Which reference equation should we use for interpreting spirometry values for First Nations Australians? A cross-sectional study.

OBJECTIVES: To evaluate the suitability of the Global Lung Function Initiative (GLI)-2012 other/mixed and GLI-2022 global reference equations for evaluating the respiratory capacity of First Nations Australians. DESIGN, SETTING: Cross-sectional study; analysis of spirometry data collected by three prospective studies in Queensland, the Northern Territory, and Western Australia between March 2015 and December 2022. PARTICIPANTS: Opportunistically recruited First Nations participants in the Indigenous Respiratory Reference Values study (Queensland, Northern Territory; age, 3-25 years; 18 March 2015 - 24 November 2017), the Healthy Indigenous Lung Function Testing in Adults study (Queensland, Northern Territory; 18 years or older; 14 August 2019 - 15 December 2022) and the Many Healthy Lungs study (Western Australia; five years or older; 10 October 2018 - 7 November 2021). MAIN OUTCOME MEASURES: Goodness of fit to spirometry data for each GLI reference equation, based on mean Z-score and its standard deviation, and proportions of participants with respiratory parameter values within 1.64 Z-scores of the mean value. RESULTS: Acceptable and repeatable forced expiratory volume in the first second (FEV1) values were available for 2700 First Nations participants in the three trials; 1467 were classified as healthy and included in our analysis (1062 children, 405 adults). Their median age was 12 years (interquartile range, 9-19 years; range, 3-91 years), 768 (52%) were female, and 1013 were tested in rural or remote areas (69%). Acceptable and repeatable forced vital capacity (FVC) values were available for 1294 of the healthy participants (88%). The GLI-2012 other/mixed and GLI-2022 global equations provided good fits to the spirometry data; the race-neutral GLI-2022 global equation better accounted for the influence of ageing on FEV1 and FVC, and of height on FVC. Using the GLI-2012 other/mixed reference equation and after adjusting for age, sex, and height, mean FEV1 (estimated difference, -0.34; 95% confidence interval [CI], -0.46 to -0.22) and FVC Z-scores (estimated difference, -0.45; 95% CI, -0.59 to -0.32) were lower for rural or remote than for urban participants, but their mean FEV1/FVC Z-score was higher (estimated difference, 0.14; 95% CI, 0.03-0.25). CONCLUSION: The normal spirometry values of healthy First Nations Australians may be substantially higher than previously reported. Until more spirometry data are available for people in urban areas, the race-neutral GLI-2022 global or the GLI-2012 other/mixed reference equations can be used when assessing the respiratory function of First Nations Australians.

Erdosteine in children and adults with bronchiectasis (BETTER trial): study protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.

The effects of vibrating shoe insoles on standing balance, walking, and ankle-foot muscle activity in adults with diabetic peripheral neuropathy.

BACKGROUND: Peripheral neuropathy is one of the most common complications of type 2 diabetes, which can lead to impaired balance and walking. Innovative footwear devices designed to stimulate foot sensory receptors, such as vibrating insoles, could offer a new route to improve motor impairments in people with diabetic peripheral neuropathy (DPN). RESEARCH QUESTION: Does wearing vibrating insoles for the first time alter measures of balance, walking, and ankle-foot muscle activity, in people with DPN? METHODS: A randomised cross-over study was conducted with 18 ambulant men and women with a diagnosis of DPN. Participants performed tests of standing balance (Bertec® force platform) under four conditions (foam/firm surface, eyes open/closed) and level-ground walking (GAITRite® instrumented walkway), whilst wearing vibrating and non-vibrating (control) insoles on two separate occasions (one insole/session). Electromyography (EMG) was used to assess soleus, medial gastrocnemius, tibialis anterior, peroneus longus activity during balance tests. Outcomes included centre of pressure (CoP) sway, EMG amplitude, spatiotemporal gait patterns, and Timed Up and Go test. One sample t-tests were used to explore %differences in outcomes between insole conditions. RESULTS: Wearing vibrating insoles led to a reduction (improvement) in CoP elliptical area, when standing on a foam surface with eyes closed, relative to non-vibrating insoles (P=0.03). Applying perceptible vibrations to the soles of the feet also reduced the EMG amplitude in soleus (P=0.01 and P=0.04) and medial gastrocnemius (P=0.03 and P=0.09) when standing with eyes closed on firm and foam surfaces. SIGNIFICANCE: Our findings of signs of improved balance and altered muscle activity with suprasensory vibrating insoles provides new insights into how these devices can be used to inform innovative rehabilitation approaches in individuals with DPN. This will be strengthened by further research into possible clinical benefits of these devices - given that the effects we detected were small with uncertain clinical meaning.

