Innate immune cell activation by adjuvant AS01 in human lymph node explants is age-independent.

Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components MPL and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus-lining macrophages, monocytes and dendritic cells. AS01 induced dendritic cell maturation and a strong pro-inflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests the onset of the immune response to AS01 requires a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.

Differences in Factors Associated With Preterm and Term Stillbirth: A Secondary Cohort Analysis of the DESiGN Trial.

OBJECTIVE: To identify whether maternal and pregnancy characteristics associated with stillbirth differ between preterm and term stillbirth. DESIGN: Secondary cohort analysis of the DESiGN RCT. SETTING: Thirteen UK maternity units. POPULATION: Singleton pregnant women and their babies. METHODS: Multiple logistic regression was used to assess whether the 12 factors explored were associated with stillbirth. Interaction tests assessed for a difference in these associations between the preterm and term periods. MAIN OUTCOME MEASURE: Stillbirth stratified by preterm (<37+0 weeks') and term (37+0-42+6 weeks') births. RESULTS: A total of 195 344 pregnancies were included. Six hundred and sixty-seven were stillborn (3.4 per 1000 births), of which 431 (65%) were preterm. Significant interactions were observed for maternal age, ethnicity, IMD, BMI, parity, smoking, PAPP-A, gestational hypertension, pre-eclampsia and gestational diabetes but not for chronic hypertension and pre-existing diabetes. Stronger associations with term stillbirth were observed in women with obesity compared to BMI 18.5-24.9 kg/m2 (BMI 30.0-34.9 kg/m2 term adjusted OR 2.1 [95% CI 1.4-3.0] vs. preterm aOR 1.1 [0.8-1.7]; BMI ≥ 35.0 kg/m2 term aOR 2.2 [1.4-3.4] vs. preterm aOR 1.5 [1.2-1.8]; p-interaction < 0.01), nulliparity compared to parity 1 (term aOR 1.7 [1.1-2.7] vs. preterm aOR 1.2 [0.9-1.6]; p-interaction < 0.01) and Asian ethnicity compared with White (p-interaction < 0.01). A weaker or lack of association with term, compared to preterm, stillbirth was observed for older maternal age, smoking and pre-eclampsia. CONCLUSION: Differences in association exist between mothers experiencing preterm and term stillbirth. These differences could contribute to design of timely surveillance and interventions to further mitigate the risk of stillbirth.

Impact of margin thermal ablation after endoscopic mucosal resection of large (≥20 mm) non-pedunculated colonic polyps on long-term recurrence.

BACKGROUND AND AIMS: The efficacy of colorectal endoscopic mucosal resection (EMR) is limited by recurrence and the necessity for conservative surveillance. Margin thermal ablation (MTA) after EMR has reduced the incidence of recurrence at the first surveillance colonoscopy at 6 months (SC1). Whether this effect is durable to second surveillance colonoscopy (SC2) is unknown. We evaluated long-term surveillance outcomes in a cohort of LNPCPs that have undergone MTA. METHODS: LNPCPs undergoing EMR and MTA from four academic endoscopy centres were prospectively recruited. EMR scars were evaluated at SC1 and in the absence of recurrence, SC2 colonoscopy was conducted in a further 12 months. A historical control arm was generated from LNPCPs that underwent EMR without MTA. The primary outcome was recurrence at SC2 in all LNPCPs with a recurrence-free scar at SC1. RESULTS: 1152 LNPCPs underwent EMR with complete MTA over 90 months until October 2022. 854 LNPCPs underwent SC1 with 29/854 (3.4%) LNPCPs demonstrating recurrence. 472 LNPCPs free of recurrence at SC1 underwent SC2. 260 LNPCPs with complete SC2 follow-up formed the control arm from January 2012 to May 2016. Recurrence at SC2 was significantly less in the MTA arm versus controls (1/472 (0.2%) vs 9/260 (3.5%); p<0.001)). CONCLUSION: LNPCPs that have undergone successful EMR with MTA and are free of recurrence at SC1 are unlikely to develop recurrence in subsequent surveillance out to 2 years. Provided the colon is cleared of synchronous neoplasia, the next surveillance can be potentially extended to 3-5 years. Such an approach would reduce costs and enhance patient compliance.

