improved connections within and between general practices, support organisations and marginalised patients. Conclusion These co-produced strategies could be locally adapted and evaluated elsewhere. Investing in this different way of working may improve inclusion of marginalised groups, health equity and staff wellbeing.

Abstract Objective: To assess the performance of a deep learning system (DLS) to discriminate between optic disc drusen (ODD) and papilledema caused by intracranial hypertension, using standard color ocular fundus photographs collected in a large international multi-ethnic population. Design: Retrospective study. Participants: The study included 4,508 color fundus images in 2,180 patients from 30 neuro-ophthalmology centers (19 countries) participating in the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI) Group. Methods: We trained, validated, and tested a dedicated DLS for binary classification of ODD vs. papilledema (including various subgroups within each category), on conventional mydriatic digital ocular fundus photographs. For training and internal validation, we used 857 ODD images and 3,230 papilledema images, in 1,959 patients. External-testing was subsequently performed on an independent dataset (221 patients) including 207 images with ODD (96 visible and 111 buried), provided by 3 centers of the Optic Disc Drusen Studies Consortium, and 214 images of papilledema (92 mild-to-moderate and 122 severe) from a previously validated study. Main outcome measures: Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to discriminate between ODD and papilledema. Results: Overall, the DLS could accurately distinguish between all ODD and papilledema (all severities included): AUC 0.97 (95% confidence interval [CI], 0.96 to 0.98), accuracy 90.5% (95% CI, 88.0% to 92.9%), sensitivity 86.0% (95% CI, 82.1% to 90.1%), and specificity 94.9% (95% CI, 92.3% to 97.6%). The performance of the DLS remained high for discrimination of buried ODD from mild-to-moderate papilledema: AUC 0.93 (95% CI, 0.90 to 0.96), accuracy 84.2% (95% CI, 80.2%-88.6%), sensitivity 78.4% (95% CI, 72.2% to 84.7%), and specificity 91.3% (95% CI, 87.0% to 96.4%). Conclusions: A dedicated DLS can accurately distinguish between ODD and papilledema caused by elevated intracranial pressure, even when considering buried ODD vs mild-to-moderate papilledema. Future studies are required to validate the utility of this DLS in clinical practice.

Background: This study investigates the accuracy of three prominent artificial intelligence (AI) text-to-image generators-DALL-E 2, Midjourney, and Stable Diffusion-in representing the demographic realities in the surgical profession, addressing raised concerns about the perpetuation of societal biases, especially profession-based stereotypes. Methods: A cross-sectional analysis was conducted on 2,400 images generated across eight surgical specialties by each model. An additional 1,200 images were evaluated based on geographic prompts for three countries. Images were generated using a prompt template, "A photo of the face of a [blank]", with blank replaced by a surgical specialty. Geographic-based prompting was evaluated by specifying the most populous countries for three continents (United States, Nigeria, and China). Results: There was a significantly higher representation of female (average=35.8% vs. 14.7%, P<0.001) and non-white (average=37.4% vs. 22.8%, P<0.001) surgeons among trainees than attendings. DALL-E 2 reflected attendings' true demographics for female surgeons (15.9% vs. 14.7%, P=0.386) and non-white surgeons (22.6% vs. 22.8%, P=0.919) but underestimated trainees' representation for both female (15.9% vs. 35.8%, P<0.001) and non-white (22.6% vs. 37.4%, P<0.001) surgeons. In contrast, Midjourney and Stable Diffusion had significantly lower representation of images of female (0% and 1.8%, respectively) and non-white (0.5% and 0.6%, respectively) surgeons than DALL-E 2 or true demographics (all P<0.001). Geographic-based prompting increased non-white surgeon representation (all P<0.001), but did not alter female representation (P=0.779). Conclusions: While Midjourney and Stable Diffusion amplified societal biases by depicting over 98% of surgeons as white males, DALL-E 2 depicted more accurate demographics, although all three models underestimated trainee representation. These findings underscore the necessity for guardrails and robust feedback systems to prevent AI text-to-image generators from exacerbating profession-based stereotypes, and the importance of bolstering the representation of the evolving surgical field in these models' future training sets.