Rapid diagnostic tests and antimicrobial stewardship programs for the management of bloodstream infection: What is their relative contribution to improving clinical outcomes? A systematic review and network meta-analysis.

BACKGROUND: Evidence about the clinical impact of rapid diagnostic tests (RDT) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BC) embedded within antimicrobial stewardship programs (ASP) is unknown. METHODS: We performed network meta-analyses (NMA) using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS) and time to optimal therapy (TOT). RESULTS: Eighty-eight papers were selected, including 25,682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The NMA showed a significant reduction in mortality associated with the use of RDT + ASP vs BC alone (OR 0.72, 95%CI 0.59, 0.87) and with the use of RDT + ASP vs BC + ASP (OR 0.78 95%CI 0.63, 0.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP vs BC alone (0.91, 95%CI 0.84, 0.98) while no difference in LOS was shown between any other groups. A reduced TOT was shown when RDT + ASP was compared to BC alone (-29 h, 95%CI -35, -23), BC + ASP (-18 h, 95%CI -27, -10) and to RDT alone (-12 h, 95%CI -20, -3). CONCLUSION: The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC.

Win ratio analyses of piperacillin-tazobactam versus meropenem for ceftriaxone non-susceptible Escherichia coli or Klebsiella pneumoniae bloodstream infections: Post-hoc insights from the MERINO trial.

BACKGROUND: Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritise outcome measures by relative clinical importance. METHODS: The win ratio methodology was applied post-hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse and secondary infection. A win ratio of one would correspond to no difference between the two antibiotics, while a ratio less than one favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. RESULTS: With the hierarchy of all-cause mortality, microbiological relapse and secondary infection, the win ratio estimate was 0.40 (95% CI: 0.22, 0.71; p=0.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI: 0.68, 0.92). The addition of length of stay to the primary composite, greatly minimised the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI: 0.60-0.99; p=0.04). CONCLUSIONS: The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials.

Host response signature trends in persistent bacteraemia and metastatic infection due to Staphylococcus aureus and Gram-negative bacilli: a prospective multicentre observational study.

BACKGROUND: A prompt diagnosis of bacteraemia and sepsis is essential. Markers to predict the risk of persistent bacteraemia and metastatic infection are lacking. SeptiCyte RAPID is a host response assay stratifying patients according to the risk of infectious vs sterile inflammation through a scoring system (SeptiScore). In this study we explore the association between SeptiScore and persistent bacteraemia as well as metastatic and persistent infection in the context of a proven bacteraemia episode. METHODS: This is a prospective multicentre observational 14-month study on patients with proven bacteraemia caused by Staphylococcus aureus or Gram-negative bacilli. Samples for assessment by SeptiCyte were collected with paired blood cultures for 4 consecutive days after the index blood culture. RESULTS: We included 86 patients in the study, 40 with S. aureus and 46 with Gram-negative bacilli bacteraemia. SeptiScores over the follow-up were higher in patients with Gram-negative compared to S. aureus bacteraemia (median 6.4, IQR 5.5-7.4 vs 5.6 IQR 5.1-6.2, p = 0.002). Higher SeptiScores were found to be associated with positive blood cultures at follow-up (AUC = 0.86, 95%CI 0.68-1.00) and with a diagnosis of metastatic infection at day 1 and 2 of follow-up (AUC = 0.79, 95%CI 0.57-1.00 and AUC = 0.82, 95%CI 0.63-1.00 respectively) in the context of Gram-negative bacteraemia while no association between SeptiScore and the outcomes of interest was observed in S. aureus bacteraemia. Mixed models confirmed the association of SeptiScore with positive blood cultures at follow-up (p = 0.04) and metastatic infection (p = 0.03) in the context of Gram-negative bacteraemia but not S. aureus bacteraemia after adjusting for confounders. CONCLUSIONS: SeptiScores differ in the follow-up of S. aureus and Gram-negative bacteraemia. In the setting of Gram-negative bacteraemia SeptiScore demonstrated a good negative predictive value for the outcomes of interest and might help rule out the persistence of infection defined as metastatic spread, lack of source control or persistent bacteraemia.