Study protocol for the ROLEX-DUO randomised placebo-controlled trial: ROmosozumab Loaded with EXercise - DUal effects on bone and muscle in postmenopausal Osteoporosis and Osteopenia.

INTRODUCTION: Novel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance and impact (HiRIT) exercise has shown benefit in improving bone density in postmenopausal women with osteoporosis/osteopenia. Whether HiRIT can enhance the therapeutic effects of osteoporosis pharmacotherapy has not been established. ROLEX-DUO is a randomised controlled trial designed to assess the efficacy of romosozumab on various bone and muscle outcomes in combination with different exercise interventions in women with postmenopausal osteoporosis/osteopenia. METHODS AND ANALYSIS: ROLEX-DUO is an 8-month randomised placebo-controlled trial conducted at two tertiary referral centres for patients with osteoporosis/osteopenia in Sydney, New South Wales, Australia. The study is implementing the combination of romosozumab or placebo with different forms of exercise in postmenopausal women with osteoporosis/osteopenia without recent fragility fracture (n=102). Eligible women will be randomised 1:1:1 into one of three groups: (1) romosozumab with supervised HiRIT, (2) romosozumab with unsupervised low-intensity exercise or (3) placebo with unsupervised low-intensity exercise. Co-primary outcomes are the mean percentage change in lumbar spine bone mineral density (BMD), and mean change in five times sit-to-stand test performance (seconds) at 8 months. Secondary/exploratory outcomes include BMD changes at the femoral neck, total hip and distal radius, three-dimensional dual-energy X-ray absorptiometry (DXA) hip outcomes, DXA-derived lean and fat mass, serum markers of bone turnover (procollagen type 1 peptide, C-telopeptide of type 1 collagen) and bone biomarkers (dickkopf-1), serum extracellular vesicle analyses, 36-Item Short Form Survey (SF-36) quality-of-life scores, Menopause-Specific Quality Of Life (MENQOL) Questionnaire menopause symptom burden scores, number of falls and fractures. Mixed-effects models will be performed to compare longitudinal outcome results between groups using intention-to-treat analysis. ETHICS AND DISSEMINATION: The trial was approved by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH01794, protocol V.8, dated 03 July 2024). Participants will provide written informed consent prior to inclusion. Findings will be disseminated via peer-reviewed journals, scientific conferences and summary reports to funding bodies. TRIAL REGISTRATION NUMBER: ACTRN12623000867695.

Antiarrhythmic preferences and outcomes post DC cardioversion for atrial fibrillation, an Australian rural perspective.

INTRODUCTION: Direct current cardioversion (DCCV) remains one of the recommended management strategies for symptomatic atrial fibrillation (AF). Antiarrhythmic drugs (AAD) are prescribed post procedure to maintain sinus rhythm (SR). Limited literature exists on the AAD prescribing practices and their efficacy, post-DCCV in rural Australia. OBJECTIVE: The primary aim was to determine the preferred AAD post-DCCV and the factors affecting AAD prescribing practices. The secondary aim was to assess the efficacy of the AAD in maintaining SR. DESIGN: A retrospective observational audit of patients with non-valvular AF who underwent successful elective DCCV for symptomatic AF, during 2015-2020 at a regional hospital in New South Wales (NSW) (Dubbo Base Hospital). Patients were followed up for a duration of 12 months post-DCCV. RESULTS: 233 patients underwent successful DCCV during the study duration. Amiodarone was the preferred AAD of choice post-DCCV followed by sotalol and flecainide, respectively (36.5% vs. 27.8% vs. 1.3%). 35.2% patients were not prescribed AAD. Amiodarone and sotalol had similar but modest efficacies and neither were superior to no AAD, in maintaining SR 12 months post-DCCV (AF recurrence rate 61.5% vs. 68.2% vs. 71.6% respectively, p = 0.37). Antecedent cerebrovascular accident (CVA), pulmonary disease, smoking, prior treatment with digoxin, diuretics and left ventricular (LV) dysfunction were factors that influenced AAD prescribing practices. CONCLUSION: The study demonstrates equal efficacies of amiodarone, sotalol and no AAD in maintaining SR 12 months post-DCCV. Prescribing practices post-DCCV at Dubbo Base Hospital differ from observed national trends and guidelines. AAD prescription requires a multifaceted approach with a key consideration to prioritise safety over efficacy, being mindful of challenges in delivering optimal healthcare in a rural setting.