Background: Previous prediction models have predicted a single outcome (e.g. gait) from several patient characteristics at one point (e.g. on admission). However, in clinical practice, it is important to predict an overall patient characteristic by incorporating multiple outcomes. This study aimed to develop a prediction model of overall patient characteristics in acute stroke patients using latent class analysis.Methods: This retrospective observational study analyzed stroke patients admitted to acute care hospitals (37 hospitals, N=10,270) between January 2005 and March 2016 from the Japan Association of Rehabilitation Database. Overall, 6,881 patients were classified into latent classes based on their outcomes. The prediction model was developed based on patient characteristics and functional ability at admission. We selected the following outcome variables at discharge for classification using latent class analysis: Functional Independence Measure (functional abilities and cognitive functions), subscales of the National Institutes of Health Stroke Scale (upper extremity function), length of hospital stay, and discharge destination. The predictor variables were age, Functional Independence Measure (functional abilities and comprehension), subscales of the National Institutes of Health Stroke Scale (upper extremity function), stroke type, and amount of rehabilitation (physical, occupational, and speech therapies) per day during hospitalization.Results: Patients (N=6,881) were classified into nine classes based on latent class analysis regarding patient characteristics at discharge (class size: 429%). Class 1 was the mildest (shorter stay and highest possibilities of home discharge), and Class 2 was the most severe (longer stay and the highest possibility of transfers inckuding deaths). Different gradations characterized Classes 39; these patient characteristics were clinically acceptable. Predictor variables at admission that predicted class membership were significant (odds ratio: 0.0107.9, P<.001).Conclusions: Based on these findings, the model developed in this study could predict an overall patient characteristic combining multiple outcomes, including the appropriate rehabilitation intensity. In actual clinical practice, internal and external validation is required.

Background: Circulating tissue transglutaminase IgA (TTG IgA) concentrations are sensitive and specific indicators of celiac disease, but discrepancies between serologic and histologic findings still occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as non-invasive means of evaluating disease activity. Methods: Participants with positive celiac serologies and controls with negative celiac serologies were enrolled at the time of upper endoscopy. Blood, stool and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin and alpha-1-antitrypsin and plasma lipcalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and TTG IgA concentration. Results: Lipocalin-2 was significantly elevated in the stool (p=0.007) but not the plasma of participants with positive celiac serologies compared to controls. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100mg/dL was specific, but not sensitive for biopsy proven celiac disease. Conclusions: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role in the local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease and did not correlate with degree of histologic changes on biopsy. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared to controls, an elevation of greater than 100mg/dL was 90% specific for biopsy proven celiac disease.

BACKGROUND: Transcatheter repair of mitral regurgitation (MR) is less invasive than surgery, but has greater five-year mortality and re-intervention risks, as well as more limited functioning. The study objective was to quantify patient preferences for risk-benefit tradeoffs associated with transcatheter and surgical options for MR. METHODS: A discrete-choice experiment survey was administered to patients with MR recruited through a patient advocacy organization. Attributes (and levels) included: procedure type (transcatheter versus surgical); risk of 30-day mortality (2%, 5%, and 10%); risk of five-year mortality (20%, 30%, and 45%) and physical functioning for five years (corresponding to improvements from New York Heart Association [NYHA] class III to I or class III to II); number of hospitalizations (1, 4, and 8) in the next five years; and risk of additional surgery in the next five years (10%, 20%, and 30% or 40%). A mixed-logit regression model was fit to estimate preference weights. RESULTS: 201 individuals completed the survey: 63% were female; mean age was 74 years. On average, respondents preferred transcatheter repair over surgery. To undergo a less invasive procedure (i.e., transcatheter repair), respondents would accept up to a 13.3% (95% confidence interval [CI]: 8.7% to 18.5%) increase in re-intervention risk above a baseline of 10%, 4.6 (95% CI: 3.1 to 6.2) more hospitalizations above a baseline of one, a 9.3% (95% CI: 5.2% to 14.3%) increase in mortality risk above a baseline of 20%, or more limited physical functioning representing nearly one NYHA class (0.8, 95% CI: 0.5 to 1.3) over five years. CONCLUSIONS: Patients in general preferred a transcatheter procedure over surgery. When holding constant all other factors, a functional improvement from NYHA class III to class I maintained over five years would be needed, on average, for patients to prefer surgery over a transcatheter procedure.