Persistence of Detectable Pathogens by Culture-Independent Systems (T2 Magnetic Resonance) in Patients With Bloodstream Infection: Prognostic Role and Possible Clinical Implications.

BACKGROUND: Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic value and guide management decisions is unknown. METHODS: We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance-DNAemia [MR-DNAemia]) and clinical outcomes. RESULTS: Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR, .54; 95% CI, .39-.75) and did not differ according to the causative pathogen (P = .5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45-2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12-3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35-3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21-2.56). CONCLUSIONS: T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs.

Levetiracetam for the treatment of mild cognitive impairment in Parkinson's disease: a double-blind controlled proof-of-concept trial protocol.

BACKGROUND: Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson's disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer's disease. This project investigates the feasibility of a trial to establish the efficacy of a repurposed antiepileptic drug, levetiracetam, in low doses as a putative treatment to target DG/CA3 hyperactivation and improve episodic memory deficits in aMCI in PD. Based on previous work, it is hypothesized that levetiracetam will normalize DG/CA3 overactivation in PD-aMCI participants and improve memory performance. METHODS: Twenty-eight PD-aMCI participants, 28 PD participants without memory impairment (PD-nMI), and 28 healthy controls will be recruited. PD-aMCI participants will undertake a 12-week randomized, placebo-controlled, double-blind cross-over trial with a 14-day treatment of 125 mg levetiracetam or placebo twice daily, separated by a 4-week washout period. After each treatment period, participants will complete an episodic memory task designed to tax hippocampal subregion-specific function during high-resolution functional magnetic resonance imaging (fMRI). PD-nMI and healthy controls will undergo the fMRI protocol only, to compare baseline DG/CA3 subfield activity. RESULTS: Episodic memory task performance and functional activation in the DG/CA3 subfield during the fMRI task will be primary outcome measures. Global cognition, PD severity, and adverse events will be measured as secondary outcomes. Recruitment, eligibility, and study completion rates will be explored as feasibility outcomes. CONCLUSIONS: This study, the first of its kind, will establish hippocampal subregion functional impairment and proof of concept of levetiracetam as an early therapeutic option to reduce dementia risk in PD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04643327 . Registered on 25 November 2020.

A prospective, observational study of frailty, quality of life and dialysis in older people with advanced chronic kidney disease.

BACKGROUND: Frailty is prevalent in older people with chronic kidney disease (CKD) and robust evidence supporting the benefit of dialysis in this setting is lacking. We aimed to measure frailty and quality of life (QOL) longitudinally in older people with advanced CKD and assess the impact of dialysis initiation on frailty, QOL and mortality. METHODS: Outpatients aged ≥65 with an eGFR ≤ 20ml/minute/1.73m2 were enrolled in a prospective observational study and followed up four years later. Frailty status was measured using a Frailty Index (FI), and QOL was evaluated using the EuroQol 5D-5L instrument. Mortality and dialysis status were determined through inspection of electronic records. RESULTS: Ninety-eight participants were enrolled. Between enrolment and follow-up, 36% of participants commenced dialysis and 59% died. Frailty prevalence increased from 47% at baseline to 86% at follow-up (change in median FI = 0.22, p < 0.001). Initiating dialysis was not significantly associated with change in FI. QOL declined from baseline to follow-up (mean EQ-5D-5L visual analogue score of 70 vs 63, p = 0.034), though commencing dialysis was associated with less decline in QOL. Each 0.1 increment in baseline FI was associated with 59% increased mortality hazard (HR = 1.59, 95%CI = 1.20 to 2.12, p = 0.001), and commencing dialysis was associated with 59% reduction in mortality hazard (HR = 0.41, 95%CI = 0.20 to 0.87, p = 0.020) irrespective of baseline FI. CONCLUSIONS: Frailty increased substantially over four years, and higher baseline frailty was associated with greater mortality. Commencing dialysis did not affect the trajectory of FI but positively influenced the trajectory of QOL from baseline to follow-up. Within the limitations of small sample size, our data suggests that frail participants received similar survival benefit from dialysis as non-frail participants.