Examining the impact of a group treatment using cognitive and social cognition remediation for young offenders: The justice health NSW school-link advantage pilot study.

AIM: Young offenders experience higher rates of neurodevelopmental and mental health disorders than the general population, and significant access barriers to health treatment. Treatment combining Cognitive Remediation Therapy (CRT) and Social Cognition Remediation Therapy (SCRT) has demonstrated benefits for functional improvements and social development. However, there is limited information regarding group treatment programs in custodial settings for young offenders. This pilot study explores the effectiveness and feasibility of a group treatment program for youth offenders with cognitive deficits and mental health concerns in youth detention. METHODS: The School-Link Advantage pilot study designed and tested a 10-week group treatment program combining CRT and SCRT for young offenders in custody. The closed groups incorporated interactive activities focussed on emotional recognition and regulation skills, optimizing executive functioning, understanding values, exploring belief systems, improving relationships, and safety planning. RESULTS: Of the 22 male participants recruited in an Australian Youth Justice Centre, 12 completed all aspects of the treatment program, reflecting a 54.5% completion rate in a typically challenging to engage population cohort. Results demonstrated significant improvements in the ability to store and retrieve information, recognize information, and control emotions. Planning and organizing skills also showed considerable development. CONCLUSIONS: This pilot study suggests that a combined CRT and SCRT group treatment program has the potential to effectively target cognitive challenges associated with mental health disorders in young offenders in custody. These promising outcomes suggest exploring randomized controlled trials with increased cultural sensitivity for diverse populations.

Together is better - RibScore and SCARF in the prediction of pulmonary complications and association with SSRF.

BACKGROUND: Optimal treatment of patients with rib fractures requires identification of those patients at risk of pulmonary complications. It is also important to determine which patients would benefit from Surgical Stabilisation of Rib Fractures (SSRF). This study aims to validate two scoring systems (RibScore and SCARF score) in predicting complications and association with SSRF in an Australian trauma population. Clinical observation suggests that complications and criteria for SSRF is associated with anatomical and physiological factors. Therefore it is hypothesized that utilisation of an anatomical (RibScore) and physiological (SCARF) in conjunction will have improved predictive ability. METHOD: Retrospective cohort study of rib fracture patients admitted to an Australian Level I trauma centre from Jan 2017 to Jan 2021. RibScore and SCARF score were calculated. Multivariate logistic regression was performed to determine risk factors associated with complications and SSRF, as well the scoring systems' ability via ROC AUC. RESULTS: 1157 patients were included. Higher median RibScore (1vs0; p < 0.001) and SCARF score (3vs1, p < 0.001) was associated with development of complications. Similarly for SSRF, RibScore (3vs0; p < 0.001), SCARF score (3vs1; p < 0.001) were higher. On multivariate analysis, increasing RibScore and SCARF score were associated with an increased risk of respiratory failure, pneumonia, death, and SSRF. The sensitivity for a patient with a high risk score in either RibScore or SCARF increased to 96.3 % in identifying pulmonary complications (from 66.7 % in RibScore and 88 % in SCARF, when used individually) and 91.9 % in identifying association with SSRF (from 86.5 % in RibScore and 70.3 % in SCARF). CONCLUSION: RibScore and SCARF score demonstrate predictive ability for complications and SSRF in an Australian trauma rib fracture population. Combining a radiological score with a clinical scoring system demonstrates improved sensitivity over each score individually for identifying patients at risk of complications from rib fractures, those who may require SSRF, and those who are low risk. STUDY TYPE: Retrospective Cohort Study LEVEL OF EVIDENCE: Level III.

Temperature probe placement in very preterm infants during delivery room stabilization: an open-label randomized trial.