Background: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD. Methods: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine and liquor on average of 19 years in 2,428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure). Results: We identified 60 metabolites associated with cumulative average alcohol consumption (p<0.05/211=0.00024). For example, one g/day increase of alcohol consumption was associated with higher levels of cholesteryl esters (e.g., CE 16:1, beta=0.023, SE=0.002, p=6.3e-45) and phosphatidylcholine (e.g., PC 32:1, beta=0.021, SE=0.002, p=3.1e-38). Survival analysis identified that 10 alcohol-associated metabolites were also associated with a differential CVD risk after adjusting for age, sex, and batch. Further, we built two alcohol consumption weighted metabolite scores using these 10 metabolites and showed that, with adjustment age, sex, batch, and common CVD risk factors, the two scores had comparable but opposite associations with incident CVD, hazard ratio 1.11(95% CI=[1.02, 1.21], p=0.02) vs 0.88 (95% CI=[0.78, 0.98], p=0.02). Summary: We identified 60 long-term alcohol consumption-associated metabolites. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD.

Introduction: COVID-19 and tuberculosis (TB) exhibit similar symptomatic presentation and clinical parameters. Common underlying immunological mechanisms also highlight potential routes of immunopathogenic interaction between these diseases during co-infection. To explore immunological similarities, differences and interactions, single-cell RNA-seq (scRNA-seq) was performed on whole blood infected with Mycobacterium tuberculosis (Mtb), SARS-CoV-2, or both pathogens. Methods: Whole blood from four healthy adults, were subjected to ex vivo infection with Mtb and/or SARS-CoV-2 ancestral strain, or were maintained in an uninfected state, for 24 or 96 hours. At each timepoint, for each condition, the four biological replicates were captured, fixed and cryopreserved to be processed for scRNA-seq as a single batch. Following quality control filtering, genotype-based demultiplexing was performed to obtain data from each biological replicate for pseudobulk differential expression analysis. Results: Thirteen distinct clusters of cells were identified based on marker gene expression. Profound differences in the proportions of monocytes, T cells and neutrophils were observed between infection conditions and timepoints. The greatest divergence between pathogen responses occurred within myeloid cells at early timepoints of infection. Co-infection had the greatest synergistic effect 24 hours post-infection with 238 immunological pathways uniquely enriched, including IFN-{gamma} and TNF production, whilst by 96 hours post-infection there was a large overlap of 182 shared pathways between Mtb, SARS-CoV-2 and co-infection. SARS-CoV-2-only infection resulted in widespread cell death by 96 hours post-infection, while Mtb-only and co-infected samples remained enriched for monocyte, T cell and NK cell signatures, sharing negative regulation of extrinsic apoptotic signalling. Distinct from Mtb, SARS-Co-V-2 had unique regulating of {beta} T cell activation and differentiation at both time points. Conclusion: These data provide a high-resolution characterisation of distinct and overlapping immunological responses generated by SARS-CoV-2 and Mtb when a single infection or co-infection occurs. This sheds light on the potential effects of novel or existing host-directed therapies that target these pathways, which is particularly crucial for settings where dual presentation is common.

ABSTRACT Background: Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up. Methods: We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. Results: The estimated TB recurrence risk was 6.6 per 1000 (95% confidence interval (CI):3.2,11.2) when deaths were handled as non-recurrences, and 6.7 per 1000 (95% CI:2.8,12.2) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 24.2 (95% CI:14.1,37.0), 10.5 (95% CI:5.6,16.6), and 7.8 (95% CI:3.9,13.2) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small but apparent impact on estimates. Conclusion: The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.

Age-related macular degeneration (AMD) is a blinding condition associated with depression and loneliness. This facilitates unhealthy lifestyle behaviours which drives AMD progression. We developed the first online lifestyle intervention for AMD, called Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) to promote positive lifestyle changes, reduce loneliness and depression. This qualitative study explored enablers and barriers to participation in MINGLE for older Australians with AMD. Thirty-one participants with AMD were interviewed using a semi-structured in-depth approach. Thematic analysis revealed nine themes. Enablers to participation were: socialising and learning about AMD, motivation to improve health, program accessibility and structure. Barriers were: lack of time, unfamiliarity with technology, limited knowledge regarding holistic interventions, vision-related issues, mobility and negative perception of group interactions. Multiple factors influence the participation of AMD patients in MINGLE and these must be considered when developing and implementing the MINGLE program to maximise participation.