Bloodstream infections in neutropenic and non-neutropenic patients with haematological malignancies: epidemiological trends and clinical outcomes in Queensland, Australia over the last 20 years.

Knowledge of the epidemiology of bloodstream infection (BSI) in haematology patients is essential to guide patient management. We investigated the epidemiology of BSI in patients with haematological malignancies in Queensland over the last 20 years (2000-2019), including all episodes diagnosed by the state-wide microbiology service. We identified 7749 BSI in 5159 patients, 58% associated with neutropenia. Gram-negatives were the main causative pathogens (58.3%), more frequent in neutropenic than non-neutropenic patients (3308/5309, 62.3% vs 1932/3678, 52.5%, p < 0.001). Amongst 8987 isolates the most common were E. coli (15.4%) and Pseudomonas spp. (14.2%). Pseudomonas spp. (16.6% vs 10.7%, p < 0.001), Klebsiella spp. (11.6% vs 6.8%, p < 0.001), viridans-group streptococci (4.4% vs 1.2%, p < 0.001) and E. faecium (2.4% vs 0.9%, p < 0.001) were more common in neutropenic than non-neutropenic patients, while S. aureus was less common (5.9% vs 15.6%, p < 0.001). Several antimicrobial resistance rates increased over time and had higher prevalence in neutropenic than non-neutropenic patients, including ciprofloxacin-resistant E. coli (94/758, 12.4% vs 42/506, 8.3%, p = 0.021), trimethoprim-sulfamethoxazole-resistant E. coli (366/764, 47.9% vs 191/517, 36.9%, p < 0.001), penicillin-resistant streptococci (51/236, 21.6% vs 28/260, 10.8%, p < 0.001) and vancomycin-resistant enterococci (46/250, 18.4% vs 9/144, 6.3%, p < 0.001). Carbapenem-resistant Pseudomonas spp. (OR 7.32, 95%CI 2.78-19.32) and fungi, including yeasts and moulds (OR 3.33, 95%CI 2.02-5.48) were associated to the highest odds of 30-day case-fatality at a multivariable logistic regression analysis. Neutropenia was associated with survival (OR 0.66, 95%CI 0.55-0.78). Differences were observed in the BSI epidemiology according to neutropenic status, with an overall increase of resistance over time associated to adverse outcome.

Melioidosis Queensland: An analysis of clinical outcomes and genomic factors.

BACKGROUND: The clinical and genomic epidemiology of melioidosis varies across regions. AIM: To describe the clinical and genetic diversity of B. pseudomallei across Queensland, Australia. METHODS: Whole genome sequencing of clinical isolates stored at the melioidosis reference lab from 1996-2020 was performed and analysed in conjunction with available clinical data. RESULTS: Isolates from 292 patients were analysed. Bacteraemia was present in 71% and pneumonia in 65%. The case-fatality rate was 25%. Novel sequence types (ST) accounted for 51% of all isolates. No association was identified between the variable virulence factors assessed and patient outcome. Over time, the proportion of First Nation's patients declined from 59% to 26%, and the proportion of patients aged >70 years rose from 13% to 38%. CONCLUSION: This study describes a genomically diverse and comparatively distinct collection of B. pseudomallei clinical isolates from across Queensland, Australia. An increasing incidence of melioidosis in elderly patients may be an important factor in the persistently high case-fatality in this region and warrants further investigation and directed intervention.