BACKGROUND: Variation in practice exists for temperature probe positioning during stabilization of very preterm infants (<32 weeks gestation). We explored the influence of temperature probe sites on thermoregulation. METHODS: An open-label, stratified, balanced, parallel, randomized trial was conducted. Inborn infants were randomly assigned temperature probe to the axilla or to the upper back. The primary outcome was normothermia (local range: 36.8-37.3 °C and World Health Organization (WHO) range: 36.5-37.5 °C) at admission to the neonatal intensive care unit. RESULTS: Between 1 November 2018 and 4 July 2022, 178 infants were randomly assigned to one of the two sites (n = 89 each), 175 included in the final analysis. Normothermia (local range) was achieved for 39/87 infants (44.8%) assigned to the upper back compared to 28/88 infants (31.8%) assigned to the axilla [risk difference:13%; 95% CI -1.3-27.3]. Normothermia (WHO range) was achieved for 78/87 infants (89.7%) assigned to the upper back compared to 70/88 infants (79.6%) assigned to the axilla [risk difference:10.1%; 95% CI -0.5-20.7]. No infant recorded temperatures >38 °C or developed skin injury. CONCLUSIONS: In very preterm infants, upper back site was equally effective as the axilla in maintaining normothermia, with no increase in adverse events. CLINICAL TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000293965). IMPACT: Substantial variation in practice exists for the site of securing a temperature probe during delivery room stabilization of very preterm infants and the influence of temperature probe site on thermoregulation remains unknown. In this study, upper back site was equally effective as the axilla in maintaining normothermia, with no increase in adverse events. Clinicians could adopt upper back site for maintaining normothermia. This study may contribute data to future international participant data prospective meta analysis of randomized controlled trials worldwide on temperature probe positioning in very preterm infants, increasing translation of research findings to optimize thermoregulation and clinical outcomes.

Are migrants during the periconception period less likely to be supplementing with folic acid: An Australian cohort study.

BACKGROUND: Folic acid (FA) supplementation before and in early pregnancy is known to improve outcomes such as reducing neural tube defects; however, little is known about groups in Australia at risk of low FA use. AIM: To determine whether differences exist in FA supplementation rates between Australian-born women and migrant women, with a secondary aim of examining the sociodemographic characteristics of women who are not supplementing with FA in early pregnancy. METHODS: A retrospective cohort study from January 2018-July 2022 in a high-migrant population in Western Sydney, Australia. Multivariate logistic regression analysis was conducted adjusting for confounders including place of birth, age, ethnicity, parity, history of diabetes, and type of conception. FINDINGS: There were 48,045 women who met inclusion criteria; 65% of whom were migrants. We identified that 39.4% of the study population did not report FA supplementation by early pregnancy. Women who were migrants were more likely to report FA usage than those born in Australia (aOR 1.24; 95%CI 1.17-1.31). Women least likely to report use of FA were women < 20 years of age (aOR 0.54; 95%CI 0.44-0.67) and multiparous women (aOR 0.84; 95%CI 0.82-0.86). Women with type 1 or type 2 diabetes were more likely to report FA use (aOR 1.66; 95%CI 1.11-2.48, aOR 1.30; 95%CI 1.05-1.61). CONCLUSION: A significant proportion of the population did not report FA supplementation before or during early pregnancy. To increase uptake of FA supplementation, clinicians and public health messaging should target at-risk groups.

A streamlined multidisciplinary metabolic clinic in psychiatric recovery service: a pilot study.

