Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.

Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-Risk Settings: A Randomized Controlled Trial.

BACKGROUND: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease. METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario). RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences. CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.

Restricting access to antibiotics: The effectiveness of a 'no repeats' government policy intervention.

BACKGROUND: Australia has a high rate of antibiotic use. Government policy interventions are one strategy to optimise the use of antibiotics. On 1 April 2020, the Australian Government Department of Health introduced a policy intervention to increase the quality use of four antibiotics. OBJECTIVES: To assess if the government policy intervention improved the appropriate supply of the four antibiotics amoxicillin, amoxicillin-clavulanic acid, cefalexin and roxithromycin. METHOD: This study employed a retrospective cohort study design comparing a 10% sample (n = 345,018) of four antibiotics prescribed and dispensed in Australia during a three-month period (May, June, July) in 2019, and again in 2020 (after the policy intervention). The 10% sample of PBS data was obtained from the Australian Government Department of Health. Descriptive statistics, bivariate and multivariable logistic regression analysis were carried out. RESULTS: The results suggest the policy change improved the appropriate supply of original prescriptions in 2020 compared to 2019 OR = 1.75 (95% CI = 1.68-1.82, p < 0.001), and appropriate supply of repeat prescriptions OR = 1.56 (95% CI = 1.25-1.96, p < 0.001). In 2020, the proportion of appropriate supply of original prescriptions increased by an absolute difference of 1.8% (95% CI = 1.6-1.9%; P < 0.001), and appropriate supply of repeat prescriptions increased by 3.9% (95% CI = 2.2-5.5%; P < 0.001). The total number of antibiotic prescriptions prescribed and dispensed in 2019 (N = 219,960) reduced in 2020 (N = 125,058) after the policy intervention. CONCLUSION: The study provides evidence for the impact of a government policy intervention to improve the appropriate supply of antibiotics, although some of the reduction in antibiotic use was likely due to the concomitant COVID-19 pandemic. Further research is required to assess the impact of the intervention outside a pandemic.

Prevalence Rates of Depression and Anxiety among Young Rural and Urban Australians: A Systematic Review and Meta-Analysis.

Globally, depression and anxiety are major public health concerns with onset during adolescence. While rural Australia experiences overall lower health outcomes, variation in mental health prevalence rates between rural and urban Australia is unclear. The aim of this paper was to estimate the pooled prevalence rates for depression and anxiety among young Australians aged between 10 and 24 years. Selected studies from a systematic literature search were assessed for risk of bias. Random effects model using DerSimonian and Laird method with Freeman-Tukey Double Arcsine Transformation was fitted. Sensitivity analyses were performed. Prevalence estimates were stratified by region and disorder. The overall pooled prevalence of depression and anxiety was 25.3% (95% CI, 19.9-31.0%). In subgroup analysis, anxiety prevalence was 29.9% (95% CI, 21.6-39.0%); depression: 21.3% (95% CI, 14.9-28.5%); and depression or anxiety: 27.2% (95% CI, 20.3-34.6%). Depression and anxiety prevalence were higher in urban 26.1% (95% CI, 17.3-35.9%) compared to rural areas 24.9% (95% CI, 17.5-33%), although the difference was not statistically significant. The heterogeneity was high with an I2 score of 95.8%. There is need for further research on healthcare access, mental health literacy and help-seeking attitude in Australia.

Examination of the nutritional intake of patients undergoing opioid replacement therapy: A systematic review.

AIM: This systematic review aimed to determine the level of existing research that investigates the intake, specifically macro and micronutrient intake, of patients undergoing opioid replacement therapy. METHODS: A systematic review was conducted across PubMed, Embase, Cochrane and CINAHL databases using a pre-determined protocol. Studies published between 2001 and 2022 assessing macronutrient or micronutrient intake in opioid replacement therapy patients were included. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was utilised for quality appraisal.  Data from each of the included papers was synthesised in a narrative manner. Data extracted included all measurements of nutrition including macronutrient, and micronutrient intake and any bioanalysis results and methods utilised. RESULTS: Seven papers (one cohort study and six cross-sectional studies, n = 443) were included that investigated an aspect of nutritional intake in patients receiving opioid replacement therapy. The majority of included papers reported an assessment of both macro and micronutrient and resulting energy intake as determined by food consumption. The included papers described a picture of irregular nutritional intake in patients undergoing opioid replacement therapy. CONCLUSION: Minimal research into the nutritional intake of opioid replacement therapy patients exists. The existing research is suggestive of irregular nutritional intake from both macro and micronutrient consumption and indicates a need for further studies and increased attention on this vulnerable patient group.