Effect of Active Motor Learning Interventions on Gross Motor Function and Mobility in Children Aged 2 to 6 Years With Bilateral Cerebral Palsy: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this systematic review is to identify evidence-based interventions to promote active motor learning in children aged 2 to 6 years with bilateral cerebral palsy. SUMMARY OF KEY POINTS: Seven randomized clinical trials of active motor learning interventions targeting gross motor function and mobility were included. Two studies compared context-focused therapy to child-focused therapy. Five studies compared active motor therapy to usual care. Context-focused therapy, child-focused therapy, and active motor therapy were comparable to usual care to improve functional mobility and gross motor function. CONCLUSIONS AND RECOMMENDATIONS FOR CLINICAL PRACTICE: There are limited active intervention studies targeting gross motor function for young children with bilateral cerebral palsy. The authors recommend consideration of the clinical good practice guidelines, dosage parameters, and improved reporting methods when implementing active motor learning interventions targeting gross motor function and mobility for children with cerebral palsy.

Monitoring for micronutrient deficiency after bariatric surgery-what is the risk?

BACKGROUND: Bariatric surgery may increase the risk of micronutrient deficiencies; however, confounders including preoperative deficiency, supplementation and inflammation are rarely considered. OBJECTIVE: To examine the impact of bariatric surgeries, supplementation and inflammation on micronutrient deficiency. SETTING: Two public hospitals, Australia. METHODS: Participants were recruited to an observational study monitoring biochemical micronutrient outcomes, supplementation dose, inflammation and glycaemic control, pre-operatively and at 1-3, 6 and 12 months after gastric bypass (GB; Roux-en-Y Gastric Bypass and Single Anastomosis Gastric Bypass; N = 66) or sleeve gastrectomy (SG; N = 144). Participant retention at 12 months was 81%. RESULTS: Pre-operative micronutrient deficiency was common, for vitamin D (29-30%), iron (13-22%) and selenium (39% GB cohort). Supplement intake increased after surgery; however, dose was <50% of target for most nutrients. After SG, folate was vulnerable to deficiency at 6 months (OR 13 [95% CI 2, 84]; p = 0.007), with folic acid supplementation being independently associated with reduced risk. Within 1-3 months of GB, three nutrients had higher deficiency rates compared to pre-operative levels; vitamin B1 (21% vs. 6%, p < 0.01), vitamin A (21% vs. 3%, p < 0.01) and selenium (59% vs. 39%, p < 0.05). Vitamin B1 deficiency was independently associated with surgery and inflammation, selenium deficiency with improved glycaemic control after surgery and inflammation, whilst vitamin A deficiency was associated with inflammation only. CONCLUSION: In the setting of prophylactic post-surgical micronutrient prescription, few nutrients are at risk of de novo deficiency. Although micronutrient supplementation and monitoring remains important, rationalising high-frequency biochemical testing protocols in the first year after surgery may be warranted.

Vertebral CT attenuation outperforms standard clinical fracture risk prediction tools in detecting osteoporotic disease in lung cancer screening participants.

OBJECTIVES: Compare accuracy of vertebral Hounsfield Unit (VHU) attenuation and FRAX and Garvan Fracture Risk Calculators in identifying low bone mineral density (BMD) and prevalent vertebral compression fractures (VF) in lung cancer screening (LCS) participants. METHODS: Baseline CT scans from a single site of the International Lung Screen Trial were analysed. BMD was measured using VHU (of the most caudally imaged vertebra) and quantitative CT (QCT) (low BMD defined as <110 HU and <120 mg/cm3, respectively). Prevalent VF were classified semi-quantitatively. 10-year FRAX and Garvan fracture risks were calculated using dual energy X-ray absorptiometry (DXA) femoral neck T-score where available. Discrimination was assessed by area under receiver-operating characteristic curves (AUC). RESULTS: 535 LCS participants were included; 41% had low VHU-BMD, 56% had low QCT-BMD and 10% had ≥1 VF with ≥25% vertebral height loss. VHU demonstrated 94% specificity and 70% sensitivity in identifying low QCT-BMD. VHU was superior to fracture risk tools in discriminating low QCT-BMD (AUC: VHU 0.94 vs FRAX 0.67, Garvan 0.64 [p < 0.05]). In 64 participants with recent DXA scans, VHU was superior to FRAXT-score and GarvanT-score in discriminating low QCT-BMD (AUC: VHU 0.99, FRAXT-score 0.71, GarvanT-score 0.71 [p < 0.05]). VHU was non-inferior to FRAXT-score and GarvanT-score in discriminating VF (AUC: VHU 0.65, FRAXT-score 0.53, GarvanT-score 0.61). CONCLUSIONS: VHU outperforms clinical risk calculators in detecting low BMD and discriminates prevalent VF equally well as risk calculators with T-scores, yet is significantly simpler to perform. ADVANCES IN KNOWLEDGE: VHU measurement could aid osteoporosis assessment in high-risk smokers undergoing LCS.