Background: The metabolic syndrome (MetS) is a collection of risk factors for cardiovascular disease and type-2 diabetes, that includes central obesity, hypertension, hyperglycaemia and dyslipidaemia. An audit indicated inadequate MetS screening in an Australian psychiatric recovery service. Objectives: We aimed to improve MetS screening, identification and intervention by offering streamlined lifestyle education, clinical reviews and discharge planning. This pilot program prioritized holistic, culturally-sensitive, patient-centric, and trauma-informed approaches to enhance metabolic health outcomes. Methods: A Metabolic Clinic was piloted in two psychiatric rehabilitation cottages (n=35), which involved disciplines of dietetics, exercise physiology, diversional therapy, occupational therapy, peer workforce, social work, clinical psychology, pharmacy, nursing and medical. Another cottage (n=15) was assigned as the comparison and received standard care. A 12-week, 3-times-per-week lifestyle and behavioral program, called MetFit, was devised and offered to those identified at screening for the treatment cottages. Outcome measures were feasibility measures, the five metabolic parameters (waist circumference, blood pressure, fasting serum triglycerides, high-density lipoprotein, and glucose), functional measures, and a meal questionnaire. Results: The treatment cottages had qualitative advantages in screening and identifying MetS. Of four enrolled consumers in MetFit, an improvement of triglycerides (p=0.08), squats (p=0.02), and push-ups (p=0.07) was observed. Major challenges of enrolment included an overall lack of acknowledgment of its importance, poor motivation of consumers and resources limitation. Conclusions: The one-stop provision of groups, peer support and inpatient pathway with multidisciplinary team-integration was generally accepted by consumers and the MDT and has iteratively demonstrated the urgent need for consumer-centered physical care and a cultural shift to foster collaboration within a psychiatric service.

Altered left atrial metrics in patients with cryptogenic stroke: A systematic review and meta-analysis.

BACKGROUND: There is no defined cause for cryptogenic stroke/embolic stroke of undetermined source (CS-ESUS). As atrial fibrillation (AF) develops in a significant proportion of these patients, it has been suggested that left atrial (LA) myopathy may predispose to CS-ESUS. We investigated alterations in echocardiographic measures of LA size and function in patients with CS-ESUS. METHODS: A systematic literature review and meta-analysis was performed. PubMed, EMBASE, Cochrane Library, Web of Science and SCOPUS were searched for articles published between 1 January 1990 and 10 February 2023. All observational studies of adult CS-ESUS patients with LA volume or function measurements performed by transthoracic echocardiogram were included. Individual random effects meta-analyses were performed on LA measurements in the CS-ESUS patients using subgroup analysis of comparator groups. RESULTS: We included 29 articles with 3927 CS-ESUS patients. Analysis of weighted mean differences showed CS-ESUS patients had altered LA structure and function parameters, with a larger maximum indexed LA volume, reduced LA emptying fraction and/or LA reservoir strain, compared to healthy controls and noncardioembolic stroke patients. Conversely, CS-ESUS patients had a smaller left atrium with better function, compared to cardioembolic stroke patients and CS-ESUS patients who subsequently developed atrial fibrillation. CONCLUSIONS: LA volume and function are altered in CS-ESUS patients compared to healthy controls and other stroke aetiologies. An underlying atrial myopathy in a subset of CS-ESUS patients may be involved in both thrombogenesis and dysrhythmia (specifically AF). While LA functional assessment is not currently recommended following stroke, it may offer an opportunity for recurrent stroke risk stratification.

Examining the clinical effectiveness of continuation and maintenance electroconvulsive therapy in schizophrenia.

OBJECTIVE: There are few studies that examine the effectiveness of Continuation/Maintenance Electroconvulsive Therapy (C/M-ECT) in schizophrenia, despite the documented effectiveness of acute ECT treatment. We aimed to investigate the clinical effectiveness of C/M-ECT for in-patients with Schizophrenia in a naturalistic setting. We examined the medical records of 46 in-patients who were diagnosed with Schizophrenia and had received C/M-ECT belonging to non-acute extended care service in a public psychiatry hospital in Sydney, Australia. The focus of analysis was on 138 treatment cycles (71 acute only cycles and 67 acute-continuation/maintenance cycles) across 45 subjects. A linear mixed effects model was used to describe the change in clinical global impression-severity (CGI-S) over time 4 time points viz., pre-post acute and pre-post continuation/maintenance ECT. RESULTS: Acute-only cycles and acute-continuation/maintenance cycles had identical pre- (M = 5, C.I. = 4-6), post-cycle CGI-S scores, and identical CGI-S difference scores (M = 0, C.I. = -1 - 1). Broadly in each continuation/maintenance cycle, we observed an initial sharp decrease in CGI-S scores followed by a logarithmic increase in scores over time, with satisfactory CGI-S score maintenance observed for approximately 6 months. Bitemporal ECT influenced CGI-S across maintenance ECT (p < 0.05) indicating smaller declines in CGI-S scores over time. CONCLUSION: In schizophrenia, C/M ECT preserves effects on illness severity for at least upto 6 months following an acute course of ECT. Bitemporal ECT vis a vis other electrode positions differentiated clinical severity over time.