Built Environment Features and Cardiometabolic Mortality and Morbidity in Remote Indigenous Communities in the Northern Territory, Australia.

Indigenous Australians experience poorer health than non-Indigenous Australians, with cardiometabolic diseases (CMD) being the leading causes of morbidity and mortality. Built environmental (BE) features are known to shape cardiometabolic health in urban contexts, yet little research has assessed such relationships for remote-dwelling Indigenous Australians. This study assessed associations between BE features and CMD-related morbidity and mortality in a large sample of remote Indigenous Australian communities in the Northern Territory (NT). CMD-related morbidity and mortality data were extracted from NT government health databases for 120 remote Indigenous Australian communities for the period 1 January 2010 to 31 December 2015. BE features were extracted from Serviced Land Availability Programme (SLAP) maps. Associations were estimated using negative binomial regression analysis. Univariable analysis revealed protective effects on all-cause mortality for the BE features of Education, Health, Disused Buildings, and Oval, and on CMD-related emergency department admissions for the BE feature Accommodation. Incidence rate ratios (IRR's) were greater, however, for the BE features Infrastructure Transport and Infrastructure Shelter. Geographic Isolation was associated with elevated mortality-related IRR's. Multivariable regression did not yield consistent associations between BE features and CMD outcomes, other than negative relationships for Indigenous Location-level median age and Geographic Isolation. This study indicates that relationships between BE features and health outcomes in urban populations do not extend to remote Indigenous Australian communities. This may reflect an overwhelming impact of broader social inequity, limited correspondence of BE measures with remote-dwelling Indigenous contexts, or a 'tipping point' of collective BE influences affecting health more than singular BE features.

Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials.

BACKGROUND: Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules. METHODS: PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 µg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849). FINDINGS: Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related. INTERPRETATION: Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children. FUNDING: National Health and Medical Research Council (NHMRC).

Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial.

BACKGROUND: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP. METHODS: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1-3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13-14 days duration) or standard (5-6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks. RESULTS: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86-1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance. CONCLUSIONS: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits.

Metabolically Healthy and Unhealthy Obese Phenotypes among Arabs and South Asians: Prevalence and Relationship with Cardiometabolic Indicators.

Obesity is a public health crisis in Kuwait. However, not all obese individuals are metabolically unhealthy (MuHO) given the link between obesity and future cardiovascular events. We assessed the prevalence of the metabolically healthy obese (MHO) phenotype and its relationship with high sensitivity C-reactive protein (hs-CRP), serum alanine aminotransferase (ALT), and insulin resistance (HOMA-IR) in Arab and South Asian ethnic groups in Kuwait. The national cross-sectional survey of diabetes and obesity in Kuwait adults aged 18-60 years were analysed. The harmonised definition of metabolic syndrome was used to classify metabolic health. Multinomial logistic regression analysis was used to model the relationship between the MHO and MuHO phenotypes and hs-CRP, ALT and HOMA-IR levels. Overall, the prevalence of MHO for body mass index (BMI)- and waist circumference (WC)-defined obesity was 30.8% and 56.0%, respectively; it was greater in women (60.4% and 61.8%, respectively) than men (39.6% and 38.2%, respectively). Prevalence rates were also lower for South Asians than for Arabs. The MHO phenotype had hs-CRP values above 3 µg/mL for each age group category. Men compared to women, and South Asians compared to Arabs had a lower relative risk for the MHO group relative to the MuHO group. This study shows there is high prevalence of MHO in Kuwait.

Association of Built Environmental Features with Rates of Infectious Diseases in Remote Indigenous Communities in the Northern Territory, Australia.

The health of Indigenous Australians is far poorer than non-Indigenous Australians, including an excess burden of infectious diseases. The health effect of built environmental (BE) features on Indigenous communities receives little attention. This study's objective was to determine associations between BE features and infectious disease incidence rates in remote Indigenous communities in the Northern Territory (NT), Australia. Remote Indigenous communities (n = 110) were spatially joined to 93 Indigenous Locations (ILOC). Outcomes data were extracted (NT Notifiable Diseases System) and expressed as ILOC-specific incidence rates. Counts of buildings were extracted from community asset maps and grouped by function. Age-adjusted infectious disease rates were dichotomised, and bivariate binomial regression used to determine the relationships between BE variables and infectious disease. Infrastructure Shelter BE features were universally associated with significantly elevated disease outcomes (relative risk 1.67 to 2.03). Significant associations were observed for Services, Arena, Community, Childcare, Oval, and Sports and recreation BE features. BE groupings associated with disease outcomes were those with communal and/or social design intent or use. Comparable BE groupings without this intent or use did not associate with disease outcomes. While discouraging use of communal BE features during infectious disease outbreaks is a conceptually valid countermeasure, communal activities have additional health benefits themselves, and infectious disease transmission could instead be reduced through repairs to infrastructure, and more infrastructure. This is the first study to examine these associations simultaneously in more than a handful of remote Indigenous communities to illustrate community-level rather than aggregated population-level associations.