A single-blind, parallel-group randomised trial of a Technology-assisted and remotely delivered Cognitive Behavioural Therapy intervention (Tech-CBT) versus usual care to reduce anxiety in people with mild cognitive impairment and dementia: study protocol for a randomised trial.

BACKGROUND: Anxiety is commonly experienced by people living with mild cognitive impairment (MCI) and dementia. Whilst there is strong evidence for late-life anxiety treatment using cognitive behavioural therapy (CBT) and delivery via telehealth, there is little evidence for the remote delivery of psychological treatment for anxiety in people living with MCI and dementia. This paper reports the protocol for the Tech-CBT study which aims to investigate the efficacy, cost-effectiveness, usability and acceptability of a technology-assisted and remotely delivered CBT intervention to enhance delivery of anxiety treatment for people living with MCI and dementia of any aetiology. METHODS: A hybrid II single-blind, parallel-group randomised trial of a Tech-CBT intervention (n = 35) versus usual care (n = 35), with in-built mixed methods process and economic evaluations to inform future scale-up and implementation into clinical practice. The intervention (i) consists of six weekly sessions delivered by postgraduate psychology trainees via telehealth video-conferencing, (ii) incorporates voice assistant app technology for home-based practice, and (iii) utilises a purpose-built digital platform, My Anxiety Care. The primary outcome is change in anxiety as measured by the Rating Anxiety in Dementia scale. Secondary outcomes include change in quality of life and depression, and outcomes for carers. The process evaluation will be guided by evaluation frameworks. Qualitative interviews will be conducted with a purposive sample of participants (n = 10) and carers (n = 10), to evaluate acceptability and feasibility, as well as factors influencing participation and adherence. Interviews will also be conducted with therapists (n = 18) and wider stakeholders (n = 18), to explore contextual factors and barriers/facilitators to future implementation and scalability. A cost-utility analysis will be undertaken to determine the cost-effectiveness of Tech-CBT compared to usual care. DISCUSSION: This is the first trial to evaluate a novel technology-assisted CBT intervention to reduce anxiety in people living with MCI and dementia. Other potential benefits include improved quality of life for people with cognitive impairment and their care partners, improved access to psychological treatment regardless of geographical location, and upskilling of the psychological workforce in anxiety treatment for people living with MCI and dementia. TRIAL REGISTRATION: This trial has been prospectively registered with ClinicalTrials.gov: NCT05528302 [September 2, 2022].

The effect of early childhood respiratory infections and pneumonia on lifelong lung function: a systematic review.