Investigating short-stay admission to a neonatal intensive care unit as a risk factor for reduced breast feeding at discharge in infants ≥36 weeks' gestation: a retrospective cohort study.

OBJECTIVE: This study aims to determine the effect of infant-mother separation following a short-stay (≤72 hours) admission to a Level 5 neonatal unit versus no admission on infant-feeding outcomes at hospital discharge. DESIGN: Retrospective cohort study. SETTING: An Australian Level 5 neonatal unit within a tertiary referral hospital. PARTICIPANTS: Mothers and their infants born between 1 January 2018 and 31 December 2020 had a short-stay admission to the neonatal unit or no admission. All participants met admission criteria to the postnatal ward and were discharged home at ≤72 hours (n=12 540). Postnatal ward admission criteria included ≥36 weeks' gestation and birth weight ≥2.2 kg. MAIN OUTCOME MEASURES: Infant feeding at discharge from hospital. Multivariate logistic regression analysis was conducted, adjusting for confounders associated with known breastfeeding issues. These included age, ethnicity, parity, obesity, socioeconomic score, hypertensive disorders of pregnancy, diabetes, infant gestation and birthweight centile, caesarean section birth, postpartum haemorrhage and skin-to-skin contact. RESULTS: Of the 12 540 live births meeting inclusion criteria, 1000 (8%) infants were admitted to the neonatal unit. The primary reasons for admission were suspicion of sepsis (24%), maternal diabetes (19%) and jaundice (16%). We found a reduction in full breast feeding at hospital discharge in cases of a short admission to the neonatal unit compared with no admission (aOR 0.40; 95% CI 0.34 to 0.47; p<0.001). We identified that women of different ethnicities had differing levels of risk for formula supplementation at hospital discharge. The ethnic grouping least likely to be fully breast feeding at discharge was Southeast Asian women (aOR 0.47; 95% CI 0.39 to 0.57; p<0.001). CONCLUSIONS: Identifying mother-infant dyads at risk of non-exclusive breast feeding at hospital discharge will help target resources for practice improvement.

Variations in indexation of left atrial volume across different races.

Background: Left atrial volume (LAV) has prognostic value. Guidelines propose indexation to body surface area (BSA), however studies demonstrate this can overcorrect for body size. Limited studies investigate indexation across different ethnicities. We sought to evaluate the effect of ethnicity on indexation. Methods: Using data from the World Alliance of Societies of Echocardiography (WASE) cohort, healthy subjects were classified by race as White, Black, Asian, or Other. Biplane LAV was indexed to traditional isometric measurements (BSA, height, weight, ideal body weight (IBW) and IBW derived BSA (IBSA)), as well as previously-derived allometric height exponents (2.7 and 1.72). Additionally, an allometric height exponent for our cohort was derived (linear regression of the logarithmic transformation of LAV = a(height)b) as 1.87. All indices were then assessed using Spearman correlation, with a good index retaining correlation of LAV/index to raw LAV (r∼1), while avoiding overcorrection by the index (r∼0). Results: There were 1366 subjects (White: 524, Black: 149, Asian: 523, Other: 170; median age 44 years, 653 females (47.8%)). In the entire group, BSA, IBSA, height1.87 and height1.72 performed well with retaining correlation to raw LAV (r > 0.9 for all), and minimising overcorrection to body size (r < 0.1 for all). On race-specific analysis, BSA overcorrected for body size in the White population (r = 0.128). Height1.72 minimised overcorrection for body size in all populations (r ≤ 0.1 for all races). Conclusion: Despite a cohort with normal BMI, there was still disparity in LAV indexation with BSA across races. Allometric height indexation, particularly using height1.72, is a possible solution, although further validation studies in BMI extremes are required.

Neurofeedback for post-traumatic stress disorder: systematic review and meta-analysis of clinical and neurophysiological outcomes.