Anthropometric cut-points for discriminating diabetes and the metabolic syndrome among Arabs and Asians: the Kuwait Diabetes Epidemiology Program.

This study aimed to determine anthropometric cut-points for screening diabetes and the metabolic syndrome (MetS) in Arab and South Asian ethnic groups in Kuwait and to compare the prevalence of the MetS based on the ethnic-specific waist circumference (WC) cut-point and the International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute WC criteria. The national population-based survey data set of diabetes and obesity in Kuwait adults aged 18-60 years was analysed. Age-adjusted logistic regression and receiver operating characteristic (ROC) analyses were conducted to evaluate for 3589 individuals the utility of WC, waist:height ratio (WHtR) and BMI to discriminate both diabetes and ≥3 CVD risk factors. Areas under the ROC curve were similar for WC, WHtR and BMI. In Arab men, WC, WHtR and BMI cut-offs for diabetes were 106 cm, 0·55 and 28 kg/m2 and for ≥3 CVD risk factors, 97 cm, 0·55 and 28 kg/m2, respectively. In Arab women, cut-offs for diabetes were 107 cm, 0·65 and 33 kg/m2 and for ≥3 CVD risk factors, 93 cm, 0·60 and 30 kg/m2, respectively. WC cut-offs were higher for South Asian women than men. IDF-based WC cut-offs corresponded to a higher prevalence of the MetS across sex and ethnic groups, compared with Kuwait-specific cut-offs. Any of the assessed anthropometric indices can be used in screening of diabetes and ≥3 CVD risk factors in Kuwaiti Arab and Asian populations. ROC values were similar. The WC threshold for screening the MetS in Kuwaiti Arabs and South Asians is higher for women.

Racial disparities in COVID-19 pandemic cases, hospitalisations, and deaths: A systematic review and meta-analysis.

BACKGROUND: People from racial minority groups in western countries experience disproportionate socioeconomic and structural determinants of health disadvantages. These disadvantages have led to inequalities and inequities in health care access and poorer health outcomes. We report disproportionate disparities in prevalence, hospitalisation, and deaths from COVID-19 by racial minority populations. METHODS: We conducted a systematic literature search of relevant databases to identify studies reporting on prevalence, hospitalisations, and deaths from COVID-19 by race groups between 01 January 2020 - 15 April 2021. We grouped race categories into Blacks, Hispanics, Whites and Others. Random effects model using the method of DerSimonian and Laird were fitted, and forest plot with respective ratio estimates and 95% confidence interval (CI) for each race category, and subgroup meta-regression analyses and the overall pooled ratio estimates for prevalence, hospitalisation and mortality rate were presented. RESULTS: Blacks experienced significantly higher burden of COVID-19: prevalence ratio 1.79 (95% confidence interval (CI) = 1.59-1.99), hospitalisation ratio 1.87 (95% CI = 1.69-2.04), mortality ratio 1.68 (95% CI = 1.52-1.83), compared to Whites: prevalence ratio 0.70 (95% CI = 0.0.64-0.77), hospitalisation ratio 0.74 (95% CI = 0.65-0.82), mortality ratio 0.82 (95% CI = 0.78-0.87). Also, Hispanics experienced a higher burden: prevalence ratio 1.78 (95% CI = 1.63-1.94), hospitalisation ratio 1.32 (95% CI = 1.08-1.55), mortality ratio 0.94 (95% CI = 0.84-1.04) compared to Whites. A higher burden was also observed for Other race groups: prevalence ratio 1.43 (95% CI = 1.19-1.67), hospitalisation ratio 1.12 (95% CI = 0.89-1.35), mortality ratio 1.06 (95% CI = 0.89-1.23) compared to Whites. The disproportionate burden among Blacks and Hispanics remained following correction for publication bias. CONCLUSIONS: Blacks and Hispanics have been disproportionately affected by COVID-19. This is deeply concerning and highlights the systemically entrenched disadvantages (social, economic, and political) experienced by racial minorities in western countries; and this study underscores the need to address inequities in these communities to improve overall health outcomes.

Mass drug administration campaigns for scabies and impetigo: protocol for a systematic review and meta-analysis.