Early childhood respiratory infections, including pneumonia, are an important global public health issue, with more than 40 million annual cases resulting in approximately 650 000 deaths. A growing number of published studies have examined the effects of early childhood lower respiratory tract infections (LRTIs) or pneumonia on lung function, particularly as part of large early-life exposure studies. To our knowledge, there is no published systematic review of these data. We searched PubMed, Embase, and Web of Science for studies published between database inception and May 12, 2022. Case-control, cohort, and cross-sectional studies were included if they reported forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) values of participants older than 5 years. Article titles and abstracts were screened in Rayyan before retrieval, assessment, and data extraction of the full text. Primary outcome measures were differences in mean FEV1 or FVC values between exposed groups (ie, children aged ≤5 years with LRTIs) and non-exposed groups. This study is registered with PROSPERO, CRD42021265295. Database searches yielded 3070 articles, and 14 studies were included in this systematic review, providing a total of 23 276 participants, including 9969 children and 13 307 adults. Eight of 14 articles reported significant reductions in FEV1 values, and six of 12 studies reported reductions in FVC values in children and adults with a history of early childhood LRTIs or pneumonia, compared with unexposed controls (p<0·05). Most studies reporting reductions in lung function described deficits consistent with a restrictive spirometry pattern. Only two of 14 studies reported data from low-income and middle-income countries or disadvantaged populations in middle-income and high-income countries, and there were scarce data available on the effect of LRTI severity and recurrence on lung function. LRTIs in early childhood could be associated with a restrictive spirometry pattern in later childhood and adulthood. Data are needed from low-income and middle-income nations, and from disadvantaged populations in middle-income and high-income countries in which early childhood respiratory infection burden is disproportionately high. Data are also needed on the effect of LRTI severity and recurrence on future lung function.

Communities Setting the Direction for Their Right to Nutritious, Affordable Food: Co-Design of the Remote Food Security Project in Australian Indigenous Communities.

Despite long histories of traditional food security, Indigenous peoples globally are disproportionately exposed to food insecurity. Addressing this imbalance must be a partnership led by Indigenous peoples in accordance with the UN Declaration of the Rights of Indigenous Peoples. We report the co-design process and resulting design of a food security research project in remote Australia and examine how the co-design process considered Indigenous peoples' ways of knowing, being, and doing using the CREATE Tool. Informed by the Research for Impact Tool, together Aboriginal Community Controlled Health Organisation staff, Indigenous and non-Indigenous public health researchers designed the project from 2018-2019, over a series of workshops and through the establishment of research advisory groups. The resulting Remote Food Security Project includes two phases. Phase 1 determines the impact of a healthy food price discount strategy on the diet quality of women and children, and the experience of food (in)security in remote communities in Australia. In Phase 2, community members propose solutions to improve food security and develop a translation plan. Examination with the CREATE Tool showed that employing a co-design process guided by a best practice tool has resulted in a research design that responds to calls for food security in remote Indigenous communities in Australia. The design takes a strengths-based approach consistent with a human rights, social justice, and broader empowerment agenda. Trial registration: The trial included in Phase 1 of this project has been registered with Australian New Zealand Clinical Trials Registry: ACTRN12621000640808.

Healthy Food Prices Increased More Than the Prices of Unhealthy Options during the COVID-19 Pandemic and Concurrent Challenges to the Food System.

Food prices have escalated due to impacts of the COVID-19 pandemic on global food systems, and other regional shocks and stressors including climate change and war. Few studies have applied a health lens to identify the most affected foods. This study aimed to assess costs and affordability of habitual (unhealthy) diets and recommended (healthy, equitable and more sustainable) diets and their components in Greater Brisbane, Queensland, Australia from 2019 to 2022 using the Healthy Diets Australian Standardised Affordability and Pricing protocol. Affordability was determined for reference households at three levels of income: median, minimum wage, and welfare-dependent. The recommended diet cost increased 17.9%; mostly in the last year when the prices of healthy foods, such as fruit, vegetables and legumes, healthy fats/oils, grains, and meats/alternatives, increased by 12.8%. In contrast, the cost of the unhealthy foods and drinks in the habitual diet 'only' increased 9.0% from 2019 to 2022, and 7.0% from 2021 to 2022. An exception was the cost of unhealthy take-away foods which increased by 14.7% over 2019-2022. With government COVID-19-related payments, for the first time recommended diets were affordable for all and food security and diets improved in 2020. However, the special payments were withdrawn in 2021, and recommended diets became 11.5% less affordable. Permanently increasing welfare support and providing an adequate minimum wage, while keeping basic, healthy foods GST-free and increasing GST to 20% on unhealthy foods, would improve food security and diet-related health inequities. Development of a Consumer Price Index specifically for healthy food would help highlight health risks during economic downturns.