Background: Posttraumatic stress disorder (PTSD) is a debilitating condition affecting millions of people worldwide. Existing treatments often fail to address the complexity of its symptoms and functional impairments resulting from severe and prolonged trauma. Electroencephalographic Neurofeedback (NFB) has emerged as a promising treatment that aims to reduce the symptoms of PTSD by modulating brain activity.Objective: We conducted a systematic review and meta-analysis of ten clinical trials to answer the question: how effective is NFB in addressing PTSD and other associated symptoms across different trauma populations, and are these improvements related to neurophysiological changes?Method: The review followed the Preferred Reporting Items for Systematic Reviews and Meta analyses guidelines. We considered all published and unpublished randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) involving adults with PTSD as a primary diagnosis without exclusion by type of trauma, co-morbid diagnosis, locality, or sex. Ten controlled studies were included; seven RCTs and three NRSIs with a total number of participants n = 293 (128 male). Only RCTs were included in the meta-analysis (215 participants; 88 male).Results: All included studies showed an advantage of NFB over control conditions in reducing symptoms of PTSD, with indications of improvement in symptoms of anxiety and depression and related neurophysiological changes. Meta-analysis of the pooled data shows a significant reduction in PTSD symptoms post-treatment SMD of -1.76 (95% CI -2.69, -0.83), and the mean remission rate was higher in the NFB group (79.3%) compared to the control group (24.4%). However, the studies reviewed were mostly small, with heterogeneous populations and varied quality.Conclusions: The effect of NFB on the symptoms of PTSD was moderate and mechanistic evidence suggested that NFB leads to therapeutic changes in brain functioning. Future research should focus on more rigorous methodological designs, expanded sample size and longer follow-up.

Neurofeedback (NFB) was found to have moderate beneficial effects on PTSD symptoms, and positive effects on secondary outcomes such as depression and anxiety, according to a meta-analysis of seven randomised controlled trials (RCTs).The beneficial effects of NFB were observed across diverse populations, including those with different types of trauma (military and civilians) and from different ethnic backgrounds.Results suggest that modulation of alpha rhythm might be a viable NFB protocol in patients with PTSD, as changes in neurophysiological functioning, such as connectivity in the Default Mode Network (DMN) and Salience Network (SN), were observed post-NFB and were correlated with a decrease in PTSD severity.

Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD. METHODS: Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ. DISCUSSION: The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Role of a radiopaque agent and surveillance radiographs for peripherally inserted central catheters in newborn infants.

BACKGROUND: Controversy exists regarding the use of a radiopaque agent to identify peripherally inserted central catheter (PICC) tip positions in newborn infants and of serial radiography to monitor PICC tip migration. OBJECTIVE: To investigate the roles of (1) the injection of a radiopaque agent to identify PICC tip position and (2) the performance of weekly radiography to monitor PICC migration. MATERIALS AND METHODS: This retrospective single-centre cohort study included newborn infants who received a PICC between 1 January 2016 and 31 December 2020. A radiopaque agent was injected to identify PICC tip position and radiographs were performed weekly to detect PICC migration. RESULTS: We identified 676 PICC episodes in 601 infants. A radiopaque agent was used for 590 of these episodes. There was no difference in the proportion of central PICC tip positions based on radiopaque agent use status (490/590, 83% for the radiopaque agent used group versus 73/85, 85.8% for the radiopaque agent not used group, P=0.51). Irrespective of the site of PICC insertion, outward migration was observed for most centrally placed PICCs over their entire in situ duration. Inward migration was identified in 23 out of 643 PICC episodes (3.6%) only on radiographs obtained on or before day 7. Based on serial radiographs, the odds for PICC tips remaining in a central position were lower the longer the PICC remained in situ (adjusted odds ratio-OR 0.93; 95% confidence interval 0.92-0.95). There was no difference in PICC migration between side and limb of insertion. CONCLUSION: PICC tips can be identified without injection of a radiopaque agent. Serial radiographs identified PICC migration over the in situ duration. This study has implications for reducing exposure to a radiopaque agent and ongoing migration surveillance practices.