Background: A quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis and supplement the clinical decision-making process. Materials and Methods: 202 persons with multiple sclerosis were enrolled in a longitudinal study with measurements at two time points with an average follow-up time of 5.4 years. Clinical measures included the Expanded Disability Status Scale, Timed 25-foot Walk, 9-Hole Peg and Symbol Digit Modalities Tests. Subjects underwent magnetic resonance imaging to determine the volumetric measures of the whole brain, gray matter, deep gray matter and lateral ventricles. Serum samples were analyzed using a custom immunoassay panel on the Olink platform and concentrations of 18 protein biomarkers were measured. Linear mixed-effects models and adjustment for multiple comparisons were performed. Results: Subjects had a significant 55.6% increase in Chemokine Ligand 20 (9.7pg/mL vs. 15.1pg/mL, p<0.001) and Neurofilament light polypeptide (10.5 pg/ml vs. 11.5 pg/ml, p=0.003) at the follow-up time point. Additional changes in CUB domain-containing protein 1, Contactin 2, Glial fibrillary acidic protein, Myelin oligodendrocyte glycoprotein, and Osteopontin were noted but did not survive multiple comparisons correction. Worse clinical performance in the 9-HPT was associated with Neurofilament light polypeptide (p=0.001). Increases in several biomarker candidates were correlated with greater neurodegenerative changes as measured by different brain volumes. Conclusion: Multiple proteins representing diverse biological pathways (neuroinflammation, immune modulation, and neuroaxonal integrity) associate with physical, cognitive and radiographic outcomes. Future studies should determine the utility of multiple protein assays in routine clinical care.

Objective: To assess regional variation in the use of late preterm steroids use after the publication of the Antenatal Late Preterm Steroids (ALPS) Trial and to understand factors associated with a region's pace of adoption. Methods: This was a repeated cross-sectional study using US natality data across hospital referral regions (HRRs) within the US from February 2015 to October 2017. Inclusion criteria included live-born, non-anomalous, singleton, late preterm (34-36 completed weeks of gestation) neonates born to individuals without pregestational diabetes. HRRs were categorized as either a "slower" or "faster" adopter of antenatal late preterm steroids based on the observed versus expected pace of antenatal steroid adoption in a 1-year period after the trial's dissemination compared to a 1-year pre-dissemination period. Patient and regional factors hypothesized a priori to be associated with the uptake of late preterm steroids were compared between faster and slower adopters. Results: There were 666,097 late preterm births in 282 HRRs during the study period. Of the included HRRs, 136 (48.2%) were considered faster adopters and 146 (51.8%) slower adopters. Faster adopters increased their steroid use by 12.1-percentage points (5.9% to 18.0%) compared to a 5.5-point increase (3.7% to 9.2%) among slower adopters (p<0.001). Most examined patient and regional factors were not associated with a region's pace of adoption. The only factor associated with being a faster adopter was the regional prevalence of prior preterm birth (adjusted odds ratio 2.04, 95% confidence interval 1.48-2.82). Conclusion: There was widespread geographic variation in the adoption of antenatal steroid administration for late preterm births that largely remained unexplained by population factors. Future research should focus on patient, provider, and system-level factors that may be influencing the adoption of late preterm steroids. Namely, this work can provide insights to barriers to timely or equitable access to new evidence-based practices and can guide future dissemination strategies with the goal of more uniform adoption.

Introduction: Wim Hof, also known as the iceman, developed a method called Wim Hof Method which he claims to have several benefits on physical and mental health. The aim of this systematic review is to identify and synthesise the results of the studies conducted on Wim Hof Method on physiological and psychological health-related outcomes. Materials and Methods: Medline and Web of Science were searched. Studies were included if they met the predetermined inclusion/exclusion criteria. Data extraction and quality assessment were performed on the included studies. The effects of Wim Hof Method were categorised into physiological or psychological related outcomes and narrative synthesis was conducted. Results: Nine papers were included in this review which consisted of eight individual trials. The findings of this systematic review suggest that the Wim Hof Method may affect the reduction of inflammation in healthy and non-healthy participants as it increases epinephrine levels, causing an increase in interleukin-10 and a decrease in pro-inflammatory cytokines. Additionally, Wim Hof breathing method was suggested to not enhance the performance of an exercise as minute ventilation, tidal volume, and breathing frequency were statistically insignificant. Conclusion: Taken together, the findings of this review show promising use of Wim Hof Method in the inflammatory response category. The focus of future studies should move away from investigating the use of Wim Hof breathing method to enhance exercise performance and towards exploring the benefits of Wim Hof Method in non-healthy participants with inflammatory disorders.