Introduction: Scabies is recognised as a neglected tropical disease, disproportionately affecting the most vulnerable populations around the world. Impetigo often occurs secondarily to scabies. Several studies have explored mass drug administration (MDA) programmes, with some showing positive outcomes-but a systematic evaluation of such studies is yet to be reported. The main aim of this systematic review is to generate comprehensive evidence on the effect and feasibility of MDA programmes in reducing the burden of scabies and impetigo. Methods and analysis: A systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Electronic databases to be searched will include CINAHL EBSCOhost, Medline Ovid, ProQuest, Science Direct, PubMed and SCOPUS. In addition, grey literature will be explored via the Australian Institute of Health and Welfare, Australian Indigenous HealthInfoNet, Informit, OaIster database and WHO. No language restrictions will be applied. All treatment studies following an MDA protocol, including randomised/quasi-controlled trials, and prospective before-after interventional studies, will be considered. The main outcome is the change in prevalence of scabies and impetigo The Cochrane collaboration risk of bias assessment tool will be used for assessing the methodological quality of studies. A random-effect restricted maximum likelihood meta-analysis will be performed to generate pooled effect (OR) using STATA V.16. Appropriate statistical tests will be carried out to quantify heterogeneity between studies and publication bias. Ethics and dissemination: Ethical approval is not required since data will be extracted from published works. The findings will be communicated to the scientific community through a peer-reviewed journal publication. This systematic review will present an evidence on the effect of MDA interventions on scabies and impetigo, which is instrumental to obtain a clear understanding of the treatments widely used in these programmes. PROSPERO registration number: CRD42020169544.

A community-based service enhancement model of training and employing Ear Health Facilitators to address the crisis in ear and hearing health of Aboriginal children in the Northern Territory, the Hearing for Learning Initiative (the HfLI): study protocol for a stepped-wedge cluster randomised trial.

BACKGROUND: Almost all Aboriginal children in remote communities have persistent bilateral otitis media affecting hearing and learning throughout early childhood and school years, with consequences for social and educational outcomes, and later employment opportunities. Current primary health care and specialist services do not have the resources to meet the complex needs of these children. METHOD/DESIGN: This stepped-wedge cluster randomised trial will allocate 18 communities to one of five 6-monthly intervention start dates. Stratification will be by region and population size. The intervention (Hearing for Learning Initiative, HfLI) consists of six 20-h weeks of training (delivered over 3 months) that includes Certificate II in Aboriginal Primary Health Care (3 modules) and competencies in ear and hearing data collection (otoscopy, tympanometry and hearScreen), plus 3 weeks of assisted integration into the health service, then part-time employment as Ear Health Facilitators to the end of the trial. Unblinding will occur 6 months prior to each allocated start date, to allow Community Reference Groups to be involved in co-design of the HfLI implementation in their community. Relevant health service data will be extracted 6-monthly from all 18 communities. The primary outcome is the difference in proportion of children (0 to 16 years of age) who have at least one ear assessment (diagnosis) documented in their medical record within each 6-month period, compared to control periods (no HfLI). Secondary outcomes include data on sustainability, adherence to evidence-based clinical guidelines for otitis media, including follow-up and specialist referrals, and school attendance. Structured interviews with staff working in health and education services, Ear Health Trainees, Ear Health Facilitators and families will assess process outcomes and the HfLI broader impact. DISCUSSION: The impact of training and employment of Ear Health Facilitators on service enhancement will inform the health, education and employment sectors about effectiveness of skills and job creation that empowers community members to contribute to addressing issues of local importance, in this instance ear and hearing health of children. TRIAL REGISTRATION: ClinicalTrials.gov NCT03916029 . Registered on 16 April 2019.

Comparison of Profiles of First Nations and Non-First Nations Children With Bronchiectasis Over Two 5-Year Periods in the Northern Territory, Australia.