Diagnostic accuracy of the Hammersmith Neonatal Neurological Examination in predicting motor outcome at 12 months for infants born very preterm.

AIM: To evaluate the predictive validity of the Hammersmith Neonatal Neurological Examination (HNNE) performed early (at 32 weeks postmenstrual age) and at term-equivalent age (TEA) for 12-month motor outcomes in infants born very preterm. METHOD: This was a diagnostic study using data from a prospective birth cohort. A total of 104 infants born preterm at less than 31 weeks gestational age (males n = 61; mean = 28 weeks 1 day [SD 1 week 6 days], range 23 weeks 1 day-30 weeks 6 days) underwent HNNE early and at TEA, which were scored by comparison with term data. Motor outcomes at 12 months corrected age were determined using the Bayley Scales of Infant and Toddler Development, Third Edition (scores ≤85). Cut-off points were determined using receiver operating characteristic curves. RESULTS: Sixteen (15%) infants born preterm had motor impairment at 12 months corrected age. The HNNE total score cut-off points with the best combination of sensitivity and specificity at early and TEA assessments were 15.2 or lower (sensitivity 77%, 95% confidence interval [CI] = 46%-95%; specificity 74%, 95% CI = 63%-83%) and 23.5 or lower (sensitivity 67%, 95% CI = 38%-88%; specificity 66%, 95% CI = 54%-76%) respectively. The most predictive subscale at the early assessment was reflexes (sensitivity 86%, 95% CI = 57%-98%; specificity 62%, 95% CI = 51%-72%; cut-off point ≤3); at TEA, it was spontaneous movements (sensitivity 73%, 95% CI = 45%-92%; specificity 60%, 95% CI = 48%-70%; cut-off point ≤2). INTERPRETATION: The HNNE provides moderate predictive accuracy for motor outcome at 12 months corrected age in infants born very preterm. Although modest at both time points, early assessment had stronger predictive ability for motor outcomes than TEA when scored using term data, highlighting the value of performing the HNNE earlier in the neonatal period. Performing HNNE earlier may assist risk stratification when planning follow-up services.

Developing Fractional Exhaled Nitric Oxide Predicted and Upper Limit of Normal Values for a Disadvantaged Population.

BACKGROUND: Fractional exhaled nitric oxide (Feno), used as a biomarker, is influenced by several factors including ethnicity. Normative data are essential for interpretation, and currently single cutoff values are used in children and adults. RESEARCH QUESTION: Accounting for factors that influence Feno, (1) what are appropriate predicted and upper limit of normal (ULN) Feno values in an underserved population (First Nations Australians), (2) how do these values compare with age-based interpretive guidelines, and (3) what factors influence Feno and what is the size of the effect? STUDY DESIGN AND METHODS: Feno data of First Nations Australians (age < 16 years, n = 862; age ≥ 16 years, n = 348) were obtained. Medical history using participant questionnaires and medical records were used to define healthy participants. Flexible regression using spline functions, as used by the Global Lung Function Initiative, were used to generate predicted and ULN values. RESULTS: Look-up tables for predicted and ULN values using age (4-76 years) and height (100-200 cm) were generated and are supplied with a calculator for clinician use. In healthy First Nations children (age < 18 years), ULN values ranged between 25 and 60 parts per billion (ppb) when considering only biologically plausible age and height combinations. For healthy adults, ULN values ranged between 39 and 88 ppb. Neither the current Feno interpretation guidelines, nor the currently recommended cutoff of 50 ppb for First Nations children 16 years of age or younger were appropriate for use in this cohort. Our modelling revealed that predicted and ULN values of healthy participants varied nonlinearly with age and height. INTERPRETATION: Because single pediatric, adult, or all-age Feno cutoff values used by current interpretive guidelines to define abnormality fail to account for factors that modify Feno values, we propose predicted and ULN values for First Nations Australians 4 to 76 years of age. Creating age- and height-adjusted predicted and ULN values could be considered for other ethnicities.