BACKGROUND: Although the burden of bronchiectasis is recognized globally, pediatric data are limited, particularly on trends over the years. Also, no published data exists regarding whether vitamin D deficiency or insufficiency and human T-cell lymphotropic virus type 1 (HTLV-1) infection, both found to be related to severe bronchiectasis in First Nations adults, also are important in children with bronchiectasis. RESEARCH QUESTION: Among children with bronchiectasis, (1) have the clinical and BAL profiles changed between two 5-year periods (period 1, 2007-2011; period 2, 2012-2016) and (b) are vitamin D deficiency or insufficiency, HTLV-1 infection, or both associated with radiologic severity of bronchiectasis? STUDY DESIGN AND METHODS: We analyzed the data from children with bronchiectasis prospectively enrolled at Royal Darwin Hospital, Australia, at the first diagnosis; that is, no child was included in both periods. Data collected include demographics, BAL, routine investigation bloods, and high-resolution CT scan of the chest evaluated using the Bhalla and modified Bhalla scores. RESULTS: The median age of the 299 children was 2.2 years (interquartile range, 1.5-3.7 years). One hundred sixty-eight (56%) were male and most were First Nations (92%). Overall, bronchiectasis was high over time, particularly among First Nations children. In the later period, numbers of non-First Nations children more than tripled, but did not reach statistical significance. In period 2 compared with period 1, fewer First Nations children demonstrated chronic cough (period 1, 61%; period 2, 47%; P = .03), and were younger, First Nations children were less likely to have received azithromycin (period 1, 42%; period 2, 21%; P < .001), and the BAL fluid of First Nations children showed lower Haemophilus influenzae and Moraxella catarrhalis infection. HTLV-1 infection was not detected, and vitamin D deficiency or insufficiency did not correlate with severity of bronchiectasis. INTERPRETATION: Bronchiectasis remains high particularly among First Nations children. Important changes in their profiles that arguably reflect improvements were present, but overall, the profiles remained similar. Although vitamin D deficiency was uncommon, its role in children with bronchiectasis requires further evaluation. HTLV-1 infection was nonexistent and is unlikely to play any role in First Nations children with bronchiectasis.

Prevalence of overweight and obesity, and associations with socio-demographic factors in Kuwait.

BACKGROUND: Kuwait is amongst countries in the Gulf region with high income economy. According to the World Health Organisation (WHO), one in five adults in the Gulf region is obese. This study sought to evaluate the prevalence and magnitude of association between overweight, obesity, central obesity, and socio-demographic factors in Kuwait. METHODS: A population-based cross-sectional survey of diabetes and obesity in Kuwait - part of the Kuwait Diabetes Epidemiology Program - was conducted between 2011 and 2014, targeting adults aged 18-82 years using the WHO STEPwise approach to non-communicable disease surveillance. Body mass index (BMI) was calculated to classify overweight and obesity, and waist circumference (WC) used to express central obesity. Multivariable logistic regression was used to estimate relationships between socio-demographic factors, overweight (25.0-29.9 kg/m2), obesity (≥30.0 kg/m2) or central obesity (WC ≥ 80 cm women; WC ≥ 94 cm men). RESULTS: Records for gender (56% Men), age, BMI, governorate, and nationality existed for 4901 individuals. Mean age and BMI were 43 years and 30 kg/m2, respectively. Non-Kuwaiti nationals were more prevalent than Kuwaitis (76% vs 24%). Prevalence rates for overweight, obesity and central obesity were 40.6% (95%CI: 38.4-42.8%), 42.1% (95%CI: 40.0-44.3%) and 73.7% (95%CI: 71.7-75.6%), respectively. The youngest age group (18-29 years) had rates of 38.2% (95%CI: 29.2-47.7%), 27.2% (95%CI: 19.0-36.7%) and 49.9% (95%CI: 40.6-59.1%) for overweight, obesity and central obesity, respectively. In covariate-adjusted analyses, the odds of being overweight was 26% greater for men than for women. Conversely, women had a 54% (95%CI: 19-99%) and 7-fold (95%CI, 5-10-fold) greater odds of obesity/central obesity, respectively, than men. Greater educational attainment, physical activity, and non-Kuwaiti status were associated with lower odds of obesity/central obesity. History of smoking, elevated blood pressure, higher income, being married, greater age and female sex related to greater odds of obesity/central obesity. CONCLUSION: Overweight was greater in men, obesity greater in women. Overweight and obesity prevalence were high in young adults aged 18-29 years, a significant public health concern. Efforts to integrate mandatory physical education to the school curriculum and promoting the creation of recreation spaces/parks to promote physical activities, will play a vital role in the early prevention of overweight/obesity in Kuwait.

Otitis media outcomes of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal conjugate vaccine schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial.

BACKGROUND: Aboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), with recommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months. METHODS: In an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2-4-6 months (_PPP), Synflorix™ (S) at 2-4-6 months (_SSS), or Synflorix™ at 1-2-4 months plus Prevenar13™ at 6 months (SSSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severity hierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM). RESULTS: Between September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86, and 90% in the _PPP, _SSS, and SSSP groups, respectively. There were no significant differences in prevalence of any form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57, 82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7 months, 277 (71.4%) had OM that met criteria for specialist referral; rAOM, pOME, or CSOM. CONCLUSIONS: Despite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life. TRIAL REGISTRATION: ACTRN12610000544077 registered 06/07/2010 and ClinicalTrials.gov NCT01174849 registered 04/08/2010.